EPA/600/8-86/032b
March 1987
Integrated Risk Information System
Chemical Files
Volume II
U.S. Environmental Protection Agency
Region V, Library
230 South Dearborn Street:
Chicago, Illinois €0604
Office of Health and Environmental Assessment
Office of Research and Development
U.S. Environmental Protection Agency
Washington, DC 20460
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UtlS. Environmental Protection Agency
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
P OFFICE OF RESEARCH AND DEVELOPMENT
ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
CINCINNATI. OHIO 45268
April 14, 1987
ERRATA
Integrated Risk Information System (IRIS) - Volume II. Chemical Files
The following two chemical files have been removed from IRIS. Please
remove these files from your Vol-'ume II Binder.
1. Methyl Ethyl Ketone Peroxide
CAS #1338-23-4
„ i
2. Cresols
CAS #1319-77-3
Corrections have been made to the following three chemical files 1n
Volume II.
1. Phenyl Mercuric Acetate
CAS #62-38-4
2. Tetraethyl Lead
CAS #78-00-2
3. 1,1,2-TMchloro-l,2,2-trlfluorethene
CAS #76-13-1
Please replace pages 1 and 2 of each of these files with the attached
corrected pages.
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INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
CAS No. and Synonym Index (Revised 11/16/86)
The pages in this volume are not numbered (except within individual chemical
files) because chemical files will be changed when new information becomes
available. The IRIS chemical files contained in this volume are arranged in
alphabetical order. The names under which chemicals are filed are listed
alphabetically in the first part of this index. A listing in CAS No. order
follows. CAS numbers are unique in that two chemicals will not have the same
number, but one substance may have more than one number. In addition, a risk
assessment for a particular substance may apply to various forms of that
substance which have different CAS numbers but are not explicitly listed
(e.g., Dalapon and Sodium Dalapon). Part 3 of this index is an alphabetical
list of synonyms for all the chemicals on IRIS. The synonym index is
included because the chemical name used on IRIS may not be the name with
which the user is familiar. Each synonym is followed by the name of the IRIS
chemical file which contains the information for that chemical. The synonyms
are presented in the format: "synonym -- file name". Continuations of
synonyms too long for one line are indented on the next line.
1. ALPHABETICAL LIST OF CHEMICALS ON IRIS
Acrylic acid
Aldicarb
Aluminum phosphide
Allyl alcohol
Ant imony
Barium
Barium cyanide
Beryllium
1,1-Biphenyl
Bis(2-ethylhexyl)phthalate
Bromomethane
Butylphthalyl butylglycolate
Calcium cyanide
Carbaryl
Carbon tetrachloride
Chlorine cyanide
Chloroform
Chromium (III)
Copper cyanide
Cresols
Cyanide
Cyanogen
Dalapon
2,4-DB
Decabromodiphenyl ether
Dibutylnitrosamine
Dibutyl phthalate
1,1-Dichloroethylene
Dichlorodifluoromethane
2,4-Dichlorophenol
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IRIS Index: page 2 of 15
Diethylnitrosamine
Dimethoate
Dimethyldoorknob
DimethyInitrosamine
Dimethyl terephthalate
Dinitrochickenwire
Dinoseb
1,2-Diphenylhydrazine
Epichlorohydrin
Ethyl benzene
Ethylphthalyl ethylglycolate
Fluoride
Fluridone
Formic acid
Furan
Hexachlorbutadiene
Hexachlorocyclopentadiene
Hydrogen cyanide
Hydrogen sulfide
Isophorone
Lindane
MCPA
MCPP
Methylene chloride
Methyl ethyl ketone
Methyl ethyl ketone peroxide
Methyl mercury
Nitrate
Nitric oxide
Nitrite
Nitrobenzene
Nitrogen dioxide
N-Nitrosopyrrolidine
Pentachlorobenzene
Pentachlorophenol
Phenol
m-Phenylenediamine
Phenyl mercuric acetate
Phosphine
Potassium cyanide
Potassium silver cyanide
Selenious acid
Selenourea
Silver
Silver cyanide
Sodium cyanide
Sodium diethyldithiocarbamate
Strychnine
Styrene
1,2,4,5-Tetrachlorobenzene
Tetrachloroethylene
2,3,4,6-Tetrachlorophenol
Tetraethyl lead
Thallic oxide
Thallium acetate
Thallium carbonate
Thallium chloride
Thallium nitrate
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IRIS Index: page 3 of 15
Thallium selenite
Thallium (I) sulfate
Toluene
1,2,4-Trichlorobenzene
Trichloromonofluoromethane
2,4,5-Tr ichlorophenol
2,4,6-Trichlorophenol
1,1,2-Trichloro-l,2,2-trifluoroethane
Vanadium pentoxide
Zinc cyanide
2. CAS NO. LISTING OF CHEMICALS ON IRIS
55-18-5 Diethylnitrosamine
56-23-5 Carbon tetrachloride
57-12-5 Cyanide
57-24-9 Strychnine
58-89-9 Lindane
58-90-2 2,3,4,6-Tetrachlorophenol
60-51-5 Dimethoate
62-38-4 Phenyl mercuric acetate
62-75-9 Dimethylnitrosamine
63-25-2 Carbaryl
64-18-6 Formic acid
67-66-3 Chloroform
74-83-9 Bromomethane
74-90-8 Hydrogen cyanide
75-09-2 Methylene chloride
75-35-4 1,1-Dichloroethylene
75-69-4 Trichloromonofluoromethane
75-71-8 Dichlorodifluoromethane
76-13-1 1,1,2-Trichloro-l,2,2-trifluoroethane
77-47-4 Hexachlorocyclopentadiene
78-00-2 Tetraethyl lead
78-59-1 Isophorone
78-93-3 Methyl ethyl ketone
79-10-7 Acrylic acid
84-72-0 Ethylphthalyl ethylglycolate
84-74-2 Dibutyl phthalate
85-70-1 Butylphthalyl butylglycolate
87-68-3 Hexachlorobutadiene
87-86-5 Pentachlorophenol
88-06-2 2,4,6-Trichlorophenol
88-85-7 Dinoseb
92-52-4 1,1-Biphenyl
93-65-2 MCPP
94-74-6 MCPA
94-82-6 2,4-DB
95-94-3 1,2,4,5-Tetrachlorobenzene
95-95-4 2,4,5-Trichlorophenol
98-95-3 Nitrobenzene
100-41-4 Ethylbenzene
100-42-5 Styrene
106-89-8 Epichlorohydrin
107-18-6 Allyl alcohol
108-45-2 m-Phenylenediamine
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IRIS Index: page 4 of 15
108-88-3 Toluene
108-95-2 Phenol
110-00-9 Furan
116-06-3 Aldicarb
117-81-7 Bis(2-ethylhexyl)phthlate
120-61-6 Dimethyl terephthalate
120-82-1 1,2,4-Trichlorobenzene
120-83-2 2,4-Dichlorophenol
122-66-7 1,2-Diphenylhydrazine
127-18-4 Tetrachloroethylene
127-20-8 Dalapon
143-33-9 Sodium cyanide
148-18-5 Sodium diethyldithiocarbamate
151-50-8 Potassium cyanide
460-19-5 Cyanogen
506-61-6 Potassium silver cyanide
506-64-9 Silver cyanide
506-77-4 Chlorine cyanide
542-62-1 Barium cyanide
544-92-3 Copper cyanide
557-21-1 Zinc cyanide
563-68-8 Thallium acetate
592-01-8 Calcium cyanide
608-93-5 Pentachlorobenzene
630-10-4 Selenourea
924-16-3 Dibutylnitrosamine
930-55-2 N-Nitrosopyrrolidine
1163-19-5 Decabromodiphenyl ether
1314-32-5 Thallic oxide
1314-62-1 Vanadium pentoxide
1319-77-3 Cresols
1338-23-4 Methyl ethyl ketone peroxides
6533-73-9 Thallium carbonate
7440-22-4 Silver
7440-36-0 Antimony
7440-39-3 Barium
7440-41-7 Beryllium
7446-18-6 Thallium (I) sulfate
7783-00-8 Selenious acid
7783-06-4 Hydrogen sulfide
7791-12-0 Thallium chloride
7803-51-2 Phosphine
10102-43-9 Nitric oxide
10102-44-0 Nitrogen dioxide
10102-45-1 Thallium nitrate
12039-52-0 Thallium selenite
12345-67-8 Dinitrochickenwire
14797-55-8 Nitrate
14797-65-0 Nitrite
16065-83-1 Chromium (III)
16984-48-8 Fluoride
20859-73-8 Aluminum phosphide
22967-92-6 Methyl mercury
59756-60-4 Fluridone
98765-43-2 Dimethyldoorknob
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IRIS Index: page 5 of 15
3. LIST OF SYNONYMS
AA -- Allyl alcohol
Acede cresylique (French) -- Cresols
Acetic Acid, 0,0-Dimethyldithiophosphoryl-,
N-Monomethylamide Salt -- Dimethoate
Acetic Acid, Phenylmercury Deriv -- Phenyl mercuric acetate
Acetoxyphenylmercury -- Phenyl mercuric acetate
Acide formique (French) -- Formic acid
Acido formico (Italian) -- Formic acid
Acroleic acid -- Acrylic acid
Acrylic acid, glacial -- Acrylic acid
Aethylbenzol (German) -- Ethyl benzene
Aethylmethylketon (German) -- Methyl ethyl ketone
Alcool allilco (Italian) -- Allyl alcohol
Alcool allylique (French) -- Allyl alcohol
Aldecarb -- Aldicarb
Allilowy alkohol (Polish) -- Allyl alcohol
Allylalkohol (German) - - Allyl alcohol
Allylic alcohol -- Allyl alcohol
A1P - - Aluminum phosphide
alpha-Naftyl-N-methylkarbamat (Czech) -- Carbaryl
alpha-Naphthyl N-methylcarbamate -- Carbaryl
Al-Phos -- Aluminum phosphide
Aluminum Monophosphide - - Aluminum phosphide
Ameisensaeure (German) -- Formic acid
Aminic acid -- Formic acid
m-Aminoaline -- m-Phenylenediamine
3-Aminoaniline -- m-Phenylenediamine
Antymon (Polish) -- Antimony
Argentum -- Silver
Barium dicyanide -- Barium cyanide
BEHP -- Bis(2-ethylhexyl)phthalate
m-Benzenediamine -- m-Phenylenediamine
1,3-Benzenediamine -- m-Phenylenediamine
1,2-Benzenedicarboxylic acid,
bis(2-ethylhexyl) ester -- Bis(2-ethylhexyl)phthalate
1,2-Benzenedicarboxylic Acid Dibutyl Ester -- Dibutyl Phthalate
1,2-Benzenedicarboxylic acid, diethyl ester -- Diethyl phthalate
1,4-Benzenedicarboxylic acid, dimethyl ester -- Dimethyl terephthalate
Benzene Hexachloride-gamma-isomer -- Lindaiie
Benzene, hydrazodi- -- 1,2-Diphenylhydrazine
Benzene, nitro- -- Nitrobenzene
Benzene, pentachloro- -- Pentachlorobenzene
Benzene, 1,2,4,5-tetrachloro- -- 1,2,4,5-Tetrachlorobenzene
Benzene, 1,2,4-trichloro- -- 1,2,4-Trichlorobenzene
Benzene, vinyl- -- Styrene
Bibenzene -- 1,1-Biphenyl
Bioxyde d'azote (French) -- Nitric oxide
1,1'-Biphenyl -- 1,1-Biphenyl
Bis(2-ethylhexyl)-1,2-benzenedicarboxylate -- Bis(2-ethylhexyl)phthalate
1,3-Butadiene, hexachloro- -- Hexachlorbutadiene
1-Butanamine, N-butyl-N-nitroso- -- Dibutylnitrosamine
Butanone -- Methyl ethyl ketone
Butanone 2 (French) -- Methyl ethyl ketone
Butaphene -- Dinoseb
Butoxon -- 2,4-DB
Butoxone -- 2,4-DB
Butylamine, N-nitrosodi- -- Dibutylnitrosamine
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IRIS Index: page 6 of 15
Butyl glycolyl butyl phthalate -- Butylphthalyl butylglycolate
N-Butyl-N-nitroso-1-butamine -- Dibutylnitrosamine
N-Butylphthalate -- Dlbutyl Phthalate
Butyl phthalate butyl glycolate -- Butylphthalyl butylglycolate
Calcyanide -- Calcium cyanide
Carbamic acid, diethyldithio-, sodium salt -- Sodium diethyldithiocarbamate
Carbamic Acid, Methyl-, 0-((2- Methyl-2-(Methylthio)Propylidene)Amino)
derivative -- Aldicarb
Carbamine - - Carbaryl
Carbamodithioic acid, diethyl-, sodium salt -- Sodium diethyldithiocarbamate
Carbamyl - - Aldicarb
Carbanolate -- Aldicarb
Carbaril (Italian) -- Carbaryl
Garbethoxymethy1 ethyl phthalate -- Ethylphthalyl ethylglycolate
Carbon chloride -- Carbon tetrachloride
Carbon dichloride -- Tetrachloroethylene
Carbon disulphide -- Carbon disulfide
Carbon nitride -- Cyanogen
Carbon nitride ion -- Cyanide
Carbon sulfide -- Carbon disulfide
Carbon tet -- Carbon tetrachloride
Chickenwire, 1,2-dinitro -- Dinitrochickenwire
l-Chloor-2,3-epoxy-propaan (Dutch) -- Epichlorohydrin
2-(4-Chloor-2-Methyl-Fenoxy)-Propionzuur (Dutch) -- MCPP
Chlorcyan - - Chlorine cyanide
l-Chlor-2,3-epoxy-propan (German) -- Epichlorohydrin
2-(4-Chlor-2-Methyl-Phenoxy)-Propionsaeure (German) -- MCPP
Chlorocyan -- Chlorine cyanide
Chlorocyanide -- Chlorine cyanide
Chlorocyanogen -- Chlorine cyanide
l-Chloro-2,3-epoxypropane -- Epichlorohydrin
3-Chloro-l,2-epoxypropane -- Epichlorohydrin
(Chloromethyl)ethylene oxide -- Epichlorohydrin
(4-Chloro-2-methylphenoxy)-acetic acid -- MCPA
2-(4-Chloro-2-Methylphenoxy)Propionic Acid -- MCPP
3-Chloro-l,2-propylene oxide -- Epichlorohydrin
Chloropropylene oxide -- Epichlorohydrin
Chlorure de cyanogene (French) -- Chlorine cyanide
Chlorure de methylene (French) -- Methylene chloride
Chlorure de vinylidene (French) -- 1,1-Dichloroethylene
Chromic ion -- Chromium (III)
Chromium (3+) -- Chromium (III)
Cinnamene -- Styrene
Cinnamenol -- Styrene
Cinnamol -- Styrene
l-Cloro-2,3-epossipropano (Italian) -- Epichlorohydrin
CMPP -- MCPP
Cresol -- Cresols
Cresoli (Italian) -- Cresols
Cresylic acid -- Cresols
Cupral -- Sodium diethyldithiocarbamate
Cupricin -- Copper cyanide
Cuprous cyanide -- Copper cyanide
Cyanide ion -- Cyanide
Cyanide of Potassium -- Potassium Cyanide
Cyanide of Sodium -- Sodium Cyanide
Cyanogas -- Calcium cyanide
Cyanogen chloride -- Chlorine cyanide
Cyanogene (French) -- Cyanogen
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IRIS Index: page 7 of 15
Cyanogran - - Sodium Cyanide
Cyanure d'argent (French) -- Silver cyanide
Cyanure de calcium (French) -- Calcium cyanide
Cyanure de zinc (French) -- Zinc cyanide
Cyanure (French) -- Cyanide
Cyclohexane,1,2,3,4,5,6-Hexachloro-, Gamma-Isomer -- Lindane
Cyclon -- Hydrogen Cyanide
Czterochlorek wegla (Polish) -- Carbon tetrachloride
Czterochloroetylen (Polish) -- Tetrachloroethylene
Dalapon sodium salt -- Dalapon
DANA -- Diethylnitrosamine
DBDPO -- Decabromobiphenyl ether
DBN -- Dibutylnitrosamine
DBNA -- Dibutylnitrosamine
2,4-D Butyric -- 2,4-DB
1,1-DCE -- 1,1-Dichloroethylene
DCM -- Methylene chloride
DCP -- 2,4-Dichlorophenol
2,4-DCP -- 2,4-Dichlorophenol
DDC -- Sodium diethyldithiocarbamate
Decabromodiphenyl oxide -- Decabromobiphenyl ether
DEDC -- Sodium diethyldithiocarbamate
DEDK -- Sodium diethyldithiocarbamate
DEHP -- Bis(2-ethylhexyl)phthalate
DEN -- Diethylnitrosamine
DENA -- Diethylnitrosamine
Diaethylnitrosamin (German) -- Diethylnitrosamine
m-Diaminobenzene -- m-Phenylenediamine
1,3-Diaminobenzene -- m-Phenylenediamlne
Dibutylamine, N-nitroso -- Dibutylnitrosamine
Dibutyl 1,2-Benzenedicarboxylate -- Dibutyl Phthalate
Dibutyl o-carboxybenzoyloxyacetate -- Butylphthalyl butylglycolate
Dibutyl o-(o-carboxybenzoyl) glycolate -- Butylphthalyl butylglycolate
Dibutyl-o-Phthalate -- Dibutyl Phthalate
Dichlormethan, uvasol -- Methylene chloride
1,1-Dichloroethene -- 1,1-Dichloroethylene
1,1-Dichloromethane -- Methylene chloride
4-(2,4-Dichlorophenoxy)butyric acid -- 2,4-DB
2,2-Dichloropropionic acid, sodium salt -- Dalapon
2,2-Dichlorproplonsaeure natrium (German) -- Dalapon
Dicyan -- Cyanogen
Dicyanogen -- Cyanogen
Diethylamine, N-nitroso -- Diethylnitrosamine
Diethyldithiocarbamic acid, sodium salt -- Sodium diethyldithiocarbamate
Di(2-ethylhexyl)orthophthalate -- Bis(2-ethylhexyl)phthalate
Di(2-ethylhexyl)phthalate -- Bis(2-ethylhexyl)phthalate
Diethylnitrosoamine -- Diethylnitrosamine
Diethyl o-carboxybenzoyloxyacetate -- Ethylphthalyl ethylglycolate
Diethyl phthalate -- Diethyl phthalate
Difluorodichloromethane -- Dichlorodifluoromethane
1,2-Dihpenylhydrazine -- 1,2-Diphenylhydrazine
Dihydrogen Monosulfide -- Hydrogen Sulphide
Dihydrogen Sulfide -- Hydrogen Sulphide
Dimethylamine, N-nitroso -- Dimethylnitrosamine
Dimethyl 1,4-benzenedicarboxylate -- Dimethyl terephthalate
Dimethylester kyseliny isoftalove (Czech) -- Dimethyl terephthalate
Dimethylnitrosamin (German) -- Dimethylnitrosamine
Dimethylnitrosoamine -- Dimethylnitrosamine
Di-n-butylnitrosamine -- Dibutylnitrosamine
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IRIS Index: page 8 of 15
Di-n-butylnitrosamin (German) -- Dibutylnitrosamine
Di-n-Butylphthalate -- Dibutyl Phthalate
Dinitrobutylphenol -- Dlnoseb
2,4-Dinitro-6-(l-Methylpropyl)Phenol -- Dinoseb
Dinitro-Ortho-Sec-Butyl Phenol -- Dinoseb
Dioctyl phthalate -- Bis(2-ethylhexyl)phthalate
Diphenyl -- 1,1-Biphenyl
Dithallium Carbonate -- Thallium Carbonate
Dithallium Sulfate -- Thallium (I) Sulfate
Dithallium Trioxide -- Thallic Oxide
Dithiocarb -- Sodium diethyldithiocarbamate
Dithiocarbamate -- Sodium diethyldithiocarbamate
Dithiocarbonic anhydride -- Carbon disulfide
Dithiophosphate -- Dimethoate
Divanadium Pentoxide -- Vanadium Pentaoxide
Divinylene Oxide -- Furan
2,4-DM -- 2,4-DB
DMDK -- Dimethyldoorknob
DMN - - Dimethylnitrosamine
DMNA -- Dimethylnitrosamine
DMT -- Dimethyl terephthalate
DNBP -- Dinoseb
DNCW - - Dinitrochickenwire
DNOSBP -- Dinoseb
DNSBP -- Dinoseb
Doorknob, dimethyl -- Dimethyldoorknob
OOP -- Bis(2-ethylhexyl)phthalate
2,2-DPA -- Dalapon
DPB -- Dibutyl Phthalate
Dvruchlorodwufluorometan (Polish) -- Dichlorodifluoromethane
ECH -- Epichlorohydrin
Epichloorhydrine (Dutch) -- Epichlorohydrin
Epichlorhydrine (French) -- Epichlorohydrin
Epichlorhydrin (German) -- Epichlorohydrin
Epichlorohydryna (Polish) -- Epichlorohydrin
Epicloridrina (Italian) -- Epichlorohydrin
1,4-Epoxy-l,3-Butadiene -- Furan
l,2-Epoxy-3-chloropropane -- Epichlorohydrin
Ethanedinitrile -- Cyanogen
Ethane, 1,1,2-trichloro-1,2,2-trifluoro- -- Trichlorotrifluoroethane
Ethene, tetrachloro- -- Tetrachloroethylene
Ethenylbenzene - - Styrene
Ether, decabromodiphenyl -- Decabromobiphenyl ether
Ethylamine, N-nitrosodi- -- Diethylnitrosamine
Ethylbenzeen (Dutch) -- Ethyl benzene
Ethylbenzol -- Ethyl benzene
Ethyl carbethoxymethyl phthalate -- Ethylphthalyl ethylglycolate
Ethylenecarboxylic acid -- Acrylic acid
Ethylene, 1,1-dichloro- -- 1,1-Dichloroethylene
Ethylene, phenyl- -- Styrene
Ethylene tetrachloride -- Tetrachloroethylene
Ethylene, tetrachloro- -- Tetrachloroethylene
2-Ethylhexyl phthalate -- Bis(2-ethylhexyl)phthalate
Ethyl methyl cetone (French) -- Methyl ethyl ketone
Ethylmethylketon (Dutch) -- Methyl ethyl ketone
Ethyl methyl ketone -- Methyl ethyl ketone
Ethyl methyl ketone peroxide -- Methyl ethyl ketone peroxide
Ethyl phthalate -- Diethyl phthalate
Etilbenzene (Italian) -- Ethyl benzene
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IRIS Index: page 9 of 15
Etylobenzen (Polish) -- Ethyl benzene
m-Fenylendiamin (Czech) -- m-Phenylenediamine
Fluorocarbon-12 -- Dichlorodifluoromethane
Fluorocarbon 113 -- Trichlorotrlfluoroethane
Fluorocarbon no. 11 -- trichloromonofluoromethane
Fluorotrichloromethane - - trichloromonofluoromethane
Fluorotrojchlorometan (Polish) -- trichloromonofluoromethane
FMA -- Phenyl mercuric acetate
Formonitrile -- Hydrogen Cyanide
Formylic acid -- Formic acid
Formyl Trichloride -- Chloroform
Fosforowodor (Polish) -- Phosphine
Freon 10 - - Carbon tetrachloride
Freon 11 -- trichloromonofluoromethane
Freon 12 -- Dichlorodifluoromethane
Freon 113 -- Trichlorotrifluoroethane
Freon 20 -- Chloroform
Freon 30 -- Methylene chloride
Furfuran - - Furan
gamma-HCH -- Lindane
gamma-Hexachloran -- Lindane
gamma-Hexachlorobenzene -- Lindane
gamma-1,2,3,4,5,6-Hexachlorocyclohexane -- Lindane
Gammahexane -- Lindane
Gammexane -- Lindane
Glazd penta -- Pentachlorophenol
Glucinium -- Beryllium
Glucinum -- Beryllium
Glycerol epichlorhydrin -- Epichlorohydrin
Glycolic acid, butyl ester, butyl phthalate -- Butylphthalyl butylglycolate
Glycolic acid, phthalate, dibutyl ester -- Butylphthalyl butylglycolate
Grundier Arbezol -- Pentachlorophenol
HCBD -- Hexachlorbutadiene
HCCH - - Lindane
HCCPD -- Hexachlorocyclopentadiene
HCH - - Lindane
Hexachlorane - - Lindane
Hexachlor-l,3-butadien (Czech) -- Hexachlorbutadiene
1,3-Hexachlorobutadiene -- Hexachlorbutadiene
1,2,3,4,5,6-Hexachlorocyclohexane, gamma-Isomer -- Lindane
Hexachloropentadiene -- Hexachlorocyclopentadiene
Hydrazine, 1,2-dihpenyl- -- 1,2-Diphenylhydrazine
Hydrazobenzene -- 1,2-Dtphenylhydrazine
Hydrocyanic Acid, Potassium Salt -- Potassium Cyanide
Hydrocyanic Acid, Sodium salt -- Sodium Cyanide
Hydrogen carboxylic acid -- Formic acid
Hydrogen phosphide -- Phosphine
Hydrosulfuric Acid -- Hydrogen Sulphide
Hydroxybenzene -- Phenol
3-Hydroxypropene -- Allyl alcohol
Hydroxytoluole (German) - - Cresols
Isocyanide -- Cyanide
Karbaryl (Polish) -- Carbaryl
KCN -- Potassium Cyanide
Ketone, ethyl methyl -- Methyl ethyl ketone
Kresole (German) -- Cresols
Kresolen (Dutch) -- Cresols
Krezol (Polish) -- Cresols
Kwas metaniowy (Polish) -- Formic acid
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IRIS Index: page 10 of 15
Kyanid stribrny (Czech) -- Silver cyanide
Kyanostribrnan draselny (Czech) -- Potassium silver cyanide
Lead, Tetraethyl- -- Tetraethyl Lead
Lemonene -- 1,1-Biphenyl
MCP - - MCPA
2,4-MCPA -- MCPA
MEBR -- Bromomethane
MEK -- Methyl ethyl ketone
MEK peroxide -- Methyl ethyl ketone peroxide
Mercury (1+), Methyl- -- Methyl mercury
Mercury,(Acetato-0)Phenyl- -- Phenyl mercuric acetate
Mercury(II) Acetate, Phenyl- -- Phenyl mercuric acetate
Metaxon -- MCPA
Methane, Bromo- -- Bromomethane
Methane dichloride -- Methylene chloride
Methane, dichloro- -- Methylene chloride
Methane tetrachloride -- Carbon tetrachloride
Methane, tetrachloro- -- Carbon tetrachloride
Methane, Trichloro- -- Chloroform
Methanoic acid -- Formic acid
Methenyl Chloride -- Chloroform
Methenyl Trichloride -- Chloroform
Methoxone -- MCPA
Methyl-acetone -- Methyl ethyl ketone
Methyl acetone -- Methyl ethyl ketone
Methylamine, N-nitrosodi- -- Dimethylnitrosamine
Methylbenzene -- Toluene
Methylbenzol - - Toluene
Methyl bromide -- Bromomethane
Methylcarbamate 1-naphthalenol -- Carbaryl
Methylcarbamate 1-naphthol -- Carbaryl
Methylcarbamic acid, 1-naphthyl ester -- Carbaryl
Methyl 4-carbomethoxybenzoate -- Dimethyl terephthalate
2-Methyl-4-chlorophenoxyacetic acid -- MCPA
2-(2-Methyl-4-Chlorophenoxy)Propionic Acid -- MCPP
2-Methyl-4-chlorphenoxyessigsaeure (German) -- MCPA
Methylene dichloride -- Methylene chloride
Methyl ethyl ketone hydroperoxide -- Methyl ethyl ketone peroxide
Methylmercury -- Methyl mercury
Methylmercury (1+) -- Methyl mercury
Methylmercury (II) Cation -- Methyl mercury
2-Methyl-2-(Methylthio)Propanal, 0-((Methylamino)Carbonyl) Oxime -- Aldicarb
Methyl phenol -- Cresols
Methyl Trichloride -- Chloroform
Metiletilchetone (Italian) -- Methyl ethyl ketone
Metylenu chlorek (Polish) -- Methylene chloride
Metyloetyloketon (Polish) -- Methyl ethyl ketone
Mierenzuur (Dutch) -- Formic acid
Monobromomethane - - Bromomethane
Monofluorotrichloromethane -- trichloromonofluoromethane
Monohydrated Selenium Dioxide -- Selenious Acid
Monophenol - - Phenol
1-Naphthyl N-methylcarbamate -- Carbaryl
NCI-C00135 -- Dimethoate
NCI-C00204 -- Lindane
NCI-C02200 -- Styrene
NCI-C02686 -- Chloroform
NCI C02835 -- Sodium diethyldithiocarbamate
NCI-C04580 -- Tetrachloroethylene
-------
IRIS Index: page 11 of 15
NCI-C04637 -- trichloromonofluoromethane
NCI-C07272 -- Toluene
NCI-C08640 -- Aldicarb
NCI-C50055 -- Dimethyl terephthalate
NCI-C50102 -- Methylene chloride
NCI-C50124 -- Phenol
NCI-C52733 -- Bis(2-ethylhexyl)phthalate
NCI-C54262 -- 1,1-Dichloroethylene
NCI-C54933 -- Pentachlorophenol
NCI-C54988 -- Tetraethyl lead
NCI-C55287 -- Decabromodiphenyl ether
NCI-C55345 -- 2,4-Dichlorophenol
NCI-C55378 -- Pentachlorophenol
NCI-C55389 -- Pentachlorophenol
NCI-C55447 -- Methyl ethyl ketone peroxide
NCI-C55607 -- Hexachlorocyclopentadiene
NCI-C56202 -- Furan
NCI-C56393 -- Ethyl benzene
NCI-C56655 -- Pentachlorophenol
NCI-C60048 -- Diethyl phthalate
NCI-C60082 -- Nitrobenzene
NCI-C61187 -- 2,4,5-Trichlorophenol
NDBA - - Dibutylnitrosamine
NDEA -- Diethylnitrosamine
NDMA -- Dimethylnitrosamine
Neantine -- Diethyl phthalate
N-Ethyl-N-nitroso-ethanamine -- Diethylnitrosamine
Nitriloacetonitrile -- Cyanogen
Nitrito -- Nitrogen Dioxide
Nitrobenzol -- Nitrobenzene
Nitrogen monoxide -- Nitric oxide
Nitrogen Oxide (N02) -- Nitrogen Dioxide
Nitrogen oxide (NO) -- Nitric oxide
Nitrogen Peroxide -- Nitrogen Dioxide
Nitrogen Tetroxide -- Nitrogen Dioxide
Nitrosodiethylamine -- Diethylnitrosamine
Nitrosodimethylamine -- Dimethylnitrosamine
1-Nitrosopyrrolidine -- N-Nitrosopyrrolidine
Nitrosyl radical -- Nitric oxide
Nitrous acid, ion(l-) -- Nitrite
N-Methylcarbamate de 1-naphtyle (French) -- Carbaryl
N-Methyl-1-naftyl-carbamaat (Dutch) -- Carbaryl
N-Methyl-1-naphthyl carbamate -- Carbaryl
N-Methyl-1-naphthyl-carbamat (German) -- Carbaryl
N-Methyl-N-nitrosomethanamine -- Dimethylnitrosamine
N-Metil-1-naftil-carbammato (Italian) -- Carbaryl
N.N'-Bianiline -- 1,2-Diphenylhydrazine
N-Nitrosobutylamine -- Dibutylnitrosamine
N-Nitrosodiethylamine -- Diethylnitrosamine
N-Nitrosodimethylamine -- Dimethylnitrosamine
N-N-pyr -- N-Nitrosopyrrolidine
NO-pyr -- N-Nitrosopyrrolidine
NPYR -- N-Nitrosopyrrolidine
o-Benzenedicarboxylic Acid, Dibutyl Ester -- Dibutyl Phthalate
Octyl phthalate -- Bis(2-ethylhexyl)phthalate
Omal -- 2,4,6-Trichlorophenol
0,0-Dimethyl S-(N-Methylcarbamoylmethyl) Phosphorodithioate -- Dimethoate
Orvinylcarbinol -- Allyl alcohol
Oxacyclopentadiene -- Furan
-------
IRIS Index: page 12 of 15
Oxalic acid dinitrile -- Cyanogen
Oxalonitrile -- Cyanogen
Oxirane, 2-(chloromethyl) -- Epichlorohydrin
Oxole -- Furan
Oxybenzene -- Phenol
PCE -- Tetrachloroethylene
PCL - - Hexachlorocyclopentadiene
PCP - - Pentachlorophenol
Penta -- Pentachlorophenol
Pentabromophenyl ether -- Decabromobiphenyl ether
Pentachloorfenol (Dutch) -- Pentachlorophenol
2,3,4,5,6-pentachlorobenzene, 1-Hydroxy- -- Pentachlorophenol
Pentachlorophenate -- Pentachlorophenol
2,3,4,5,6-Pentachlorophenol -- Pentachlorophenol
Pentachlorphenol (German) -- Pentachlorophenol
Pentaclorofenolo (Italian) -- Pentachlorophenol
PER -- Tetrachloroethylene
PERC -- Tetrachloroethylene
Perchloorethyleen, per (Dutch) -- Tetrachloroethylene
Perchlor -- Tetrachloroethylene
Perchloraethylen, per (German) -- Tetrachloroethylene
Perchlorethylene -- Tetrachloroethylene
Perchlorethylene, per (French) -- Tetrachloroethylene
Perchlorobutadiene -- Hexachlorbutadiene
Perchlorocyclopentadiene -- Hexachlorocyclopentadiene
Perchloroethylene -- Tetrachloroethylene
Perchlorom^thane -- Carbon tetrachloride
Perclene -- Tetrachloroethylene
Percloroetilene (Italian) -- Tetrachloroethylene
PERK - - Tetrachloroethylene
Phenachlor -- 2,4,6-Trichlorophenol
Phenethylene -- Styrene
Phenic Acid -- Phenol
Phenol, 2,4-dichloro- -- 2,4-Dichlorophenol
Phenol, 2-(l-Methylpropyl)-4,6-Dinitro- -- Dinoseb
Phenol, pentachloro- -- Pentachlorophenol
Phenol, 2,3,4,6-tetrachloro- -- 2,3,4,6-Tetrachlorophenol
Phenol, 2,4,5-trichloro- -- 2,4,5-Trichlorophenol
Phenol, 2,4,6-trichloro- -- 2,4,6-Trichlorophenol
Phenomercuric Acetate -- Phenyl mercuric acetate
Phenyl Alcohol -- Phenol
Phenylbenzene -- 1,1-Biphenyl
1,3-Phenylenediamine -- m-Phenylenediamine
Phenylethane -- Ethyl benzene
Phenylethylene -- Styrene
Phenyl Hydrate -- Phenol
Phenyl Hydroxide -- Phenol
Phenylic Acid -- Phenol
Phenylic Alcohol -- Phenol
Pheny line thane - - Toluene
Phosphamid -- Dimethoate
Phosphamide - - Dimethoate
Phosphorodithioic Acid, 0,0-Dimethyl
S-(2-(Methylamino)-2-Oxoethyl) Ester -- Dimethoate
Phosphorus trihydride -- Phosphine
Phosphorwasserstoff (German) -- Phosphine
PHPH -- 1,1-Biphenyl
Phthalic acid, bis(2-ethylhexyl) ester -- Bis(2-ethylhexyl)phthalate
Phthalic acid, butoxycarbonylmethyl
butyl ester -- Butylphthalyl butylglycolate
-------
IRIS Index: page 13 of 15
Phthalic acid, butyl ester, butyl glycolate -- Butylphthalyl butylglycolate
Phthalic Acid, Dibutyl Ester -- Dibutyl Phthalate
Phthalic acid, diethyl ester -- Diethyl phthalate
Phthalic acid, ethyl ester, ethyl glycolate -- Ethylphthalyl ethylglycolate
Phthalol -- Diethyl phthalate
Phthalsaeurediaethylester (German) -- Diethyl phthalate
Plumbane, Tetraethyl- -- Tetraethyl Lead
PMA - - Phenyl mercuric acetate
PMAC -- Phenyl mercuric acetate
PMAL - - Phenyl mercuric acetate
PMAS -- Phenyl mercuric acetate
Propanal, 2-Methyl-2-(Methylthio)-,
0-((Methylamino)Carbonyl) Oxime -- Aldicarb
Propane, l-chloro-2,3-epoxy- -- Epichlorohydrin
Propenoic acid -- Acrylic acid
2-Propenoic acid -- Acrylic acid
Propenol - - Allyl alcohol
l-Propen-3-ol -- Allyl alcohol
2-Propen-l-ol -- Allyl alcohol
Propenyl alcohol -- Allyl alcohol
Propionic acid, 2,2-dichloro-.sodium salt -- Dalapon
Propionic Acid, 2-(2-Methyl-4-Chlorophenoxy)- -- MCPP
Prussic Acid -- Hydrogen Cyanide
Prussite -- Cyanogen
Pyrrole, tetrahydro-N-nitroso- -- N-Nitrosopyrrolidine
Pyrrolidine, 1-nitroso- -- N-Nitrosopyrrolidine
QCB -- Pentachlorobenzene
RCRA waste number POOS •
RCRA waste number P013
RCRA waste number P015
RCRA waste number P029 •
RCRA waste number P021 •
RCRA waste number P030 •
RCRA waste number P031 •
RCRA waste number P033
RCRA waste number P099 •
RCRA waste number P096
RCRA waste number P104
RCRA waste number P103
RCRA waste number P114
RCRA waste number P121
RCRA waste number U008
RCRA waste number U028
RCRA waste number U041
RCRA waste number U052
RCRA waste number U075
RCRA waste number U078
RCRA waste number U081
RCRA waste number U088
RCRA waste number U123
RCRA waste number U121
RCRA waste number U128
RCRA waste number U159
RCRA waste number U160
RCRA waste number U183
RCRA waste number U214
RCRA waste number U217
RCRA waste number U212
RCRA waste number U220
Allyl alcohol
Barium cyanide
Beryllium
Copper cyanide
Calcium cyanide
Cyanide
Cyanogen
Chlorine cyanide
Potassium silver cyanide
Phosphine
Silver cyanide
Selenourea
Thallium selenite
Zinc cyanide
Acrylic acid
Bis(2-ethylhexyl)phthalate
Epichlorohydrin
Cresols
Dichlorodifluoromethane
1,1-Dichloroethylene
2,4-Dichlorophenol
Diethyl phthalate
Formic acid
trichloromonofluoromethane
Hexachlorbutadiene
Methyl ethyl ketone
Methyl ethyl ketone peroxide
Pentachlorobenzene
Thallium acetate
Thallium nitrate
2,3,4,6-Tetrachlorophenol
Toluene
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IRIS Index: page 14 of 15
RCRA waste number U230 -- 2,4,5-Trichlorophenol
RCRA waste number U2071 -- ,2,4,5-Tetrachlorobenzene
Sevin -- Carbaryl
Sewer Gas -- Hydrogen Sulphide
Silber (German) -- Silver
Silver potassium cyanide -- Potassium silver cyanide
S-Methylcarbamoylmethyl 0,0-Dimethyl Phosphorodithioate -- Dimethoate
Sodium dalapon -- Dalapon
Sodium DEDT -- Sodium diethyldithiocarbamate
Soviet technical herbicide 2M-4C -- MCPA
S t ib ium -- Ant imony
Stirolo (Italian) -- Styrene
Strychnidin-10-one -- Strychnine
Strychnin -- Strychnine
Strychnos -- Strychnine
Styreen (Dutch) -- Styrene
Styren (Czech) -- Styrene
Styrol (German) - - Styrene
Sulfone aldoxycarb -- Aldicarb
Sulfureted Hydrogen -- Hydrogen Sulphide
Sulfur Hydride -- Hydrogen Sulphide
Sulphuret of carbon -- Carbon disulfide
TCM -- Chloroform
TCP -- 2,3,4,6-Tetrachlorophenol
TEL -- Tetraethyl Lead
Temic -- Aldicarb
Temik -- Aldicarb
Terephthalic acid, dimethyl ester -- Dimethyl terephthalate
Terephthalic acid methyl ester -- Dimethyl terephthalate
Tetrachlooretheen (Dutch) -- Tetrachloroethylene
Tetrachloorkoolstof (Dutch) -- Carbon tetrachloride
Tetrachloormetaan -- Carbon tetrachloride
Tetrachloraethen (German) -- Tetrachloroethylene
Tetrachlormethan (German) -- Carbon tetrachloride
1,1,2,2-Tetrachloroethylene -- Tetrachloroethylene
Tetrachloromethane -- Carbon tetrachloride
2,4,5,6-Tetrachlorophenol -- 2,3,4,6-Tetrachlorophenol
Tetrachlorure de carbone (French) -- Carbon tetrachloride
Tetrachorkohlenstoff uvasol -- Carbon tetrachloride
Tetracloroetene (Italian) -- Tetrachloroethylene
Tetraclorometano (Italian) -- Carbon tetrachloride
Tetracloruro di carbonic (Italian) -- Carbon tetrachloride
Tetraethylplumbane -- Tetraethyl Lead
Tetraform (VAN) -- Carbon tetrachloride
Tetrole -- Furan
Thallium(l+) acetate -- Thallium acetate
Thallium (1+) Chloride -- Thallium Chloride
Thallium(3+) Oxide -- Thallic Oxide
Thallium Carbonate (T12C03) -- Thallium Carbonate
Thallium(I) acetate -- Thallium acetate
Thallium(I) Carbonate(2:1) -- Thallium Carbonate
Thallium (I) Chloride -- Thallium Chloride
Thallium(III) Oxide -- Thallic Oxide
Thallium monoacetate -- Thallium acetate
Thallium Monochloride -- Thallium Chloride
Thallium mononitrate -- Thallium nitrate
Thallium monoselenide -- Thallium selenite
Thallium Oxide (Tl 203) -- Thallic Oxide
Thallium Peroxide -- Thallic Oxide
-------
IRIS Index: page 15 of 15
Thallium selenide -- Thallium selenite
Thallium Sulfate -- Thallium (I) Sulfate
Thallous acetate -- Thallium acetate
Thallous nitrate -- Thallium nitrate
Thiocarb -- Sodium diethyldithiocarbamate
T1C1 -- Thallium Chloride
Tolueen (Dutch) -- Toluene
Toluen (Czech) -- Toluene
Toluol -- Toluene
Toluolo (Italian) -- Toluene
Trichlorofluoromethane -- trichloromonofluoromethane
Trichloroform -- Chloroform
Trichloromethane -- Chloroform
Trichlorotrifluoroethane -- Trichlorotrifluoroethane
Tricresol -- Cresols
1,1,2-Trifluoro-1,2,2-trichloroethane -- Trichlorotrifluoroethane
Trojchlorobenzen (Polish) -- 1,2,4-Trichlorobenzene
UN 1026 -- Cyanogen
UN 1028 -- Dichlorodifluoromethane
UN 1098 -- Allyl alcohol
UN 1175 -- Ethyl benzene
UN 1193 -- Methyl ethyl ketone
UN 1232 -- Methyl ethyl ketone
UN 1294 -- Toluene
UN 1303 -- 1,1-Dichloroethylene
UN 1399 -- Barium
UN 1400 -- Barium
UN 1565 -- Barium cyanide
UN 1567 -- Beryllium
UN 1575 -- Calcium cyanide
UN 1589 -- Chlorine cyanide
UN 1673 -- m-Phenylenediamine
UN 1684 -- Silver cyanide
UN 1713 -- Zinc cyanide
UN 1779 -- Formic acid
UN 1854 -- Barium
UN 2023 -- Epichlorohydrin
UN 2022 -- Cresols
UN 2055 -- Styrene
UN 2076 -- Cresols
UN 2127 -- Methyl ethyl ketone peroxide
UN 2199 -- Phosphine
UN 2218 -- Acrylic acid
UN 2279 -- Hexachlorbutadiene
UN 2321 -- 1,2,4-Trichlorobenzene
UN 2550 -- Methyl ethyl ketone peroxide
UN 2727 -- Thallium nitrate
UN 2871 -- Antimony
Vanadium Oxide -- Vanadium Pentaoxide
VDC -- 1,1-Dichloroethylene
Vinylbenzen (Czech) -- Styrene
Vinylbenzene -- Styrene
Vinylbenzol -- Styrene
Vinylcarbinol -- Allyl alcohol
Vinylformic acid -- Acrylic acid
Vinylidene chloride -- 1,1-Dichloro.ethylene
Vinylidene chloride (II) -- 1,1-Dichloroethylene
Xenene -- 1,1-Biphenyl
Zaclondiscoids -- Hydrogen Cyanide
Zinc dicyanide -- Zinc cyanide
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Acrylic Acid; CAS No. 79-10-7 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Acrylic Acid
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
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Acrylic Acid: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Acrylic Acid
CAS No.: 79-10-7 Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Reduced body weights 83 mg/kg/day (NOAEL) 1000 1 8E-2
altered organ weights mg/kg/day
250 mg/kg/day (LOAEL)
Rat oral subchronic
s tudy (dr inking
water)
DePass et al. (1983)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
DePass, L.R., M.D. Woodside, R.H. Carman and C.S. Weil. 1983. Subchronic
and reproductive toxicology studies on acrylic acid In drinking water of the
rat. Drug Chem. Toxicol. 6(1): 1-20.
In this subchronic study acrylic acid was incorporated into the drinking
water of rats (15/group/sex) for 3 months at doses of 750, 250, 83 and 0
mg/kg/day. At the high (750 rag/kg) and middle (250 rag/kg) dose levels reduc-
tion in body weight and changes in organ weights were observed. These
effects coincided with a dose-related reduction in food and water consump-
tion. At the 83-mg/kg dose the only effect was a reduction in water consump-
tion. No significant treatment-related histological effects were seen at any
dose level. A NOAEL of 83 mg/kg was established in this study.
In a short-term inhalation study (Gage, 1970) no adverse effects were
observed in eight rats exposed to 80 ppm (about 240 mg/cu. m) acrylic acid, 6
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Acrylic Acid: page 3 of 5
hours/day, 5 days/week for 4 weeks. This exposure is approximately equiva-
lent to an oral exposure of 14 mg/kg/day (i.e., 240 mg/cu. m x 0.223 cu.
m/day x 6 hours/24 hours x 5 days/7 days x 0.5/1.0 / 0.35 = 14 mg/kg/day).
Eight rats exposed at 300 ppm (about 51 mg/kg/day) experienced nose irrita-
tion, lethargy and reduced weight gain. Histological and hematological
examinations were normal. Higher doses for shorter periods of time resulted
in liver, kidney and lung damage.
The subchronic oral study of DePass et al. (1983) appears to be the most
appropriate for deriving an ADI, in view of the limited data available.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. (10 to account for subchronic to chronic conversion, 10 for
interspecies extrapolation and 10 to protect sensitive individuals)
MF = 1
4. ADDITIONAL COMMENTS
No oral chronic data are available.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Low RfD: Medium
The confidence in the study is medium due to the number of animals/dose
used, because several parameters were studied, and because a good dose-
severity relationship was obtained. The confidence in the data base is low
because of the general lack of supporting studies. The overall confidence in
the RfD is rated medium to low.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, August 1985.
U.S. EPA. 1985. Acrylic Acid: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
Agency RfD Work Group Review: 08/19/85
Verification Date: 08/19/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
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Acrylic Acid: page 4 of 5
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Acrylic Acid
CAS No.: 79-10-7
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Acrylic Acid
CAS No.: 79-10-7
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Acrylic Acid
CAS No.: 79-10-7
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Acrylic acid
CAS No.: 79-10-7 Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
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Acrylic Acid: page 5 of 5
A. RISK MANAGEMENT ACTIONS
Risk Status Risk Considers
Management Management Econ/Tech
Action Date Value Feasibility Reference
Reportable Final 5000 Ibs no 50 FR 13456
Quantity (RQ) 1985 04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on acute toxicity and ignitability. Available data
indicate that the oral LD50 for rats is between 100 and 500 mg/kg. The
closed cup flash point is between 100 degrees F and 140 degrees F.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
V. SUPPLEMENTARY DATA
Chemical: Acrylic Acid
CAS No.: 79-10-7
Information is not available at this time.
Synonyms: ACROLEIC ACID; ACRYLIC ACID (ACGIH); ACRYLIC ACID (DOT); ACRYLIC
ACID, inhibited (DOT); ACRYLIC ACID, GLACIAL; ETHYLENECARBOXYLIC ACID;
PROPENE ACID; PROPENOIC ACID; 2-PROPENOIC ACID (9CI); RCRA WASTE NUMBER U008;
UN 2218 (DOT); VINYLFORMIC ACID
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Aldicarb; CAS No. 116-06-3 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Aldicarb
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
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Aldicarb: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Aldicarb
CAS No.: 116-06-3
Preparation Date: 07/31/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Cholinesterase
inhibition
Rat subchronic to
chronic aldicarb
sulfoxide feeding
study
Weil and Carpenter
(1968)
0.125 mg/kg bw/day
(NOAEL)
0.25 mg/kg bw/day
(LOAEL)
100
1.3E-3
mg/kg/day
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Weil, C.S. and C.P. Carpenter. 1968. Temik sulfoxide. Results of feeding in
the diet of rats for six months and dogs for three months. Mellon Institute
Report No. 31-141. EPA Pesticide Petition No. 9F0798.
Rats (15/sex/group) were fed Temik (aldicarb) sulfoxide at dosage levels
of 0, 0.125, 0.25, 0.5 or 1.0 mg/kg bw/day for 6 months. Some animals were
sacrificed at 3 months for interim results. The results of both the 3- and
6-month studies indicated a substantial reduction of cholinesterase levels in
plasma, erythrocytes and brain at the three highest dose levels; somewhat less
inhibition was observed at 0.125 mg/kg/day, but was judged not adverse. No
mortality or gross or microscopic tissue effects were noted; growth retar-
dation occurred at the highest dose only. An additional 3-month study using
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Aldicarb: page 3 of 7
the same protocol (Weil and Carpenter, 1968), with the addition of a lower
dosage group (0.0625 mg/kg/day) confirmed the NOAEL of 0.125 mg/kg/day. A
2-year feeding study of aldicarb sulfoxide in rats showed increased mortality
at 0.6 mg/kg/day.
Long-term dog and rat studies on the effects of aldicarb itself are
inconclusive, since no effects have been observed at the highest dose levels
tested. These dose levels are 0.1 mg/kg/day for cholinesterase effects
and 0.3 mg/kg/day for non-cholinesterase effects. Effects on body weight and
mortality have been observed at 0.5 and 3.2 mg/kg/day, respectively, for rats
fed aldicarb for 90 days. Very limited human data show inhibition of plasma
cholinesterase with cholinergic symptoms after a single dose of 0.1 rag/kg
aldicarb (Raines, 1971).
Data on the long-term effects of aldicarb on cholinesterase activity at
dose levels >0.1 mg/kg/day are not available. However, NOAELs of 0.125 and
0.8 mg/kg/day have been established for the sulfoxide and sulfone metabolites
of aldicarb, respectively. Since the sulfoxide is the major metabolite, and
the acute toxicity of aldicarb is much closer to that of the sulfoxide, aldi-
carb sulfoxide is considered an appropriate surrogate for aldicarb itself.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. The UF of 100 includes uncertainties in the extrapolation from
laboratory animals to humans (lOa) and in the range of human sensitivity
(lOh). Since the critical effect is duration-independent, no extrapolation
from subchronic to chronic exposure is necessary.
MF = 1
4. ADDITIONAL COMMENTS
No teratogenic or other reproductive effects due to aldicarb are evident
in the limited data available.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The critical study appears to be of fairly good quality and is given a
medium to high confidence rating. Additional studies are moderately sup-
portive. The RfD is given medium confidence because the surrogate model is
felt to be reasonable.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1985. Drinking Water Criteria Document for Aldicarb. Environ-
mental Criteria and Assessment Office, Cincinnati, OH. ECAO-CIN-420.
The 1985 Office of Drinking Water document has received Agency review and has
been reviewed by several outside experts.
Agency RfD Work Group Review: 12/02/85, 02/05/86, 05/15/86
Verification Date: 05/15/86
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Aldicarb: page 4 of 7
7. U.S. EPA CONTACTS
Primary: J.F. Risher FTS/684-7595 or 513/569-7595
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Aldicarb
CAS No.: 116-06-3
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Aldicarb
CAS No.: 116-06-3
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Aldicarb
CAS No.: 116-06-3
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Aldicarb
CAS No.: 116-06-3 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
-------
Aldicarb: page 5 of 7
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
1 Ib
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Pesticide Active
Ingredient:
a.
b.
Registration
Standard
Special
Review
Current
1984
Final
1984
various no
see below no
Reg. Standard
1984
49 FR 28320
07/17/84
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity. Available data indicate that the
96-Hour Median Threshold Limit for aldicarb is less than 0.1 ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
Pesticide Active Ingredient
a. Registration Standard: Aldicarb Pesticide Registration Standard. March
1984. Office of Pesticides and Toxic Substances. Environmental Protection
Agency, 401 M Street, S.W., Washington, D.C.
Contact: Office of Pesticide Programs
202/557-7760 or FTS/557-7760
b. Special Review: For specific details on the Special Review process for
this active ingredient please check the references listed.
Contact: Office of Pesticide Programs, Special Review Branch
202/557-7420 or FTS/557-7420
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Aldicarb: page 6 of 7
V. SUPPLEMENTARY DATA
Chemical: Aldicarb
CAS No.: 116-06-3 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Aldicarb is a carbamate pesticide (Hayes, 1981). This material is super
toxic; the probable oral lethal dose for humans is less than 5 mg/kg, or a
taste (less than 7 drops) for a 150-lb. person (Gosselin, 1976); it is
extremely toxic by both oral and dermal routes (Doull, 1980).
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Symptoms include headache, blurred
vision, nausea, vomiting, diarrhea, and abdominal pain. In severe cases,
unconsciousness and convulsions may occur (Rumack, 1975 to Present).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: C H N 0 S
7 14 2 2
Molecular Weight: 190.23
Boiling Point: Not Found
Specific Gravity (H20=l): 1.1950 at 25C
Vapor Pressure (mmHg): Less than 0.5 at 20C
Melting Point: 210-214F, 99-101C
Vapor Density (AIR=1): Not Found
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: 6 g/liter at 25C
Flash Point [Method Used]: Not Found
Flammable Limits: Not Found
Appearance and Odor: White crystals, slightly sulfurous odor; commercial
formulations are granular.
Conditions or Materials to Avoid: Unstable in alkali; poor stability at
122F, 50C (Sunshine, 1969). Incompatible with highly alkaline substances
(Farm Chemicals Handbook, 1983).
Hazardous Decomposition or Byproducts: When heated, aldicarb emits very
toxic fumes of nitrogen oxides and sulfur oxides (Sax, 1984).
Use: This material is used as an insecticide, acaricide, and nematocide.
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Aldicarb: page 7 of 7
Synonyms: Propionaldehyde, 2-Methyl-2-(Methylthio)-, 0-(Methyl-
carbamoyl)0xime; 2-Methyl-2-(Methylthio)Propanal, 0-((Methylamino)Carbonyl)
Oxime; 2-Methyl-2-(Methylthio)Propionaldehyde O-(Methylcarbamoyl)Oxime;
Aldecarb; Carbamic Acid, Methyl-, 0-((2- Methyl-2-(Methylthio)Propylidene)
Amino) Derivative; Carbamyl; Carbanolate; ENT 27,093; NCI-C08640; QMS 771;
Propanal, 2-Methyl-2-(Methylthio)-, 0-((Methylamino)Carbonyl)Oxime;
Propionaldehyde, 2-Methyl-2-(Methylthio)-, O-(Methylcarbamoyl)Oxime; UC 21149;
Union Carbide 21149; Union Carbide UC-21149; Temik TSK; Sulfone aldoxycarb;
Temic; Ambush; Propanal, 2-Methyl-2-(Methylthio)-, 0-((Methylamino)Carbonyl)
Oxime; Temic; Temik; Temik 10 G; Temik G 10
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Allyl Alcohol; CAS No. 107-18-6 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Allyl Alcohol
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
ALlyl Alcohol: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Allyl Alcohol
CAS No.: 107-18-6
Preparation Date: 05/12/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Impaired renal func-
tion and increased
liver and kidney
weights
Subchronic oral rat
study (drinking
water)
Carpanini et al.
(1978)
50 ppm drinking water
equivalent to 4.8
mg/kg/day (NOEL)
100 ppm drinking
water equivalent to
6.9 mg/kg/day (LOAEL)
1000 1 5E-3
mgAg/day
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Carpanini, F.M.B., I.F. Gaunt, J. Hardy, S.D. Gangalli, K.R. Butterworth and
H.G. Lloyd. 1978. Short-term toxicity of allyl alcohol in rats. Toxi-
cology. 9: 29-45.
Carpanini et al. (1978) exposed groups of Wistar rats (15/sex/dose) to
drinking water containing 0, 50, 100, 200 or 800 ppm (mg/L) allyl alcohol for
15 weeks. Based on water consumption data, these concentration were equiva-
lent to dosages of 0, 4.8, 8.3, 14.0 and 48.2 mg/kg/day for males and 0, 6.2,
6.9, 17.1 and 58.4 for females, respectively. Food intake and growth were
depressed at the 100, 200 and 800 ppm dose levels. Results of hematologic
and clinical chemistry tests were unremarkable. There were no histopatho-
logical lesions attributable to treatment in any of the organs examined; how-
-------
Allyl Alcohol: page 3 of 5
ever, the relative organ weights of the liver, kidney and spleen were sig-
nificantly increased in a dose-related fashion at all except the 50 ppm
level. Several tests of renal function were performed, indicating impaired
renal function in males at greater than or equal to 100 ppm (8.3 mg/kg/day)
and in females at greater than or equal to 200 ppm (17.1 mg/kg/day). Based on
actual drinking water consumption data, the LOAEL of 100 ppm was equivalent to
dosages of 8.3 and 6.9 mg/kg/day, and the NOEL of 50 ppm was equal to 4.8 and
6.2 mg/kg/day for males and females, respectively. Although the 6.2 mg/kg/day
dosage in females is the highest NOEL, it is too close to the LOAEL of 6.9
mg/kg/day to be considered for deriving an ADI. Therefore, an ADI of 0.005
mg/kg/day was derived using the NOEL of 4.8 mg/kg/day in males and an
uncertainty factor of 1000.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. An uncertainty factor of 1000 was used; 10 for interspecies
extrapolation, 10 to approximate chronic exposure and 10 for intraspecies
variability in the human population.
MF = 1
4. ADDITIONAL COMMENTS
The results of the Carpanini et al. (1978) study are similar to those
found by Dunlap et al. (1958) in which rats treated with allyl alcohol in
drinking water for 90 days had significantly increased liver and kidney
weights at greater than or equal to 250 ppm. Two subchronic inhalation
studies were also available (Dunlap, 1958; Torkelson, 1959) in which dose
related increased liver and kidney damage was observed.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The study defined a clear NOEL and LOAEL, using a moderate number of ani-
mals of both sexes and several dose levels. However, only one species of
animal was tested for a subchronic period (15 weeks). The data base contains
several subchronic oral and inhalation studies which support the findings of
the critical study; however, no chronic, carcinogenic or pertinent
reproductive data are available. No pertinent epidemiological studies were
located. Therefore, a medium confidence in the study, data base and RfD is
recommended.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1985. Health and Environmental Effects Profile for Allyl Alcohol.
Environmental Criteria and Assessment Office, Cincinnati, OH. ECAO-Cin-P121.
Agency RfD Work Group Review: 02/26/86
Verification Date: 02/26/86
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
-------
Allyl Alcohol: page 4 of 5
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Allyl Alcohol
CAS No.: 107-18-6
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Allyl Alcohol
CAS No.: 107-18-6
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Allyl Alcohol
CAS No.: 107-18-6
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Allyl Alcohol
CAS No.: 107-18-6 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
-------
Allyl Alcohol: page 5 of 5
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
100 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity (as established under CWA
Section 311(b)(4)), and chronic toxicity. Available data indicate that the
aquatic 96-Hour Median Threshold Limit for allyl alcohol is between 1 and 10
ppm. RQ assignments based on chronic toxicity reflect two primary
attributes of the hazardous substance, the minimum effective dose (MED)
levels for chronic exposure (mg/day for 70 kg man) and the type of effect
(liver necrosis, teratogenicity, etc). In accordance with the methodology
described in the Agency's "Technical Background Document to Support
Rulemaking Pursuant to CERCLA Section 102, Volume 1" of March 1981 and 50 FR
13468 (04/04/85), a composite score is determined from an evaluation of
these two attributes. Allyl alcohol was determined to have a composite
score between 21 and 40, corresponding to a chronic toxicity RQ of 100
pounds.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
V. SUPPLEMENTARY DATA
Chemical: Allyl Alcohol
CAS No.: 107-18-6
Information is not available at this time.
Synonyms: AA; ALCOOL ALLILCO (Italian); ALCOOL ALLYLIQUE (French); ALLILOWY
ALKOHOL (Polish); ALLYL AL; ALLYL ALCOHOL (ACGIH); ALLYL ALCOHOL (DOT);
ALLYLALKOHOL (German); ALLYLIC ALCOHOL; 3-HYDROXYPROPENE; ORVINYLCARBINOL- 2-
PROPENE-1-OL; PROPENOL; l-PROPENOL-3; PROPEN-l-OL-3; 1-PROPEN-3-OL; 2-PROPEN-
1-OL; PROPENYL ALCOHOL; 2-PROPENYL ALCOHOL; RCRA WASTE NUMBER POOS; SHELL
UNKRAUTTED A; UN 1098 (DOT); VINYLCARBINOL; WEED DRENCH
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Aluminum Phosphide; CAS No. 20859-73-8 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Aluminum Phosphide
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Aluminum Phosphide: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCIMOGEN1C HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Aluminum Phosphide
CAS No.: 20859-73-8 Preparation Date: 01/06/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Body weight and 0.51 mg/kg of food or 100 1 4E-4
clinical parameters 0.025 mg/kg/day mg/kg/day
(phosphine) con-
Rat chronic oral verted to 0.043 mg/
study kg/day aluminum
phosphide (NOAEL)
Hackenburg (1972)
* Dose Conversion Factors & Assumptions: Food consumption: 5% bw;
molecular weight: A1P/PH3: x 57.95/34.0 thus, 0.51 mg/kg of food x 0.05 kg
food/kg bw/day x 57.95/34.0 = 0.043 mg/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
Hackenburg, U. 1972. Chronic ingestion by rats of standard diet treated
with aluminum phosphide. Toxicol. Appl. Pharmacol. 23(1): 147-158.
Aluminum phosphide pellets and tablets (Phastoxin) are used as fumigants
for wheat and other grains (Dieterich et al., 1967). Upon exposure to
moisture in the air, they immediately decompose to phosphine gas, with little
trace residue of phosphide remaining, which could be lost in handling of the
grain.
A chronic feeding study of aluminum phosphide-fumigated chow fed to 30
rats/sex was conducted by Hackenburg (1972). The average concentration was
-------
Aluminum Phosphide: page 3 of 7
0.51 mg phosphine/kg food for a 2-year period. At the end of the treatment
period, there were no differences between treated and control rats in blood
or urine chemistry, or histological parameters.
The phosphine gas measured in the Hackenburg (1972) study was liberated
by decomposition of aluminum phosphide pellets. Acute toxicity data gen-
erated (Sax, 1984) suggest that the phosphide moiety contributes the most to
the acute toxicity of this compound, as opposed to any deleterious effect due
to aluminum cation. The steep slope of the dose-response curve of phosphine
gas (Klimmer, 1969) implies that phosphine is extremely hazardous at doses
slightly above a NOEL. Therefore, it is appropriate to derive an RfD for
aluminum phosphide based upon the RfD for phosphine.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. After correcting for the molecular weight of aluminum phosphide
relative to that of phosphine (57.95/34.00), and by application of an
uncertainty factor of 100 (10 for interspecies conversion and 10 for
sensitive population), an RfD for aluminum phosphide of 0.00043 (0.00025
mg/kg/day phosphine x 1.70) can be derived.
MF = 1
4. ADDITIONAL COMMENTS
The ACGIH (1984) has recommended a TLV of 0.3 ppm (0.42 mg/cu. m) for
phosphine, based principally upon an epidemiological study by Jones (1964)
where workers were exposed intermittently to about 10 ppm phosphine gas.
Based on this TLV, an RfD of 0.0021 mg/kg/day (i.e., 0.42 mg/cu. m x 10 cu.
m/day x 5 day/7 day x 0.5/70 kg/10 = 0.0021 mg/kg/day) can be derived. How-
ever, an RfD for phosphine of 0.00025 mg/kg/day based on the 2-year rat study
by Hackenburg (1972) (described above) has been derived for providing ade-
quate protection against adverse human health effects.
5. CONFIDENCE IN THE RfD
Study: High Data Base: High RfD: High
The confidence in the study was rated high because of the moderate number
of animals/dose, the extensive methodology employed to assure proper admin-
istration of the test compound, and the extensive number of parameters mea-
sured. The data base was rated high because the effectiveness and safety of
this chemical has been long reported through supporting studies. The overall
rating for the RfD is, thus, high.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, August 1985.
U.S. EPA. 1985. Aluminum Phosphide: Review and Evaluation of ADI. Contract
No. 68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
Agency RfD Work Group Review: 08/19/85
Verification Date: 08/19/85
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Aluminum Phosphide: page 4 of 7
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Aluminum Phosphide
CAS No.: 20859-73-8
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Aluminum Phosphide
CAS No.: 20859-73-8
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Aluminum Phosphide
CAS No.: 20859-73-8
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Aluminum Phosphide
CAS No.: 20859-73-8 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
-------
Aluminum Phosphide: page 5 of 7
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk Status Risk Considers
Management Management Econ/Tech
Action Date Value Feasibility Reference
Reportable Final 100 Ibs no 50 FR 13456
Quantity (RQ) 1985 04/04/85
Pesticide Active
Ingredient:
a. Registration Current n.a. no Reg. Standard
Standard 1986 February 1986
b. Special n.a.
Review
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity and reactivity. Available data
indicates that the 96-Hour Median Threshold Limit for aluminium phosphide is
between 1 and 10 ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
Pesticide Active Ingredient
a. Registration Standard: Aluminum Phosphide Registration Standard. October
1981, as amended February 1986. Registration Support and Emergency Response
Branch, Office of Pesticide Programs.
Contact: Office of Pesticide Programs
202/557-7420 or FTS/557-7420
b. Special Review: none
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Aluminum Phosphide: page 6 of 7
V. SUPPLEMENTARY DATA
Chemical: Aluminum Phosphide
CAS No.: 20859-73-8 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Acute toxicity occurs primarily by the inhalation route when aluminum
phosphide decomposes into the toxic gas, phosphine (Rumack, 1975 to Present).
The human median lethal dose for aluminum phosphide has been reported to be
20 mg/kg (NIOSH/RTECS, 1985). Rated as super toxic: probable oral lethal
dose is less than 5 mg/kg or less than 7 drops for a 70 kg (150 Ib.) person
(Gosselin , 1984, pp. 11-119-120).
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Symptoms of phosphine gas poisoning
include restlessness, headache, dizziness, fatigue, nausea, vomiting, coma,
convulsions (Rumack, 1975 to Present); lowered blood pressure, pulmonary
edema, and respiratory failure; disorders of the kidney, liver, heart, and
brain may be observed (Hayes, 1982, pp. 133-135).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: A1P
Molecular Weight: 57.95
Boiling Point: Not Found
Specific Gravity (H20=l): 2.85 at 15C/4C
Vapor Pressure (mmHg): Not Found
Melting Point: Does not melt or decompose at temperatures up to 1000
Vapor Density (AIR=1): Not Found
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: Not Found
Flash Point [Method Used]: Not Found
Flammable Limits: Not Found
Appearance and Odor: Aluminum phosphide exists as dark gray or dark
yellow crystals.
Conditions or Materials to Avoid: Avoid moist air (Merck, 1976), water
(Peer Review Committee), dilute mineral acids, and dilute or concentrated
hydrochloric acid (Bretherick, 1979).
-------
Aluminum Phosphide: page 7 of 7
Hazardous Decomposition or Byproducts: Phosphine gas (Peer Review
Committee; Bretherick, 1979).
Use: Aluminum phosphide is used as an insecticidal fumigant for grain,
peanuts, processed food, animal feed, leaf tobacco, cottonseed, and as a
space fumigant for flour mills, warehouses, and railcars (Farm Chemicals
Handbook, 1984, p. C12); used in semiconductor research (Merck, 1976).
Synonyms: AIP; Al-Phos; Aluminum Phosphide (AP); Aluminum Monophosphide;
Celphos; Delicia; Delicia Gastoxin; Detia; Detia Gas EX-B; Detia-EX-B;
Phostoxin; Phostoxin-A; Quickphos
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Antimony; CAS No. 7440-36-0 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Antimony
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Antimony: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Antimony
CAS No.: 7440-36-0 Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Longevity, blood NOEL: None 1000 1 4E-4
glucose and cho- mg/kg/day
lesterol 0.35 mg/kg bw/day
(LOAEL)
Rat chronic oral
bioassay
Schroeder et al.
(1970)
* Dose Conversion Factors & Assumptions: 5 mg/L (5 ppm) converted to 0.350
mg/kg/day (author's estimate)
2. PRINCIPAL AND SUPPORTING STUDIES
Schroeder, H.A., M. Mitchner and A.P. Nasor. 1970. Zirconium, niobium,
antimony, vanadium and lead in rats: Life term studies. J. Nutrition. 100-
59-66.
An experimental group of 50 male and 50 female rats was administered 5
ppm potassium antimony tartrate in water. Over the period of study, growth
rates of treated animals were not affected, but male rats survived 106 and
females 107 fewer days than did controls at median life spans. Nonfasting
blood glucose levels were decreased in treated males, and cholesterol levels
were altered in both sexes. Since there was only one level of antimony admin-
istered, a NOEL was not established in this study. A decrease in mean heart
-------
Antimony: page 3 of 6
weight for the males was noted. No increase in tumors was seen as a result of
treatment.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. An uncertainty factor of 1000 (10 for interspecies conversion,
10 to protect sensitive individuals and 10 because the effect level was a
LOAEL and no NOEL was established) was applied to the LOAEL of 0.35 mg/kg
bw/day.
MF = 1
4. ADDITIONAL COMMENTS
In a similar study (Kanisawa and Schroeder, 1969), groups of CD-I mice
(54/sex) were given potassium antimony tartrate in drinking water at 0 or 5
mg/L (5 ppm) for 540 days (18 months). Lifespans were significantly reduced
in both males and females but the degree of antimony toxicity was less severe
in mice than rats. Bradley and Fredrick (1941) and Browning (1961) reported
disturbances in glucose and cholesterol metabolism in rats ingesting 5 mg/L
antimony, but no signs of injury to the heart were observed in rats receiving
doses up to 100 mg/kg/day. Substantially higher doses of antimony trioxide
were tolerated by rats in studies by Suoragawa (1981) and Gross et al. (1955),
suggesting a NOAEL of 500 mg/kg, but these studies are of inadequate duration
to assess adverse effects on toxicity.
According to the Ambient Water Quality Criteria document, multimedia
antimony exposures are essentially negligible by comparison to occupational
exposures at which discrete clinical health effects have been observed. Myo-
cardial effects are among the best-characterized human health effects associ-
ated with antimony exposure. Studies by Breiger et al. (1954) suggest an
inhalation NOEL for myocardial damage to be approximately 0.5 mg/cu. m. This
exposure is approximately equivalent to an oral reference dose of 0.003 mg/kg
bw/day (i.e., 0.5 mg/cu. m x 10 cu. m/day x 0.5 / 1.0 x 5 days/7 days / 70 kg
/ lOh). Parallel studies in rats and rabbits resulted in observation of EGG
alterations following exposure to 3.1-5.6 mg/cu. m. There are, hoover, no
adequate data on oral exposure to antimony which permit reasonable estimate
of no effect levels regarding heart damage.
One study (Belyaeva, 1967) indicated that women workers exposed in an
antimony plant experienced a greater incidence of spontaneous abortions than
did a control group of nonexposed working women. A high rate of premature
deliveries among women workers in antimony smelting and processing was also
observed (Aiello, 1955).
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Low RfD: Low
Confidence in the chosen study is rated as low because only one species
was used, only one dose level was used, no NOEL was determined, and gross
pathology and histopathology were not well described. Confidence in the data
base is low due to lack of adequate oral exposure investigations. Low
confidence in the RfD follows.
-------
Antimony: page 4 of 6
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1980. Ambient Water Quality Criteria Document for Antimony.
Environmental Criteria and Assessment Office, Cincinnati, OH. EPA
440/5-80-020.
The ADI in the 1980 Ambient Water Quality Criteria Document was extensively
reviewed by the Agency and was reviewed by the public.
U.S. EPA. 1985. Health and Environmental Effects Profile for Antimony
Oxides. Environmental Criteria and Assessment Office, Cincinnati, OH.
ECAO-CIN-P127.
Limited peer review and extensive Agency-wide review, 1985.
U.S. EPA. 1985. Antimony: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
ECAO-Cin Internal Review, 1986.
Agency RfD Work Group Review: 11/06/85
Verification Date: 11/06/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Antimony
CAS No.: 7440-36-0
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Antimony
CAS No.: 7440-36-0
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
-------
Antimony: page 5 of 6
Chemical:
CAS No.:
III. DRINKING WATER HEALTH ADVISORIES
Ant imony
7440-36-0
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical:
CAS No.:
Antimony
7440-36-0
Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are publish ,d
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Status
Date
Risk
Management
Value
Considers
Econ/Tech
Feasibility
Reference
Reportable Final
Quantity (RQ) 1986
Water Quality
Criteria (WQC):
a. Human Health Final
1986
b. Aquatic Toxicity
1) Freshwater Final
1986
2) Marine
5000 Ibs
146 ug/1
no
no
Acute no
9,000 ug/1 (LEL)
Chronic
1,600 ug/1 (LEL)
none
FR
in press
51 FR 8361
03/11/86
ibid.
-------
Antimony: page 6 of 6
B. RISK MANAGEMENT RATIONALE
RQ
No data have been found to permit the ranking of this hazardous
substance. The available data for acute hazards may lie above the upper
limit for the 5000-pound RQ, but since it is a designated hazardous
substance, the largest assignable RQ is 5000 pounds.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC of 146 ug/1 is based on consumption of contaminated
aquatic organisms and water. A WQC of 45,000 ug/1 has also been established
based on consumption of contaminated aquatic organisms alone.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value indicates that the
minimum data were not available and the concentration given is not a criteria
value but the lowest effect level found in the literature.
V. SUPPLEMENTARY DATA
Chemical: Antimony
CAS No.: 7440-36-0
Information is not available at this time.
Synonyms: ANTIMONY (ACGIH); ANTIMONY BLACK; ANTIMONY POWDER (DOT); ANTIMONY,
REGULUS; ANTYMON (Polish); C.I. 77050; STIBIUM; UN 2871 (DOT)
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Barium, ionic; CAS No. 7440-39-3 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Barium, ionic
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: none
V. Supplementary Data: none
-------
Barium: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Barium, Ionic
CAS No.: 7440-39-3 Preparation Date: 01/30/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Increased blood 0.51 mg/kg/day (NOEL) 100 1 5E-2
pressure mg/kg/day
5.1 mg/kg/day (LOAEL)
Subchronic to chronic
(8-16 month) rat
drinking water study
Perry et al. (1983)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
The Office of Drinkng Water (ODW) believes that no single study considered
alone is appropriate to calculate a lifetime RfD for barium. Rather, ODW
believes that a barium RfD must be based on the weight of the evidence (i.e.,
the Perry et al., 1983 rat study) "in the light of" the Brenniman et al.
(1981) epidemiological study and the various other rodent studies (Schroeder
and Mitchener, 1975a,b; Tardiff et al., 1980). Because of the number of
studies involved, the complete reference citations are given in the
Documentation and Review subsection.
Brenniman et al. (1981) concluded that there was no statistically
significant difference in blood pressure between those ingesting drinking
water containing barium at 7.3 mg/L as compared to 0.1 mg/L. A concentration
of 7.3 mg/L corresponds to a dose of 0.20 mg/kg/day (assuming a 70-kg adult
drinks 2 L/day).
-------
Barium: page 3 of 5
Perry et al. (1983) exposed weanling rats to barium at 1, 10 or 100 ppm in
drinking water for up to 16 months (average daily barium doses of 0.051, 0.51
and 5.1 rug/kg, respectively). There were no signs of toxicity at any barium
dose level. Systolic blood pressure measurements revealed no increase in
pressure in animals exposed to 1 ppm for 16 months, an increase of 4 mm Hg
(p<0.01) in animals exposed to 10 ppm barium for 16 months, and an increase
in systolic pressure of 16 mm Hg (p<0.001) in animals exposed to 100 ppm
barium for 16 months. The animals in this study were maintained in a special
contaminant-free environment and fed a diet designed to reduce exposure to
trace metals. It is possible that the restricted intake of certain benefi-
cial metals (e.g., Ca and K) may have predisposed the test animals to the
hypertensive effects of barium (U.S. EPA, 1985).
Schroeder and Kitchener (1975a,b) exposed rats and mice to 5 mg/L barium
in drinking water for a lifetime (approximately 0.25 mg/kg/day for rats and
0.825 mg/kg/day for mice). No adverse effects were observed; however, blood
pressure was not measured.
Tardiff et al. (1980) exposed rats to barium at 0, 10, 50 or 250 ppm in
drinking water for 4, 8 and 13 weeks. The barium concentrations were approx-
imately 0, 2.75, 13.7 and 66.25 mg/kg/day at the beginning of the study and
0, 1.7, 6.6 and 31.5 mg/kg/day at the end of the study. Although the barium
body burden increased with increasing barium dosage, no conclusive signs jf
barium toxicity were observed in these animals. Blood pressure was not mea-
sured.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. According to NAS/ODW guidelines, an uncertainty factor of 1000 is
appropriate for use when a LOAEL from an animal study is employed. However,
a major limitation of this study is the minimized exposure to tr?,-e metals
(i.e., Ca) in the food, water and laboratory environment, and this may have
contributed to the observed effects. To accommodate for this, ODW feels that
selection of an uncertainty factor of 100 is more appropriate. Thus, the
LOAEL identified in the Perry et al. (1983) study (5.1 mg/kg/day) has been
used in the derivation of this RfD without an additional 10-fold urcertainty
factor for the lack of a NOAEL.
MF = 1
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Studies: Medium Data Base: Medium RfD: Medium
As previously stated, ODW does not believe any single study, considered
alone, is adequate to calculate an RfD. However, ODW believes that medium
confidence can be placed in the total data base used to determine the RfD.
6. DOCUMENTATION AND REVIEW
Brenniman, G.R., W.H. Kojola, P.S. Levy, B.W. Carnow and T. Namekata. 1981.
High barium levels in public drinking water and its association with elevated
blood pressure. Arch. Environ. Health. 36(1): 28-32.
-------
Barium: page 4 of 5
Perry, H.M., S.J. Kopp, M.W. Erlanger and E.F. Perry. 1983. Cardiovascular
effects of chronic barium ingestion. In: Trace substances in environmental
health, XVII, D.D. Hemphill, Ed. Proc. Univ. Missouri's 17th Ann. Conf. on
Trace Substances in Environmental Health. University of Missouri Press,
Columbia, MO.
Schroeder, H.A. and M. Mitchener. 1975a. Life-term effects of mercury,
methyl mercury and nine other trace metals on mice. J. Nutr. 105: 452-458.
Schroeder, H.A. and M. Mitchener. 1975b. Life-term studies in rats: Effects
of aluminum, barium, beryllium and tungsten. J. Nutr. 105: 421-427.
Tardiff, R.G., M. Robinson and N.S. Ulmer. 1980. Subchronic oral toxicity
of BaC12 in rats. J. Environ. Pathol. Tox. 4: 267-275.
U.S. EPA. 1985. Draft Drinking Water Health Effects Criteria Document on
Barium. Office of Drinking Water, Washington, DC. NTIS PB 86-118031/AS.
Agency RfD Work Group Review: 07/08/85, 07/22/85
Verification Date: 7/22/85
7. U.S. EPA CONTACTS
Primary: K.L. Bailey FTS/382-5535 or 202/382-5535
Office of Drinking Water
Secondary: P.A. Fenner-Crisp FTS/382-7589 or 202/382-7589
Office of Drinking Water
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Barium, ionic
CAS No.: 7440-39-3
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Barium, ionic
CAS No.: 7440-39-3
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
-------
Barium: page 5 of 5
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Barium, ionic
CAS No.: 7440-39-3
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Barium, ionic
CAS.No.: 7440-39-3
Information is not available at this time.
V. SUPPLEMENTARY DATA
Chemical: Barium, ionic
CAS No.: 7440-39-3
Information is not available at this time.
Synonyms: Barium; Barium, alloys, non-pyrophoric; Barium, alloys, pyrophoric:
Barium, metal, non-pyrophoric; UN 1399 (DOT); UN 1400 (DOT); UN 1854 (DOT)
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Barium Cyanide; CAS No. 542-62-1 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Barium Cyanide
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Barium Cyanide: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Barium Cyanide
CAS No.: 542-62-1
Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
study
Perry et al. (1983)
Experimental Doses *
UF
MF
RfD
Hypertension
Rat oral chronic
10 ppm barium In
drinking water
(NOAEL)
100 1 7E-2
mg/kg/day
100 ppm (LOAEL)
estimated as 5.1
mg/kg/day (U.S. EPA,
1985) converted to 7
mg Ba (CN)2
* Dose Conversion Factors & Assumptions: Exposure dose was based on U.S.
EPA (1985) estimate; molecular weight ratio of Ba(CN)2/Ba is 189/137; thus,
5.1 mg/kg/day x (189/137) = 7 mg/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
Perry, H.M., E.F. Perry, M.N. Erlanger and S.J. Kopp. 1983. Cardiovascular
effects of chronic barium ingestion. In: Proc. 17th Ann. Conf. Trace Sub-
stances in Environmental Health, Vol. 17. University of Missouri Press,
Columbia, MO. p. 155-164.
Perry et al. (1983) exposed 10 female rats/group to 0, 1, 10 or 100 ppm
barium in drinking water for up to 16 months. Barium exposure produced no
change In growth rate, and no evidence of toxicity was recognized. Limited
and preliminary physiologic and biochemical parameters, such as myocardial
pathophysiology and disturbances in myocardial metabolism, were significantly
depressed in rats exposed to 100 ppm barium (Perry et al., 1983; Kopp et al.,
1985) . In addition, rats from this exposure group showed increased average
systolic blood pressure (16 mm Hg average elevation).
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Barium Cyanide: page 3 of 5
A moderate increase (6 mm Hg) in systolic blood pressure was observed in
rats exposed to 10 ppm barium; however, the U.S. EPA (1985) determined that
the increase seen after 16 months is not large enough to constitute an
adverse health effect.
Brenniman et al. (1979, 1981) reported a significant increase in death
rate for cardiovascular diseases in communities whose water supply contained
an average of 7 mg Ba/L, compared with communities whose water supply con-
tained an average of 0.1 mg Ba/L. The exposure levels tested in these
studies did not evaluate a continuous range of exposure to barium and so,
although a NOEL may well have been identified, it is impossible to identify
the highest NOAEL within the framework of their experimental designs.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. The U.S. EPA (1985) justified the use of an uncertainty factor of
100 (10 for interspecies extrapolation and 10 for sensitive population) to the
estimated dose of 5.1 mg/kg/day barium on the grounds that the rats in the
Perry et al. (1985) study were exposed to very low levels of all essential
metals (specifically calcium).
MF = 1
4. ADDITIONAL COMMENTS
If an RfD for barium cyanide is based on cyanide (0.02 mg/kg/day CN/0.28,
% CN), an RfD of 0.08 mg/kg/day for barium cyanide would result in a daily
intake of 0.06 mg/kg/day of barium. An RfD of 0.07 mg/kg/day (0.051 mg/kg/
day Ba/0.72, % Ba) for barium cyanide is somewhat lower than would be derived
by analogy to cyanide (0.08 mg/kg/day) and is, therefore, recommended to pro-
vide adequate protection against adverse health effects.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Low Rf L> : Low
The confidence in the study is rated medium because three doses were used
and a sensitive indicator (i.e., blood pressure changes) of the critical
effect of barium (i.e., cardiac toxicity) was measured. The confidence in
the study is not rated any higher because of the use of only one sex and the
low level of essential element exposure that may have predisposed the animals
to barium toxicity. The data base is rated low because it is limited to a
few studies. The overall confidence in the RfD is rated low.
6. DOCUMENTATION AND REVIEW
Limited peer review and ECAO-Cincinnati internal review, August, 1985.
U.S. EPA. 1985. Drinking Water Criteria Document for Barium. Office of
Drinking Water, Washington, DC.
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
-------
Barium Cyanide: page 4 of 5
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Barium Cyanide
CAS No.: 542-62-1
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Barium Cyanide
CAS No.: 542-62-1
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Barium Cyanide
CAS No.: 542-62-1
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Barium Cyanide
CAS No.: 542-62-1 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
-------
Barium Cyanide: page 5 of 5
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk Status Risk Considers
Management Management Econ/Tech
Action Date Value Feasibility Reference
Reportable Final 10 Ibs no 50 FR 13456
Quantity (RQ) 1985 04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ was based on aquatic toxicity, as established under CWA
Section 311(b)(4). Available data indicate that the aquatic 96-Hour Median
Threshold Limit for barium cyanide is between .1 and 1 ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
V. SUPPLEMENTARY DATA
Chemical: Barium Cyanide
CAS No.: 542-62-1
Information is not available at this time.
Synonyms: BARIUM CYANIDE, BARIUM DICYANIDE, RCRA WASTE NUMBER P013, UN 1565
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Beryllium; CAS No. 7440-41-7 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Beryllium
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: review pending
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Beryllium: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Beryllium
CAS No.: 7440-41-7
Preparation Date: 07/31/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses
UF
MF
RfD
Decreased growth
Rat, chronic oral
bioassay
Decreased body
weight
Mouse, chronic oral
bioassay
Schroeder and
MItchner (1975a)
NOAEL: 5 ppm in
drinking water (0.54
mg/kg bw/day)
100
5E-3
mg/kg/day
0.95 mg/kg/day
(NOAEL)
* Dose Conversion Factors & Assumptions: 5 ppm (5 mg/L) x 0.035 L/day /
0.325 kg bw = 0.54 mg/kg bw/day
2. PRINCIPAL AND SUPPORTING STUDIES
Schroeder, H.A. and M. Mitchner. 1975. Life-term studies in rats: Effects
of aluminum, barium, beryllium and tungsten. J. Nutr. 105: 421-427.
Fifty-two weanling Long-Evans rats of each sex received 0 or 5 ppm Be (as
BeS04) in drinking water. Exposure was for the lifetime of the animals. At
natural death the rats were dissected and gross and microscopic changes were
noted in heart, kidney, liver and spleen. There were no effects of treatment
-------
Beryllium: page 3 of 6
on these organs or on life span, urinalysis, serum glucose, cholesterol, and
uric acid, or on numbers of tumors. Male rats experienced decreased growth
rates from 2-6 months of age.
Similar studies were carried out on Swiss (CD strain) mice, in groups of
54/sex. Female animals showed decreased body weight as compared to untreated
mice at 6 of 8 intervals. Male mice exhibited slight increases in body
weight. No other effects of treatment were observed except for increased
incidence of leukemia lymphoma in the females.
An unpublished investigation by Morgareidge et al. (1975) (cited in U.S.
EPA, 1980) indicates a much higher dose level (approximately 25 mg/kg/day) in
the diet may be a NOEL.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. The uncertainty factor of 100 reflects a factor of 10 each for
interspecies conversion and for the protection of sensitive human
subpopulations.
MF = 1
4. ADDITIONAL COMMENTS
Data on the teratogenicity or reproductive effects of Be are limited. It
has been reported to produce embryolethality and terata in chick embryos
(Puzanova et al., 1978).
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Medium RfD: Low
Confidence in the study is rated as low since only one dose level was
administered. Numerous inhalation investigations and a supporting chronic
oral bioassay in mice, along with the work by Morgareidge et al. (1975), which
indicates that a higher dose level might be a NOEL, afford a medium confidence
in the data base. The overall confidence in the RfD is low, reflecting the
need for more toxicity data by the oral route.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1985. Drinking Water Criteria Document for Beryllium. Office of
Drinking Water, Washington, DC.
The 1985 Drinking Water Criteria Document for Beryllium is currently under-
going Agency review.
Agency RfD Work Group Review: 12/02/85
Verification Date: 12/02/85
7. U.S. EPA CONTACTS
Primary: V. Molak FTS/684-7585 or 513/569-7585
Office of Research and Development
-------
Beryllium: page 4 of 6
Secondary: P. Fenner-Crisp FTS/684-7589 or 202/382-7589
Office of Drinking Water
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Beryllium
CAS No.: 7440-41-7
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Beryllium
CAS No.: 7440-41-7
This chemical is among those substances evaluated by the U.S. EPA for
evidence of human carcinogenic potential. This does not imply that this
chemical is necessarily a carcinogen. The evaluation for this chemical is
under review by an inter-office Agency work group. A risk assessment summary
will be included on IRIS when the review has been completed.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Beryllium
CAS No.: 7440-41-7
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Beryllium
CAS No.: 7440-41-7 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
-------
Beryllium: page 5 of 6
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Statutory
1980
Risk
Management
Value
1 Ib
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
2) Marine
Clean Air Act
Regulatory
Decision:
Nat. Emissions Final
Standards for 1978
Hazardous Air
Pollutants (NESHAP)
3.7 ng/1
no
Acute no
130 ug/1 (LEL)
Chronic
5.3 ug/1 (LEL)
none
45 FR 79318
11/28/80
ibid.
various
yes
40 CFR Part 61
Subparts C & D
B. RISK MANAGEMENT RATIONALE
RQ
The statutory RQ of 1 pound established pursuant to CERCLA Section
102(b) is retained until the assessment of potential carcinogenicity is
complete.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC of 3.7 ng/1 represents a cancer risk level of 1E-6
based on consumption of contaminated organisms and water. A WQC of 64.1
ng/1 (cancer risk level of 1E-6) has also been established based on
consumption of contaminated organisms alone.
-------
Beryllium: page 6 of 6
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value indicates that the
minimum data were not available and the concentration given is not a criteria
value but the lowest effect level found in the literature.
CAA Regulatory Decision
NESHAP
Beryllium was listed as a hazardous air pollutant under section 112 of
the CAA in 1971 on the basis that it can cause the chronic lung disease
berylliosis. Emission standards promulgated for extraction, ceramic, and
propellant plants, foundries, incinerators, and machine shops are 10 g/24 hr
or attainment of an ambient concentration near the source of 0.01 ug/m3, 30
day average. This ambient concentration was judged adequate to protect the
public health with an ample margin of safety. More complex standards were
also promulgated for beryllium rocket motor firing. The NESHAPs are now
under review, which will consider new health evidence that beryllium may be a
carcinogen.
Contact: Emission Standards and Engineering Division
FTS/629-5571 or 919/541-5571
V. SUPPLEMENTARY DATA
Chemical: Beryllium
CAS No.: 7440-41-7
Information is not available at this time.
Synonyms: Beryllium; Beryllium-9; Beryllium, metal powder; Glucinum; RCRA
waste number P015; UN 1567 (DOT)
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
1,1-Biphenyl; CAS No. 92-52-4 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR 1,1-Biphenyl
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: none
V. Supplementary Data: none
-------
1,1-Biphenyl: page 2 of 4
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: 1,1-Biphenyl
CAS No.: 92-52-4
Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Kidney damage
Rat chronic oral
study
Ambrose et al. (1960)
0.1% of diet (NOAEL)
(50 mg/kg bw/day)
0.5% of diet (LOAEL)
100
10
5E-2
mg/kg/da7
* Dose Conversion Factors & Assumptions:
E6 mg/kg) = 50 mg/kg/day
(0.1 g/100 g) x (0.05/day) x (1
2. PRINCIPAL AND SUPPORTING STUDIES
Ambrose, A.M., A.N. Booth, F. DeEds and A.J. Cox, Jr. 1960. A toxicological
study of biphenyl, a citrus fungistat. Food Res. 25: 328-336.
Fifteen weanling albino rats of each sex were placed in each of eight
experimental groups: 0.0, 0.001, 0.005, 0.01, 0.05, 0.10, 0.50 and 1.0%
biphenyl in the diet. Dietary levels of 0.5% biphenyl and greater were asso-
ciated with kidney damage, reduced hemoglobin levels, decreased food intake
and decreased longevity. One animal in each of the lower dose groups and
control group had detectable blood in the renal pelvis. A supporting unpub-
lished work (Stanford Research Institute, n.d.) was cited in which a NOAEL of
0.1% biphenyl in the diet was found in both a subchronic rat feeding study and
a three-generation rat reproduction study.
A NOAEL of 0.1% of diet Is chosen because of the uncertainty of the sig-
nificance of the effects observed at lower doses as compared to the more c.er-
-------
1,1-BIphenyl: page 3 of 4
tain AEL of 0.5% of diet. The observation of the same NOAEL in a supporting
study is also a contributing factor.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. Factors of 10 each for interspecies conversion and for protection
of sensitive human subpopulations were applied to the NOAEL of 50
mg/kg/day.
MF = 10. An additional factor of 10 was applied to account for intraspecies
variability demonstrated by uncertainty in the threshold suggested by the
data in the critical study.
4. ADDITIONAL COMMENTS
Limited teratogenicity data on 1,1-biphenyl indicate it is not terato-
genic. No fetal or maternal toxicity resulted from pregnant Wistar rat dams
receiving 125, 250 or 500 mg/kg 1,1-biphenyl by gavage on days 6-15 of gesta-
tion (Khera et al., 1979). Some evidence (not significant) of fetotoxicity
(reduced fetal weights, decreased number of liver fetuses and increased
resorptions) was observed at 1000 mg/kg, but maternal mortality occurred -.t
this dose level as well. No significant effects were reported by Ambrose et
al. (1960) who gave 0, 0.1 and 0.5% biphenyl in the diet to weanling rats 60
days before mating through weaning of their offspring. Biphenyl at 1% in the
diet produced unspecified adverse effects in a three-generation unpublished
study on rats (SRI, n.d.).
5. CONFIDENCE IN THE RfD
Study: High Data Base: Low RfD: Medium
The critical study was a well-conducted chronic bioassay covering a wide
dose range with an adequate number of both animals and toxicity parameters
assessed. The only supporting data is unpublished, so that the confidence in
the data base is low. Confidence in the RfD is medium as follows.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1984. Health and Environmental Effects Profile for 1,1-Biphenyl.
Environmental Criteria and Assessment Office, Cincinnati, OH. ECAO-CIN-P085.
The ADI in the 1984 Health and Environmental Effects Profile document has
received an Agency review with the help of two external scientists.
Agency RfD Work Group Review: 10/09/85
Verification Date: 10/09/85
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
-------
1,1-BIphenyl: page 4 of 4
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: 1,1-Biphenyl
CAS No.: 92-52-4
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: 1,1-Biphenyl
CAS No.: 92-52-4
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: 1,1-Biphenyl
CAS No.: 92-52-4
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: 1,1-Biphenyl
CAS No.: 92-52-4
Information is not available at this time.
V. SUPPLEMENTARY DATA
Chemical: 1,1-Biphenyl
CAS No.: 92-52-4
Information is not available at this time.
Synonyms: BIPHENYL; BIBENZENE; 1,1'-BIPHENYL; BIPHENYL (ACGIH); DIPHENYL;
LEMONENE; PHENADOR-X; PHENYLBENZENE; PHPH; XENENE
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Bis(2-ethylhexyl)phthlate (BEHP); CAS No. 117-81-7 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Bis(2-ethylhexyl)phthlate
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: review pending
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Bis(2-ethylhexyl)phthlate (BEHP): page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Bis(2-ethylhexyl)phthlate (BEHP)
CAS No.: 117-81-7 Preparation Date: 05/12/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Increased relative NOAEL: None 1000 1 2E-2
liver weight mg/kg/day
LOAEL: 0.04% of diet
Guinea pig sub- (19 mg/kg bw/day)
chronic-to-chronic
oral bioassay
Carpenter et al.
(1953)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Carpenter, C.P., C.S. Weil and H.F. Smyth. 1953. Chronic oral toxicity of
di(2-ethylhexyl)phthalate for rats, guinea pigs and dogs. Arch. Indust. Hyg.
Occup. Med. 8: 219--226.
The following numbers of guinea pigs were fed diets containing BEHP for a
period of 1 year: 24 males and 23 females consumed feed with 0.13% BEHP; 23
males and 23 females, 0.04%; and 24 males and 22 females on the control diet.
No treatment-related effects were observed on mortality, body weight, kidney
weight, or gross pathology and histopathology of kidney, liver, lung spleen,
or testes.
Statistically significant increases In relative liver weights were
observed in both groups of treated females (64 and 19 mg/kg bw/day).
-------
Bis(2-ethylhexyl)phthlate (BEHP): page 3 of 6
Groups of 32 male and 32 female Sherman rats were maintained for 2 years
on diets containing either 0.04, 0.13 or 0.4% BEHP (equivalent to 20, 60 and
about 195 g/kg bw/day based on measured food consumption). An Fl group of 80
animals was fed the 0.04% diet for 1 year. Mortality in the Fl treated and
control groups was high; 46.2 and 42.7%, respectively, survived to 1 year.
There was, however, no effect of treatment on either parental or Fl group
mortality, life expectancy, hematology or histopathology of organs. Both
parental and Fl rats receiving the 0.4% BEHP diet were retarded in growth and
had increased kidney and liver weights.
It appears that guinea pigs offer the more sensitive animal model for
BEHP toxicity. A LOAEL in this species is determined to be 19 mg/kg/day.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. Factors of 10 each were used for interspecies variation and for
protection of sensitive human subpopulations. An additional factor of 10 was
used since the guinea pig exposure was longer than subchronic but less than
lifetime, and because, while the RfD is set on a LOAEL, the effect observed
was considered to be minimally adverse.
MF = 1
4. ADDITIONAL COMMENTS
BEHP has adverse effects on fertility and reproduction in both male and
female mice (NTP, 1984). In males the effect is linked to degeneration of
seminiferous tubules. BEHP has been observed to be both fetotoxic and
teratogenic (Singhe, 1972; Shiot and Nishimura, 1982).
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The study by Carpenter et al. (1953) utilized sufficient numbers of guinea
pigs and measured multiple end points. The fact that there were only two con-
centrations of BEHP tested precludes a rating higher than medium. As there
are corroborating chronic animal bioassays, the data base and RfD are like-
wise rated medium.
6. DOCUMENTATION AND REVIEW
The RfD has been reviewed by the RfD Work Group. Documentation may be found
in the meeting notes of 01/22/86.
Agency RfD Work Group Review: 01/22/86
Verification Date: 01/22/86
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
-------
Bis(2-ethylhexyl)phthlate (BEHP): page 4 of 6
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Bis(2-ethylhexyl)phthlate
CAS No.: 117-81-7
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Bis(2-ethylhexyl)phthlate
CAS No.: 117-81-7
This chemical is among those substances evaluated by the U.S. EPA for
evidence of human carcinogenic potential. This does not imply that this
chemical is necessarily a carcinogen. The evaluation for this chemical is
under review by an inter-office Agency work group. A risk assessment summary
will be included on IRIS when the review has been completed.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Bis(2-ethylhexyl)phthlate
CAS No.: 117-81-7
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Bis(2-ethylhexyl)phthlate (BEHP)
CAS No.: 117-81-7 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
-------
Bis(2-ethylhexyl)phthlate (BEHP): page 5 of 6
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Statutory
1980
Risk
Management
Value
1 Ib
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
2) Marine
Final
1980
15 mg/1
no
Acute no
940 ug/1 (LEL)
Chronic
3 ug/1 (LEL)
Acute no
2944 ug/1 (LEL)
Chronic
3.4 ug/1 (LEL)
45 FR 79318
11/28/80
ibid.
ibid.
B. RISK MANAGEMENT RATIONALE
RQ
The statutory RQ of 1 pound established pursuant to CERCLA Section
102(b) is retained until the assessment of potential carcinogenicity is
complete.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC of 15 mg/1 is based on consumption of contaminated
aquatic organisms and water. A WQC of 50 mg/1 has also been established
based on consumption of contaminated aquatic organisms alone.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value indicates that the
minimum data were not available and the concentration given is not a criteria
value but the lowest effect level found in the literature. These criteria
are based on combinations of phthalate esters, not on a specific chemical.
-------
Bis(2-ethylhexyl)phthlate (BEHP): page 6 of 6
V. SUPPLEMENTARY DATA
Chemical: Bis(2-ethylhexyl)phthlate
CAS No.: 117-81-7
Information is not available at this time.
Synonyms: Phthalic acid, Bis(2-ethylhexyl) ester; BEHP; 1,2- Benzene-
dicarboxylic acid, Bis(2-ethylhexyl) ester; Bis(2-ethylhexyl)-1,2- benzene-
dicarboxylate; Bisoflex 81; Bisoflex DOP; Compound 889; DAF 68; DEHP;
Di(2-ethylhexyl)orthophthalate; Di(2-ethylhexyl)phthalate; Dioctyl phthalate;
Di-sec-octyl phthalate; DOP; Ergoplast FDD; Ethylhexyl phthalate; 2-Ethylhexyl
phthalate; Eviplast 80; Eviplast 81; Fleximel; Flexol DOP; Flexol plasticizer
DOP; Good-Rite GP 264; Hatcol DOP; Hereoflex 260; Kodaflex DOP; Mollan 0; NCI-
C52733; Nuoplaz DOP; Octoil; Octyl phthalate; Palatinol AH; Phthalic acid,
dioctyL ester; Pittsburgh PX-138; Platinol DOP; RC Plasticizer DOP; RCRA waste
number U028; Reomol DOP; Reomol D 79P; Sicol 150; Staflex DOP; Truflex DOP;
Vestinol AH; Vinicizer 80; Witcizer 312
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Bromomethane; CAS No. 74-83-9 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Bromomethane
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Bromomethane: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Bromomethane
CAS No.: 74-83-9 Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Rabbit, inhalation 3.8 mg/kg/day (NOAEL) 1000 10 4E-4
subchronic assay mg/kg/day
7.4 mg/kg/day (LOAEL)
Irish et al. (1940)
* Dose Conversion Factors & Assumptions: For use of animal inhalation data
the following equation modified from U.S. EPA (1980) is used: NOAEL = 65
mg/cu. m x 2.0 cu. m/day x 7.5 hour/24 hour x 5 day/7 day x 0.5 / 3.8 kg =
3.8 mg/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
Irish, D.D., E.M. Adams, H.C. Spencer and V.K. Rowe. 1940. The response
attending exposure of laboratory animals to vapors of methyl bromide. J.
Ind. Hyg. Toxicol. 22: 218-230.
This was a study in which rats, rabbits, guinea pigs and monkeys were
exposed to bromomethane by inhalation for 7.5-8 hour/day, 5 days/week for 6
months or until the majority of the animals had died or exhibited severe
reactions. Variable numbers of animals were exposed to 17, 33, 66, 100 or 220
ppm. The highest NOAELs were: 17 ppm (3.8 mg/kg/day), rabbits; 33 ppm,
monkeys; 66 ppm, rats; and 100 ppm, guinea pigs. Rabbits exposed to 33 ppm
(7.4 mg/kg/day) and higher concentrations developed pulmonary damage and
paralysis. Monkeys also developed paralysis, and guinea pigs and rats
exhibited various types of lung pathology. Rabbits were the most sensitive to
bromomethane toxicity in this study; the NOAEL and LOAEL are determined to be
3.8 and 7.4 mg/kg/day, respectively.
-------
Bromomethane: page 3 of 6
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. Factors of 10 each were used for extrapolation from animal data,
use of a subchronic assay, and for protection of sensitive human
subpopulations.
MF - 10. An additional modifying factor of 10 was used due to both the low
number of test animals at the NOAEL and because of the marked severity of
effects at the LEL.
4. ADDITIONAL COMMENTS
Subchronic inhalation bioassays (NTP, 1984) established NOELs of 20 ppm
(80 mg/cu. m) in mice and 30 ppm (120 mg/cu. m) in rats. Since these values
are substantially higher than the LEL for rabbits reported by Irish, the
results of these bioassays do not affect the RfD.
No statistically significant effects by bromomethane on teratogenicity or
fetotoxicity were noted in rats or rabbits (Sikov et al., 1980). Bromo-
methane is being tested by NTP for reproductive and developmental toxicity
and was scheduled for mutagenicity testing in FY84.
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Low RfD: Low
The paper by Irish et al. (1940) is unclear as to numbers of control ani-
mals and there is no statistical interpretation of the data. There are
limited data on human exposure (Waters, 1942; Johnstone, 1945). Confidence
in the study, data base and RfD are rated low.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1982. Errata: Halomethanes Ambient Water Quality Criterion for
the Protection of Human Health. Environmental Criteria and Assessment
Office, Cincinnati, OH. ECAO-CIN-D023.
The ADI in the 1982 Errata to the Ambient Water Quality Criteria document was
reviewed by the Agency.
Agency RfD Work Group Review: 12/02/85, 02/05/86
Verification Date: 02/05/86
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
-------
Bromomethane: page 4 of 6
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Bromomethane
CAS No.: 74-83-9
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Bromomethane
CAS No.: 74-83-9
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Bromomethane
CAS No.: 74-83-9
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Bromomethane
CAS No.: 74-83-9 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Bromomethane: page 5 of 6
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
1000 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Pesticide Active
Ingredient:
a. Registration Current various no Methyl Bromide
Standard 1986 Reg. Std.
b. Special none
Review
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on acute toxicity. The available data indicate
that bromomethane has an inhalation LClo for guinea pigs of between 40 and
400 mg/kg.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
Pesticide Active Ingredient
a. Registration Standard: Registration standards for pesticide active
ingredients consider several factors, including environmental fate, toxicity,
residue chemistry, and end use patterns for pesticide products containing the
active ingredient, and tolerances. For specific details on the registration
standard for this active ingredient please check the references listed.
Methyl Bromide Registration Standard. August 1986. Registration Support and
Emergency Response Branch, Office of Pesticide Programs.
Contact: Office of Pesticide Programs
202/557-7760 or FTS/557-7760
b. Special Review: none
V. SUPPLEMENTARY DATA
Chemical: Bromomethane
CAS No.: 74-83-9 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
-------
Bromomethane: page 6 of 6
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Bromomethane (methyl bromide) is a dangerous cumulative poison with
delayed symptoms of central nervous system intoxication that may appear as
long as several months after exposure (White-Stevens, 1971). High
concentrations can produce fatal pulmonary edema. Severe neurological signs
may appear when there is a sudden exposure to high concentrations following
continuous slight exposure (Encyc Occupat Health and Safety, 1971). Methyl
bromide has practically no odor or irritating effects and therefore no
warning, even at hazardous concentrations (Clayton and Clayton, 1981-82).
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Symptoms may appear 3-12 hours after
inhalation, including dizziness, headache, anorexia, nausea, vomiting,
abdominal pain, weakness, blurred vision, mental confusion, tremors,
convulsions, rapid respiration, collapse, and coma. Later there may be
bronchopneumonia, kidney failure, and severe weakness. Skin contact may
cause blistering, if evaporation is delayed (Gosselin, 1976).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: CH Br
3
Molecular Weight: 94.95
Boiling Point: 38.4F, 3.56C
Specific Gravity (H20=l): Liquid: 1.730 at OC/4C
Vapor Pressure (mmHg): 1420 at 20C
Melting Point: -136F, -93.6C
Vapor Density (AIR=1): 3.27
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: 1.34 g/100 g at 25C
Flash Point [Method Used]: None
Flammable Limits:
LEL: 10%
UEL: 16%
Appearance and Odor: Colorless gas; usually odorless, but has a sweetish
chloroform-like odor at high concentrations.
Conditions or Materials to Avoid: Not Found
Hazardous Decomposition or Byproducts: When heated to decomposition, it
emits toxic fumes of bromides (Sax, 1979).
Use: This material is used as an insecticide, rodenticide, fumigant, and
nematocide; as a chemical intermediate (SRI); and as a fire extinguishing
agent (Clayton and Clayton, 1981-82).
Synonyms: Brom-o-gas; Bromomethane; Curafume; Dowfume MC-2 Soil Fumigant;
Dowfume MC-33; Edco; Embafume; Halon 1001; Haltox; Iscobrome; Kayafume; MB;
MBX; MEBR; Metafume; Methane, Bromo-; Methogas; Monobromomethane; Pestmaster;
Profume; R 40B1; Rotox; Terabol; Terr-o-gas 100; Zytox
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Butylphthalyl Butylglycolate; CAS No. 85-70-1 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Butylphthalyl Butylglycolate
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD:
II. Risk Estimates for Carcinogens:
III. Drinking Water Health Advisories:
IV. Risk Management Summaries:
V. Supplementary Data:
none
none
none
none
none
-------
Butylphthalyl Butylglycolate (BPBG): page 2 of 4
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Butylphthalyl Butylglycolate (BPBG)
CAS No.: 85-70-1
Preparation Date: 04/17/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
General toxicity
Rat, chronic oral
bioassay
B.F. Goodrich Co.
(1950)
20,000 ppm of diet
(estimated as 1000
mg/kg/day) (NOEL)
LOAEL: None
1000
mgAg/day
* Dose Conversion Factors & Assumptions:
diet/kg bw/day = 1000 mg/kg bw/day
20,000 mg/kg of diet x 0.05 kg/
2. PRINCIPAL AND SUPPORTING STUDIES
B.F. Goodrich Company. 1950. A study on the toxicity of butylphthalyl
butylglycolate (Santicizer B-16). Report to Monsanto, St. Louis, MO.
Twenty Sherman rats received either 200, 2000 or 20,000 ppm butylphthalyl
butylglycolate (BPBG) in the diet for 2 years. A control group of 40 rats
received only the stock diet. Since there was a transient depression of
growth during treatment weeks 5-15, a second set of experimental animals was
treated. These rats were maintained on diets containing 20, 200 or 2000 ppm
for 1 year. There were no significant effects of treatment upon the fol-
lowing: behavior, body weight, mortality, tumor incidence, hematology or
gross pathology (with special attention given to the endocrine system).
Two mongrel dogs treated for 2 years with 140 mg BPBG/day in capsule
form likewise showed no evidence of a toxic response.
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Butylphthalyl Butylglycolate (BPBG) : page 3 of 4
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. An uncertainty factor of 10 was used to account for interspecies
variation, and a second 10-fold factor was used to protect sensitive human
subpopulations. An additional 10-fold factor was applied to account for
the uncertainty that the chosen effect level may have been a LOAEL
(histopathology was not evaluated in the critical study).
MF = 1
4. ADDITIONAL COMMENTS
The minimum oral lethal dose was determined in this study to be 2.1-3.2
g/kg bw for rabbits and 3.2-4.7 g/kg bw for rats.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Low RfD: Low
This study employed a sufficient number of animals and was of chronic
duration and is, therefore, rated medium. Since this is the only long-term
treatment study reported for BPBG, confidence in the data base and RfD are
rated low.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1980. Ambient Water Quality Criteria for Phthalate Esters. Envi-
ronmental Criteria and Assessment Office, Cincinnati, OH. EPA 440/5-80-067.
The RfD in the 1980 Ambient Water Quality Criteria for Phthalate Esters has
received extensive peer and public review.
Agency RfD Work Group Review: 01/22/86
Verification Date: 01/22/86
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Butylphthalyl Butylglycolate
CAS No.: 85-70-1
Information is not available at this time.
-------
Butylphthalyl Butylglycolate (BPBG): page 4 of 4
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Butylphthalyl Butylglycolate
CAS No.: 85-70-1
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Butylphthalyl Butylglycolate
CAS No.: 85-70-1
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Butylphthalyl Butylglycolate
CAS No.: 85-70-1
Information is not available at this time.
V. SUPPLEMENTARY DATA
Chemical: Butylphthalyl Butylglycolate
CAS No.: 85-70-1
Information is not available at this time.
Synonyms: PHTHALIC ACID, BUTYL ESTER, ESTER with BUTYL GLYCOLATE; BUTYL
CARBOBUTOXYMETHYL PHTHALATE; BUTYL GLYCOLYL BUTYL PHTHALATE; BUTYL PHTHALATE
BUTYL GLYCOLATE; BUTYL PHTHALYL BUTYL GLYCOLATE; DIBUTYL 0-(o-CARBOXYBENZOYL)
GLYCOLATE; DIBUTYL o-CARBOXYBENZOYLOXYACETATE; GLYCOLIC ACID, BUTYL ESTER,
BUTYL PHTHALATE; GLYCOLIC ACID, PHTHALATE, DIBUTYL ESTER; PHTHALIC ACID,
BUTOXYCARBONYLMETHYL BUTYL ESTER; PHTHALIC ACID, BUTYL ESTER, BUTYL
GLYCOLATE; SANTICIZER B-16
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Calcium Cyanide; CAS No. 592-01-8 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Calcium Cyanide
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
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Calcium Cyanide: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Calcium Cyanide
CAS No.: 592-01-8 Preparation Date: 01/06/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Rat chronic oral 10.8 mg/kg/day CN 100 5 4E-2
study (NOAEL) converted to mg/kg/day
19.1 mg/kg/day of
Howard and Hanzal calcium cyanide
(1955)
Weight loss, thyroid 30 mg/kg/day CN
effects and myelin (LOAEL)
degeneration (53 mg/kg/day CaCN)
Rat subchronic to
chronic oral bioassay
Philbrick et al.
(1979)
* Dose Conversion Factors & Assumptions: molecular weight conversion factor
= 92/(2 x 26) [ MW Ca(CN) - 92; MW CN = 26 ]
2
2. PRINCIPAL AND SUPPORTING STUDIES
Howard, J.W. and R.F. Hanzal. 1955. Chronic toxicity for rats of food
treated with hydrogen cyanide. Agric. Food Chem. 3: 325-329.
Since calcium is present in a very high level physiologically, RfDs for
Ca(CN)2 can be calculated based on the maximum molar equivalents of cyanide
generated in aqueous or dilute acid solution.
-------
Calcium Cyanide: page 3 of 5
In this 2-year dietary study, rats (10/sex/group) were administered food
fumigated with HCN. The average daily concentrations were 73 and 183 mg CN/kg
diet. From the data reported on food consumption and body weight, daily
estimated doses were 4.3 mg and 10.8 mg CN/kg bw. The average food CN
concentrations were estimated based on the authors' data for concentration at
the beginning and end of each food preparation period and by assuming a first -
order rate of loss for the intervening period. There were no treatment-
related effects on growth rate, no gross signs of toxicity, and no histo-
pathological lesions.
Studies by Philbrick et al. (1979) showed decreased weight gain and
thyroxin levels and myelin degeneration in rats at 30 mg/kg/day CN. Other
chronic studies either gave higher effect levels or used the subcutaneous
route (Crampton et al., 1979; Lessell, 1971; Berthing et al., 1960). Human
data do not provide adequate information from which tc derive an RfD because
effective dose levels of chronically ingested CN are not documented.
Therefore, the study of Howard and Hanzel (1955) provides the highest NOAEL,
10.8 mg/kg/day for CN, and is chosen for the derivation of an RfD for CN of
1.5 mg/day or 0.02 mg/kg/day.
Cyanide is metabolized extensively in the liver, indicating that the only
relevant route of administration for quantitative risk assessment in the
derivation of an oral RfD is the oral route of administration.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. According to the U.S. EPA (1985), an uncertainty factor of 100 is
used to derive the RfD (10 for species extrapolation, 10 for sensitive
population).
MF = 5. A modifying factor of 5 is used to account for the apparent tolerance
to cyanide when it is ingested with food rather than when it is administered
by gavage or by drinking water.
4. ADDITIONAL COMMENTS
Decreased protein efficiency ratio was produced by dietary cyanide treat-
ment of rats during gestation, lactation and postweaning growth phase in the
Tewe and Maner (1981a) experiment: the dose level of cyanide (10.6 mg/kg/
day) producing that effect is slightly lower than the currently accepted
NOAEL of 10.8 mg/kg/day (U.S. EPA, 1985). Furthermore, Tewe and Maner
(1981b) tested sows. Possible effects observed at about 9.45 mg/kg/day were
proliferation of glomerular cells of the kidneys and reduced activity of the
thyroid glands in the gilts. However, the number of animals in this experi-
ment was very small. A Japanese study (Amo, 1973) indicated that 0.05 mg/
kg/day of cyanide obtained from drinking water decreased the fertility rate
and survival rate in the Fl generation and produced 100% mortality in the F2
generation in mice. However, these data are not consistent with the body of
available literature. Thus, until additional chronic studies are available,
an RfD of 3 mg/day for a 70-kg man is recommended.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The confidence in the study is medium because adequate records of food
consumption and body weight were maintained and animals of both sexes were
-------
Calcium Cyanide: page 4 of 5
tested at two doses for 2 years. The data base is rated medium because a
small but sufficient number of studies support the chosen study. The confi-
dence in the RfD follows. Additional chronic/reproductive studies are needed
to support a higher level of confidence in the RfD.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, July 1985.
U.S. EPA. 1985. Cyanides: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Calcium Cyanide
CAS No.: 592-01-8
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Calcium Cyanide
CAS No.: 592-01-8
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Calcium Cyanide
CAS No.: 592-01-8
Information is not available at this time.
-------
Calcium Cyanide: page 5 of 5
IV. RISK MANAGEMENT SUMMARIES
Chemical:
CAS No.:
Calcium Cyanide
592-01-8
Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
10 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ was based on aquatic toxicity, as established under CWA
Section 311(b)(4). Available data indicate that the aquatic 96-Hour Median
Threshold Limit for calcium cyanide is between .1 and 1 ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
V. SUPPLEMENTARY DATA
Chemical:
CAS No.:
Calcium Cyanide
592-01-8
Information is not available at this time.
Synonyms: CALCIUM CYANIDE; CALCIUM CYANIDE, SOLID (DOT); CALCYANIDE;
CYANOGAS; CYANURE DE CALCIUM (French); RCRA WASTE NUMBER P021; UN 1575 (DOT)
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Carbaryl; CAS No. 63-25-2 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Carbaryl
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Carbaryl: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) Is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Carbaryl
CAS No.: 63-25-2
Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Kidney and liver
toxicity
Rat chronic feeding
study
Carpenter et al.
(1961)
200 ppm of diet (9.6
mg/kg/day (NOAEL)
400 ppm of diet 15.6
nig/kg/day (LOAEL)
100
1E-1
nig/kg/day
Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Carpenter, C.P., C.U. Weil, P.E. Polin, et al. 1961. Mammalian toxicity of
1-naphthayl-N-methylcarbamate (Sevin insecticide). J. Agric. Food Chem. 9:
30-39.
Groups of 20 CF-N rats/sex were fed carbaryl at 0, 50, 100, 200 or 400
ppm of diet for 2 years. Food consumption and body weight records were main-
tained. Interim sacrifices (4-8 animals) from concurrent auxiliary groups
were performed at 6, 9 and 12 months for organ weight comparisons and histo-
pathological analysis. Hematological analyses were done at irregular
intervals throughout the study. Surviving animals were sacrificed at 2 years
with gross and histopathological examinations performed. The only noteworthy
effects reported were slight histopathological changes in the kidneys and
liver at the high-dose level. Diffuse cloudy swelling of renal tubules was
-------
Carbaryl: page 3 of 6
observed at 1 and 2 years. A statistically significant increase in cloudy
swelling of the hepatic cords was also observed after 2 years. Based on body
weight and food consumption data, the LOAEL of 400 ppm was equivalent to a
dose of 15.6 mg/kg bw/day. The NOAEL established was 9.6 rag/kg bw/day.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. UF = lOa x lOh. The UF of 100 includes uncertainties in
interspecies and intrahuman variability.
MF = 1
4. ADDITIONAL COMMENTS
Effect and no-effect levels (14 and 7 mg/kg/day, respectively) similar to
those found in the critical study were observed for rat body weight reduction
and cholinesterase inhibition in a 1-year study. In subchronic rat studies,
higher dose levels (85-200 mg/kg/day) caused kidney toxicity and biochemical
changes. Kidney lesions were observed in dogs fed carbaryl at 5 mg/kg/day
for 1 year; however, the effect was not clearly associated with treatment
since the lesions appeared in control animals but not in lower dose groups.
Carbaryl was teratogenic for several species, with widely varying NOELs.
The lowest effect levels of 5-6 mg/kg were observed for dogs, with NOELs of
2-3 mg/kg. Other LOELs were higher than the established chronic LOAEL of
15.6 mg/kg/day. Carbaryl was not teratogenic for monkeys at 20 mg/kg. The
dog studies were judged inappropriate for human health risk assessment be-
cause of differences in the metabolism of carbaryl between dogs and humans.
Carbaryl has induced numerical chromosome aberrations (aneupl ,'idy and
polyploidy) in experimental animals. Carbaryl has not been found to be car-
cinogenic, but the data are equivocal.
5. CONFIDENCE IN THE RfD
Study: High Data Base: Medium RfD: Medium
The critical study was well designed and clearly reported with unequivo-
cal effect levels established. The data base is moderately supportive of the
nature of the critical effect, if somewhat sparse. The principal problem is
the observation of teratogenicity in dogs at lower doses. Because the sig-
nificance of these data cannot be discounted entirely, confidence in the RfD
should be considered medium to low.
6. DOCUMENTATION AND REVIEW
Limited Agency review of 1984 Health and Environmental Effects Profile with
the help of two external scientists.
U.S. EPA. 1984. Health and Environmental Effects Profile for Carbaryl.
Environmental Criteria and Assessment Office, Cincinnati, OH. ECAO-CIN-P039.
Agency RfD Work Group Review: 05/31/85
Verification Date: 05/31/85
-------
Carbaryl: page 4 of 6
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Carbaryl
CAS No.: 63-25-2
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Carbaryl
CAS No.: 63-25-2
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Carbaryl
CAS No.: 63-25-2
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Carbaryl
CAS No.: 63-25-2 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
-------
Carbaryl: page 5 of 6
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
100 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Pesticide Active
Ingredient:
a .
b.
Registration
Standard
Special
Review
Current n . a .
1984
Final n.a.
1980
no Reg. Standard
March, 1984
no 45 FR 81829
12/12/80
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity, as established under CWA
Section 311(b)(4). The available data indicate that carbaryl has an aquatic
96-Hour Median Threshold Limit between 1 and 10 ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
Pesticide Active Ingredient
a. Registration Standard: Carbaryl Pesticide Registration Standard. March
1984. Office of Pesticides and Toxic Substances. Environmental Protection
Agency, 401 M Street, S.W., Washington, B.C.
Contact: Office of Pesticide Programs
202/557-7760 or FTS/557-7760
b. Special Review: For specific details on the Special Review process for
this active ingredient please check the references listed.
Contact: Office of Pesticide Programs, Special Review Branch
202/557-7420 or FTS/557-7420
-------
Carbaryl: page 6 of 6
V. SUPPLEMENTARY DATA
Chemical: Carbaryl
CAS No.: 63-25-2
Information is not available at this time.
Synonyms: ARYLAM, CARBAMINE, CARBARIL (Italian), CARBARYL, CARBATOX,
CARBATOX-60, CARBATOX 75, CARPOLIN, CARYLDERM, CEKUBARYL, CRAG SEVIN, DENAPON,
DEVICARB, DICARBAM, ENT 23,969, EXPERIMENTAL INSECTICIDE 7744, GAMONIL,
GERMAIN'S, HEXAVIN, KARBARYL (Polish), KARBASPRAY, KARBATOX, KARBOSEP,
N-METHYLCARBAMATE DE 1-NAPHTYLE (French), METHYLCARBAMATE 1-NAPHTHALENOL,
METHYLCARBAMATE 1-NAPHTHOL, METHYLCARBAMIC ACID, 1-NAPHTHYL ESTER,
N-METHYL-1-NAFTYL-CARBAMAAT (Dutch), N-METHYL-1-NAPHTHYL-CARBAMAT (German),
N-METHYL-alpha-NAPHTHYLCARBAMATE, N-METHYL-1-NAPHTHYL CARBAMATE,
N-METHYL-alpha-NAPHTHYLURETHAN, N-METIL-1-NAFTIL-CARBAMMATO (Italian), NAG, NA
2757, aIpha-NAFTYL-N-METHYLKARBAMAT (C z e ch), 1-NAPHTHOL N-METHYLCARBAMATE,
alpha-NAPHTHYL N-METHYLCARBAMATE, 1-NAPHTHYL METHYLCARBAMATE, 1-NAPHTHYL
N-METHYLCARBAMATE, 1-NAPHTHYL-N-METHYL-KARBAMAT (German), OMS-29, PANAM,
RAVYON, RYLAM, SEFFEIN, SEPTENE, SEVIMOL, SEVIN, SOK, TERCYL, TOXAN,
TRICARNAM, UC 7744, UNION CARBIDE 7,744
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Carbon Tetrachloride; CAS No. 56-23-5 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on cheiM ^s included in IRIS only
after a comprehensive review of chronic toxicitv >:-^a by work groups
composed of U.S. EPA scientists from several Agen..y Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risK assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk .Management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Sec;, .on V) ,,\ij.y :.ot be based on the most cxirrent risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for n. particular situation,
note the date of their development, the date of th..- n-ost recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Carbon Tetrachloride
I, Chronic Systemic Toxicity: Noncarclnogenic Healch Effects
A. Oral RfD: available
B. Inhalation RfD: vine
II. Risk Estimates for Carcinogens: ,.., pending
III. Drinking Water Health Advisories: . ;•.
IV. R.isk Management Summaries: available
V. Supplementary Data: n.-ne
-------
Carbon Tt,. L au.iior ide : page 2 of /
• ;.IRONIC '-.•..:; '. rOXICiTY: NONCAkCINCGLNIG HEALTH EFFECTS
INTtK: 1.;..,, i<. : './ C.;:K .v.'.C < :. TEMiC TOXICIiY J^vTA
The Ft,, ,--,-•(. ..•-->:••.• f'Pi > ., '•>-.; on t.>- assumption that thresholds may exist
for ,_._,.•..•.- • --: t_i. ••- - i-,1 csiiuiiit necrosis, but may not exist for
other touU. -.Cruets su.-vh ?.:-. car jinogenieity. The RfD is considered to be the
l,?v>-l V-n •-T, - . t-.,- ait-- ;." '•'-'" • <- i']v.- . - health effects associated with a
t'ir '!'--• -' :' •..-:.-;•"-. ,.- -.' hvr.'-'i:: -r^o^ed for a lifetime, RfDs can
aliic i , .',: _--ve,. .-o. ,,- '.,«.).icaroi -::)j-:enlc ' ,ac lib effects of compounds which are
a.li-,o carcinogens. ~<\ \o'rore. .' ".;-. esse.ri-c''al to refer to section II, and
ot!v. •• irco;- a:> -t.1 . -. ' ^~i-- s----.'.: Information pertaining to the
cur -..'. .,Vt .,'icit ^ -:„ .:i_... o'>:-.r. •-. "d . L-'Ie-ic;; ^er'er to the Background Document on
the RfU (f.ppeiifJIi. A) ir. -_-ei'/ic^ Core 4 -••./: an elaboration of these concepts.
^ j- >-, • v r; j> ') r A jj EXPOSTJ F "
Chenu .. J , , d-cl.on /'_'_/:;,':; ic'.ice
CAS : ,: , .,' ~'J.'l- j Preparation Date: 04/20/86
-.11
I ;-:pe,'\;mental Dcses * UF MF RfD
Li--.-: u:.;;,.r . I :;:g/kg/ ir.y (NOAEL) 1000 1 7E-4
mg/kg/day
Subchrotiic rat gavage 10 mg/kg/day (LOAEL)
(1.935)
* lose Corsv'?,:-..-; Ion Factors 6t Assumptions: 1 mg/kg/day (NOAEL) x 5/7 = 0.71
mg/kg/day (5 day/week dosing regimen)
2. PRINCIPAL /\NU S'JPI-'ORTING STUDIES
Bruckner, J.V., W.F. MacKenzie, S. Muralidhara, R. Luthra, G.M. Kyle and D.
Acosta. 1985. Oral toxicity of carbon tetrachloride: Acute, subacute and
subchronic studies in rats. Fundamentals of Applied Toxicology (In press).
Male Sprague-Dawley rats were given 1, 10 or 33 mg CC14/kg/day by corn oil
gavage, 5 days/week for 12 weeks. Liver lesions, as evidenced by mild
centrilobular vacuolization and statistically significant increases in serum
sorbitoi dehydrogenase activity, were observed at the 10 and 33 mg/kg/day
doses.
-------
Carbon Tetrachloride: page 3 of 7
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. (lOa x lOh x 10s) UF allows for Interspecies and intrahuman
variability and extrapolation from subchronic to chronic duration of exposure
MF
4. ADDITIONAL COMMENTS
None
5. CONFIDENCE IN THE RfD
Study: High Data Base: Medium RfD: Medium
Good dose-response was observed in the liver, which is the target organ
for CC14 toxicity. Some question remains about the use of subchronic data to
adequately predict chronic effects in rats.
6. DOCUMENTATION AND REVIEW
U.S. EPA. Drinking Water Criteria Document for Carbon Tetrachloride. Office
of Drinking Water, Washington, DC. (1985).
Public review of RfD following ODW proposal of RMCL in June 1984.
Science Advisory Board review of RfD on January 14, 1986.
Agency RfD Work Group Review: 06/24/85, 07/08/85
Verification Date: 07/08/85
7. U.S. EPA CONTACTS
Primary: K. Khanna FTS/382-7588 or 202/382-7588
Office of Drinking Water
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Carbon Tetrachloride
CAS No.: 56-23-5
Information is not available at this time.
-------
Carbon Tetrachlorlde: page 4 of 7
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Carbon Tetrachlorlde
CAS No.: 56-23-5
This chemical is among those substances evaluated by the U.S. EPA for
evidence of human carcinogenic potential. This does not imply that this
chemical is necessarily a carcinogen. The evaluation for this chemical is
under review by an inter-office Agency work group, A risk assessment summary
will be included on IRIS when the review has been completed.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Carbon Tetrachlorlde
CAS No.: 56-23-5
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Carbon Tetrachloride
CAS No.: 56-23-5 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Carbon Tetrachlorlde: page 5 of 7
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Water Quality
Criteria (WQC) :
a . Human Health
Status
Date
Statutory
1985
Final
Risk
Management
Value
5000 Ibs.
0 . 40 ppb
Considers
Econ/Tech
Feasibility Reference
No 50 FR 13456
no 45 FR 791318
1980
b. Aquatic Toxicity
l)Freshwater Final
1980
2) Marine
Final
1980
Clean Air Act
Regulatory
Decision:
Nat. Emissions Current
Standards for 1985
Hazardous Air
Pollutants (NESHAP)
Hazardous Waste Final
Constituent 1985
(App. VIII)
Pesticide Active
Ingredient:
a. Registration none
Standard
b. Special Final
Review 1983
Acute No
35,200 ug/1
Chronic
none
Acute No
50,000 ug/1
Chronic
none
Under no
development
Listed no
Registration
voluntarily
canceled
11/28/80
Ibid.
Ibid.
50 FR 32621
08/13/85
40 CFR Part 261
App VIII
B. RISK MANAGEMENT RATIONALE
RQ
The carcinogenicity and chronic toxicity of carbon tetrachloride is being
assessed. When the assessment is complete, the RQ of 5000 pounds may be
adjusted downward.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
-------
Carbon Tetrachloride: page 6 of 7
a. Human health: Carbon tetrachloride Is classified as a carcinogen, and
under the assumption of no threshold for a carcinogen the recommended WQC is
zero. However, if zero cannot be obtained and exposure is via ingestion of
water and aquatic organisms 0.40 ppb is associated with an upper bound excess
lifetime risk of l.OE-6 [other risk levels to consider: l.OE-5 (4.0 ppb) and
l.OE-7 (0.04 ppb)]. If exposure is only via the Ingestion of aquatic
organisms, the WQC associated with an upper bound excess lifetime risk of
l.OE-6 Is 6.94 ug/1.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The data are assumed to be statistically
representative and are used to calculate concentrations which will not have
significant short or long term effects on 95% of the organisms exposed.
Recent criteria (1985 and later) contain duration and frequency stipulations:
the acute criteria maximum concentration is a 1-hour average and the chronic
criteria continuous concentration is a 4-day average which are not to be
exceeded more than once every three years, on the average (see Stephen et al.
1985). Earlier criteria (1980-1984) contained instantaneous acute and
24-hour average chronic concentrations which were not to be exceeded. (FR 45:
79318: November 28, 1980).
CAA Regulatory Decision
NESHAP
EPA's preliminary risk assessment from ambient air exposures indicates
that public health risks are significant (about 70 cases per year in the
U.S.). Because carbon tetrachloride is extremely stable in the atmosphere,
these risks are due to a worldwide build-up of carbon tetrachloride caused by
emissions from the U.S. as well as other countries. Since these risks were
considered significant, EPA indicated that it intends to add carbon
tetrachloride to the list of hazardous air pollutants for which it intends to
establish emission standards under section 112(b)(l)(A) of the Clean Air Act.
The EPA will decide whether to add carbon tetrachloride to the list only
after studying possible techniques that might be used to control emissions
and further assessing the public health risks. The EPA will add carbon
tetrachloride to the list if emission standards are warranted. This decision
did not consider the role of carbon tetrachloride in reducing stratospheric
ozone. This issue is being evaluated separately and will consider the effect
of a number of trace gases on stratospheric ozone.
Contact: Chief, Pollutant Assessment Branch
FTS/629-5645 or 919/541-5645
Pesticide Active Ingredient
a. Registration Standard: none
b. Special Review: For specific details on the Special Review process for
this active ingredient please check the references listed.
Contact: Office of Pesticide Programs, Special Review Branch
202/557-7420 or FTS/557-7420
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Carbon Tetrachloride: page 7 of 7
V. SUPPLEMENTARY DATA
Chemical: Carbon Tetrachloride
CAS No.: 56-23-5
Information is not available at this time.
Synonyms: Methane, tetrachloro- (9CI); Carbon tetrachloride (ACN)(DOT) (SCI);
Acritet; Benzinoform; Carbo tetrachloride; Carbon chloride; Carbon chloride
(CC14); Carbon tet; Carbona; Czterochlorek wegla (Polish); ENT 4,705; ENT
4705; Fasciolin; Flukoids; Freon 10; Halon 104; Mecatorina; Methane
tetrachloride; Necatorina; Necatorine; Perchloromethane; R 10;
Tetrachloorkoolstof (Dutch); Tetrachloormetaan; Tetrachlorkohlenstoff, tetra
(German); Tetrachlormethan (German); Tetrachlorocarbon; Tetrachloromethane;
Tetrachlorure de carbone (French); Tetrachorkohlenstoff uvasol;
Tetraclorometano (Italian); Tetracloruro di carbonio (Italian); Tetrafinol;
Tetraform (VAN); Tetrasol; Univerm; Ventox; Vermoestricid; WLN: GXGGG.
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Chlorine Cyanide; CAS No. 506-77-4 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Chlorine Cyanide
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries; available
V. Supplementary Data: none
-------
Chlorine Cyanide: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Chlorine Cyanide (cyanogen chloride)
CAS No.: 506-77-4
Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Rat chronic oral
study
Howard and Hanzal
(1955)
10.8 mg/kg/day CN
(NOAEL) converted to
25.3 mg/kg/day of
chlorine cyanide
100
5E-2
Weight loss, thyroid
effects and myelin
degeneration
Rat subchronic to
chronic oral bioassay
Philbrick et al.
(1979)
30 mg/kg/day CN
(LOAEL)
(70 mg/kg/day C1CN)
* Dose Conversion Factors & Assumptions:
= 61/26 [ MW C1CN = 61; MW CN - 26 ]
molecular weight conversion factor
2. PRINCIPAL AND SUPPORTING STUDIES
Howard, J.W. and R.F. Hanzal. 1955. Chronic toxicity for rats by food
treated with hydrogen cyanide. Agric. Food Chem. 3: 325-329.
Since chloride is present in very high levels physiologically, an ADI of
3.5 mg/day is recommended based on the maximum number of molar equivalents
(one) of cyanide released in aqueous solutions or dilute acids.
-------
Chlorine Cyanide: page 3 of 5
In this 2-year dietary study, rats (10/sex/group) were administered food
fumigated with HCN. The average daily concentrations were 73 and 183 mg CN/kg
diet. From the data reported on food consumption and body weight, daily
estimated doses were 4.3 mg and 10.8 mg CN/kg bw. The average food CN
concentrations were estimated based on the authors' data for concentration at
the beginning and end of each food preparation period and by assuming a first-
order rate of loss for the intervening period. There were no treatment-
related effects on growth rate, no gross signs of toxicity, and no histo-
pathological lesions.
Studies by Philbrick et al. (1979) showed decreased weight gain and
thyroxin levels and myelin degeneration in rats at 30 mg/kg/day CN. Other
chronic studies either gave higher effect levels or used the subcutaneous
route (Crampton et al., 1979; Lessell, 1971; Herthing et al., 1960). Human
data do not provide adequate information from which to derive an ADI because
effective dose levels of chronically ingested CN are not documented.
Therefore, the study of Howard and Hanzel (1955) provides the highest NOAEL,
10.8 mg/kg/day for CN, and Is chosen for the derivation of an ADI for CN of
1.5 mg/day or 0.02 mg/kg/day.
Cyanide is metabolized extensively In the liver, Indicating that the only
relevant route of administration for quantitative risk assessment In the
derivation of an oral ADI Is the oral route of administration.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. According to the U.S. EPA (1985), an uncertainty factor of 100 is
used to derive the ADI (10 for species extrapolation, 10 for sensitive
population).
MF » 5. A modifying factor of 5 is used to account for the apparent tolerance
to cyanide when it is ingested with food rather than when it is administered
by gavage or by drinking water.
4. ADDITIONAL COMMENTS
Decreased protein efficiency ratio was produced by dietary cyanide treat-
ment of rats during gestation, lactation and postweaning growth phase In the
Tewe and Maner (1981a) experiment: the dose level of cyanide (10.6 mg/kg/
day) producing that effect is slightly lower than the currently accepted
NOAEL of 10.8 mg/kg/day (U.S. EPA, 1985). Furthermore, Tewe and Maner
(1981b) tested sows. Possible effects observed at about 9.45 mg/kg/day were
proliferation of glomerular cells of the kidneys and reduced activity of the
thyroid glands in the gilts. However, the number of animals in this experi-
ment was very small. A Japanese study (Amo, 1973) Indicated that 0.05 mg/
kg/day of cyanide obtained from drinking water decreased the fertility rate
and survival rate in the Fl generation and produced 100% mortality in the F2
generation In mice. However, these data are not consistent with the body of
available literature. Thus, until additional chronic studies are available,
an ADI of 3 mg/day for a 70-kg man is recommended.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The confidence in the study is medium because adequate records of food
consumption and body weight were maintained and animals of both sexes were
-------
Chlorine Cyanide: page 4 of 5
tested at two doses for 2 years. The data base is rated medium because a
small but sufficient number of studies support the chosen study. The confi-
dence in the RfD follows. Additional chronic/reproductive studies are needed
to support a higher level of confidence in the RfD.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, July 1985.
U.S. EPA. 1985. Cyanides: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Chlorine Cyanide
CAS No.: 506-77-4
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Chlorine Cyanide
CAS No.: 506-77-4
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Chlorine Cyanide
CAS No.: 506-77-4
Information is not available at this time.
-------
Chlorine Cyanide: page 5 of 5
IV. RISK MANAGEMENT SUMMARIES
Chemical: Chlorine Cyanide (Cyanogen Chloride)
CAS No.: 506-77-4
Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
10 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
E. RISK MANAGEMENT RATIONALE
RQ
The final RQ was based on aquatic toxicity, as established under CWA
Section 311(b)(4). Available data indicate that the aquatic 96-Hour Median
Threshold Limit for chlorine cyanide is between .1 and 1 ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
V. SUPPLEMENTARY DATA
Chemical:
CAS No.:
Chlorine Cyanide
506-77-4
Information is not available at this time.
Synonyms: CHLORCYAN, CHLOROCYAN, CHLOROCYANIDE, CHLOROCYANOGEN, CHLORURE DE
CYANOGENE (French), CYANOGEN CHLORIDE, RCRA WASTE NUMBER P033, UN 1589
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Chloroform; CAS No. 67-66-3 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Chloroform
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: under review
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Chloroform: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) Is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD Is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action In humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it Is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Chloroform
CAS No.: 67-66-3
Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Fatty cyst forma-
tion in liver
Dog, chronic oral
bioassay
Heywood et al. (1979)
NOEL: None
12.9 mg/kg/day
(LOAEL)
1000
1E-2
mg/kg/day
* Dose Conversion Factors & Assumptions:
12.9 mg/kg/day
15 mg/kg/day x 6 days/7 days —
2. PRINCIPAL AND SUPPORTING STUDIES
Heywood, R., R.J. Sortwell, P.R.B. Noel, et al. 1979. Safety evaluation of
toothpaste containing chloroform. III. Long-term study In beagle dogs. J.
Environ. Pathol. Toxicol. 2: 835-851.
In this study beagle dogs were administered chloroform In a toothpaste
base (0.5 ml of toothpaste base/kg/day) in gelatin capsules. A control group
composed of 16 males and 16 females received the vehicle, and additional
control groups of eight animals/sex were administered an alternative tooth-
paste or were left untreated. Experimental groups of eight male and eight
female dogs received 15 or 30 mg chloroform/kg/day for 6 days/week. Treat-
ment was continued for 7.5 years. Fatty cysts, considered to be treatment-
related, were observed in livers of some dogs In both treatment groups.
Nodules of altered hepatocytes were considered treatment-related but not dose-
-------
Chloroform: page 3 of 7
dependent. A dose-related increase In SGPT levels was noted and a less marked
increase in SCOT was noted in the high-dose animals. The LOAEL was determined
to be 15 mg/kg/day, and an ADI was set at 0.02 mg/kg/day. This value
supersedes the ADI of 0.13 mg/kg/day based on an NCI (Epstein, 1977) bioassay
which was established in the 1982 Toxicity-Based Protective Ambient Water
Levels for Various Carcinogens.
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 1000. Uncertainty factors of 10 each were applied to the LOAEL of 12.9
rag/kg/day to account for the interspecies conversion, protection of sensitive
human subpopulations, and concern that the effect seen was a LOAEL and not a
NOEL.
MF - 1
4. ADDITIONAL COMMENTS
Chloroform is considered to be highly fetotoxic, but not teratogenic
(Swetz, 1974; Thompson et al., 1974).
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The critical study (Heywood et al., 1979) was of chronic duration, used a
fairly large number of dogs, and measured multiple end points. Only two
treatment doses were used, however, and no NOEL was determined, so that the
confidence level in the study is rated at medium. A companion study in rats,
using only one treatment dose (Palmer et al., 1979), identified 60 mg/kg/day
by gavage as a LOAEL for decreased weight gain, plasma cholinesterase and
relative liver weight. Other data in the literature (Jorgenson et al.,
1982) also Indicate changes in liver fat to be treatment-related, rating
confidence in the data base at medium. Medium confidence in the RfD follows.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1985. Drinking Water Criteria Document for Trihalomethanes.
Office of Drinking Water, Washington, DC. External Review Draft.
The 1985 Drinking Water Criteria Document for Trihalomethanes is currently
undergoing Agency review.
Agency RfD Work Group Review: 12/02/85, 05/15/86
Verification Date: 12/02/85
7. U.S. EPA CONTACTS
Primary: Ambika Bathija FTS/382-7591 or 202/382-7591
Office of Drinking Water
Secondary: M.L. Dourson FTS/684-7534 or 513/569-7534
Office of Research and Development
-------
Chloroform: page 4 of 7
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Chloroform
CAS No.: 67-66-3
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Chloroform
CAS No.: 67-66-3
This chemical is among those substances evaluated by the U.S. EPA for
evidence of human carcinogenic potential. This does not imply that this
chemical is necessarily a carcinogen. The evaluation for this chemical is
under review by an inter-office Agency work group. A risk assessment summary
will be included on IRIS when the review has been completed.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Chloroform CAS No.: 67-66-3
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Chloroform
CAS No.: 67-66-3 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
-------
Chloroform: page 5 of 7
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Statutory
1980
Risk
Management
Value
5000 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
40 FR 13456
04/04/85
Water Quality
Criteria (WQC):
a. Human Health
Final
1980
0.19 ug/1
no
45 FR 79318
11/28/80
b. Aquatic Toxicity
1) Freshwater Final
1980
2) Marine
Clean Air Act (CAA)
Regulatory Decision:
Nat. Emissions Current
Standards for 1985
Hazardous Air
Pollutants (NESHAP)
Pesticide Active
Ingredient:
a. Registration
Standard
b. Special
Review
n.a.
Final
1982
Acute no
28,900 ug/1 (LEL)
Chronic
1,240 ug/1 (LEL)
none
Under no
development
PD 1 no
RPAR
Termination yes
ibid.
50 FR 39626
09/27/85
41 FR 14588
04/06/76
n.a.
B. RISK MANAGEMENT RATIONALE
RQ
The statutory RQ of 5000 pounds established under Section 311(b)(4)
ofthe Clean Water Act is retained until the assessment of potential
carcinogenicity is complete.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC of 0.19 ug/1 represents a cancer risk level of
IE-6, based on consumption of contaminated organisms and water. A WQC of
-------
Chloroform: page 6 of 7
15.7 ug/1 (cancer risk level of 1E-6) has also been established based on
consumption of contaminated organisms alone.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value indicates that the
minimum data were not available and the concentration given is not a criteria
value but the lowest effect level found in the literature.
CAA Regulatory Decision
NESHAP: Chloroform is a probable human carcinogen (EPA Group B2) and
according to EPA's preliminary risk assessment from ambient air exposures,
public health risks are significant (13 cancer cases per year and maximum
lifetime Individual risks of 7.1E-4). Thus, EPA indicated that it intends to
add chloroform to the list of hazardous air pollutants for which it intends
to establish emission standards under section 112(b)(l)(A) of the Clean Air
Act. The EPA will decide whether to add chloroform to the list only after
studying possible techniques that might be used to control emissions of
chloroform and further assessing the public health risks. The EPA will add
chloroform to the list if emission standards are warranted.
Contact: Chief, Pollutant Assessment Branch
FTS/629-5645 or 919/541-5645
Pesticide Active Ingredient
a. not available
b. Special Review: For specific details on the Special Review process for
this active ingredient please check the references listed.
Contact: Office of Pesticides Programs, Special Review Branch
202/557-7420 or FTS/557-7420
V. SUPPLEMENTARY DATA
Chemical: Chloroform
CAS No.: 67-66-3 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Chloroform is classified as moderately toxic. A probable oral lethal
dose for humans is 0.5 to 5 g/kg (between 1 ounce and 1 pint) for a 150-lb.
person. The mean lethal do?,e is probably near 1 fluid ounce (44 g)
(Gosselin, 1976). Also, it is a central nervous system depressant and a
-------
Chloroform: page 7 of 7
gastrointestinal irritant (Challen PS et al., 1958. Br J Ind Med 15:243).
Chloroform has caused rapid death attributable to cardiac arrest.
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Symptoms of acute exposure include
fainting sensation, vomiting, dizziness, salivation, nausea, fatigue, and
headache (ACGIH, 1971-1979). Other symptoms are respiratory depression, coma,
kidney damage, and liver damage (IARC, 1972-1985). Liquid in the eye causes
tearing and conjunctivitis (Grant, 1974). Symptoms of chronic exposure
include loss of appetite, hallucinations, moodiness, and physical and mental
sluggishness (NIOSH, 1974).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: CHC1
3
Molecular Weight: 119.39
Boiling Point: 143F, 61. 7C
Specific Gravity (H20-1): 1.4832 at 20C/4C
Vapor Pressure (mmHg): 100 at 10.4C
Melting Point: -82.3F, -63.5C
Vapor Density (AIR-1): 4.12
Evaporation Rate (Butyl acetate-1): (Carbon Tetrachloride - 1) 1.18
Solubility in Water: 1 mL/200 mL at 25C
Flash Point [Method Used]: None
Flammable Limits: None
Appearance and Odor: Chloroform is a clear, colorless and mobile liquid
with a characteristic odor.
•»
Conditions or Materials to Avoid: Chloroform develops acidity from
prolonged exposure to air and light (General Electric Co., 1979, MSDS #315).
Chloroform explodes when in contact with aluminum powder or magnesium powder
or with alkali metals (e.g., lithium, sodium, and potassium) (NFPA, 1978) and
dinitrogen tetroxide. Chloroform reacts vigorously with acetone in the
presence of potassium hydroxide or calcium hydroxide (Bretherick, 1975). It
is oxidized by strong oxidizers such as chromic acid forming phosgene and
chlorine (IARC, 1972-1985). Chloroform reacts vigorously with
triisopropylphosphine (Bretherick, 1975).
Hazardous Decomposition or Byproducts: When heated, Chloroform emits
hydrogen chloride, chlorine, toxic and corrosive oxides of carbon and
chlorine (General Electric Co., 1979, MSDS #315) and phosgene (ITI, 1982).
Use: Chloroform is used as a grain fumigant; solvent for pesticides,
adhesives (IARC, 1972-1985) fats, oils, rubbers, alkaloids, waxes (Merck,
1976); chemical intermediate for dyes and pesticides; and a component of
cough syrups, toothpastes, and linaments (SRI). Not registered as a
pesticide in the U.S. (USEPA/Pesticide Index, 1985).
Synonyms: Formyl Trichloride; Freon 20; Methane, Trichloro-; Methane
Trichloride; Methenyl Chloride; Methenyl Trichloride; Methyl Trichloride;
NCI-C02686; R-20; R 20 (Refrigerant); TCM; Trichloroform; Trichloromethane
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Chromium (III); CAS No. 16065-83-1 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Chromium (III)
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Chromium (III): page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Chromium (III), Insoluble Salts
CAS No.: 16065-83-1 Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Rat chronic feeding NOEL: 5% Cr203 in 100 10 1
study diet 5 days/week for mg/kg/day
600 feedings (1800 (as an
g/kg bw average total insoluble
dose) salt)
Ivankovic and
Preussmann (1975) LOAEL: None
* Dose Conversion Factors & Assumptions: 1800 g Cr203/kg bw x 1000 mg/g x
0.6849 Cr/g Cr203 / 600 feeding days x 5 feeding days/7 days = 1468
mg/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
Ivankovic, S. and R. Preussmann. 1975. Absence of toxic and carcinogenic
effects after administration of high doses of chromic oxide pigment in sub-
acute and long-term feeding experiments in rats. Food Cosmet. Toxicol. 13:
347-351.
Groups of 60 male and female rats were fed chromic oxide (Cr203) baked in
bread at dietary levels of 0, 1, 2 or 5%, 5 days/week for 600 feedings (840
total days). The primary purpose of this study was to assess the carcino-
genic potential of Cr203. Body weight and food consumption were monitored.
The average total amounts of ingested Cr203 were given as 360, 720 and 1800
g/kg bw for the 1, 2 and 5% treatment groups, respectively. The animals were
maintained on control diets following termination of exposure until they
-------
Chromium (III): page 3 of 6
became moribund or died. All major organs were examined histologically.
Other toxicological parameters were not mentioned explicitly, but may have
included some or all of those described for the accompanying subchronic study
(see below). No effects due to Cr203 treatment were observed at any dose
level.
Ivankovic and Preussmann (1975) also treated rats (both sexes, 12-19
rats/group) at dietary levels of 0, 2 or 5% Cr203 in bread, 5 days/week for
90 days. Food consumption and body weight were monitored. Toxicological
parameters included serum protein, bilirubin, hematology, urinalysis, organ
weights and histopathology. The only effects observed were reductions
(12-37%) in the absolute weights of the livers and spleens of animals in the
high-dose group. Organ weights relative to body weight were not reported.
The high dose is equivalent to 1400 mg/kg/day (dose converted using reported
data).
Other subchronic oral studies show no indication of adverse effects
attributable to trivalent chromium compounds, but dose levels were consider-
ably lower.
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 100. The factor of 100 represents two 10-fold decreases in mg/kg
bw/day dose that account for both the expected interhuman and interspecies
variability to the toxicity of the chemical in lieu of specific data.
MF - 10. The additional modifying factor of 10 is adopted to reflect
uncertainty around the NOEL because: 1) the effects observed in the 90-day
study were not explicitly addressed in the 2-year study and, thus, the highest
NOAEL in the 2-year study may be a LOAEL; 2) the absorption of chromium is so
low (<1%) and is influenced by a number of factors; thus, a considerable
potential variation in absorption exists; and 3) animals were allowed to die
naturally after feeding stopped (2 years) and only then was histology
performed.
4. ADDITIONAL COMMENTS
This RfD is limited to metallic chromium (III) of insoluble salts.
Examples of insoluble salts include chromic III oxide (Cr203), chromium III
chloride (CrC13) and chromium III sulfate [Cr2(S04)3].
Very limited data suggest that Cr III may have respiratory effects on
humans. No data on chronic or subchronic effects of inhaled Cr III in ani-
mals can be found. Adequate teratology data do not exist, but reproductive
effects are not seen at dietary levels of 5% Cr203.
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Low RfD: Low
The critical study is rated low because of the lack of explicit detail of
study protocol and results. Low confidence in the data base reflects the
lack of high-dose supporting data. The low confidence in the RfD reflects
the foregoing, but also reflects the lack of an observed effect level. Thus,
the RfD, as given, should be considered conservative, since the MF addresses
only those factors which might lower the RfD.
-------
Chromium (III): page 4 of 6
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1984. Health Effects Assessment for Trivalent Chromium. Prepared
by the Environmental Criteria and Assessment Office, Cincinnati, OH, OHEA for
the Office of Solid Waste and Emergency Response. ECAO-CIN-H035.
The ADI in the 1984 Health Effects Assessment document received an Agency
review with the help of two external scientists.
Agency RfD Work Group Review: 11/21/85, 02/05/86
Verification Date: 11/21/85
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Chromium (III)
CAS No.: 16065-83-1
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Chromium (III)
CAS No.: 16065-83-1
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Chromium (III)
CAS No.: 16065-83-1
Information is not available at this time.
-------
Chromium (III): page 5 of 6
Chemical: Chromium (III), Insoluble Salts
CAS No.: 16065-83-1
IV. RISK MANAGEMENT SUMMARIES
Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
none
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
2) Marine
170 mg/1
Acute
various
Chronic
various
none
no
no
45 FR 79318
11/28/80
ibid.
B. RISK MANAGEMENT RATIONALE
RQ
Though "Chromium (III), insoluble salts" is not specifically designated
as a CERCLA hazardous substance, insoluble chromium (III) salts would be
considered hazardous substances under the CERCLA broad generic listing for
"CHROMIUM AND COMPOUNDS." There is no corresponding reportable quantity
(RQ) for this generic class of compounds, but the releaser is still liable
for cleanup costs if the designated federal, On-Scene Coordinator (OSC)
decides to take response action with respect to the release of an insoluble
-------
Chromium (III): page 6 of 6
chromium (III) salt which is not otherwise specifically listed as a CERCLA
hazardous substance. There are two chromium (III) salts which are
specifically listed as CERCLA hazardous substances, chromic acetate and
chromic sulfate. Both have been assigned final RQs of 1000 pounds based on
aquatic toxicity (as established under section 311(b)(4) of the Clean Water
Act).
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
WQC
Contact: Office of Water Regulations and Standards
202-382-5AOO or FTS-382-5400
a. Human health: The WQC of 170 mg/1 is based on consumption of contaminated
aquatic organisms and water. A WQC of 3433 mg/1 has also been established
based on consumption of contaminated aquatic organisms alone.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The data are assumed to be statistically
representative and are used to calculate concentrations which will not have
significant short or long term effects on 95% of the organisms exposed.
Recent criteria (1985 and later) contain duration and frequency stipulations:
the acute criteria maximum concentration is a 1-hour average and the chronic
criteria continuous concentration is a 4-day average which are not to be
exceeded more than once every three years, on the average (see Stephen et al.
1985) . Earlier criteria (1980-1984) contained instantaneous acute and
24-hour average chronic concentrations which were not to be exceeded. (FR 45:
79318: November 28, 1980). These criteria vary with water hardness. For
freshwater aquatic life the concentration (in ug/1) of total recoverable
trivalent chromium should not exceed the numerical value given by the
equations "e**(0.8190 [In (hardness)]+3.688)" for acute exposure and
"e**(0.8190 [In (hardness)]+l.561)" for chronic exposure (** indicates
exponentiation; hardness is in mg/1). For example, at a hardness of 50 mg/1,
the acute and chronic WQC would be 980 and 120 ug/1 respectively.
V. SUPPLEMENTARY DATA
Chemical: Chromium (III)
CAS No.: 16065-83-1
Information is not available at this time.
Synonyms: CHROMIUM, ION (Cr 3+); CHROMIC ION; CHROMIUM (3+); CHROMIUM (III);
CHROMIUM (III) ION; CHROMIUM ION (3+)
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Copper Cyanide; CAS No. 544-92-3 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Copper Cyanide
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Copper Cyanide: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) Is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Copper Cyanide
CAS No.: 544-92-3 Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Rat chronic oral 10.8 mg/kg/day CN 100 5 7E-2
study (NOAEL) converted to mg/kg/day
37.2 mg/kg/day copper
Howard and Hanzal cyanide
(1955)
Weight loss, thyroid 30 mg/kg/day CN
effects and myelin (LOAEL)
degeneration (103 mg/kg/day Cu(CN)2)
Rat subchronic to
chronic oral bloassay
Philbrick et al.
(1979)
* Dose Conversion Factors & Assumptions: molecular weight conversion factor
- 89.5/26) [ MW Cu(CN) - 89.5; MW CN - 26 ]
2
2. PRINCIPAL AND SUPPORTING STUDIES
Howard, J.W. and R.F Hanzal. 1955. Chronic toxicity to rats of food treated
with hydrogen cyanide. Agric. Food Chem. 3: 325-329.
Copper cyanide has not been tested for toxicity. Copper cyanide can
exist as cupric cyanide or cuprous cyanide. Cupric cyanide is extremely
-------
Copper Cyanide: page 3 of 6
unstable and dissociates to form cyanide and a cuprous cyanide complex. An
RfD can be derived for cupric cyanide based on the molar equivalents of free
cyanide only, since cuprous cyanide (CuCN) is not soluble in water or dilute
acid. An RfD calculated based on molar equivalents (1) of free CN would be
5.20 rag/day.
In this 2-year dietary study, rats (10/sex/group) were administered food
fumigated with HCN. The average daily concentrations were 73 and 183 mg CN/kg
diet. From the data reported on food consumption and body weight, daily
estimated doses were 4.3 mg and 10.8 mg CN/kg bw. The average food CN
concentrations were estimated based on the authors' data for concentration at
the beginning and end of each food preparation period and by assuming a first
order rate of loss for the intervening period. There were no treatment
related effects on growth rate, no gross signs of toxicity, and no histo-
pathological lesions.
Studies by Philbrick et al. (1979) showed decreased weight gain and
thyroxin levels and myelin degeneration in rats at 30 mg/kg/day CN. Other
chronic studies either gave higher effect levels or used the subcutaneous
route (Crampton et al., 1979; Lessell, 1971; Berthing et al., 1960). Human
data do not provide adequate information from which to derive an RfD because
effective dose levels of chronically ingested CN are not documented.
Therefore, the study of Howard and Hanzel (1955) provides the highest NOAEL,
10.8 mg/kg/day for CN, and is chosen for the derivation of an RfD for CN of
1.5 rag/day or 0.02 mg/kg/day.
Cyanide is metabolized extensively in the liver, indicating that the only
relevant route of administration for quantitative risk assessment in the
derivation of an oral RfD is the oral route of administration.
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 100. According to the U.S. EPA (1985), an uncertainty factor of 100 is
used to derive the RfD (10 for species extrapolation, 10 for sensitive
population).
MF = 5. A modifying factor of 5 is used to account for the apparent tolerance
to cyanide when it is ingested with food rather than when it is administered
by gavage or by drinking water.
4. ADDITIONAL COMMENTS
Decreased protein efficiency ratio was produced by dietary cyanide treat-
ment of rats during gestation, lactation and postweaning growth phase in the
Tewe and Maner (1981a) experiment: the dose level of cyanide (10.6 mg/kg/
day) producing that effect is slightly lower than the currently accepted
NOAEL of 10.8 mg/kg/day (U.S. EPA, 1985). Furthermore, Tewe and Maner
(1981b) tested sows. Possible effects observed at about 9.45 mg/kg/day were
proliferation of glomerular cells of the kidneys and reduced activity of the
thyroid glands in the gilts. However, the number of animals in this experi-
ment was very small. A Japanese study (Amo, 1973) indicated that 0.05 mg/
kg/day of cyanide obtained from drinking water decreased the fertility rate
and survival rate in the Fl generation and produced 100% mortality in the F2
generation in mice. However, these data are not consistent with the body of
available literature. Thus, until additional chronic studies are available,
an RfD of 3 mg/day for a 70-kg man is recommended.
-------
Copper Cyanide: page 4 of 6
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The confidence in the study is medium because adequate records of food
consumption and body weight were maintained and animals of both sexes were
tested at two doses for 2 years. The data base is rated low because this
chemical has not been tested. The confidence in the RfD is low because it
is based on analogy. Chronic/reproductive studies are needed to support a
higher level of confidence in the RfD.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, July 1985.
U.S. EPA. 1985. Cyanides: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Copper Cyanide
CAS No.: 544-92-3
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Copper Cyanide
CAS No.: 544-92-3
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
-------
Copper Cyanide: page 5 of 6
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Copper Cyanide
CAS No.: 544-92-3
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Copper Cyanide
CAS No.: 544-92-3 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
10 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ was based on aquatic toxicity, as established under CWA
Section 311(b)(4). Available data indicate that the aquatic 96-Hour Median
Threshold Limit for copper cyanide is between .1 and 1 ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
-------
Copper Cyanide: page 6 of 6
V. SUPPLEMENTARY DATA
Chemical: Copper Cyanide
CAS No.: 544-92-3
Information is not available at this time.
Synonyms: METHYL-CARBAMIC ACID, 1-NAPHTHYL ESTERCOPPER(I) CYANIDE,
COPPER CYANIDE , CUPRICIN, CUPROUS CYANIDE, RCRA WASTE NUMBER P029
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Cyanide (free); CAS No. 57-12-5 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Cyanide (free)
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Cyanide: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Cyanide (free)
CAS No.: 57-12-5 Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Rat chronic oral 10.8 mg/kg/day CN 100 5 2E-2
study (NOAEL) mg/kg/day
Howard and Hanzal
(1955)
Weight loss, thyroid 30 mg/kg/day CN
effects and myelin (LOAEL)
degeneration
Rat subchronic to
chronic oral bioassay
Philbrick et al.
(1979)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Howard, J.W. and R.F. Hanzal. 1955. Chronic toxicity to rats of food
treated with hydrogen cyanide. Agric. Food Chem. 3: 325-329.
Hydrogen cyanide is soluble in water and dilute acid (which includes the
gastric environment) and is readily hydrolyzed to 1 molar equivalent of CN
and 1 molar equivalent of hydrogen (Hartung, 1982).
-------
Cyanide: page 3 of 7
In this 2-year dietary study, rats (10/sex/group) were administered food
fumigated with HCN. The average daily concentrations were 73 and 183 mg CN/kg
diet. From the data reported on food consumption and body weight, daily
estimated doses were 4.3 mg and 10.8 mg CN/kg bw. The average food CN
concentrations were estimated based on the authors' data for concentration at
the beginning and end of each food preparation period and by assuming a first
order rate of loss for the intervening period. There were no treatment
related effects on growth rate, no gross signs of toxicity, and no histo-
pathological lesions.
Studies by Philbrick et al. (1979) showed decreased weight gain and
thyroxin levels and myelin degeneration in rats at 30 mg/kg/day CN. Other
chronic studies either gave higher effect levels or used the subcutaneous
route (Crampton et al., 1979; Lessell, 1971; Berthing et al., 1960). Human
data do not provide adequate information from which to derive an ADI because
effective dose levels of chronically ingested CN are not documented.
Therefore, the study of Howard and Hanzel (1955) provides the highest NOAEL,
10.8 mg/kg/day for CN, and is chosen for the derivation of an ADI for CN of
1.5 mg/day or 0.02 mg/kg/day.
Cyanide is metabolized extensively in the liver, indicating that the only
relevant route of administration for quantitative risk assessment in the
derivation of an oral ADI is the oral route of administration.
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 100. According to the U.S. EPA (1985), an uncertainty factor of 100 is
used to derive the ADI (10 for species extrapolation, 10 for sensitive
population).
MF - 5. A modifying factor of 5 is used to account for the apparent tolerance
to cyanide when it is ingested with food rather than when it is administered
by gavage or by drinking water.
4. ADDITIONAL COMMENTS
Decreased protein efficiency ratio was produced by dietary cyanide treat-
ment of rats during gestation, lactation and postweaning growth phase in the
Tewe and Maner (1981a) experiment: the dose level of cyanide (10.6 mg/kg/
day) producing that effect is slightly lower than the currently accepted
NOAEL of 10.8 mg/kg/day (U.S. EPA, 1985). Furthermore, Tewe and Maner
(1981b) tested sows. Possible effects observed at about 9.45 mg/kg/day were
proliferation of glomerular cells of the kidneys and reduced activity of the
thyroid glands in the gilts. However, the number of animals in this experi-
ment was very small. A Japanese study (Amo, 1973) indicated that 0.05 mg/
kg/day of cyanide obtained from drinking water decreased the fertility rate
and survival rate in the Fl generation and produced 100% mortality in the F2
generation in mice. However, these data are not consistent with the body of
available literature. Thus, until additional chronic studies are available,
an ADI of 3 mg/day for a 70-kg man is recommended.
-------
Cyanide: page 4 of 7
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The confidence in the study is medium because adequate records of food
consumption and body weight were maintained and animals of both sexes were
tested at two doses for 2 years. The data base is rated medium because a
small but sufficient number of studies support the chosen study. The confi-
dence in the RfD follows. Additional chronic/reproductive studies are needed
to support a higher level of confidence in the RfD.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1984. Health Effects Assessment for Cyanides. Environmental Cri-
teria and Assessment Office, Cincinnati, OH. ECAO-CIN-H011.
U.S. EPA. 1985. Drinking Water Criteria Document for Cyanides. Office of
Drinking Water, Washington, DC.
The ODW criteria document and OERR health effects assessment have both had
extensive Agency-wide and limited external review.
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Cyanide (free)
CAS No.: 57-12-5
Information is not available at this time.
-------
Cyanide: page 5 of 7
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Cyanide (free)
CAS No.: 57-12-5
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Cyanide (free)
CAS No.: 57-12-5
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Cyanide
CAS No.: 57-12-5 Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Cyanide: page 6 of 7
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
Risk
Management
Value
10 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1986
2) Marine Final
1986
200 ug/1 no
Acute no
22 ug/1
Chronic
5.2 ug/1
Acute no
1 ug/1
Chronic
none
45 FR 79318
11/28/80
51 FR 8361
03/11/86
ibid.
B. RISK MANAGEMENT RATIONALE
RQ
Cyanides (soluble cyanide salts, not elsewhere specified in Table 302.4 of
40 CFR302) were placed at RQ level A (10 pounds) on the basis of aquatic
toxicity ( a 96-Hour Median Threshold Limit between 0.1 and 1 ppm) of the
cyanide ion.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: This value is the same as the drinking water standard and
approximates a safe level assuming consumption of contaminated organisms and
water.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The data are assumed to be statistically
representative and are used to calculate concentrations which will not have
significant short or long term effects on 95% of the organisms exposed.
Recent criteria (1985 and later) contain duration and frequency stipulations:
the acute criteria maximum concentration is a 1-hour average and the chronic
criteria continuous concentration is a 4-day average which are not to be
exceeded more than once every three years, on the average (see Stephen et al.
1985). Earlier criteria (1980-1984) contained instantaneous acute and
24-hour average chronic concentrations which were not to be exceeded. (FR 45:
79318: November 28, 1980).
-------
Cyanide: page 7 of 7
V. SUPPLEMENTARY DATA
Chemical: Cyanide (free)
CAS No.: 57-12-5
Information is not available at this time.
Synonyms: CARBON NITRIDE ION, CYANIDE ANION, CYANIDE, CYANIDE ION, CYANURE
(French), ISOCYANIDE, RCRA WASTE NUMBER P030
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Cyanogen; CAS'No. 460-19-5 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Cyanogen
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Cyanogen: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) Is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix^A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Cyanogen
CAS No.: 460-19-5
Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
(1955)
Experimental Doses *
UF
MF
RfD
Rat chronic oral
study
Howard and Hanzal
10.8 mg/kg/day CN
(NOAEL) converted to
21.6 mg/kg/day of
cyanogen
100 5 4E-2
mgAg/day
Weight loss, thyroid
effects and myelin
degeneration
Rat subchronic to
chronic oral bioassay
Philbrick et al.
(1979)
30 mg/kg/day CN
(LOAEL)
(60 mg/kg/day cyanogen)
* Dose Conversion Factors & Assumptions: molecular weight conversion factor
- 52**/26 [ MW C N - 52; MW CN - 26 ]
2 2
2. PRINCIPAL AND SUPPORTING STUDIES
Howard, J.W. and R.F. Hanzal. 1955. Chronic toxicity for rats of food
treated with hydrogen cyanide. Agric. Food Chem. 3: 325-329.
The toxicity of cyanogen, itself, has not been assessed. This risk
assessment is based on the toxicity of the cyanide ion. Cyanogen does not
-------
Cyanogen: page 3 of 6
completely dissociate into free CN in water or dilute acetic acid. The Rfd
for this compound is derived from the RfD of free cyanide on an equimolar
basis, assuming that cyanogen releases only one molar equivalent of free
cyanide.
In this 2-year dietary study, rats (10/sex/group) were administered food
fumigated with HCN. The average daily concentrations were 73 and 183 mg CN/kg
diet. From the data reported on food consumption and body weight, daily
estimated doses were 4.3 mg and 10.8 mg CN/kg bw. The average food CN
concentrations were estimated based on the authors' data for concentration at
the beginning and end of each food preparation period and by assuming a first
order rate of loss for the intervening period. There were no treatment
related effects on growth rate, no gross signs of toxicity, and no histo-
pathological lesions.
Studies by Philbrick et al. (1979) showed decreased weight gain and
thyroxin levels and myelin degeneration in rats at 30 mg/kg/day CN. Other
chronic studies either gave higher effect levels or used the subcutaneous
route (Crampton et al., 1979; Lessell, 1971; Berthing et al., 1960). Human
data do not provide adequate information from which to derive an RfD because
effective dose levels of chronically ingested CN are not documented.
Therefore, the study of Howard and Hanzel (1955) provides the highest NOAEL,
10.8 mg/kg/day for CN, and is chosen for the derivation of an RfD for CN of
1.5 mg/day or 0.02 mg/kg/day.
Cyanide is metabolized extensively In the liver, indicating that the only
relevant route of administration for quantitative risk assessment In the
derivation of an oral RfD is the oral route of administration.
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 100. According to the U.S. EPA (1985), an uncertainty factor of 100 is
used to derive the RfD (10 for species extrapolation, 10 for sensitive
population).
MF = 5. A modifying factor of 5 is used to account for the apparent tolerance
to cyanide when it is ingested with food rather than when it is administered
by gavage or by drinking water.
4. ADDITIONAL COMMENTS
Decreased protein efficiency ratio was produced by dietary cyanide treat-
ment of rats during gestation, lactation and postweaning growth phase In the
Tewe and Maner (1981a) experiment: the dose level of cyanide (10.6 mg/kg/
day) producing that effect is slightly lower than the currently accepted
NOAEL of 10.8 mg/kg/day (U.S. EPA, 1985). Furthermore, Tewe and Maner
(1981b) tested sows. Possible effects observed at about 9.45 mg/kg/day were
proliferation of glomerular cells of the kidneys and reduced activity of the
thyroid glands in the gilts. However, the number of animals In this experi-
ment was very small. A Japanese study (Amo, 1973) indicated that 0.05 mg/
kg/day of cyanide obtained from drinking water decreased the fertility rate
and survival rate in the Fl generation and produced 100% mortality in the F2
generation in mice. However, these data are not consistent with the body of
available literature. Thus, until additional chronic studies are available,
an RfD of 3 mg/day for a 70-kg man is recommended.
-------
Cyanogen: page 4 of 6
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The confidence in the study is medium because adequate records of food
consumption and body weight were maintained and animals of both sexes were
tested at two doses for 2 years. The data base is rated medium because a
small but sufficient number of studies support the chosen study. The confi-
dence in the RfD follows. Additional chronic/reproductive studies are needed
to support a higher level of confidence in the RfD.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, July 1985.
»
U.S. EPA. 1985. Cyanides: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Cyanogen
CAS No.: 460-19-5
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Cyanogen
CAS No.: 460-19-5
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
-------
Cyanogen: page 5 of 6
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Cyanogen
CAS No.: 460-19-5
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Cyanogen
CAS No.: 460-19-5 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
100 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on ignitability. Cyanogen cyanide is a flammable
gas with a boiling point below 100 degrees F.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
-------
Cyanogen: page 6 of 6
V. SUPPLEMENTARY DATA
Chemical: Cyanogen
CAS No.: 460-19-5
Information Is not available at this time.
Synonyms: CARBON NITRIDE, CYANOGEN , CYANOGENE (French), DICYAN, DICYANOGEN
ETHANEDINITRILE, NITRILOACETONITRILE, OXALIC ACID DINITRILE, OXALIC NITRILE
OXALONITRILE, OXALYL CYANIDE, PRUSSITE, RCRA WASTE NUMBER P031, UN 1026
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Dalapon; CAS No. 127-20-8 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful In particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take Into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used In these assessments and the
development of risk management numbers, see Appendix E In Service Code 4.
STATUS OF DATA FOR Dalapon
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Dalapon: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Dalapon
CAS No.: 127-20-8
Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Increased kidney body 15 mg/kg/day dalapon
weight ratio
Rat oral chronic
study
Paynter et al. (1960)
sodium salt (8.45
mg/kg/day as dalapon
(NOEL)
50 mg/kg/day (LOAEL)
100
8E-2
mg/kg/day
* Dose Conversion Factors & Assumptions:
molecular weight (see text below).
Dose adjusted for purity and
2. PRINCIPAL AND SUPPORTING STUDIES
Paynter, O.E., T.W. Tusing, D.D. McCollister and V.K. Rowe. 1960. Toxicology
of dalapon sodium (2,2-dlchloropropIonlc acid, sodium salt). J. Agric. Food
Chem. 8: 47-51.
Albino Carworth rats (24 male, 20 female/group) were fed diets providing
0, 5, 15 or 50 mg commercial dalapon sodium salt/kg bw/day for 2 years.
Hematological parameters were examined at timed Intervals and histopathology
was performed at 104 weeks. A statistically significant (p<0.05) increase
over controls was observed in the kidney-to-body weight ratios of male rats
receiving 50 mg/kg/day. No differences from controls were observed for any
other criteria in any treatment group. Kidney lesions were not observed.
Increased kidney-to-body weight ratio was a consistent finding in related
studies (Paynter et al. 1960). Rats fed 26 mg dalapon/kg bw/day (dose con-
-------
Dalapon: page 3 of 5
verted to pure dalapon) for 97 days had increased kidney-to-body weight
ratios. A NOEL of 8.5 mg/kg/day was found. The effect was shown in dogs
dosed for 1 year with dalapon at 74 mg/kg/day, but not at 37 mg/kg/day.
"Slight histopathological changes" In the liver and kidney were reported for
rats at the highest doses (256 and 850 mg/kg/day).
Paynter et al. (1960) reported that the commercial grade dalapon sodium
contained 65% of the pure sodium salt of dalapon. The dose Is further
adjusted to pure dalapon by multiplying by the ratio of the molecular weight
of dalapon (143) to its sodium salt (165).
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. The 100-fold factor represents two 10-fold subunits, one to
account for the expected interhuman variability of the toxicity of this
chemical in lieu of specific data, and one to account for the expected
interspecies variability.
MF = 1
4. ADDITIONAL COMMENTS
Other Data Considered for Establishing the RfD:
1) 2-Year Feeding - Rat (see description above)
2) 3-Generation Reproduction - Rat (NOEL - 150 mg/kg)
3) 1-Year Feeding - Dog (NOEL - 100 mg/kg)
4) Teratology - Rat [Fetotoxic NOEL - 500 mg/kg; Fetotoxic LEL - 1000 mg/kg
(decreased pup weights)]
5) 1-Generation Reproduction - Dog [NOEL - 500 ppm (12.5 mg/kg-day)]
Data Gap(s) : Rabbit teratology study
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The critical study was adequate for chronic risk assessment in the NOEL-
LEL range, and is given a medium confidence rating. Additional studies are
supportive but of fair quality, rating a medium to low confidence in the data
base. A medium confidence in the RfD follows.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1984. Health and Environmental Effects Profile for Dalapon.
Environmental Criteria and Assessment Office, Cincinnati, OH. ECAO-CIN-P085.
The ADI in the 1984 Health and Environmental Effects Profile document has
received an Agency review with the help of two external scientists.
Agency RfD Work Group Review: 10/09/85
Verification Date: 10/09/85
-------
Dalapon: page 4 of 5
7. U.S. EPA CONTACTS
Primary: Reto Engler FTS/557-7491 or 202/557-7491
Office of Pesticides Programs
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Dalapon
CAS No.: 127-20-8
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Dalapon
CAS No.: 127-20-8
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Dalapon
CAS No.: 127-20-8
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Dalapon
CAS No.: 127-20-8 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
-------
Dalapon: page 5 of 5
risk assessments (In sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
5000 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
Dalapon is a synonym for 2,2-Dichloropropionic acid (CASRN 75-99-0) and
2,2-Dichloropropionic acid, sodium salt (CASRN 127-20-8). The final RQ for
2,2-Dichloropropionic acid is based on aquatic toxicity (as established
under Section 311(b)(4) of the Clean Water Act). Available data indicate
that the aquatic 96-Hour Median Threshold Limit for dalapon is between 100
and 500 ppm.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
V. SUPPLEMENTARY DATA
Chemical: Dalapon
CAS No.: 127-20-8
Information is not available at this time.
Synonyms: propionic acid, 2,2-dichloro-.sodium salt; basfapon B; dalapon;
dalapon sodium; dalapon sodium salt; 2,2-dichloropropionic acid, sodium salt;
alpha-alpha-dichloropropionic acid sodium salt; 2,2-dichlorpropionsaeure
natrium (German); 2,2-DPA; Dowpon; gramevin; natriumsalz der 2,2-
dichlorpropionsaure; radapon; sodium dalapon; sodium alpha,alpha-
dichloropropionate; sodium 2,2-dichloropropionate; unipon
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
2,4-DB; CAS No. 94-82-6 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR 2,4-DB
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: none
V. Supplementary Data: none
-------
2,4-DB: page 2 of 4
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: 2,4-DB
CAS No.: 94-82-6 Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Internal hemorrhage, 8 mg/kg/day (NOAEL) 1000 1 8E-3
mortality mg/kg/day
25 mg/kg/day (LOAEL)
Dog subchronic oral
bioassay
Rhodia, Inc., 1969
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Rhodia, Inc. 1969. MRID 0092165.
Available from EPA. Write to FOI, EPA, Washington D.C. 20460.
Four beagle dogs/sex/group were fed 2,4-DB at dose levels of 0, 2.5, 8.0,
25 or 80 mg/kg bw/day for 90 days. The two higher doses produced frank
effects including death, hemorrhage throughout the body, and aspermatogenesis
within 3-9 weeks of treatment. Slightly increased liver-to-body weight ratios
were observed at both lower dose levels, but no gross or microscopic pathology
was evident.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. The uncertainty factor of 1000 reflects 10 for both intraspecies
and interspecies variability to the toxicity of this chemical in lieu of
-------
2,4-DB: page 3 of 4
specific data, and 10 for extrapolation of a subchronic effect level to its
chronic equivalent.
MF - 1
4. ADDITIONAL COMMENTS
A subchronic rat study (CBI) showed somewhat higher effect and no-effect
levels than were observed in the dog study. Severe kidney and liver damage
was observed at 1000 ppm 2,4-DB in the diet (80-100 mg/kg bw/day). A NOEL of
about 25-30 mg/kg/day was established.
2,4-DB does not appear to be teratogenic, but the data are very limited.
Structurally related compounds (2,4-D and 2,4,5-T) are teratogenic. No data
on carcinogenicity are available. 2,4-DB has not been shown to be mutagenic.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Low RfD: Low
Confidence in the critical study is medium because of the moderate number
of animals and large number of dose groups employed, but not high, because
some data are lacking. Confidence in the data base is low, because of the
general lack of data, but tends toward medium because one moderately suppor-
tive study is available. Confidence in the RfD is low because of the weak
data base.
6. DOCUMENTATION AND REVIEW
The ADI in the 1984 Health and Environmental Effects Profile has had a
limited Agency review with the help of two external scientists.
U.S. EPA. 1984. Health and Environmental Effects Profile for 2,4-DB. Envi-
ronmental Criteria and Assessment Office, Cincinnati, OH. ECAO-CIN-P060AP.
Agency RfD Work Group Review: 05/31/85, 06/19/85
Verification Date: 06/19/85
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: 2,4-DB
CAS No.: 94-82-6
Information is not available at this time.
-------
2,4-DB: page 4 of 4
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: 2,4-DB
CAS No.: 94-82-6
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: 2,4-DB
CAS No.: 94-82-6
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: 2,4-DB
CAS No.: 94-82-6
Information is not available at this time.
V. SUPPLEMENTARY DATA
Chemical: 2,4-DB
CAS No.: 94-82-6
Information is not available at this time.
Synonyms: BUTOXON, BUTOXONE, BUTOXONE AMINE, BUTOXONE ESTER, BUTYRAC, BUTYRAC
118 , BUTYRAC 200, BUTYRAC ESTER, 2,4-DB, 4(2,4-DB), 2,4-D BUTYRIC,
gamma-(2,4-DICHLOROPHENOXY)BUTYRIC ACID, 4-(2,4-DICHLOROPHENOXY)BUTYRIC ACID ,
2,4-DM, EMBUTOX, EMBUTOX E, EMBUTOX KLEAN-UP, LEGUMEX D
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Decabromodiphenyl Ether; CAS No. 1163-19-5 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Decabromodiphenyl Ether
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: none
V. Supplementary Data: none
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Decabromodiphenyl Ether (DBDPE): page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Decabromodiphenyl Ether (DBDPE)
CAS No.: 1163-19-5 Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Rat chronic oral 1.0 mg/kg/day (NOEL) 100 1 1E-2
bioassay mg/kg/day
LOAEL: None
Kociba et al. (1975)
Liver enlargement 8 mg/kg/day (NOEL)
Rat subchronic 80 mg/kg/day (LOAEL)
oral bioassay
Norris et al.
(1973, 1975)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
End Point and Experimental Doses:
Kociba, R.J., L.O. Frauson, C.G. Humiston, et al. 1975. Results of a
two-year dietary feeding study with decabromodiphenyl oxide (DBDPO) in rats.
Combust. Toxicol. 2: 267-285.
Norris, J.M., J.W. Ehrmantraut, C.L. Gibbons, et al. 1973. Toxicological
and environmental factors involved in the selection of decadibromophenyl
oxide as a fire retardant chemical. Appl. Polym. Symp. 22: 195-219.
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Decabromodiphenyl Ether (DBDPE): page 3 of 5
Norris, J.M., J.W. Ehrmantraut, C.L. Gibbons, et al. 1975. Toxicology of
octabromobiphenyl and decabromodiphenyl oxide. Environ. Health Perspect.
11: 153-161.
Kociba et al. (1975) treated Sprague-Dawley (Spartan) rats (25/sex/dose)
with daily doses (in the diet) of 0.0, 0.01, 0.1 and 1.0 mg decabromodiphenyl
ether (oxide)/kg bw for 2 years. Parameters examined were hematology, clini-
cal chemistry, food consumption, organ weight, body weight and incidence of
histopathological lesions. No significant differences between treatment and
control groups were found. Norris et al. (1973, 1975) reported on earlier
stages of the same study.
Supporting data are reported by Norris et al. (1973, 1975) in a 30-day
oral study, in which male rats were administered decabromodiphenyl ether
(DBDPE) at dietary concentrations of 0, 0.01, 0.1 or 1.0%. These concentra-
tions correspond to doses of 0, 8, 80 or 800 mg/kg/day. A NOEL for enlarged
livers of 8 mg/kg/day was established. This short-term to subchronic NOEL is
close to the chronic NOEL of 1.0 mg/kg/day when adjusted by a factor of 10 to
account for the uncertainty in extrapolating subchronic dose to chronic dose.
The chemical analysis of the DBDPE used in these studies was reported as
follows (Kociba et al., 1975): DBDPE, 77.4%; nonabromodiphenyl ether
(NBDPE), 21.8%; and octabromodiphenyl ether (OBDPE), 0.8%. The presence of
OBDPE in this mixture has an uncertain effect on the toxicity of DBDPE, lack-
ing information on the mechanism of toxicity of DBDPE. An RfD of 0.00062
mg/kg/day has been proposed for OBDPE based on its liver enzyme reducing
capabilities (U.S. EPA, 1984). No RfD has been proposed for NBDPE due to
lack of data.
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 100. The 100-fold factor reflects both the expected intra- and
interspecies variability to the toxicity of this chemical in lieu of
specific data.
MF - 1
4. ADDITIONAL COMMENTS
Absorption and subsequent toxicity of this compound may be highly depend-
ent on the relative proportions of water and oils in the diet because of its
physical properties (low aqueous solubility and varied crystal size).
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Low RfD: Low
The critical study was well-conducted with a sufficient number of animals
and toxicity parameters, but lacked an adequate dose range. The supporting
in-house study, which established the LOAEL, was very short in duration;
since no other data pertaining to the chronic toxicity of DBDPE was found in
the available literature, confidence in the data base is rated low. Confi-
dence in the RfD is rated low because of the lack of independent support and
other uncertainties (see preceding comments).
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Decabromodiphenyl Ether (DBDPE): page 4 of 5
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1984. Health and Environmental Effects Profile for Brominated
Biphenyl Ethers. Environmental Criteria and Assessment Office, Cincinnati
OH. ECAO-CIN-P024.
The ADI in the 1984 Health and Environmental Effects Profile has received an
Agency review with the help of two external scientists.
Agency RfD Work Group Review: 10/09/86
Verification Date: 10/09/86
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Decabromodiphenyl Ether
CAS No.: 1163-19-5
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Decabromodiphenyl Ether
CAS No.: 1163-19-5
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Decabromodiphenyl Ether
CAS No.: 1163-19-5
Information is not available at this time.
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Decabromodiphenyl Ether (DBDPE): page 5 of 5
IV. RISK MANAGEMENT SUMMARIES
Chemical: Decabromodiphenyl Ether
CAS No.: 1163-19-5
Information is not available at this time.
V. SUPPLEMENTARY DATA
Chemical: Decabromodiphenyl Ether
CAS No.: 1163-19-5
Information is not available at this time.
Synonyms: ETHER, BIS(PENTABROMOPHENYL); BENZENE, 1,1'-OXYBIS(2,3,4,5,6-
PENTABROMO- (9CI); BERKFLAM B 10E; BR 55N; BROMKAL 83-10DE; BROMKAL 82-ODE;
DBDPO; DECABROMOBIPHENYL ETHER; DECABROMOBIPHENYL OXIDE; DECABROMODIPHENYL
OXIDE; DECABROMOPHENYL ETHER; DE 83R; ETHER, DECABROMODIPHENYL; FR 300; FR
300BA; FRP 53; NCI-C55287; PENTABROMOPHENYL ETHER; SAYTEX 102; SAYTEX 102E;
TARDEX 100
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INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Dibutylnitrosamine; CAS No. 924-16-3 (Revised 12/24/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Dibutylnitrosamine
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: none
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: available
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: in preparation
V. Supplementary Data: none
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Dibutylnitrosamine: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Dibutylnitrosamine
CAS No.: 924-16-3
Information is not available at this time.
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Dibutylnitrosamine
CAS No.: 924-16-3
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Dibutylnitrosamine
CAS No.: 924-16-3 Preparation Date: 12/24/86
A. U.S. EPA CLASSIFICATION AND BASIS
Classification: B2, probable human carcinogen, based on increased inci-
dences of several tumor types in rats, mice and hamsters
exposed by various routes.
1. HUMAN DATA
Human exposure to nitrosamines results from contact with mixtures con-
taining these compounds (e.g., cutting oils, tobacco products). Because of
potential confounding by the other substances in these mixtures, data is of
limited use in the evaluation of carcinogenicity of individual nitrosamines.
2. ANIMAL DATA
There is a large data base on the carcinogenicity of nitrosamines, most
of which pertains to structure-activity relationships rather than to dose-
response. Druckrey reported dibutylnitrosamine produced bladder rather than
liver tumors in rats treated by s.c. injection. Dibutylnitrosamine also
induces carcinoma of the bladder, lung and trachea in Syrian hamsters and
stomach carcinomas in Chinese hamsters treated by gavage. Liver tumors, lung
adenomas and forestomach carcinomas were observed in male CR mice fed this
compound in the diet.
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Dibutylnitrosamlne: page 3 of 6
Druckrey et al. (1967) treated BD rats with dibutylnitrosamine in dietary
concentrations providing doses of 10, 20, 37 or 75 mg/kg bw/day. Treatment
was presumably lifetime. No control data were reported. All four of the
surviving high-dose animals developed liver tumors as well as 13/16, 4/10 and
2/10 in the 37, 20 and 10 mg/kg bw/day groups. Esophageal tumors and bladder
tumors were also observed in the lower dose groups. Average time-to-tumor
was treatment dose-dependent.
Bertram and Craig (1970) exposed 50 each male and female C57B16 mice to
either 60 mg or 240 mg dibutylnitrosamine/liter in drinking water. The
treatment solution was replaced by water for 50% of all animals in the high
dose group as these animals showed heamaturia. The remainder of the high-
dose animals and all low-dose animals were maintained on the treatment
solutions until they became moribund or died. Squamous cell carcinomas of
the bladder were found in 44/90 high-dose mice and 19/89 low-dose mice; they
predominated in the males. Carcinomas and papillomas of the esophagus were
also found.
3. SUPPORTING DATA
Dibutylnitrosamine is mutagenic for E. coli and S. typhimurium and causes
mitotic recombination in S. cerevisiae, recessive lethal mutations in D.
melanogaster and chromosome aberrations in mammalian cells. Positive
responses are dependent upon the presence of mammalian metabolic enzymes
(Montesano and Bartsch, 1976).
B. ORAL QUANTITATIVE ESTIMATE
Slope Factor = 5.4/mg/kg/day
1. UNIT RISK SUMMARY TABLE
Water Concentrations Producing Risk Levels Unit Risk Model
E-4 E-5 E-6 (/ug/1)
6.4E-1 6.4E-2 6.4E-3 1.6E-4 LM
U8/1 ug/1 ug/1 extra risk
2. DOSE RESPONSE DATA
Study reference: Human Equiv.
Species/strain Admin. Dose Dose Tumor
Tumor type; Route (mg/1) (mg/kg/day) Incidence
Bertram and Craig, 1970:
Mouse/C57B16, males; 0 n.r.
bladder and esophagus tumors; 60 46/47
drinking water 240 45/45
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Dibutylnitrosamine: page 4 of 6
3. ADDITIONAL COMMENTS
Water consumption reported by the authors indicates that males received
doses of 7.6 and 29.1 mg/kg/day. Specific tumor incidences were not reported
for control animals. The authors stated that this strain has a very low
spontaneous tumor incidence. A slope factor of 1.2 mg/kg/day for dibutyl-
nitrosamine was calculated from the data of Druckrey et al. (1967), The unit
risk should not be used if the water concentration exceeds 62.5 ug/1 as above
this concentration the slope factor may differ from that stated above.
4. STATEMENT OF CONFIDENCE
Although adequate numbers of animals were treated for their lifetime,
control data were not reported. As the risk estimate is supported by an
independent study (Druckrey et al., 1967), confidence is rated medium.
C. INHALATION QUANTITATIVE ESTIMATE
Slope Factor - 5.4/mg/kg/day
1. UNIT RISK SUMMARY TABLE
Air Concentrations Producing Risk Levels
E-4 E-5 E-6
6.4E-2
ug/cu.m
6.4E-3
ug/cu . m
6.4E-4
ug/cu.m
Unit Risk Model
(/ug/cu. m)
1.6E-3 LM
extra risk
2. DOSE RESPONSE DATA
The inhalation risk estimates were calculated from the oral exposure data.
3. ADDITIONAL COMMENTS
The unit risk should not be used if air concentrations exceed
6.3 ug/cu. m as above this concentration the slope factor may differ from
that stated above.
4. STATEMENT OF CONFIDENCE
Confidence in this inhalation risk estimate derived from oral data is
rated low.
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Dibutylnltrosamine: page 5 of 6
D. DOCUMENTATION AND REVIEW
1. REFERENCES
U.S. EPA. 1980. Ambient Water Quality Criteria for Nitrosamines. Prepared
by the Environmental Criteria and Assessment Office, Cincinnati, OH for the
Office of Water Regulations and Standards.
Bertram, J.S. and A.W. Craig. 1970. Induction of bladder tumors in mice
with dibutylnitrosamines. Br. J. Cancer. 24: 352-359.
2. REVIEW
The values in the Ambient Water Quality Criteria Document for Nitro-
samines (1980) received extensive peer and public review.
Agency CRAVE Work Group Review: 07/23/86, 08/13/86, 10/29/86
Verification Date: 10/29/86
3. U.S. EPA CONTACTS
Primary: J.H. Holder (202/FTS) 382-5721
Office of Research and Development
Secondary: C.H. Ris (202/FTS) 382-7338
Office of Research and Development
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Dlbutylnitrosamine
CAS No.: 924-16-3
Information Is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Dibutylnltrosamine
CAS No.: 924-16-3
in preparation
-------
Dibutylnitrosamine: page 6 of 6
V. SUPPLEMENTARY DATA
Chemical: Dibutylnitrosamine
CAS No.: 924-16-3
Information is not available at this time.
Synonyms: butylamine, N-nitrosodi-; N-butyl-N-nitroso-1-butamine;
1-butanamine, N-butyl-N-nitroso-; DBN; DBNA; Dibutylamine, N-nitroso; NDBA;
N-nitrosobutylamine; N-nitroso-di-n-butylamine; di-n-butylnitrosamin (German);
di-n-butylnitrosamine; N,N-di-n-butylnitrosamine; RCRA waste number U172
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INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Dibutyl Phthalate; CAS No. 84-74-2 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Dibutyl Phthalate
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
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Dibutyl Phthalate: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Dibutyl Phthalate
CAS No.: 84-74-2 Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Increased mortality 0.25% of diet (125 1000 1 1E-1
mg/kg/day) (NOAEL) mg/kg/day
Rat subchronic to
chronic, oral bio- 1.25% of diet (600
assay mg/kg bw/day) (LOAEL)
Smith (1953)
* Dose Conversion Factors & Assumptions: The values of 125 mg/kg/day for
0.25% dibutyl phthalate in the diet and 600 mg/kg/day for 1.25% were
estimated from a figure depicting daily intake in mg/kg in Smith (1953).
2. PRINCIPAL AND SUPPORTING STUDIES
Smith, C.C. 1953. Toxicity of butyl sterate, dibutyl sebacate, dibutyl
phthalate and methoxyethyl oleate. Arch. Hyg. Occup. Med. 7: 310-318.
Male Sprague-Dawley rats in groups of 10 were fed diets containing 0,
0.01, 0.05, 0.25 and 1.25% dibutyl phthalate for a period of 1 year. One-
half of all rats receiving the highest dibutyl phthalate concentration died
during the first week of exposure. The remaining animals survived the study
with no apparent ill effects. There was no effect of treatment on gross
pathology or hematology. While it was stated that several organs were
sectioned and stained, no histopathology evaluation was reported.
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Dibutyl Phthalate: page 3 of 7
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 1000. A factor of 10 was applied to account for interspecies
variation, a factor of 10 for protection of sensitive human subpopulations,
and an additional factor of 10 was applied to account for both the less-
than-chronic duration of the study and deficiencies in the study, such as the
use of only male animals.
MF - 1
4. ADDITIONAL COMMENTS
Fetotoxicity was observed when mice were fed 2100 mg/kg/day diethyl
phthalate throughout gestation (Shiota and Nishimura, 1982). An increase in
terata of borderline statistical significance was observed in progeny of this
treatment group. Diethyl phthalate produces degeneration of the seminiferous
tubules, probably as a result of increased urinary excretion of Zn (Gangolli,
1982).
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Low RfD: Low
The study by Smith (1953) used few animals of one sex only. It was not
indicated in the paper whether the 50% mortality observed early in the study
was considered treatment-related, nor was the cause of death indicated. This
is the only subchronic bioassay of dibutyl phthalate reported in the litera-
ture. Confidence in the study, data base and RfD are all rated low.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1980. Ambient Water Quality Criteria for Phthalate Esters. Envi-
ronmental Criteria and Assessment Office, Cincinnati, OH. EPA 440/5-80-067.
The RfD in the 1980 Ambient Water Quality Criteria document received extensive
peer and public review.
Agency RfD Work Group Review: 01/22/86
Verification Date: 01/22/86
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
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Dibutyl Phthalate: page 4 of 7
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Dibutyl Phthalate
CAS No.: 84-74-2
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Dibutyl Phthalate
CAS No.: 84-74-2
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Dibutyl Phthalate CAS No.: 84-74-2
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Dibutyl Phthalate
CAS No.: 84-74-2 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
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Dibutyl Phthalate: page 5 of 7
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Status Risk Considers
Management Econ/Tech
Date Value Feasibility
Reference
Reportable Final
Quantity (RQ) 1985
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
2) Marine
Final
1980
10 Ibs
34 mg/1
no
no
Acute no
940 ug/1 (LEL)
Chronic
3 ug/1 (LEL)
Acute no
2,944 ug/1 (LEL)
Chronic
3.4 ug/1 (LEL)
50 FR 13456
04/04/85
45 FR 79318
11/28/80
ibid.
ibid.
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity. The available data indicate
that the aquatic 96-Hour Median Threshold Limit for dibutyl phthalate is
between 0.1 and 1 ppm.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC of 34 mg/1 is based on consumption of contaminated
aquatic organisms and water. A WQC of 154 mg/1 has also been established
based on consumption of contaminated aquatic organisms alone.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value indicates that the
minimum data were not available and the concentration given is not a criteria
value but the lowest effect level found in the literature. The values given
represent phthlate esters as a class - no specific chemicals were mentioned.
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Dibutyl Phthalate: page 6 of 7
V. SUPPLEMENTARY DATA
Chemical: Dibutyl Phthalate
GAS No.: 84-74-2 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Dibutyl phthalate is generally non-irritating to humans (Martin, 1974).
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Eye irritation with profuse tearing.
Contact with surface of eye has caused severe stinging pain with profuse
tearing (Grant, 1974). Mild throat irritation has been observed (Lefaux,
1968). Ingestion has caused nausea, dizziness, photophobia, lachrymation,
and conjunctivitis (ACGIH, 1980).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: C H 0
16 22 4
Molecular Weight: 278.34
Boiling Point: 644F, 340C
Specific Gravity (H20-1): 1.0484 at 20C/20C
Vapor Pressure (mmHg): 1.1 at 150C
Melting Point: -31F, -35C
Vapor Density (AIR-1): 9.58
Evaporation Rate (Butyl acetate-1): Not Found
Solubility in Water: 13 mg/liter at 25C
FlashPoint [Method Used]: 315F, 157C (CC); 339.8F, 171.1C (OC)
Flammable Limits:
LEL: 0.5% at 456F (235C)
UEL: Not Found
Appearance and Odor: Colorless, oily liquid with a weak aromatic odor
(NIOSH/OSHA, 1978, p. 80)
Conditions or Materials to Avoid: Liquid chlorine reacts explosively with
dibutyl phthalate (NFPA, 1978). Avoid contact with nitrates, strong
oxidizers, strong alkalies, strong acids (NIOSH/OSHA, 1978, p. 80) and
chlorine (Sax, 1984, p. 926).
Hazardous Decomposition or Byproducts: None (NFPA, 1978)
-------
DIbutyl Phthalate: page 7 of 7
Use: Plasticizer in nitrocellulose lacquers, elastomers, explosives, nail
polish, and solid rocket propellents; solvent for perfume oils; perfume
fixative; textile lubricating agent; safety glass; insecticides; printing
inks; resin solvent; paper coatings; adhesives; insect repellants for
textiles (Hawley, 1981, p. 330). Not registered as a pesticide in the U.S.
(USEPA/Pesticide Index, 1985).
Synonyms: 1,2-Benzenedicarboxylic Acid Dibutyl Ester; 1,2-Benzenedicar-
boxylic Acid, Dibutyl Ester; Benzene-o-Dicarboxylic Acid Di-n-Butyl Ester;
Butylphthalate; Celluflex DPB; DPB; Di-n-Butylphthalate; Dibutyl 1,2-Benzene
dicarboxylate; Dibutyl-o-Phthalate; Elaol; Ergoplast FOB; Genoplast B;
Hexaplast M/B; N-Butylphthalate; o-Benzenedicarboxylic Acid, Dibutyl Ester;
Palatinol C; Phthalic Acid Dibutyl Ester; Phthalic Acid, Dibutyl Ester;
Polycizer DBP; PX 104; RG Plasticizer DBP
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
1,1-Dichloroethylene; CAS No. 75-35-4 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR 1,1-Dichloroethylene
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: review pending
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
1,1-Dichloroethylene: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) Is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: 1,1-Dichloroethylene (Vinylidene Chloride)
CAS No.: 75-35-4 Preparation Date: 04/17/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Hepatic lesions
Rat chronic oral
NOAEL: None
LOAEL: 9 mg/kg/day
1000 1 9E-3
bioassay
Quast et al. (1983)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Quast, J.F., C.G. Humiston, C.E. Wade, et al. 1983. A chronic toxicity and
oncogenicity study in rats and subchronic toxicity study in dogs on ingested
vinylidene chloride. Fund. Appl. Toxicol. 3: 55-62.
Groups of 48 each male and female Sprague-Dawley rats (Spartan substrain)
were administered 50, 100 or 200 ppm 1,1-dichloroethylene In drinking water
for a period of 2 years. Control groups of 80 animals/sex were maintained
for the same period. Daily Intake was calculated by the authors to be 7, 10
or 20 mg/kg bw/day for males and 9, 14 or 30 mg/kg bw/day for females. There
were no treatment-related effects on mortality, body or organ weight, clini-
cal chemistry, unlnalysis, hematology or numbers of tumors. The only patho-
logical findings were of hepatic lesions, generally characterized by minimal
mid-zonal hepatocellular fatty change, and hepatocellular swelling. These
were noted In rats of all female treatment groups. In male rats only the 200
ppm treatment group showed a statistically significant Increase in incidence
-------
1,1-Dichloroethylene: page 3 of 6
of hepatocellular swelling, but this trend was also observed in animals
receiving 100 ppm 1,1-dichloroethylene.
As part of this same study, beagle dogs (4/sex/group) were administered
6.25, 12.5 or 25 mg/kg bw/day in gelatin capsules. Treatment for 97 days had
no effect.
This study, as well as a review of the available data, indicate that the
liver is the most sensitive target organ and rats are the most sensitive
species. The drinking water exposure reported by Quast et al. (1983) offers
a more suitable model for potential human exposure to 1,1-dichloroethylene
than does the NTP bioassay wherein animals were gavaged. It is, therefore,
appropriate to set an RfD based on the LOAEL of 9 mg/kg bw/day for hepatic
lesions in female rats.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. A factor of 10 each was used for use of a LOAEL, for
interspecies variation, and for protection of sensitive human
subpopulations.
MF - 1
4. ADDITIONAL COMMENTS
1,1-Dichloroethylene has been shown to be fetotoxic, but not teratogenic
to rodents after exposure in drinking water or by inhalation (Short et al.,
1977; Murray et al., 1979).
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The study by Quast et al. (1983) was conducted using appropriate numbers
of animals of two species, measured several end points, and was of chronic
duration (rats). As there are corroborative chronic and subchronic oral bio-
assays, confidence in the study, data base and RfD are considered medium.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1985. Drinking Water Criteria Document for 1,1-Dichloroethylene
(Vinylidene Chloride). Office of Drinking Water, Washington, DC.
This document has received a lengthy internal review and has undergone
public comments.
Agency RfD Work Group Review: 01/22/85
Verification Date: 01/22/85
7. U.S. EPA CONTACTS
Primary: P. Fenner-Crisp FTS/382-7589 or 202/382-7589
Office of Drinking Water
-------
1,1-DIchloroethylene: page 4 of 6
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: 1,1-Dichloroethylene
CAS No.: 75-35-4
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: 1,1-Dichloroethylene
CAS No.: 75-35-4
This chemical is among those substances evaluated by the U.S. EPA for
evidence of human carcinogenic potential. This does not imply that this
chemical is necessarily a carcinogen. The evaluation for this chemical is
under review by an inter-office Agency work group. A risk assessment summary
will be included on IRIS when the review has been completed.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: 1,1-Dichloroethylene
CAS No.: 75-35-4
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: 1,1-Dichloroethylene
CAS No.: 75-35-4 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis
-------
1,1-Dichloroethylene: page 5 of 6
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each EM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Statutory
1980
Risk
Management
Value
5000 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
2) Marine
Clean Air Act
Regulatory
Decision
(NESHAP or NSPS)
Final
1980
Current
1985
0.033 ug/1
no
Acute no
11,600 ug/1 (LEL)
Chronic
none
Acute no
224,000 ug/1 (LEL)
Chronic
none
Decision not
to regulate
no
45 FR 79318
11/28/80
ibid.
ibid.
50 FR 32633
08/13/85
B. RISK MANAGEMENT RATIONALE
RQ
The statutory RQ of 5000 pounds established under Section 311(b)(4)
ofthe Clean Water Act is retained until the assessment of potential
carcinogenicity is complete.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC of 0.033 ug/1 represents a cancer risk level of
IE-6, based on consumption of contaminated organisms and water. A WQC of
1.85 ug/1 (cancer risk level of 1E-6) has also been established based on
consumption of contaminated organisms alone.
-------
1,1-DIchloroethylene: page 6 of 6
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value indicates that the
minimum data were not available and the concentration given is not a criteria
value but the lowest effect level found in the literature. Values given
represent trihalomethanes as a class. No specific chemicals were mentioned.
CAA Regulatory Decision
While there is some evidence of carcinogenicity (rare kidney tumors in
one sex of one strain of one species), EPA concluded that the overall weight
of evidence was not sufficient to warrant regulation as a carcinogen. Also,
measured and modeled ambient concentrations were well below any non-cancer
health effects of concern. Thus, EPA concluded that no regulation under the
CAA of routine emissions was warranted at the current time.
Contact: Chief, Pollutant Assessment Branch
919/541-5645 or FTS/629-5645
V. SUPPLEMENTARY DATA
Chemical: 1,1-Dichloroethylene
CAS No.: 75-35-4
Information is not available at this time.
Synonyms: ETHYLENE, 1,1-DICHLORO-; CHLORURE DE VINYLIDENE (French); 1,1-DCE;
1,1-DICHLOROETHENE (9CI); 1,1-DICHLOROETHYLENE; ETHENE, 1,1-DICHLORO-; NCI-
C54262; RCRA WASTE NUMBER U078; SCONATEX; VDC; VINYLIDENE CHLORIDE;
VINYLIDENE CHLORIDE (II); VINYLIDENE CHLORIDE (ACGIH); VINYLIDENE DICHLORIDE;
VINYLIDINE CHLORIDE; 1,1-DICHLOROETHYLENE; ETHYLENE, 1,1-DICHLORO- (801); UN
1303 (DOT); VDC; VINYLIDENE CHLORIDE, inhibited; VINYLIDENE CHLORIDE,
inhibited (DOT)
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Dichlorodifluoromethane; CAS No. 75-71-8 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Dichlorodifluoromethane
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Dichlorodifluoromethane: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD Is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, It is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Dichlorodifluoromethane
CAS No.: 75-71-8 Preparation Date: 01/06/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Reduced body weight 15 mg/kg/day (NOEL) 100 1 2E-1
mg/kg/day
Rat chronic oral 150 mg/kg/day (LOAEL)
study
Sherman (1974)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Sherman, H. 1974. Long-term feeding studies In rats and dogs with dlchloro-
difluoromethane (Freon 12 Food Freezant). Haskell Laboratory for Toxicology
and Industrial Medicine Report No. 24-74.
The study reported by the Haskell Laboratory (Sherman et al., 1974)
involved 2-year feeding studies in which dogs and rats received 300 ppm or
3000 ppm of dichlorodifluoromethane. This report contained data on clinical
biochemical, urine analytical, hematological or histopathological evalua-
tions. Additionally, carcinogenic and three-generation reproductive studies
were conducted in rats. Except for decreased weight gain in rats (about 20%
in females) which received 3000 ppm (150 mg/kg/day) dichlorodifluoromethane
in the diet, no other adverse effects were attributable to this compound In
either rats or dogs.
The Haskell Laboratory study reported above Is sufficiently complete to
derive an RfD for adequate protection against adverse human health effects.
-------
Dichlorodifluoromethane: page 3 of 6
The high dose (3000 ppm or 150 mg/kg/day) caused decreased body weights in
rats and is therefore considered as a LOAEL; whereas the low dose (300 ppm or
15 mg/kg/day) in rats produced no adverse effects attributable to the oral
administration of dichlorodifluoromethane (Freon 12).
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. The NOEL from the 2-year rat study (15 mg/kg/day) and an
uncertainty factor of 100 (10 for species extrapolation and 10 for sensitive
individuals) were used to derive the RfD of 0.2 mg/kg/day or 10 mg/day for a
70-kg human being.
MF = 1
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: High Data Base: Low RfD: High
The Haskell Laboratory study is a chronic oral study in two species, which
incorporated extensive clinical and toxicological parameters. Therefore, a
high level of confidence in study is appropriate. Confidence in the data base
is low because of the lack of other data. Confidence in the RfD follows at
high to medium.
6. DOCUMENTATION AND REVIEW
This document has undergone a limited Agency review.
U.S. EPA. 1982. Errata: Halomethanes Ambient Water Quality Criteria Docu-
ment for the Protection of Human Health. Environmental Criteria and Assess-
ment Office, Cincinnati, OH. ECAO-CIN-D023.
Agency RfD Work Group Review: 07/08/85, 07/22/85
Verification Date: 07/22/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
-------
Dichlorodifluoromethane: page 4 of 6
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Dichlorodifluoromethane
CAS No.: 75-71-8
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Dichlorodifluoromethane
CAS No.: 75-71-8
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Dichlorodifluoromethane
CAS No.: 75-71-8
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Dichlorodifluoromethane
CAS No.: 75-71-8 Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Dichlorodifluoromethane: page 5 of 6
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
5000 Ibs
Considers
EC on/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
2) Marine
Final
1980
0.19 ug/1
no
Acute no
11,000 ug/1 (LEL)
Chronic
none
Acute no
12,000 ug/1 (LEL)
Chronic
6,400 ug/1 (LEL)
45 FR 79318
11/28/80
ibid.
ibid.
B. RISK MANAGEMENT RATIONALE
RQ
No data have been found to permit the ranking of this hazardous
substance. The available data for the acute hazards may lie above the upper
limit for the 5000-pound RQ, but since it is a designated hazardous
substance, the largest assignable RQ is 5000 pounds.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC of 0.19 ug/1 represents a cancer risk level of
IE-6, based on consumption of contaminated organisms and water. A WQC of
15.7 ug/1 (cancer risk level of 1E-6) has also been established based on
consumption of contaminated organisms alone. The criteria are based on
halomethanes as a class.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value Indicates that the
minimum data were not available and the concentration given is not a criteria
value but the lowest effect level found in the literature. The values are
based on halomethanes as a class - no specific chemicals are cited.
-------
Dichlorodifluoromethane: page 6 of 6
V. SUPPLEMENTARY DATA
Chemical: Dichlorodifluoromethane
CAS No.: 75-71-8
Information is not available at this time.
Synonyms: ALGOFRENE TYPE 2, ARCTON 6, DICHLORODIFLUOROMETHANE,
DIFLUORODICHLOROMETHANE, DWUCHLORODWUFLUOROMETAN (Polish), ELECTRO-CF 12, F
12, FC 12, FLUOROCARBON-12, FREON 12, ESKIMON 12, FREON F-12, FRIGEN 12 ,
GENETRON 12, HALON, ISCEON 122, ISOTRON 12, KAISER CHEMICALS 12, LEDON 12,
PROPELLANT 12, RCRA WASTE NUMBER U075, R 12 , REFRIGERANT 12, UCON 12 , UCON
12/HALOCARBON 12, UN 1028
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
2,4-Dichlorophenol; CAS No. 120-83-2 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR 2,4-Dichlorophenol
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
2,4-DIchlorophenol: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: 2,4-Dichlorophenol
CAS No.: 120-83-2 Preparation Date: 05/12/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Decreased delayed 0.3 mg/kg bw/day 100 1 3E-3
hypersensitivity (NOEL) mg/kg/day
response
3.0 mg/kg/day (LOAEL)
Rat, subchronic to
chronic
Exon and Koller
(1985)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Exon, J.H. and L.D. Koller. 1985. Toxicity of 2-chlorophenol, 2,4-dichloro-
phenol and 2,4,6-trichlorophenol. In: Water Chlorination: Chemistry, Envi-
ronmental Impact and Health Effects, Jolley et al., Ed. Vol. 5.
Female rats were exposed to 3, 30 or 300 ppm 2,4-dichlorophenol in
drinking water from weaning age through breeding at 90 days, parturition and
weaning of pups. Ten randomly selected pups/group were weaned at 3 weeks and
admin- istered 2,4-dichlorophenol for an additional 15 weeks. The authors
estimated the exposure to be approximately 0.3, 3.0 and 30.0 mg/kg bw/day for
the low, medium and high dose groups. Increases in serum antibody levels to
keyhole limpet hemocyanin, as measured by an enzyme-linked immunosorbent assay
(ELISA) were found to be treatment-related. The increase was statistically
-------
2,4-Dichlorophenol: page 3 of 5
significant in the high dose group, as were spleen and liver weights.
Delayed-type hypersensitivity responses to bovine serum albumin in Freund's
complete adjuvant were significantly decreased in those animals administered
3.0 mg/kg bw/day. The NOEL for 2,4-dichlorophenol was, therefore, determined
to be 3 ppm or 0.3 mg/kg bw/day.
This is substantially lower than the NOEL of 100 mg/kg bw/day reported by
Kobayashi et al. (1973) for nonspecific liver changes in mice fed dichloro-
phenol in the diet for 180 days.
3. UNCERTAINTY AND MODIFYING FACTORS
UF <= 100. A factor of 10 each was employed for extrapolation from animal
data to humans and for protection of sensitive human subpopulations. Since
the test animals were exposed both in utero and through milk before the
15-week administration in drinking water, an additional factor for use of a
subchronic study was not considered necessary.
MF = 1
4. ADDITIONAL COMMENTS
Exon and Koller (1985) reported that exposure of dams to 300 ppm
dichlorophenol resulted in a significant decrease in litter sizes.
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Medium RfD: Low
The study (Exon and Koller, 1985) used an adequate number of animals and
measured very sensitive end points (immunological functions) in an appropriate
manner. As these end points are not commonly used in derivation of human
health risk evaluations, confidence in the study is rated low. There are two
additional published studies of 2,4-dichlorophenol toxicity after subchronic
to chronic exposure. Confidence in the data base is rated medium and confi-
dence in the RfD is rated low.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1985. Drinking Water Criteria Document for Chlorinated Phenols.
Office of Drinking Water, Washington, DC. (External Review Draft)
The Drinking Water Criteria Document is currently undergoing review.
Agency RfD Work Group Review: 11/06/85, 01/22/86
Verification Date: 01/22/86
7. U.S. EPA CONTACTS
Primary: J. Orme FTS/382-7586 or 202/382-7586
Office of Drinking Water
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
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2,4-Dichlorophenol: page 4 of 5
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: 2,4-Dichlorophenol
CAS No.: 120-83-2
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: 2,4-Dichlorophenol
CAS No.: 120-83-2
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: 2,4-DIchlorophenol
CAS No.: 120-83-2
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: 2,4-Dichlorophenol
CAS No.: 120-83-2 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are Indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action In
Appendix E in Service Code 4.
-------
2,4-Dichlorophenol: page 5 of 5
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
100 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity. The available data indicate
that the aquatic 96-Hour Threshold Limit for 2,4-dichlorophenol is between 1
and 10 ppm.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
V. SUPPLEMENTARY DATA
Chemical:
CAS No. :
2 , 4-Dichlorophenol
120-83-2
Information is not available at this time.
Synonyms: PHENOL, 2,4-DICHLORO-; DCP; 2,4-DCP; 2,4-DICHLOROPHENOL; NCI-
C55345; RCRA WASTE NUMBER U081
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Diethylnitrosamine; CAS No. 55-18-5 (Revised 12/24/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Diethylnitrosamine
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: none
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: available
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: in preparation
V. Supplementary Data: none
-------
Diethylnitrosamine: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Diethylnitrosamine
CAS No,: 55-18-5
Information is not available at this time.
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Diethylnitrosamine
CAS No.: 55-18-5
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Diethylnitrosamine
CAS No.: 55-18-5 Preparation Date: 12/24/86
A. U.S. EPA CLASSIFICATION AND BASIS
Classification: B2, probable human carcinogen, based on induction of tumors
at multiple sites in both rodent and nonrodent species
exposed by various routes.
1. HUMAN DATA
Human exposure to nitrosamines results from contact with mixtures con-
taining these compounds (e.g., cutting oils, tobacco products). Because of
potential confounding by the other substances in these mixtures, data is of
limited use in the evaluation of carcinogenicity of individual nitrosamines.
2. ANIMAL DATA
There is a large data base on the carcinogenicity of nitrosamines, most
of which pertains to structure-activity relationships rather than to dose-
response. Diethylnitrosamine administered by gavage, in drinking water or by
feeding produces liver tumors in the following species: rats, mice,
hamsters, guinea pigs, rabbits, dogs and monkeys (Yamamoto et al., 1972;
Druckrey et al., 1967, 1963; Magee et al., 1976; Rajewski et al. , 1955;
Tomatis, 1973).
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Diethylnitrosamine: page 3 of 6
Tracheal and lung tumors have been observed in Syrian golden hamsters
upon administration of dlethylnltrosamine by gavage or by inhalation (Magee
et al., 1976). Diethylnitrosamine administered to pregnant mice, rats and
hamsters has been shown to act transplacentally, inducing tumors in the
progeny (Tomatis, 1973; Mohr, 1966; Druckrey, 1973).
Peto et al. (1984) exposed groups of 48 Colworth rats/sex to diethyl-
nitrosamine in drinking water at 15 concentrations between 0.033 and 16.896
ppm. Six animals/group were sacrificed at 6 and at 12 months and the
remainder kept on treatment until natural death. Water consumption was 41
and 72 mL/kg for adult males and females. Data on tumor incidence was not
reported for each group, but data pooled by sex indicated positive trends for
tumors of the nasopharynx, lower jaw, stomach, kidney, ovaries, seminal
vesicles, liver and esophagus. Dose-related increases in incidence of upper
GI tumors and liver cell tumors were observed in C57-BO mice and tracheal and
liver cell tumors in Syrian hamsters (Peto et al., 1981).
3. SUPPORTING DATA
Diethylnitrosamine is mutagenic for S. typhimurium, E. coli and Neuro-
spora crassa, produced mltotic recombination in S. cerevisiae, recessive
lethal mutations in D. melanogaster and chromosome aberrations in mammalian
cells. Positive responses in bacterial cells are dependent upon the addi-
tion of a mammalian metabolism system (Montesano and Bartsch, 1976).
Diethylnitrosamine is structurally related to known carcinogens.
B. ORAL QUANTITATIVE ESTIMATE
Slope Factor «• 150/mg/kg/day
1. UNIT RISK SUMMARY TABLE
Water Concentrations Producing Risk Levels
E-4 E-5 E-6
Unit Risk
Model
2.3E-2
2.3E-3
2.3E-4
4.3E-3
W
extra risk
2. DOSE RESPONSE DATA
Study reference:
Species/strain;
Tumor type; Route
Admin.
Dose
Human Equiv. Tumor
Dose Incidence
(mg/kg/day)
Peto et al., 1984:
Rats/Colworth, female;
liver tumors; Drinking water
Specific tumor incidences were not
published.
Data from Peto et al. (1984) on incidence of liver tumors of all types in
female rats were shown to follow this relationship:
CI = 32.09 (d + 0.04) **4 x t**7
-------
Diethylnitrosamine: page 4 of 6
where: CI - cumulative incidence
d - dose (mg/kg/day)
t - time in years
Using procedures described in U.S. EPA (1980) to correct for background
response, the increased risk associated with exposure to 1 ug/kg/day for 3
years = 2.27E-2, corresponding to a slope factor in rats of 22.7/mg/kg/day.
The slope factor was calculated using the cube root of the ratio of the
assumed adult human weight of 70 kg and the reported rat weight of 250 g.
3. ADDITIONAL COMMENTS
Peto et al. (1984) reported liver and esophageal tumors to be the only
treatment-related cause of death. A slope factor calculated in the Ambient
Water Quality Criteria Document for Nitrosamines (U.S. EPA, 1980) based on
data of Druckrey et al. (1963) was 43/mg/kg/day. The unit risk should not be
used if the water concentration exceeds 2.3 ug/1 as above this concentration
the slope factor may differ from that stated above.
4. STATEMENT OF CONFIDENCE
Although specific incidences were not reported, it appears that large
numbers of animals were observed. Tumor induction was dose-related as
regards both numbers of animals with tumors and latency. A risk estimate
derived from a independent study was within a factor of 4. Confidence is
rated medium to high.
C. INHALATION QUANTITATIVE ESTIMATE
Slope Factor = 150/mg/kg/day
1. UNIT RISK SUMMARY TABLE
Air Concentrations Producing Risk Levels Unit Risk Model
E-4 E-5 E-6
2.3E-3
ug/cu.m
2.3E-4
ug/cu . m
2.3E-5
ug/cu . m
4.3E-2
/ug/cu . m
W
extra risk
2. DOSE RESPONSE DATA
The inhalation risk estimates were calculated from the oral exposure data
3. ADDITIONAL COMMENTS
The unit risk should not be used if the air concentration exceeds 0.2
ug/cu.m as above this concentration the slope factor may differ from that
stated above.
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Diethylnitrosamine: page 5 of 6
4. STATEMENT OF CONFIDENCE
Confidence in this inhalation risk estimate based on oral data is rated
low to medium.
D. DOCUMENTATION AND REVIEW
1. REFERENCES
U.S. EPA. 1986. Health and Environmental Effects Profile for Nitrosamines.
Prepared for the Office of Solid Waste by the Environmental Criteria and
Assessment Office, Cincinnati, OH. ECAO-CIN-P180.
Peto, R., R. Gray, P. Brantom and P. Grasso. 1984. Nitrosamine
carcinogenesis in 5120 rodents: Chronic administration of 16 different
concentrations of NDEA, NDMA, NPYR and NPIP in the water of 4440 inbred rats,
with parallel studies on NDEA alone of the effect of age of starting (3, 6 or
20 weeks) and of species (rats, mice or hamsters). IARC Sci. Publ. 57:
627-665.
2. REVIEW
The values in the Health and Environmental Effects Profile for Nitro-
samines (U.S. EPA, 1986) received Agency review.
Agency CRAVE Work Group Review: 07/23/86, 08/13/86, 10/29/86
Verification Date: 10/29/86
3. U.S. EPA CONTACTS
Primary: J.H. Holder (202/FTS) 382-5721
Office of Research and Development
Secondary: C.H. Ris (202/FTS) 382-7338
Office of Research and Development
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Diethylnitrosamine
CAS No.: 55-18-5
Information is not available at this time.
-------
Diethylnitrosamine: page 6 of 6
IV. RISK MANAGEMENT SUMMARIES
Chemical: Diethylnitrosamine
CAS No.: 55-18-5
In preparation
V. SUPPLEMENTARY DATA
Chemical: Diethylnitrosamine
CAS No.: 55-18-5
Information is not available at this time.
Synonyms: diethylamine, N-nitroso; DANA: DEN; DENA; diethylnitrosoamine;
N,N-diethylnitrosamine; diaethylnitrosamin (German); ethylamine, N-nitrosodi-;
N-ethyl-N-nitroso-ethanamine; NDEA; nitrosodiethylamine;
N-nitrosodiethylamine; RCRA waste number U174
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Dimethoate; CAS No. 60-51-5 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet-undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Dimethoate
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: review pending
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Dimethoate: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Dimethoate
CAS No.: 60-51-5
Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Decreases in chol-
inesterase (ChE)
activity
Short-term feeding
study in humans
Edson et al. (1967)
NOEL: 0.2 mg/kg/day
LOAEL: 0.4 mg/kg/day
10 1 2E-2
mg/kg/day
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Edson, E.F., K.H. Jones and W.A. Watson.
ticide. Br. J. Med. 4: 554-555.
1967. Safety of dimethoate insec-
Thirty-six male and female adult volunteers without occupational exposure
to organophosphate insecticides were arranged in groups and given repeated
doses of dimethoate. The dimethoate was administered as a flavored aqueous
solution. Venous blood samples were taken twice before and once or twice/
week after dimethoate dosage started. ChE in whole blood was measured and its
depression taken as the critical first response to dimethoate. Activities in
red cells and plasma were also determined separately. The study was performed
under close medical supervision, and inquiry was also made for any effects
other than ChE depression, though none was detected.
The results show that no significant change occurred with 0.068 or 0.202
mg/kg/day. ChE values at 0.434 mg/kg/day began to show a slow downward trend
-------
DImethoate: page 3 of 7
by day 20, and this continued to the end of the test at 57 days. Higher doses
snowed the same effects at an earlier stage, and a somewhat faster rate. The
rate and extent of red cell ChE depression closely paralleled those of
whole-blood ChE. No localized gastrointestinal or other clinical effects
occurred in any group.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 10. The uncertainty factor of 10 accounts for the expected interhuman
variability to the toxicity of this chemical in lieu of specific data. An
additional uncertainty factor of 10-fold to adjust the results found after
short-term to chronic exposures is not considered necessary here because the
critical toxic effect, Cholinesterase inhibition, is immediate and occurs
regardless of exposure duration.
MF = 1
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: High Data Base: High RfD: High
The study is given a confidence rating of high because it was conducted in
humans with a fair amount of subjects at each of five doses. Cholinesterase
inhibition, the critical toxic effect, was measured. The supporting animal
data base is given a confidence rating of high because it is extensive and
yields similar RfD values. High confidence in the RfD follows.
6. DOCUMENTATION AND REVIEW
The ADI has been through the Registration Standard process of the OFF.
Gessert, R.A. 1982. Memorandum to P. Parsons. Dimethoate Registration
Standard; Toxicology Assessment. Office of Pesticide Programs, U.S. EPA,
Washington, DC, August 31.
Agency RfD Work Group Review: 07/08/85, 07/22/85
Verification Date: 07/22/85
7. U.S. EPA CONTACTS
Primary: R. Engler FTS/537-7490 or 202/557-7490
Office of Pesticide Programs
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
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DImethoate: page A of 7
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Dimethoate
CAS No.: 60-51-5
Information is not available at this time.
Chemical:
CAS No.:
II. RISK ESTIMATES FOR CARCINOGENS
Dimethoate
60-51-5
This chemical is among those substances evaluated by the U.S. EPA for
evidence of human carcinogenic potential. This does not imply that this
chemical is necessarily a carcinogen. The evaluation for this chemical is
under review by an inter-office Agency work group. A risk assessment summary
will be included on IRIS when the review has been completed.
III. DRINKING WATER HEALTH ADVISORIES
Chemical:
CAS No.:
Dimethoate
60-51-5
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical:
CAS No.:
Dimethoate
60-51-5
Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
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Dimethoate: page 5 of 7
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background Information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
10 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Pesticide Active
Ingredient:
a. Registration Current
Standard 1983
b. Special Final
Review 1981
Position
Document 1
P.O. 2, 3
P.O. 4
no
no
yes
yes
see B.S.a below
42 FR 45086
09/12/77
44 FR 665580
11/19/79
46 FR 5334
01/19/81
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity. Available data indicate that
the aquatic 96-Hour Median Threshold Limit for dimethoate is less than 1 ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
Pesticide Active Ingredient
a. Registration Standard: Dimethoate Pesticide Registration Standard. March
1983. Registration Support and Emergency Response Branch, Office of
Pesticide Programs.
Contact: Office of Pesticide Programs
202/557-7760 or FTS/557-7760
b. Special Review: For specific details on the Special Review process for
this active Ingredient please check the references provided.
Contact: Office of Pesticide Programs, Special Review Branch
202/557-7420 or FTS/557-7420
-------
Dimethoate: page 6 of 7
V. SUPPLEMENTARY DATA
Chemical: Dimethoate
CAS No.: 60-51-5 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Dimethoate is very toxic; the probable oral lethal dose in humans is
between 50-500 mg/kg, or between 1 teaspoon and 1 ounce for a 70-kg (150-lb.)
person. Dimethoate is a cholinesterase inhibitor, meaning it affects the
central nervous system. Death is due to respiratory arrest arising from
failure of respiratory center, paralysis of respiratory muscles, intense
bronchoconstriction or all three (Gosselin, 1976).
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Nausea, excessive salivation, sweating,
visual disturbances, headache and fatigue are common symptoms. A running
nose and sensation of tightness in the chest are common in inhalation
exposures. In severe poisonings, loss of muscular coordination and
convulsions can occur (Gosselin, 1976; Morgan, 1982). Difficulty in
breathing, frothing of the mouth and nose, and mental confusion may also be
noted (Gosselin, 1976). Symptoms from dimethoate poisoning are similar to
other organophosphorus insecticides, but may develop more slowly (Encyc
Occupat Health and Safety, 1983).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: C H NO PS
5 12 3 2
Molecular Weight: 229.28
Boiling Point: Not Found
Specific Gravity (H20=l): 1.277 at 65C
Vapor Pressure (mmHg): 8.5 x 10-6 at 77F
Melting Point: 125F, 52C, 113-117F, 45-47C for
technical product
Vapor Density (AIR=1): Not Found
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: 2-3 g/100 ml
Flash Point [Method Used]: 124F (CC)
Flammable Limits: Not Found
Appearance and Odor: A white crystalline solid (Spencer, 1982) with a
camphor-like odor (Worthing, 1979); white to greyish crystals for technical
product (Worthing, 1983)
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Dimethoate: page 7 of 7
Conditions or Materials to Avoid: The temperature of storage should not
exceed 70-80F. Keep away from sources of heat, flames, or spark-generating
equipment (Farm Chemicals Handbook, 1983). Dimethoate is unstable in
alkaline solution. Dimethoate is hydrolyzed by aqueous alkali and is stable
in aqueous solutions. The compound is stable for 2 years under environmental
conditions if stored in undamaged, original containers (Spencer, 1973).
Hazardous Decomposition or Byproducts: Not Found
Use: Dimethoate is a contact and systemic organophosphate insecticide that
is effective against a broad range of insects and mites when applied on a
wide range of crops (Worthing, 1979; SRI; White-Stevens, 1971). It has not
been produced in the U.S. since 1982 (SRI).
Synonyms: 8014 Bis HC; Acetic Acid, 0,0-Dimethyldithiophosphoryl-, N-Mono-
methylamide Salt; American Cyanamid 12,880; BI 58; CL 12880; Cygon; Cygon 4E;
Cygon Insecticide; Daphene; De-Fend; Demos-LAO; Dimethogen; Dimeton; Dimevur;
ENT 24650; Experimental Insecticide 12,880; FIP; Fosfotox; Fosfotox R; Fosfoto
R 35; Fostion MM; Lurgo; NCI-C00135; 0,0-Dimethyl S-(N-Methyl- carbamoylmethyl
Dithiophosphate; 0,0-Dimethyl S-(N-Methylcarbamoylmethyl) Phosphorodithioate;
0,0-Dimethyl S-Methylcarbamoylmethyl Phosphorodithioate;
0,0-Dimethyldithiophosphorylacetic Acid, N-Monomethylamide Salt; PEI 75;
Perfecthion; Perfekthion; Phosphamid; Phosphamide; Phosphorodithioic Acid
0,0-Dimethyl Ester, Ester With 2-Mercapto-N-Methylacetamide; Phosphor-
odithioic Acid, 0,0-Dimethyl S-(2-(Methylamino)-2-Oxoethyl) Ester; Racusan;
Rogor; Rogor 20L; Rogor 40; Rogor L; Rogor P; Roxion; S-Methylcarbamoylmethyl
0,0-Dimethyl Phosphorodithioate; Sinoratox; Systoate
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Dimethyldoorknob (DMDK); CAS No. 98765-43-2 (Revised 04/31/99)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups composed
of U.S. EPA scientists from several Agency Program Offices. The summaries
presented in Sections I and II represent a consensus reached in those
reviews. The conceptual bases of these risk assessments are described in
Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Dimethyldoorknob
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: available
III. Drinking Water Health Advisories: available
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Dimethyldoorknob: page 2 of 9
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: DimethyIdoorknob (DMDK)
CAS No.: 98765-43-2
Preparation Date: 04/31/99
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Kidney and liver
changes
Rat inhalation, 7
months at 8 hours/
day, 5 days/week
cummings (1937)
NOAEL: 70 ppm
inhalation con-
verted to an oral
dose of 19.4
mg/kg/day
LOAEL: 230 ppm
1,000
2E-2
mg/kg/day
* Dose Conversion Factors & Assumptions: 70 ppm — 475 mg/cu. m x 1 cu.
m/hour (assumed ventilation rate) x 8 hours/day x 5 days/7 days x 0.5
(assumed inhalation retention factor)/70 kg (assumed human body weight)
19.4 mg/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
cummings, e.e.
and toxicol.
1937. the chronic toxicity of dimethyldoorknob. j. ind. hyg.
cummings (1937) exposed groups of 24 rats (12/sex) to 1 of 3 doses by
inhalation for 8 hours/day, 5 days/week for 7 months. No significant changes
were observed at the low dose of 70 ppm. At 230 ppm, renal congestion and
swelling were noted. At 470 ppm, the liver also was congested and exhibited
cloudy swelling, which remained for 46 days after termination of exposure.
The kidney showed increased secretion, cloudy swelling and desquamation; the
spleen was congested and showed an increase in pigment content.
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Dimethyldoorknob: page 3 of 9
3. UNCERTAINTY AND MODIFYING FACTORS
UF =1,000. The uncertainty factor of 1,000 reflects 10 for both intraspecies
and interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation of a subchronic effect level to its
chronic equivalent.
MF = 1
4. ADDITIONAL COMMENTS
Adequate oral data could not be found.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: High RfD: Medium
Confidence in the chosen study is medium because, while only a small
number of animals/sex were tested at each dose, the number of parameters
measured was large. Confidence in the supporting data base is high to medium
because several inhalation studies support the chosen effect level. Medium to
high confidence in the RfD normally would follow, but medium is chosen because
the data are from inhalation exposures.
6. DOCUMENTATION AND REVIEW
U.S. EPA. Drinking Water Criteria Document for Dimethyldoorknob. Office
of Drinking Fountains, Washington, DC. (1985).
Extensive internal and Steering Committee review. Public
comment period was June 12 to September 15.
Agency RfD Work Group Review: 02/30/99
Verification Date: 02/30/99
7. U.S. EPA CONTACTS
Primary: F.S. Fitzgerald FTS/555-1212 or 202/555-1212
Office of Drinking Fountains
Secondary: E. De Valera FTS/555-1212 or 513/555-1212
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Dimethyldoorknob (DMDK)
CAS No.: 98765-43-2
Information is not available at this time.
-------
Dimethyldoorknob: page 4 of 9
Chemical: Dimethyldoorknob (DMDK)
CAS No.: 98765-43-2
II. RISK ESTIMATES FOR CARCINOGENS
Preparation Date: 06/31/99
A. U.S. EPA CLASSIFICATION AND BASIS
Classification: B2, probable human carcinogen; insufficient human data,
sufficient animal data.
1. HUMAN DATA
Inadequate
2. ANIMAL DATA
Hepatocellular carcinomas in male and female mice via gavage.
3. SUPPORTING DATA
Evidence for significant macromolecular covalent binding to protein, less
significant to DNA.
B. ORAL QUANTITATIVE ESTIMATE
Slope Factor = 5.lE-2/mg/kg/day
1. UNIT RISK SUMMARY TABLE
Water Concentrations
E-4 E-5
Producing Risk Levels
E-6
Unit Risk
(/ug/1)
1.5E-6
Model
LM
2. DOSE RESPONSE DATA
Study reference:
Species/strain
Tumor type ; Route
Admin. Dose
(mg/kg/day)
MCI, 1999: (untreated) 0
Mouse/B6C2Fl, female (vehicle) 0
hepatocellular carcinoma; 31.07
gavage 45.39
Metabolized
Dose
(mg/kg/day)
0
0
386
772
Tumor
Incidence
2/20
0/20
19/48
19/48
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DImethyldoorknob: page 5 of 9
3. ADDITIONAL COMMENTS
Metabolized dose was estimated by application of urinary excretion data
of Babbit and Lewis (1999).
4. STATEMENT OF CONFIDENCE
none
C. INHALATION QUANTITATIVE ESTIMATE
Slope Factor = 2.5E-l/mg/kg/day
1. UNIT RISK SUMMARY TABLE
Air Concentrations Producing Risk Levels
E-4 E-5 E-6
Unit Risk
(/ug/cu. m)
Model
4.8E-7
LM
2. DOSE RESPONSE DATA
The slope factor was calculated from oral data using metabolized dose as
estimated from Babbit and Lewis (1985) data. The unit risk was calculated on
the basis of body burden derived from human data (Barishnokov & Nuryev, 1972).
3. ADDITIONAL COMMENTS
none
4. STATEMENT OF CONFIDENCE
none
D. DOCUMENTATION AND REVIEW
1. REFERENCES
MCI. 1999. Bioassay of dimethyldoorknob for possible carcinogenicity.
U.S. EPA 1999. Health Assessment Document for Dimethyldoorknob. Prepared by
the Environmental Criteria and Assessment Office, RTP, NC.
2. REVIEW
The values in the Health Assessment document for dimethyldoorknob
received both Agency and external review.
-------
Dimethyldoorknob: page 6 of 9
Agency CRAVE Work Group Review: 04/31/99
Verification Date: 04/31/99
3. U.S. EPA CONTACTS
Primary: S. Sales (202/FTS) 555-0000
Office of Research and Development
Secondary: M. Goodbar (202/FTS) 555-0001
Office of Research and Development
Chemical: Dimethyldoorknob (DMDK)
CAS No.: 98765-43-2
III. DRINKING WATER HEALTH ADVISORIES
Preparation Date: 06/31/99
A. HEALTH ADVISORY VALUES
1. SUMMARY TABLE
Type
1-day (child)
10-day (child)
Longer term
(child)
Longer term
(adult)
Lifetime
Dexp UF Value Basis
(mg/kg/day) (ug/1)
none
340
19.4
19.4
(NOEL) 100 34,000 Johnson et al . , 1999
(NOEL) 100 1940 Doe et al . , 1999
(NOEL) 100 6800 Doe et al . , 1999
none
2. STANDARD CALCULATIONS AND ASSUMPTIONS
All Health Advisories (HAs) except the Lifetime HA do not assume exposure
by any other route (i.e., 100% of exposure to this substance is by drinking
water) and are calculated according to the equation:
HA = 1000 x Dexp x BW / WC / UF,
where 1000 = conversion from mg to ug,
Dexp = the experimentally determined NOEL, NOAEL or LOAEL (in
mg/kg-day) judged most appropriate for derivation of the
specific HA,
BW = standard reference value for human body weight
(10 kg for a child; 70 kg for an adult),
WC = standard reference value for human water consumption
(1 liter/day for a child; 2 liters/day for an adult),
UF = uncertainty factor judged appropriate for the quantity and
quality of the available data.
-------
Dimethyldoorknob: page 7 of 9
Lifetime HAs are based on the Oral Reference Dose (RfD) and assume that
only 20% of total compound intake is by drinking water. Lifetime HAs can be
derived by the equation:
HA - 1000 x Dexp / (UF x MF) x BW / WC x 0.2,
where the constants and variables are the same as for other HAs except that
Dexp is the experimentally determined NOEL, NOAEL or LOAEL (in mg/kg-day)
from which the RfD is derived, MF is the modifying factor as described in
the Oral RfD section, and 0.2 is the assumed fraction of exposure due to
drinking water ingestion.
B. EXPERIMENTAL BASIS
1. ONE-DAY HEALTH ADVISORY
Appropriate data for calculating a One-day HA are not available.
2. TEN-DAY HEALTH ADVISORY
Johnson, J., R. Jones and H. Smith. 1999. Effects of dimethyldoorknob on
Canadian rat livers. J. Can. Rats 99: 567489-985746.
Increased liver/body weight ratios were observed in male rats after
10 daily oral doses of DMDK at levels greater than 340 mg/kg.
3. LONGER-TERM HEALTH ADVISORIES
Doe et al. 1999. Toxicity of DMDK in non-Canadian rats. Rats! 1: 1-10.
DMDK was fed to rats by diet at levels of 19.4 and 194,000 mg/kg/day for
90 days. All rats fed the higher dose moved to Canada. No effects were
observed at the low dose.
4. LIFETIME HEALTH ADVISORY
none
C. ADDITIONAL INFORMATION
1. DETECTION AND TREATMENT
undetectable
2. DOCUMENTATION AND REVIEW
U.S. EPA. 1999. Drinking Fountain Criteria Document on DMDK. Office of
Drinking Fountains, Washington, D.C.
EPA review of Health Advisories in 1999.
Public review of HAs following notification of unavailability in Jan., 1999.
3. U.S. EPA CONTACT
Dr. Who FTS/182-7347
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Dimethyldoorknob: page 8 of 9
IV. RISK MANAGEMENT SUMMARIES
Chemical: Dimethyldoorknob (DMDK)
CAS No.: 98765-43-2
Preparation Date: 04/31/99
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (In sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Statutory
1980
Risk
Management
Value
1 Ib.
Considers
Econ/Tech
Feasibility
no
Reference
98 FR 11111
11/31/98
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
2) Marine
Final
1980
Clean Air Act
Regulatory
Decision:
Nat. Emissions
Standards for
Hazardous Air
Pollutants (NESHAP)
Current
1985
0.80 ppb no
Acute no
5280 ug/1
Chronic
840 ug/1
Acute no
10,280 ug/1
Chronic
450 ug/1
Under no
development
99 FR 000
ibid.
ibid.
97 FR 1234567
00/00/00
-------
Dimethyldoorknob: page 9 of 9
B. RISK MANAGEMENT RATIONALE
RQ
The CERCLA statutory RQ is subject to adjustment when assessment of
carcinogenicity is completed.
Contact: RCRA/Superfund Hotline
WQC
Contact: Office of Water Regulations and Standards
a. Human health: Dimethyldoorknob is classified as a carcinogen, and under
the assumption of no threshold for a carcinogen, the recommended WQC is zero.
However, if zero cannot be obtained and exposure is via ingestion of water
and aquatic organisms, 0.8 ug/1 is associated with an upper-bound excess
lifetime risk of l.OE-6 [other upper bound risk levels to consider: l.OE-5
(8.0 ug/1) and l.OE-7 (0.08 ug/1)]. If exposure is only via ingestion of
aquatic organisms, the WQC associated with an excess lifetime risk of l.OE-6
is 8.85 ug/1.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The data are assumed to be statistically
representative and are used to calculate concentrations which will not have
significant short or long term effects on 95% of the organisms exposed.
Recent criteria (1985 and later) contain duration and frequency stipulations:
the acute criteria maximum concentration is a 1-hour average and the chronic
criteria continuous concentration is a 4-day average which are not to be
exceeded more than once every three years, on the average (see Stephen et al.
1985). Earlier criteria (1980-1984) contained instantaneous acute and
24-hour average chronic concentrations which were not to be exceeded.
CAA Regulatory Decision
NESHAP
Dimethyldoorknob (DMDK) is a probable human carcinogen (EPA Group B2) and
according to EPA's preliminary risk assessment from ambient air exposures,
public health risks are significant (5.3 cancer cases per year and maximum
lifetime individual risks of 1.5 x 10-4). Thus, EPA indicated that it
intends to add DMDK to the list of hazardous air pollutants for which it
intends to establish emission standards under section 112(b)(l)(A) of the
Clean Air Act. The EPA will decide whether to add DMDK to the list only
after studying possible techniques that might be used to control emissions
and further assessing the public health risks. The EPA will add DMDK to the
list if emission standards are warranted.
Contact: Chief, Pollutant Assessment Branch
V. SUPPLEMENTARY DATA
Chemical: Dimethyldoorknob (DMDK)
CAS No.: 98765-43-2
Information is not available at this time.
Synonyms: Doorknob, dimethyl; DMDK
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Dimethylnitrosamine; CAS No. 62-75-9 (Revised 12/24/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Dimethylnitrosamine
I. Chronic Systemic Toxlcity: Noncarcinogenic Health Effects
A. Oral RfD: none
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: available
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: in preparation
V. Supplementary Data: available
-------
DimethyInitrosamine: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: DimethyInitrosamine
CAS No.: 62-75-9
Information is not available at this time.
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: DimethyInitrosamine
CAS No.: 62-75-9
Information is not available at this time.
—_.— .
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: DimethyInitrosamine
CAS No.: 62-75-9 Preparation Date: 12/24/86
A. U.S. EPA CLASSIFICATION AND BASIS
Classification: B2, probable human carcinogen, based on induction of tumors
at multiple sites in both rodents and nonrodent mammals
exposed by various routes.
1. HUMAN DATA
Human exposure to nitrosamines results from contact with mixtures con-
taining these compounds (e.g., cutting oils, tobacco products). Because of
potential confounding by the other substances in these mixtures, data is of
limited use in the evaluation of carcinogenicity of individual nitrosamines.
2. ANIMAL DATA
There is a large data base on the carcinogenicity of nitrosamines, most
of which pertains to structure-activity relationships rather than to dose-
response. Dimethylnitrosamine produced liver tumors in BD rats when admin-
istered in drinking water (Druckrey, 1967) and in female Porton rats when
administered in the diet (Terracini et al., 1967). Magee et al. (1976)
state that dimethylnitrosamine produced many hemangiomatous tumors and some
parenchymal cell tumors in the livers of rats after oral administration.
-------
Dimethylnitrosamine: page 3 of 7
Dlmethylnitrosamine acts as a transplacental carcinogen when admin-
istered to pregnant rats, mice and Syrian golden hamsters by several routes
(Tomatis, 1973). Increases in lung, liver and kidney tumors were observed in
both Wistar rats and Balb/C mice exposed by inhalation. Mink are very
sensitive to the effects of dimethylnitrosamine, developing tumors when fed
0.05 mg/kg 2 days/week (NAS, 1978).
Peto et al. (1984) exposed groups of 36 each male and female Colworth
rats to 15 concentrations of dimethylnitrosamine in drinking water
(0.033-16.896 ppm). Daily water consumption was 41 ml/kg for males and 72
ml/kg for females. Tumors were generally of hepatic origin and these tumors
constituted the only cause of mortality considered to be treatment related.
Tumor incidences for each treatment group were not reported, but pooled data
indicated possible positive trends for tumors of lung, skin, seminal vesicle,
lymphatic/hematopoetic system and liver.
3. SUPPORTING DATA
Dimethylnitrosamine is mutagenic for E. coli, S. typhimurium and Neuro-
spora crassa, produces mitotic recombination in S. cerevesiae, recessive
lethal mutations in D. melanogaster and chromosomal aberrations in mammalian
cells. Positive responses in bacterial cells are dependent upon the addi-
tion of a mammalian metabolism system (Montesano and Bartsch, 1976).
Dimethylnitrosamine is structurally related to known carcinogens.
B. ORAL QUANTITATIVE ESTIMATE
Slope Factor = 51/mg/kg/day
1. UNIT RISK SUMMARY TABLE
Water Concentrations Producing Risk Levels
E-4 E-5 E-6
Unit Risk
Model
6.9E-2
6.9E-3
6.9E-4
1.4E-3 W
extra risk
2. DOSE RESPONSE DATA
Study reference:
Species/strain;
Tumor type; Route
Admin.
Dose
Human Equiv.
Dose
(mg/kg/day)
Tumor
Incidence
Peto et al., 1984:
Rats/Colworth, female;
liver tumors; Drinking water
Specific tumor incidences were not
published.
Data from Peto et al. (1984) on incidence of liver tumors of all types in
female rats were shown to follow this relationship:
CI = 51.45 (d + 0.1) **6 x t**7
-------
Dimethylnitrosamine: page 4 of 7
where: CI - cumulative incidence
d - dose (mg/kg/day)
t «• time in years
Using procedures described in U.S. EPA (1980) to correct for background
response, the increased risk of 1 ug/kg/day for 3 years = 7.8E-3 or a slope
factor for rats of 7.8/mg/kg/day. The slope factor was thus calculated to
be 51/mg/kg/day by using the cube root of the ratio of the assumed human
body weight of 70 kg and the reported rat body weight of 250 g.
3. ADDITIONAL COMMENTS
A slope factor based on data by Druckrey et al. (1972) was determined to
be 26/mg/kg/day in the 1980 Ambient Water Quality Criteria Document for
Nitrosamines. The unit risk should not be used if the water concentration
exceeds 7.1 ug/1 as above this concentration the slope factor may differ from
that stated above.
4. STATEMENT OF CONFIDENCE
Although specific tumor incidence data was not reported, it appears that
large numbers of animals were treated over a wide dose range. Both tumor
incidence and latency were shown to be dose-dependent. As the risk estimate
is supported by the data of Druckrey (1967), confidence is rated medium to
high.
C. INHALATION QUANTITATIVE ESTIMATE
Slope Factor = 51/mg/kg/day
1. UNIT RISK SUMMARY TABLE
Air Concentrations Producing Risk Levels Unit Risk Model
E-4 E-5 E-6
6.9E-3 6.9E-4 6.9E-5 1.4E-2 W
ug/cu.m ug/cu.m ug/cu.m /ug/cu.m extra risk
2. DOSE RESPONSE DATA
The inhalation risk estimates were calculated from the oral exposure data.
3. ADDITIONAL COMMENTS
The above unit risk should not be used if the air concentration exceeds
0.7 ug/cu.m as above this concentration the slope factor may differ from
that stated above.
-------
Dimethylnitrosamine: page 5 of 7
4. STATEMENT OF CONFIDENCE
Confidence in this inhalation risk estimate based on oral data is rated
medium.
D. DOCUMENTATION AND REVIEW
1. REFERENCES
U.S. EPA. 1986. Health and Environmental Effects Profile for Nitrosamines.
Prepared for the Office of Solid Waste by the Environmental Criteria and
Assessment Office, Cincinnati, OH. ECAO-CIN-P180.
Peto, R., R. Gray, P. Brantom and P. Grasso. 1984. Nitrosamine
carcinogenesis in 5120 rodents: Chronic administration of 16 different
concentrations of NDEA, NDMA, NPYR and NPIP in the water of 4440 inbred rats,
with parallel studies on NDEA alone of the effect of age of starting (3, 6 or
20 weeks) and of species (rats, mice or hamsters). IARC Sci. Publ. 57:
627-665.
2. REVIEW
The values in the Health and Environmental Effects Profile for Nitro-
samines (U.S. EPA, 1986) received Agency review.
Agency CRAVE Work Group Review: 06/26/86, 08/13/86, 10/29/86
Verification Date: 10/29/86
3. U.S. EPA CONTACTS
Primary: J.H. Holder (202/FTS) 382-5721
Office of Research and Development
Secondary: C.H. Ris (202/FTS) 382-7338
Office of Research and Development
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Dimethylnitrosamine
CAS No.: 62-75-9
Information is not available at this time.
-------
Dimethylnitrosamine: page 6 of 7
IV. RISK MANAGEMENT SUMMARIES
Chemical: Dimethylnitrosamine
CAS No.: 62-75-9
in preparation
V. SUPPLEMENTARY DATA
Chemical: Dimethylnitrosamine
CAS No.: 62-75-9 Preparation Date: 12/24/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user Is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Dimethylnitrosamine is characterized as having extremely high toxicity
(Sunshine 1969). The lowest lethal oral dose In humans has been reported at
10 mg/kg/80 week intermittent exposure (NIOSH/RTECS 1985) .
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Symptoms include nausea, vomiting and
malaise (Cooper, 1980).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: C H N 0
262
Molecular Weight: 74.08
Boiling Point: 304-307F, 151-153C
Specific Gravity (H20=l): 1.0048 at 20C/4C
Vapor Pressure (mmHg): Not Found
Melting Point: Not Found
Vapor Density (AIR=1): Not Found
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: Very soluble
Flash Point (Method Used): Not Found
Flammable Limits:
LEL: Not Found
UEL: Not Found
-------
DimethyInitrosamine: page 7 of 7
Appearance and Odor: Yellow oily liquid; faint characteristic odor.
Conditions to Avoid: Avoid exposure to ultraviolet light (Clayton and
Clayton 1981, p. 3119).
Hazardous Decomposition or Byproducts: When heated to decomposition, it
emits toxic fumes of nitrogen oxides (Sax 1984, pp. 1180-1181).
Use: DimethyInitrosamine was formerly used in the production of rocket
fuels. It is presently used as an antioxidant, as an additive for lubricants
and as a softner of copolymers (Merck, 1983, p. 952). It is an intermediate
for 1,1-dimethylhydrazine (SRI).
Synonyms: dimethylamine, N-nitroso; DMNA: DMN; NDMA; dimethyInitrosoamine;
N,N-dimethyInitrosamine; dimethylnitrosamin (German); methylamine,
N-nitrosodi-; N-methyl-N-nitrosomethanamine; nitrosodimethylamine;
N-nitrosodimethylamine; RCRA waste number P082
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Dimethyl Terephthalate; CAS No. 120-61-6 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Dimethyl Terephthalate
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: none
V. Supplementary Data: none
-------
Dimethyl Terephthalate: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Dimethyl Terephthalate
CAS No.: 120-61-6
Preparation Date: 04/17/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Chronic kidney in-
flammation
Experimental Doses *
NOEL: None
UF
1000
MF
1
RfD
1E-1
ing/kg/day
Rat chronic dietary
study
NCI (1979)
2500 ppm of
diet (125 mg/kg bw/
day)
* Dose Conversion Factors & Assumptions:
be 5% of bw/day
Rat food consumption assumed to
2. PRINCIPAL AND SUPPORTING STUDIES
NCI (National Cancer Institute). 1979. Bioassay of dimethyl terephthalate
for possible carcinogenicity. DHEW/PUB/NIH 79-1376, NCI-CG-TR121.
In the NCI (1979) study mice and rats (50/sex/group) were fed dimethyl
terephthalate (DMT) at levels of 0, 2500 and 5000 ppm (diet) for 103 weeks.
A small but dose-related increase in the incidence of chronic kidney
inflammation was shown for male mice and female rats; the incidence for male
mice was 2/49, 4/49 and 11/49, and for female rats was 3/49, 5/49 and 8/49
for the control, low-dose and high-dose groups, respectively. Statistics were
not given. Subchronic preliminary studies showed mild liver effects but no
indication of kidney toxicity. The rat LOAEL is used since it is lower in
mg/kg bw/day than the mouse LOAEL (125 vs. 325 mg/kg/day, respectively).
Krasavage et al. (1973) reported a statistically significant decrease in
body weight gain for male Long-Evans rats fed DMT at about 1000 mg/kg/day for
-------
Dimethyl Terephthalate: page 3 of 5
96 days. Dose levels of 250 and 500 mg/kg/day DMT reduced body weight gain
slightly, but the reductions were not statistically significant. Hematologi-
cal, clinical chemistry, liver and kidney weight and histopathological param-
eters were similar in all treated and control animals. Krasavage et al.
(1973) also reported significantly reduced weight of offspring at weaning for
rats fed DMT at 500 and 1000 mg/kg bw/day for 2-3 months. No effects were
observed at 250 mg/kg bw/day.
Short-term studies in rats have shown that levels of about 500-1000
mg/kg/day DMT are associated with urinary acidosis and attendant calciuria.
DMT at 1500 mg/kg/day is associated with the induction of bladder stones. No
other information on the chronic toxicity of DMT was found.
The interpretation of the NCI (1979) data as evidence of dose-related
effects for kidney inflammation is weakened by the low number of doses and
magnitude of response and the lack of statistical support. However, the
effect is observed in two species, and short-term studies show urinary tract
effects at higher doses.
3. UNCERTAINTY AND MODIFYING FACTORS
UF =» 1000. The UF of 1000 includes uncertainties in the following areas:
extrapolation of experimental animal data to man, the range of human
sensitivity, and extrapolation from a LOAEL to a hypothetical NOEL.
MF = 1
4. ADDITIONAL COMMENTS
Data adequately assessing the teratogenic potential of DMT are not found.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The medium confidence level assigned to the critical study reflects both
the strengths (large number of animals, extensive histopathology, length of
study) and the weaknesses (lack of other toxicological parameters, limited
dose range) inherent to a study primarily designed to assess carcinogenic
potential. The data base is rated "medium" because of the general trend of
the magnitude of effect levels from short-term through chronic exposure, even
though the type of effect varies. Overall confidence in the RfD is medium to
low because of the equivocal nature of the critical study results.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1984. Health and Environmental Effects Profile for Dimethyl Tere-
phthalate. Environmental Criteria and Assessment Office, Cincinnati, OH.
ECAO-CIN-P037.
The ADI in the 1984 Health and Environmental Effects Profile has received an
Agency review with the help of two external scientists.
Agency RfD Work Group Review: 10/09/85
Verification Date: 10/09/85
-------
Dimethyl Terephthalate: page 4 of 5
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Dimethyl Terephthalate
CAS No.: 120-61-6
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Dimethyl Terephthalate
CAS No.: 120-61-6
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Dimethyl Terephthalate
CAS No.: 120-61-6
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Dimethyl Terephthalate
CAS No.: 120-61-6
Information is not available at this time.
-------
Dimethyl Terephthalate: page 5 of 5
V. SUPPLEMENTARY DATA
Chemical: Dimethyl Terephthalate
CAS No.: 120-61-6
Information is not available at this time.
Synonyms: TEREPHTHALIC ACID, DIMETHYL ESTER; 1,4-BENZENEDICARBOXYLIC ACID,
DIMETHYL ESTER (9CI); DIMETHYL 1,4-BENZENEDICARBOXYLATE; DIMETHYLESTER
KYSELINY ISOFTALOVE (Czech); DIMETHYL p-PHTHALATE; DIMETHYL TEREPHTHALATE;
DMT; METHYL 4-CARBOMETHOXYBENZOATE; NCI-C50055; TEREPHTHALIC ACID METHYL ESTER
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Dinitrochickenwire (DNCW); CAS No. 12345-67-8 (Revised 02/30/99)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Dinitrochickenwire
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: review unlikely
III. Drinking Water Health Advisories: available
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Dinitrochickenwire: page 2 of 9
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD Is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenlc health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Dinitrochickenwire (DNCW)
CAS No.: 12345-67-8
Preparation Date: 02/30/99
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Liver and kidney
pathology
Rat oral chronic
study
3 mg/kg/day (NOAEL)
10 mg/kg/day (LOAEL)
100
3E-2
mg/kg/day
Shakespeare et al. (1978)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Shakespeare, W., F. Quack, J. Keats, E. Hemingway and J. Keroac.
Results of 2-year toxicity and reproduction studies on dinitrochickenwire in
rats. In: Dinitrochickenwire: Chemistry, Cosmetology and Environmental
Psychology, E.O'Neil, Ed. Rat Pellet Press, NY. p. 301 (1978).
Only one chronic study regarding oral exposure (Shakespeare et al., 1978)
was located in the available literature. Twenty-five rats/sex were
administered 1 of 3 doses In the diet. At the 30 mg/kg/day level of
treatment, a reduced rate of body weight gain and increased specific gravity
of the urine were observed in females. Pigmentation of the liver and kidneys
was observed in females exposed at 10 mg/kg/day or higher levels and in males
exposed to 30 mg/kg/day. The 3 mg/kg/day level of exposure was reported as a
chronic NOEL.
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Dinttrochickenwire: page 3 of 9
A number of studies that have Investigated the teratogenicity of orally
administered dinitrochickenwire in rodents are available in the literature.
Although these studies (Johnson and Boswell, 1973; Shakespeare et al.,
1978; Machiavelli, 1973) did not reveal teratogenic effects, feto-maternal
toxicity was seen at 30 mg/kg/day (Johnson and Boswell, 1973). Since
dinitrochickenwire apparently does not cross the placental barrier, the
observed fetotoxicity may be a reflection of maternal toxicity.
The NOAEL in these studies was concluded to be 3.0 mg/kg/day
which is the same as for the chronic study reported earlier.
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 100. The 100-fold factor accounts for the expected intra- and Inter-
species variability to the toxicity of this chemical in lieu of specific data.
MF = 1
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: High Data Base: Medium RfD: Medium
The confidence in the chosen study is rated high because a moderate number
of animals/sex were used in each of three doses, a comprehensive analysis of
parameters was conducted, and a reproductive study was also run. Confidence
in the supporting data base is rated medium because only one chronic study is
available. Other subchronic studies provide adequate but weaker supporting
data. The confidence In the RfD is medium. More chronic/reproductive studies
are needed to provide a higher confidence In the RfD.
6. DOCUMENTATION AND REVIEW
U.S. EPA. Health Effects Assessment for Dinitrochickenwire. Environmental
Criteria and Assessment Office, Cincl, OH.
Limited Peer Review and Agency-wide Internal Review.
U.S. EPA. Drinking Water Criteria Document for Dinitrochickenwire. Office of
Drinking Fountains, Washington, DC.
Agency RfD Work Group Review: 05/20/99
Verification Date: 05/20/99
7. U.S. EPA CONTACTS
Primary: J. DiMaggio FTS/123-4567 or 123/456-7890
Office of Research and Development
Secondary: H.L. Mencken FTS/234-5678 or 987/654-3210
Office of Research and Development
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Dinitrochickenwire: page 4 of 9
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Dinitrochickenwire (DNCW)
CAS No.: 12345-67-8
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Dinitrochickenwire (DNCW)
CAS No.: 12345-67-8
This chemical is among those substances unlikely to be evaluated by the
U.S. EPA for evidence of human carcinogenic potential. This does not imply
that this chemical exists. Don't bother to look for a risk assessment
summary on IRIS, ever.
Chemical: Dinitrochickenwire (DNCW)
CAS No.: 12345-67-8
III. DRINKING WATER HEALTH ADVISORIES
Preparation Date: 02/30/99
A. HEALTH ADVISORY VALUES
1. SUMMARY TABLE
Type
1-day (child)
10-day (child)
Longer term
(child)
Longer term
(adult)
Lifetime
Dexp
(mg/kg/day)
10 (NOAEL)
3 (NOAEL)
3 (NOAEL)
3 (NOAEL)
UF
100
100
100
100
Value
(ug/1)
1000
300
300
1050
210
Basis
Smith et
al., 1999
Longer term HA
Jones et
Jones et
Oral RfD
al., 1999
al. , 1999
(02/30/99)
2. STANDARD CALCULATIONS AND ASSUMPTIONS
All Health Advisories (HAs) except the Lifetime HA do not assume exposure
by any other route (i.e., 100% of exposure to this substance is by drinking
-------
Dinitrochickenwire: page 5 of 9
water) and are calculated according to the equation:
HA - 1000 x Dexp x BW / WC / UF,
where 1000 — conversion from mg to ug,
Dexp = the experimentally determined NOEL, NOAEL or LOAEL (in
mg/kg-day) judged most appropriate for derivation of the
specific HA,
BW - standard reference value for human body weight
(10 kg for a child; 70 kg for an adult),
WC - standard reference value for human water consumption
(1 liter/day for a child; 2 liters/day for an adult),
UF = uncertainty factor judged appropriate for the quantity and
quality of the available data.
Lifetime HAs are based on the Oral Reference Dose (RfD) and assume that
only 20% of total compound intake is by drinking water. Lifetime HAs can be
derived by the equation:
HA = 1000 x Dexp / (UF x MF) x BW / WC x 0.2,
where the constants and variables are the same as for other HAs except that
Dexp is the experimentally determined NOEL, NOAEL or LOAEL (in mg/kg-day)
from which the RfD is derived, MF is the modifying factor as described in
the Oral RfD section, and 0.2 is the assumed fraction of exposure due to
drinking water ingestion.
B. EXPERIMENTAL BASIS
1. ONE-DAY HEALTH ADVISORY
Smith, J., R. Jones and H. Johnson. 1999. Effects of dinitrochickenwire on
the levels of hepatic glycogen. J.I.R. 99: 0-1.
Increased liver/body weight ratios were observed in male rats after
single oral doses of dinitrochickenwire at levels greater than 10 mg/kg
2. TEN-DAY HEALTH ADVISORY
Appropriate data for calculating a Ten-day HA are not available. It is
recommended that the Longer-term HA for the 10-kg child of 300 ug/1 be used as
the Ten-day HA.
3. LONGER-TERM HEALTH ADVISORIES
Jones, R., J. Smith and H. Johnson. 1999. Chlorinated dibenzodioxins and
dinitrochickenwire. Environ. Nonsense 99: 9999.
Dinitrochickenwire was fed to rats by diet at levels of 3, 10, or 30
mg/kg/day for 90 days. Increased liver and kidney weights were induced at
all doses with a technical grade containing high levels of dioxins (1,980 ppm
OCDD, 19 ppm HCDD), whereas increased liver and kidney weights were not
evident at the 3 mg/kg/day feeding level with either a purified grade
containing no dioxins or an improved technical grade containing 30 ppm OCDD
and 1 ppm HCDD.
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DInitrochickenwire: page 6 of 9
4. LIFETIME HEALTH ADVISORY
Shakespeare, W., F. Quack, J. Keats, E. Hemingway and J. Keroac. Results of
2-year toxicity and reproduction studies on dinitrochickenwire in rats.
In: Dinitrochickenwire: Chemistry, Cosmetology and Environmental Psychology,
E.O'Neil, Ed. Rat Pellet Press, NY. p. 301 (1978).
Refer to Section II.A.2 (Oral RfD) for a description of this study.
C. ADDITIONAL INFORMATION
1. DETECTION AND TREATMENT
Organoleptic Properties: Odor perception threshold (water) reported as
1,600 tig/L. Taste perception threshold (water) reported as 30 ug/L.
Analytical Methods for Detection in Drinking Water: Determination of
dinitrochickenwire is by a liquid-liquid extraction gas chromatographic
procedure.
Water Treatment: Available data on dinitrochickenwire removal from water
pertains predominantly to adsorption techniques. The use of aeration also
has been considered.
2. DOCUMENTATION AND REVIEW
U.S. EPA. 1999. U.S. Environmental Protection Agency. Final Draft of the
Drinking Water Criteria Document on Dinitrochickenwire. Office of Drinking
Water, Washington, D.C.
EPA review of Health Advisories in 1999.
Public review of HAs following notification of unavailability in Jan., 1999.
3. U.S. EPA CONTACT
Dr. Johnny Fever FTS/555-9577
IV. RISK MANAGEMENT SUMMARIES
Chemical: Dinitrochickenwire (DNCW)
CAS No.: 12345-67-8 Preparation Date: 02/30/99
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
-------
Dinitrochickenwire: page 7 of 9
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
10 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
99 FR 99999
02/30/99
Water Quality
Criteria (WQC):
a. Human Health
Final
1980
b. Aquatic Toxicity
1) Freshwater Proposed
1986
2) Marine
Hazardous Waste
Constituent
(App. VIII)
Pesticide Active
Ingredient:
a. Registration
Standard
Proposed
1986
Final
1985
n.a.
Acute no
1.0 mg/1
Chronic
30.0 ug/1
Acute no
55 ug/1
Chronic
32 ug/1
Acute no
53 ug/1
Chronic
34 ug/1
Listed no
ibid.
ibid.
ibid.
99 CFR Part 999
(App. VIII)
b. Special
Review
Final
1984
Position
Document 1
P.O. 2/3
no
yes
99 FR 99999
02/30/99
ibid.
B. RISK MANAGEMENT RATIONALE
RQ
CERCLA statutory RQ subject to adjustment when assessment of
carcinogenicity is completed.
Contact: RCRA/Superfund Hotline
-------
Dinitrochickenwire: page 8 of 9
WQC
Contact: Office of Water Regulations and Standards
a. Human health: The WQC necessary for the protection of public health is
1.0 mg/1. Its basis is a NOAEL of 3 mg/kg in a mammalian study, safety
factor of 100 and an assumption of daily ingestion of 2 liters of water and
6.5g of fish. The WQC of 30.0 ppb is based upon organoleptic effects (taste
and odor thresholds). However, organoleptic end points have limited value in
setting water quality standards, since there is no demonstrated relationship
between taste/odor effect and adverse health effects.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The data are assumed to be statistically
representative and are used to calculate concentrations which will not have
significant short or long term effects on 95% of the organisms exposed.
Recent criteria (1985 and later) contain duration and frequency stipulations:
the acute criteria maximum concentration Is a 1-hour average and the chronic
criteria continuous concentration is a 4-day average which are not to be
exceeded more than once every three years, on the average (see Sondheim et al.
1985) . Earlier criteria (1980-1984) contained instantaneous acute and
24-hour average chronic concentrations which were not to be exceeded.
Pesticide Active Ingredient
a. Registration Standard: none
b. Special Review: For specific details on the Special Review process for
this active Ingredient please check the references listed.
Contact: Office of Pesticide Programs, Special Review Branch
V. SUPPLEMENTARY DATA
Chemical: Dinitrochickenwire (DNCW)
CAS No.: 12345-67-8 Preparation Date: 02/30/99
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Dinitrochickenwire is poisonous if swallowed or inhaled. It is
very toxic: the probable oral lethal dose being (human) 50-500 mg/kg (1
teaspoon to 1 ounce) for 70-kg person (150 Ibs.) . Lethal oral doses in
humans have been reported at 29 mg/kg. It causes lung, liver, and
kidney damage, and contact dermatitis (Merton, 1976). Inhalation results
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Dinitrochickenwire: page 9 of 9
in acute poisoning centering in the circulatory system with accompanying
heart failure. Also, visual damage, scotoma, inflammation of conjuctiva,
cornea opacity, cornea numbness and slight pupil dilation are
experienced.
Medical Conditions Generally Aggravated by Exposure: Kidney and liver
diseases (Claghorn and Claghorn, 1982).
Signs and Symptoms of Exposure: Ingestidn causes increased then decreased
respiration, blood pressure, and urinary output; fever; increased bowel
action; motor weakness; collapse with convulsions; and death (Merton, 1976).
Inhalation of dust and mist causes violent sneezing and coughing.
Liquid or solid dermal contact causes smarting of skin and first-degree
burns on short exposure; it may cause secondary burns on long exposure.
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: NOG H IC1
2 4 15 6 5
Molecular Weight: 582.38
Boiling Point: 42C
Specific Gravity (H20=l): 1.2 at 22C/3C
Vapor Pressure (mmHg): 0.002 at 20C
Melting Point: 15C
Vapor Density (AIR=1): 9.02
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: 0.002 g/100 ml at 1C
Flash Point [Method Used]: Not Found
Flammable Limits: This material may burn but may not ignite readily
Under normal conditions it is not flammable
Appearance and Odor: Needle-like crystals (Merton, 1983). Colorless
crystals (pure); dark yellowish powder or flakes (crude product)
(Shakespeare, 1982). Chicken-like odor (Shakespeare,1982) and also a very
pungent odor when hot (Merton, 1976).
Conditions or Materials to Avoid: Prolonged heating above 200C produces
trace amounts of octachlorodibenzo-para-dioxin. Contact with strong
oxidizers may cause fires or explosions.
Hazardous Decomposition or Byproducts: When heated to decomposition,
dinitrochickenwire emits highly toxic fumes of dinitros (Saxaphone, 1975).
Hydrogen chicken, chlorinated wires, and carbon monowire may be released
upon decomposition.
Use: Dinitrochickenwire is used as a wood preservative; as a soil fumigant
for termites; as an herbicide, fungicide, slimicide, algicide; and as an
antibacterial agent in disinfectants and cleaners.
Synonyms: Chickenwire, 1,2-dinitro; DNCW; Noxocluck
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Dinoseb; CAS No. 88-85-7 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Dinoseb
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
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Dinoseb: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Dinoseb
CAS No.: 88-85-7
Preparation Date: 01/06/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Decreased body and
thyroid weights
Rat chronic oral
bioassay
Dow Chemical Co., 1977
NOEL: None
LOAEL: 1 mg/kg/day
1000
1E-3
mg/kg/day
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Dow Chemical Co. 1977. MRID 00025582
Available from EPA. Write to FOI, EPA, Washington D.C. 20460.
Sixty rats/sex/group were fed diets containing dinoseb at 0, 1, 3 or 10
mg/kg bw/day for up to 104 weeks. Ten animals/sex were sacrificed at 1 year
for interim results. Clinical signs of toxicity attributed to dinoseb were
evident in all treated groups (hunched posture and urine staining of coat).
A statistically significant and dose-related reduction in body weight gain
was observed at 3 and 10 mg/kg/day. This effect was evident within the first
year of treatment, and occurred despite increased food consumption.
Decreased mean relative absolute thyroid weights in all treated males and
decreased relative thyroid weights in mid-dose males were observed at the
104-week terminal kill. No consistent dose-related effects were observed for
hematology, selected blood chemistries or urinalysis values.
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Dinoseb: page 3 of 6
Ilivicky and Casida (1969) suggested that the mechanism of toxicity for
dinoseb involved an elevated metabolic rate associated with uncoupling of
oxidative phosphorylation. The observation of decreased growth rate with
increased food consumption, concurrent with decreased thyroid weight, is con-
sistent with this hypothesis.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. The uncertainty factor of 1000 reflects 10 for both intra- and
interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation from a LOAEL to its hypothesized
NOAEL.
MF = 1
4. ADDITIONAL COMMENTS
Body weight losses due to dinoseb treatment have also been reported for
rats treated at 9.1 mg/kg/day for 11 weeks and at 10 mg/kg/day for 6 months.
A 90-day dog study showed reversible heart and liver effects at 5.3 mg/kg/day
with a NOEL of 3 mg/kg/day.
Dinoseb was not carcinogenic in one rat study, and has not been found to
be mutagenic. Dinoseb was teratogenic by i.p. and s.c. administration to
mice, but not by the oral route. Male reproductive toxicity was observed for
rats fed dinoseb at 15.6 mg/kg/day for 11 weeks.
5. CONFIDENCE IN THE RfD
Study: High Data Base: Medium RfD: Medium
The confidence in the chosen study is high because of the large number of
animals/sex in three dose groups, the large number of parameters measured,
and because of the interim kill. The data base is rated medium because the
supporting studies are only subchronic in duration. Confidence in the RfD is
not higher than medium because a NOAEL was not established.
6. DOCUMENTATION AND REVIEW
The ADI in the 1984 Health and Environmental Effects Profile has received
limited Agency review with the help of two scientists.
U.S. EPA. 1984. Health and Environmental Effects Profile for Dinoseb.
Environmental Criteria and Assessment Office, Cincinnati, OH.
ECAO-CIN-PO-87AP.
Agency RfD Work Group Review: 07/08/85, 07/22/85
Verification Date: 07/22/85
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Dinoseb: page 4 of 6
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B.REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Dinoseb
CAS No.: 88-85-7
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Dinoseb
CAS No.: 88-85-7
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Dinoseb
CAS No.: 88-85-7
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Dinoseb
CAS No.: 88-85-7 Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
-------
Dinoseb: page 5 of 6
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
~~A^RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
1000 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on both aquatic toxicity and oral mammalian
toxicity. The 96-Hour Median Threshold Limit for aquatic toxicity is between
12 and 100 ppm and the oral LD50 for rats is between 10 and 100 mg/kg.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
V. SUPPLEMENTARY DATA
Chemical: Dinoseb
CAS No.: 88-85-7 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Dinoseb is extremely toxic. The probable oral lethal dose is 5-50 mg/kg;
between 7 drops and 1 teaspoonful for 70 kg person (150 Ib.) (Gosselin, 1976,
p. 11-197).
Medical Conditions Generally Aggravated by Exposure: Not Found
-------
Dinoseb: page 6 of 6
Signs and Symptoms of Exposure: Marked fatigue, tremendous thirst,
profuse sweating, flushing of face. Nausea, vomiting, abdominal pain,
occasional diarrhea. Restlessness, anxiety, excitement, occasionally leading
to convulsions. Rise in body temperature, rapid heart beat, difficulty
breathing, bluish skin and sometimes muscle cramps. Loss of consciousness,
cessation of breathing and death (Gosselin, 1976). Skin: staining of skin
and minor irritation by very small amount. Eyes: mild to moderate
irritation expected. Inhalation: dusts may be irritating and may cause
serious illness (Weed Science Society of America, 1979).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: C H N 0
10 12 2 5
Molecular Weight: 240.2
Boiling Point: Not Found
Specific Gravity (H20-1): 1.2647 at 45C
Vapor Pressure (mmHg): 1 at 151.1C
Melting Point: 100-108F, 38-42C
Vapor Density (AIR=1): 7.73
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: 0.0052 g/100 ml
Flash Point [method used]: 60.IF to 84.9F, 15.6C to 29.4C for 3
commercial products [?]
Flammable Limits: Not Found
Appearance and Odor: Orange-brown viscous liquid (Merck, 1983, p. 479);
pungent odor (Weed Science Society of America, 1979) or crystals (Sax, 1979);
orange solid when pure; technical grade is orange-brown solid (Worthing,
1983)
Conditions or Materials to Avoid: Dinoseb appears to be stable in acid
solution, but is susceptible to decomposition by ultraviolet radiation in
alkaline solution (Kearney, 1975).
Hazardous Decomposition or Byproducts: On decomposition, nitro compounds
such as this emit toxic fumes (Sax, 1979).
Use: Plant growth regulator; insecticide and herbicide (Hawley, 1981, p.
374).
Synonyms: 2,4-Dinitro-6-(1-Methylpropyl)Phenol; 2,4-Dinitro-6-sec-
Butylphenol; 2-(1-Methylpropyl)-4,6-Dinitrophenol; Phenol, 2-sec-Butyl-4,6-
Dinitro-; 4,6-Dinitro-2-(1-Methyl-n-Propyl)Phenol; 4,6-Dinitro-2-
sec-Butylphenol; 4,6-Dinitro-o-sec-Butylphenol; AATOX; Aretit; Basanite; BNP
20; BNP 30; Butaphene; Caldon; Chemox General; Chemox PE; DBNF; Dibutox;
Dinitrall; Dinitro Weed Killer; Dinitro-Ortho-Sec-Butyl Phenol;
Dinitrobutylphenol; Phenol, 2-(l-Methylpropyl)-4,6-Dinitro-; DN 289; DNBP;
DNOSBP; DNSBP; Dow General; Dow General Weed Killer; Dow Selective Weed Killer
Dytop; Elgetol; Elgetol 318; ENT 1,122; Gebutox; Hivertox; Kiloseb; Knoxweed;
Ladob; Laseb; Nitropone; Phenol, 2-(1-Methylpropyl)-4,6-Dinitro-; Phenol,
2-sec-Butyl-4,6-Dinitro-; Premerg; Sinox General; Subitex
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
1,2-Diphenylhydrazine; CAS No. 122-66-7 (Revised 12/24/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR 1,2-Diphenylhydrazine
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: none
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: available
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: in preparation
V. Supplementary Data: none
-------
1,2-Diphenylhydrazine: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: 1,2-Diphenylhydrazine
CAS No.: 122-66-7
Information is not available at this time.
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: 1,2-Diphenylhydrazine
CAS No.: 122-66-7
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: 1,2-Diphenylhydrazine
CAS No.: 122-66-7 Preparation Date: 12/24/86
A. U.S. EPA CLASSIFICATION AND BASIS
Classification: B2, probable human carcinogen based on data in both rats
and mice. Two apparently negative studies lack information
on compound purity, experimental design and statistical
treatment.
1. HUMAN DATA
None.
2. ANIMAL DATA
In a study by NCI (1978), 1,2-diphenylhydrazine was fed to 47-50 each
male and female F344 rats and B6C3F1 mice for a period of 78 weeks. TWA
food concentrations were 0.008% and 0.03% for male rats, 0.004% and 0.01%
for female rats, 0.008% and 0.04% for male mice, and 0.004% and 0.04% for
female mice. Rats were observed 28-30 weeks after cessation of treatment
and mice for an additional 17 or 18 weeks. Male rats showed a significant
treatment-related increase in incidence of hepatocellular carcinoma. Neo-
plastic liver nodules and mammary adenocarcinomas were significantly
increased in the treated female rats. High-dose male rats also showed a
significant increase in combined incidence of squamous-cell carcinomas or
squamous-cell papillomas of the Zymbal's gland, the ear canal and the skin
of the ear. A significant increase of hepatocellular carcinoma was observed
among treated female, but not male mice.
-------
1,2-Diphenylhydrazine: page 3 of 5
Pliss (1974) administered diphenylhydrazine in sunflower oil to 110 C57
mice and 163 rats either s.c., topically to the skin or by addition to food.
Tumor incidences of 22-50% were observed in mice treated by all routes; rats
administered diphenylhydrazine also had a combined tumor incidence of approx-
imately 22%. While this study suffers from design problems (animals were
added in the course of the treatment and control data was missing) it is
supportive of the classification of diphenylhydrazine as carcinogenic.
Studies by Marhold (1968) and Spitz (1950) found no evidence of diphenyl-
hydrazine carcinogenicity in male Wistar rats and mongrel dogs or in Sherman
rats, although study details are lacking.
3. SUPPORTING DATA
Diphenyl hydrazine was shown to depress testicular DNA synthesis in mice
when administered i.p. at a dose of 100 mg/kg (Seller, 1977).
B. ORAL QUANTITATIVE ESTIMATE
Slope Factor = 0.8/mg/kg/day
1. UNIT RISK SUMMARY TABLE
Water Concentrations Producing Risk Levels
E-4 E-5 E-6
Unit Risk
Model
4.5 4.5E-1
ug/1 ug/1
4.5E-2
ug/1
2.2E-5 LM
/ug/1 extra risk
2. DOSE RESPONSE DATA
Study reference:
Species/strain;
Tumor type ; Route
Admin .
Dose
(% of diet)
Human Equiv.
Dose
(mg/kg/day)
Tumor
Incidence
NCI, 1979:
Rats/Fisher 344, male; hepato-
cellular carcinomas and neo-
plastic liver nodules; diet
0
0.008
0.03
0
4
15
6/59
13/49
37/49
3. ADDITIONAL COMMENTS
Dietary doses were calculated from the TWA in diet assuming a weight of
0.38 kg, and an expected lifespan of 104 days for male rats. Human equiva-
lent doses were based on surface area. Significant tumor site data were not
pooled for total cancer rates as data were unavailable. Control data were
pooled low- and high-dose controls. The unit risk value should not be used
if the water concentration exceeds 450 ug/1 as above this concentration the
slope factor may differ from that stated above.
-------
1,2-Diphenylhydrazine: page 4 of 5
4. STATEMENT OF CONFIDENCE
An NCI bioassay found diphenylhydrazine to produce tumors In a dose-
dependent fashion in both rats and mice. Magnitude of effects between
species cannot be compared as the total results were not equivalent for
modeling. Data for mice or female rats required mortality adjustment for
corroboration which could not be carried out. Confidence in the risk
estimate is rated low to medium as not all nodules may progress to tumors.
C. INHALATION QUANTITATIVE ESTIMATE
Slope Factor - 0.8/mg/kg/day
1. UNIT RISK SUMMARY TABLE
Air Concentrations Producing
E-4
4.5E-1
ug/cu.m
E-5
4.5E-2
ug/cu.m
Risk Levels
E-6
4.5E-3
ug/cu . m
Unit Risk
2.2E-4
/ug/cu . m
Model
LM
extra risk
2. DOSE RESPONSE DATA
The inhalation risk estimates were calculated from the oral exposure data.
3. ADDITIONAL COMMENTS
The unit risk value should not be used if the air concentration exceeds
45 ug/cu.m as above this concentration the slope factor may differ from that
stated above.
4. STATEMENT OF CONFIDENCE
Confidence in this inhalation risk estimate derived from oral data can be
rated no higher than low.
D. DOCUMENTATION AND REVIEW
1. REFERENCES
NCI (National Cancer Institute). 1979. Bioassay of Hydraazobenzene for
Possible Carcinogenicity. U.S. DHEW Publ. No. NIH 78-1342.
U.S. EPA. 1980. Ambient Water Quality Criteria for Diphenylhydrazine.
Environmental Criteria and Assessment Office, Cincinnati, OH. EPA
440/5-80-062.
-------
1,2-Diphenylhydrazine: page 5 of 5
2. REVIEW
The values in the Ambient Water Quality Criteria Document for Diphenyl-
hydrazine (1980) received extensive peer and public review.
Agency CRAVE Work Group Review: 07/23/86, 10/29/86
Verification Date: 10/29/86
3. U.S. EPA CONTACTS
Primary: R.E. McGaughy (202/FTS) 382-5898
Office of Research and Development
Secondary: H.J. Gibb (202/FTS) 382-5898
Office of Research and Development
III. DRINKING WATER HEALTH ADVISORIES
Chemical: 1,2-Diphenylhydrazine
CAS No.: 122-66-7
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: 1,2-Diphenylhydrazine
CAS No.: 122-66-7
in preparation
V. SUPPLEMENTARY DATA
Chemical: 1,2-Diphenylhydrazine
CAS No.: 122-66-7
Information is not available at this time.
Synonyms: hydrazobenzene; benzene, hydrazodi-; N,N'-bianiline;
(sym)-dihpenylhydrazine; 1,2-dihpenylhydrazine; hydrazine, 1,2-dihpenyl-
NCI-C01854; RCRA waste number U109
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Epichlorohydrin; CAS No. 106-89-8 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Epichlorohydrin
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: available
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Epichlorohydrin: page 2 of 10
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Epichlorohydrin
CAS No.: 106-89-8
Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Kidney lesions
Lifetime rat inhala-
tion study
Laskin et al. (1980)
NOAEL: None
LOAEL: 10 ppm or
37.8 mg/cu.m (2.152
mg/kg bw/day)
1000
2E-3
mg/kg/day
* Dose Conversion Factors & Assumptions: 37.8 mg/cu.m x 0.5 x 0.0093 cu.m/
hour x 6 hour x 5 days/7 days / 0.35 kg = 2.152 mg/kg bw/day
2. PRINCIPAL AND SUPPORTING STUDIES
Endpoint and Experimental Doses:
Laskin, S., A.R. Sellakumar, M. Kuschner, et al. 1980. Inhalation carcino-
genicity of epichlorohydrin in noninbred Sprague-Dawley rats. J. Natl. Can-
cer Inst. 65: 751-757.
Groups of 100 male Sprague-Dawley rats were exposed to 10 ppm (37.8
mg/cu.m) or 30 ppm (114 mg/cu.m) epichlorohydrin, 6 hours/day, 5 days/week,
for the lifetime of the animals (136 weeks). Renal tubular degeneration was
observed in all treatment groups and controls. The incidences of renal dam-
age were 14% in untreated controls, 24% in sham-treated controls, 37% for 10-
ppm animals and 65% for 30-ppm animals. The severity of kidney lesions was
greater in treated animals than in controls. Treated animals also exhibited
severe lung congestion and pneumonia. Early mortality was observed in a
dose-dependent fashion.
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Epichlorohydrin: page 3 of 10
Dose-conversion assumptions were made for the ratio of inhalation to oral
absorption (0.5), rat inhalation rate (0.0093 cu. m/hour) and rat body weight
(0.35 kg). An inhalation absorption coefficient of 0.45 can be calculated
from data provided In Smith et al. (1979), which supports the dose-conversion
assumption.
Rats were gavaged (in water) with epichlorohydrin at doses of 2 or 10
mg/kg bw/day for 2 years (Van Esch, 1981); dose-related decreases in
leukocytes and increased hyperplasia of the stomach were observed.
The adversity of the effects is difficult to judge, but the effect level is
identical to that calculated for the inhalation study. Kawabata (1981)
administered epichlorohydrin in drinking water to male Wistar rats at doses
equivalent to 18, 39, and 89 mg/kg/day. Weight gain was decreased at all
treatment groups. Several organ weight ratios were affected. The lower dose
can be considered a LOAEL. In one short-term study, 100% mortality was
observed after 21 doses of 94 mg/kg.
Small organ weight changes were reported for kidney and liver in two
strains of rats at 25 ppm In 90-day inhalation studies (Quast et al., 1979),
with mild histopathological lesions at 50 ppm; no effects were observed at 5
ppm or for mice exposed to 50 ppm. The effects and effective exposure levels
are consistent with those reported in Laskin et al. (1980), with consideration
of the difference in duration.
The primary target organ for the systemic effects of epichlorohydrin is
the kidney. Other inhalation studies show effects on the kidneys and on male
fertility at higher doses. Kidney effects are also observed after l.p.
administration of low doses of epichlorohydrin to rats.
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 1000. The UF Includes variability in interspecies extrapolation, range
of human sensitivities and extrapolation from a LOAEL to a hypothetical NOEL.
MF = 1
4. ADDITIONAL COMMENTS
A comparison of acute effects in separate studies shows that an inhala-
tion exposure was associated with the same level of toxlcity as an equivalent
oral dose (calculated with assumptions given here), lending some support to
the route interconversion method.
Epichlorohydrin was not embryotoxic, fetotoxic or teratogenic in rats and
rabbits at inhalation exposures of up to 25 ppm for 7 hours/day during gesta-
tion (Pilny et al., 1979).
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The critical study is well-designed as an inhalation careinogenesis bio-
assay but does not cover all toxlcological parameters. The data base Is
highly supportive of the nature of the critical effect, but lacks adequate
oral toxicity data. Confidence in the RfD is dependent on the validity of
the inter-route conversion model, which In this case appears defendable, and
on the accuracy of the no-effect level estimate.
-------
Epichlorohydrin: page 4 of 10
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1985. Drinking Water Criteria Document for Epichlorohydrin.
Office of Drinking Water, Washington, DC. Final draft.
The document is currently undergoing extensive Agency and external review.
Agency RfD Work Group Review: 12/18/85
Verification Date: 12/18/85
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Epichlorohydrin
CAS No.: 106-89-8
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Epichlorohydrin
CAS No.: 106-89-8
Preparation Date: 12/03/86
A. U.S. EPA CLASSIFICATION AND BASIS
Classification:
B2, probable human carcinogen. Human data are inadequate.
Multiple studies in rats and mice administered epichloro-
hydrin by various routes were positive. As epichlorohydrin
is a strong alkylating agent, tumors are produced at the site
of application.
1. HUMAN DATA
Inadequate. A retrospective cohort mortality study has been conducted on
864 workers from epichlorohydrin producing plants in Louisiana and Texas
(Enterline, 1981). Deaths were compared by cause with those expected for the
states of Louisiana and Texas. An interim report showed workers to have less
than expected overall mortality, but an increase (not significant) in both
respiratory cancer and leukemia mortality. An update on the exposed cohort,
however, indicated a reversal of this trend. The study is complicated by the
fact that of those 10 workers diagnosed with lung cancer, seven were smokers,
-------
Epichlorohydrin: page 5 of 10
one was a nonsmoker and the smoking history of two was not known.
Furthermore, there is no apparent dose-response trend, and there is the
confounding exposure to the isopropyl alcohol manufacturing process
concomitant with epichlorohydrin.
A retrospective cohort mortality study of 533 chemical workers
(Shillenburger et al., 1979) and an historic prospective study of European
workers (Tassignon et al., 1983) failed to demonstrate a connection between
epichlorohydrin and Increased cancer mortality. The first study is
inadequate for valid carcinogenicity assessment because of low exposure,
short exposure duration, short study period and the young age of the cohort.
The second study suffers from some of the same limitations as well as that of
a small cohort size with at least 10 years exposure (274 Individuals).
2. ANIMAL DATA
Sufficient. Epichlorohydrin has produced cancers of various types at the
site of application when administered by several routes. While ineffective
as a complete skin carcinogen, epichlorohydrin produced papillomas in mice
when used as an initiator followed by phorbol myristate acetate promotion
(Van Duuren et al., 1974). Local sarcomas developed in mice at the site of
single subcutaneous injections of epichlorohydrin (Kotin and Falk, 1963).
Wester et al. (1985) administered 0, 2 or 10 mg/kg/day epichlorohydrin by
gavage to groups of 50 each male and female Wistar rats. Mortality was high
in all female rats during the first 12 months because of a high fiber diet.
The incidence of forestomach carcinomas was significantly increased in the
high-dose rats. Konishi et al. (1980) reported similar results In male
Wistar rats given epichlorohydrin in the drinking water. Drinking water was
administered to 18 animals each with 0, 375, 750 or 1500 ppm epichlorohydrin.
Poor health of treated animals necessitated that untreated water be given
intermittently during weeks 60-81. All surviving high-dose rats developed
forestomach hyperplasia; forestomach papillomas were significantly increased
and two squamous cell carcinomas were also noted, as well as squamous cell
carcinomas of the oral cavity.
Inhalation exposure of male Sprague-Dawley rats was undertaken by Laskin
et al. (1980). Animals (140) were exposed to 100 ppm, 6 hours/day for 30
days and observed for their lifetime. Nasal cavity tumors, including
squamous cell carcinomas developed In 15/140 rats compared to none in either
150 concurrent or in 1920 historical controls. Groups of 100 animals were
exposed to 10 or 30 ppm, 6 hours/day, 5 days/week for their lifetime. By 136
weeks, 100% mortality was noted. One nasal cavity tumor and two respiratory
tract tumors were observed among the high-dose rats.
3. SUPPORTING DATA
Epichlorohydrin is a direct acting mutagen by virtue of its activity as
an alkylating agent. Positive results have been obtained in mutagenicity
tests in several bacterial species, Neurospora, Saccharomyces, Drosophilia
(including recessive lethal), and cultured mammalian cells (reviewed in Sram
et al., 1981). Epichlorohydrin causes mitotic recombination in yeast and
sister-chromatid-exchange and chromosomal aberrations in mammalian cells.
The latter were observed in lymphocytes obtained from exposed workers (Sram
et al., 1981; Kucerova et al., 1977; Picciano, 1979).
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Epichlorohydrin: page 6 of 10
B. ORAL QUANTITATIVE ESTIMATE
Slope Factor - 9.9E-3/mg/kg/day
1. UNIT RISK SUMMARY TABLE
Water Concentrations Producing Risk Levels
E-4 E-5 E-6
Unit Risk
(/ug/1)
Model
3.6E2
3.6E1
3.6
ug/1
2.8E-7
LM
extra risk
2. DOSE RESPONSE DATA
Study reference:
Species/strain
Tumor type; Route
Human Equiv.
Admin. Dose Dose Tumor
(ppm in d.w.) (mg/kg/day) Incidence
Konishi et al . , 1980:
Rat/Wistar, male;
and carcinomas of
stomach; drinking
papillomas
the fore-
water
0
375
750
1500
0
27.1
55.7
108.6
0/10
0/9
2/10
9/12
3. ADDITIONAL COMMENTS
Doses are equivalent human doses assuming 70 kg bw, and 2 L water con-
sumption using the formula: f. water (rat) x water concentration (rat) =
f water(human) x water concentration(human);
where: f water(rat) - 0.078 (fraction of body weight consumed as water) and
f water(human) - 0.029.
As epichlorohydrin is an alkylating agent, its effect in the forestomach
is considered to be a local reaction. The unit risk value should not be used
if the water concentration exceeds 36,000 ug/1 as above this concentration
the slope factor may differ from that stated above.
4. STATEMENT OF CONFIDENCE
The above study provides the only drinking water data available.
Limitations include the following: The study was terminated at 81 weeks,
epichlorohydrin concentration in the water was likely to be overestimated
because of its short half-life, dose levels administered were toxic to the
animals; pathology data obtained on animals dying during the study course
were not considered reliable by the authors, and few animals were used.
Confidence in the risk estimate is rated low.
-------
Epichlorohydrin: page 7 of 10
C. INHALATION QUANTITATIVE ESTIMATE
Slope Factor = 4.8E-3/mg/kg/day
1. UNIT RISK SUMMARY TABLE
Air Concentrations Producing Risk Levels
E-4 E-5 E-6
Unit Risk
Model
8.3E1
ug/cu.m
8.3
ug/cu . m
8.3E-1
ug/cu . m
1.2E-6
/ug/cu . m
LM
extra risk
2. DOSE RESPONSE DATA
Study reference:
Species/strain;
Tumor type; Route
Laskin et al. , 1980:
Rat/Sprague-Dawley, male; nasal
cavity tumors; Inhalation exposure
Admin .
Dose
(ppm in air)
0
10
30
Human Equiv .
Dose
(mg/kg/day)
Tumor
Incidence
0/150
0/100
1/100
3. ADDITIONAL COMMENTS
Historical control for these tumors is 0/1920.
As epichlorohydrin was administered as a partially soluble vapor, the
concentrations in ppm administered to the experimental animals are con-
sidered equivalent to the same concentrations in humans. A risk estimate
including the time-to-tumor, dosing regimen and lung cancer incidence data
from 30 days exposure to 100 ppm gives a slope factor of 4.6E-2/ppm. Data
from the epidemiologic study by Enterline (1981) were used to calculate the
slope factor of 0.15/ppm assuming an average exposure of 5 ppm and exposure
duration of 13.4 years. The unit risk value should not be used if the air
concentration exceeds 8300 ug/cu.m. as above this concentration the slope
factor may differ from that stated above.
4. STATEMENT OF CONFIDENCE
Analysis was based on nonsignificant increases in incidence. Risk
estimates based on the Laskin (1980) and Enterline (1981) studies varied by
at least 1 order of magnitude. The Laskin et al. (1980) study showed a
strong dose rate effect as evidenced by the tumor response with the high
exposure, short duration group. Thus, the confidence is rated low.
-------
Epichlorohydrin: page 8 of 10
D. DOCUMENTATION AND REVIEW
1. REFERENCES
U.S. EPA. 1984. Health Assessment Document for Epichlorohydrin. Prepared by
the Environmental Criteria and Assessment Office, Cincinnati, OH for the
Office of Air Quality Planning and Standards, Washington, DC.
U.S. EPA. 1985. Health and Environmental Effects Profile for Epichloro-
hydrin. Prepared by the Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Solid Waste, Washington, DC. ECAO-CIN-P128.
Konishi, T., A. Kawabata, A. Denda, et al. 1980. Forestomach tumors induced
by orally administered epichlorohydrin in male Wistar rats. Gann. 71:922-923.
Laskin, S., A. Sellakumar, M. Kuschner, et al. 1980. Inhalation carcinogen-
icity of epichlorohydrin in non-inbred Sprague-Dawley rats. J. Natl. Cancer
Inst. 65: 551-757.
2. REVIEW
The values in the 1984 Health Assessment Document for Epichlorohydrin
have received both Agency and outside review. Those in the 1985 Health and
Environmental Effects Profile for Epichlorohydrin have been reviewed by
Agency groups.
Agency CRAVE Work Group Review: 08/13/86, 10/29/86
Verification Date: 10/29/86
3. U.S. EPA CONTACTS
Primary: S. Bayard (202/FTS) 382-5722
Office of Research and Development
Secondary: R. McGaughy (202/FTS) 382-5898
Office of Research and Development
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Epichlorohydrin
CAS No.: 106-89-8
Information is not available at this time.
-------
Epichlorohydrin: page 9 of 10
IV. RISK MANAGEMENT SUMMARIES
Chemical: Epichlorohydrin
CAS No.: 106-89-8 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk Status Risk Considers
Management Management Econ/Tech
Action Date Value Feasibility Reference
Reportable Statutory 1000 Ibs no 50 FR 13456
Quantity (RQ) 1980 04/04/85
Clean Air Act Current Decision not no 50 FR 24575
Regulatory 1985 to Regulate 06/11/85
Decision:
(NESHAP or NSPS)
B. RISK MANAGEMENT RATIONALE
RQ
The statutory RQ of 1000 pounds established under Section 311(b)(4) of
the Clean Water Act is retained until assessments of potential
carcinogenicity and chronic toxicity are complete.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
CAA Regulatory Decision
Although epichlorohydrin is considered a probable human carcinogen
(IARC 2B), the risk to the public due to routine emissions (0.0014
cancers per year and maximum lifetime risk of 1.1E-5) was not considered
significant. Thus, EPA concluded that no regulatory program directed at
epichlorohydrin was warranted under the CAA.
Contact: Chief, Pollutant Assessment Branch
FTS/629-5645 or 919/541-5645
-------
Epichlorohydrln: page 10 of 10
V. SUPPLEMENTARY DATA
Chemical: Epichlorohydrln
CAS No.: 106-89-8
Information is not available at this time.
Synonyms: (chloromethyl)ethylene oxide; 1,2-epoxy-3-chloropropane;
l-chloor-2,3-epoxy-propaan (Dutch); l-chlor-2,3-epoxy-propan (German);
l-chloro-2,3-epoxypropane; l-cloro-2,3-epossipropano (Italian);
2,3-epoxypropyl chloride; 2-(chloromethyl)oxirane; 3-chloro-1,2-epoxypropane;
3-chloro-l,2-propylene oxide; chloromethyloxirane; chloropropylene oxide; ECH;
epi-chlorohydrin; epichloorhydrine (Dutch); epichlorhydrin (German);
epichlorhydrine (French); epichlorohydryna (Polish); epicloridrina (Italian);
gamma-chloropropylene oxide; glycerol epichlorhydrin; oxirane,(chloromethyl)-;
oxirane, 2-(chloromethyl); propane, l-chloro-2,3-epoxy-; RCRA waste number
U041; UN 2023
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Ethylbenzene; CAS No. 100-41-4 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A fie B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a. particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Ethylbenzene
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV, Risk Management Summaries: available
V. Supplementary Data: none
-------
Ethylbenzene: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Ethylbenzene
CAS No.: 100-41-4 Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Liver and kidney NOEL: 136 mg/kg/day 1000 1 1E-1
toxicity mg/kg/day
LOAEL: 408 mg/ kg/day
Rat subchronic to
chronic oral bio-
assay
Wolf et al. (1956)
* Dose Conversion Factors & Assumptions: 5 days/7 days; thus, 136 mg/kg/
day x 5 days/7 days =97.1 mg/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
Wolf, M.A., V.K. Rowe, D.D. McCollister, R.L. Hollingsworth and F. Oyen.
1956. Toxicological studies of certain alkylated benzenes and benzene.
Arch. Ind. Health. 14: 387-398.
The chosen study is a rat 182-day oral bioassay in which ethylbenzene was
given 5 days/week at doses of 13.6, 136, 408 or 680 mg/kg/day in olive oil
gavage. There were 10 albino female rats/dose group and 20 controls.
The criteria considered in judging the toxic effects on the test animals
were growth, mortality, appearance and behavior, hematological findings,
terminal concentration of urea nitrogen in the blood, final average organ and
body weights, histopathological findings, and bone marrow counts. The LOAEL
-------
Ethylbenzene: page 3 of 6
of 408 mg/kg/day is associated with histopathological changes in liver and
kidney.
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 1000. The uncertainty factor of 1000 reflects 10 for both intraspecies
and interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation of a subchronic effect level to its
chronic equivalent.
MF = 1
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Low RfD: Low
Confidence in the chosen study is low because rats of only one sex were
tested and the experiment was not of chronic duration. Confidence in the
supporting data base is low because other oral toxicity data were not found.
A low confidence in the RfD follows.
6. DOCUMENTATION AND REVIEW
A recent ORD document reaffirms the ADI from the ODW criteria document. Both
documents have had extensive Agency review, with the help of selected outside
scientists.
An identical ADI was publicly reviewed during the 1980 Ambient Water Quality
Criteria series.
U.S. EPA. 1980. Ambient Water Quality Criteria for Ethylbenzene. Environ-
mental Criteria and Assessment Office, Cincinnati, OH. EPA 440/5-80-048.
U.S. EPA. 1985. Drinking Water Criteria Document for Ethylbenzene. Office
of Drinking Water, Washington, DC. (Public review draft)
U.S. EPA. 1985. Health Effects Assessment for Ethylbenzene. Environmental
Criteria and Assessment Office, Cincinnati, OH. ECAO-CIN-H008.
Agency RfD Work Group Review: 05/20/85
Verification Date: 05/20/85
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
-------
Ethylbenzene: page 4 of 6
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Ethylbenzene
CAS No.: 100-41-4
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Ethylbenzene
CAS No.: 100-41-4
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Ethylbenzene
CAS No.: 100-41-4
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Ethylbenzene
CAS No.: 100-41-4 Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated In the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information In making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background Information on each RM action In
Appendix E in Service Code 4.
-------
Ethylbenzene: page 5 of 6
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
1000 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
2) Marine
Final
1980
1.4 mg/1
no
Acute no
32,000 ug/1 (LEL)
Chronic
none
Acute no
430 ug/1 (LEL)
Chronic
none
45 FR 79318
11/28/80
ibid.
ibid.
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity, as established under Section
311(b)(4) of the Clean Water Act, and ignitability. Available data indicates
that the aquatic 96-Hour Median Threshold Limit for ethylbenzene is between
10 and 100 ppm. The closed cup flash point is less than 100 degrees F and
the boiling point is greater than 100 degrees F.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC of 1.4 mg/1 is based on consumption of contaminated
aquatic organisms and water. A WQC of 3.28 mg/1 has also been established
based on consumption of contaminated aquatic organisms alone.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value indicates that the
minimum data were not available and the concentration given is not a criteria
value but the lowest effect level found in the literature.
-------
Ethylbenzene: page 6 of 6
V. SUPPLEMENTARY DATA
Chemical: Ethylbenzene
CAS No.: 100-41-4
Information is not available at this time.
Synonyms: AETHYLBENZOL (German), EB, ETHYLBENZEEN (Dutch), ETHYL BENZENE,
ETHYLBENZOL, ETILBENZENE (Italian), ETYLOBENZEN (Polish), NCI-C56393,
PHENYLETHANE, UN 1175
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Ethylphthalyl Ethylglycolate; CAS No. 84-72-0 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Ethylphthalyl Ethylglycolate
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: none
V. Supplementary Data: none
-------
Ethylphthalyl Ethylglycolate (EPEG): page 2 of 4
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Ethylphthalyl Ethylglycolate (EPEG)
CAS No.: 84-72-0
Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Kidney damage and
reduced lifespan
Rat, chronic oral
bioassay
Hodge et al. (1953)
0.5% of diet or 250
mg/kg/day (NOEL)
5% of diet or 2500
mg/kg/day (LOAEL)
100
mg/kg/day
* Dose Conversion Factors & Assumptions: It is assumed that a rat eats 5%
of its body weight/day; thus, 5000 mg/kg diet (i.e., 0.5% of diet) x 0.05
kg diet/kg bw/day =250 mg/kg bw/day
2. PRINCIPAL AND SUPPORTING STUDIES
End Point and Experimental Doses:
Hodge, H.C., E.A. Maynard, H.J. Blanchett, R.E. Hyatt, V.K. Rowe and H.C.
Spencer. 1953. Chronic oral toxicity of ethylphthalyl ethyl glycolate in
rats and dogs. Arch. Ind. Hyg. Occup. Med. 8: 289-295.
Groups of 25 male and 25 female rats were administered either 0, 0.05,
0.5 or 5% ethylphthalyl ethyl glycolate (EPEG) in the diet for 2 years. Over
the 2-year period, seven blood samples were taken for hematology, and urin-
alyses were performed at the same time; gross histopathology was examined at
the end of the study. No effects were observed in the low-dose groups, but
the 5% group experienced decreased growth and survival. Kidneys of this
-------
Ethylphthalyl Ethylglycolate (EPEG): page 3 of 4
group were granular, sometimes swollen and of a pale yellow color. The
kidney pelvis was dilated, and there were deposits of crystalline calcium
oxalate in renal tubules.
Paired groups of dogs received doses of 0.01, 0.05 or 0.25 g EPEG/kg/day
for 1 year. No effects of the test compounds were seen.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. The 100-fold factor represents two 10-fold subunits; one each for
the expected intrahuman and Interspecies variability of the toxicity of this
chemical in lieu of specific data.
MF - 1
4. ADDITIONAL COMMENTS
There are no published data regarding mutagenicity, carcinogenicity or
reproductive effects of EPEG.
$
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Low RfD: Low
Confidence in this study is rated medium since there were sufficient
numbers of rats, several end points were measured and there were comparative
studies on two species. This was, however, the only study of a chronic or
subchronic nature referred to in the 1980 Ambient Water Quality Criteria
Document. The confidence in the data base is, therefore, rated ds low. A low
to medium confidence in the RfD follows.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1980. Ambient Water Quality Criteria for Phthalate Esters. Envi-
ronmental Criteria and Assessment Office, Cincinnati, OH. EPA 440/5-80-067.
The ADI in the 1980 Ambient Water Quality Criteria document was extensively
reviewed by the Agency and was reviewed by the public.
Agency RfD Work Group Review: 11/06/85
Verification Date: 11/06/85
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
-------
Ethylphthalyl Ethylglycolate (EPEG): page 4 of 4
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Ethylphthalyl Ethylglycolate
CAS No.: 84-72-0
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Ethylphthalyl Ethylglycolate
CAS No.: 84-72-0
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Ethylphthalyl Ethylglycolate
CAS No.: 84-72-0
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Ethylphthalyl Ethylglycolate
CAS No.: 84-72-0
Information is not available at this time.
V. SUPPLEMENTARY DATA
Chemical: Ethylphthalyl Ethylglycolate
CAS No.: 84-72-0
Information is not available at this time.
Synonyms: PHTHALIC ACID, ETHYL ESTER, ESTER with ETHYL GLYCOLATE; 1,2-
BENZENEDICARBOXYLIC ACID, 2-ETHOXY-2-OXOETHYL-, ETHYL ESTER (9CI);
CARBETHOXYMETHYL ETHYL PHTHALATE; DIETHYL o-CARBOXYBENZOYLOXYACETATE; ETHYL
CARBETHOXYMETHYL PHTHALATE; ETHYL PHTHALYL ETHYL GLYCOLATE; SANTICIZER E-15
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Fluoride; CAS No. 16984-48-8 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a inore
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Fluoride
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Fluoride: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Fluoride
CAS No.: 16984-48-8
Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Objectionable dental
fluorosis, a cosmetic
effect
Epidemiological study
in children
Hodge (1950), cited
in: Underwood (1977)
1 ppm (NOAEL con-
verted to 0.06 mg/
kg/day
2 ppm (LOAEL)
1 1 6E-2
mg/kg/day
•* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Hodge, H.C. 1950. The concentration of fluorides in drinking water to give
the point of minimum caries with maximum safety. J. Am. Dent. Assoc. 40:
436. Cited in: Underwood, E.J. 1977. Trace Elements in Human and Animal
Nutrition. Academic Press, NY.
Fluoride-related compounds are used in the prevention of dental caries.
Extensive human epidemiological studies with large populations have been
carried out over the last 40 years. The NOAEL (1 ppm) and LOAEL (2 ppm) in
drinking water are defined within a narrow dose range. Underwood (1977) is
the secondary reference cited as the basis for the RfD (ADI). Hodge (1950) is
the primary reference cited in Underwood (1977).
Hodge (1950) studied children consuming fluoride in their drinking
water. Fluoride levels of 0-14 ppm were investigated. Dental mottling was
-------
Fluoride: page 3 of 6
the parameter of interest. Fluoride levels of 2-10 ppm produced a linear
dose-response curve (increasing mottling with increasing dose). Fluoride
levels of 0.1-1.0 ppm produced no observable effect. An assumption of 20 kg
bw and 1 L/day water consumption for children was used, since the children
studied were 12-14 years old. It is further assumed that a 20-kg child
consumes 0.01 mg of fluoride/kg bw/day in the diet (50 FR 20164). Thus, a
total intake would be approximately 0.06 mg/kg/day.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1. Uncertainty factors were not deemed necessary since the NOAEL is
that of the critical effect (i.e., dental fluorosis) in a sensitive
population of humans (i.e., children) for a length of exposure that
encompasses both the critical toxic effect and the sensitive population.
MF = 1
4. ADDITIONAL COMMENTS
Dental fluorosis results from excess exposure to fluoride during the age
of calcification of the teeth (up to about 8 years of age for anterior
teeth). Dental fluorosis in its mild form is characterized by white opaque
areas covering 50% of a given tooth; in its severe form, dental fluorosis is
characterized by brown to black stains and pitting (50 FR 20164). There is
considerable controversy over whether objectionable dental fluorosis
(moderate and severe) is a toxic and/or adverse health effect. However, the
U.S. EPA has determined that objectionable dental fluorosis is a cosmetic
effect and not a toxic and/or adverse health effect (50 FR 47142). Numerous
epidemiological studies have been conducted in the U.S. concerning the
relationship between dental fluorosis and fluoride levels in drinking water
(50 FR 20164). Based on these studies, the NOAEL for objectionable dental
fluorosis is approximately 1.0 ppm fluoride in drinking water. Assuming a
child weighs 20 kg, drinks 1.0 L of water/day and ingests fluoride at 0.01
mg/kg/day in the diet (50 FR 20164), a NOAEL of 1 ppm fluoride in drinking
water corresponds to 0.06 mg/kg/day. Since data are available for the only
susceptible population (children), an uncertainty factor of 1 is atpropriate.
It has been estimated that the development of crippling skeletal fluoro-
sis in man requires the consumption of 20 mg or more of fluoride/person/day
over a 20-year period, i.e., 0.28 mg/kg/day (U.S. EPA, 1985). While the NOEL
for crippling skeletal fluorosis in humans is unknown, a safe level of
fluoride exposure can be determined. No cases of crippling skeletal fluoro-
sis have been observed in the United States associated with the consumption
of 2 L of water/day containing 4 ppm fluoride (50 FR 20614). Assuming a 70
kg adult ingests 0.01 mg fluoride/day in the diet and consumes 8 mg fluoride/
day in drinking water (2 L/day containing 4 ppm fluoride), this would cor-
respond to a total intake of 0.12 mg/kg/day. Thus, 0.12 mg fluoride/kg/day
is a safe exposure level for this more severe end point in adults.
5. CONFIDENCE IN THE RfD
Study: High Data Base: High RfD: High
Confidence in both the study and the data base is high because the large
number of studies conducted in children all support the chosen NOAEL.
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Fluoride: page 4 of 6
Confidence in the RfD is high because little uncertainty remains in the
toxicity data base.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, July 1985.
U.S. EPA. 1985. Fluorine: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. 1985. Federal Register, Vol. 50, p. 20164, 47142.
Agency RfD Work Group Review: 08/05/85, 02/05/85, 02/26/85
Verification Date: 02/26/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: K. Bailey FTS/382-5535 or 202/382-5535
Office of Drinking Water
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Fluoride
CAS No.: 16984-48-8
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Fluoride
CAS No.: 16984-48-8
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Fluoride
CAS No.: 16984-48-8
Information is not available at this time.
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Fluoride: page 5 of 6
IV. RISK MANAGEMENT SUMMARIES
Chemical:
CAS No.:
Fluoride
16984-48-8
Preparation Date: 11/04/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent Inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Status
Date
Risk
Management
Value
Considers
Econ/Tech
Feasibility
Reference
Clean Air Act
Regulatory
Decision:
New Source
Performance
Standard (NSPS)
Final
1976
various
yes
40 CFR Part 61
Subparts S-X
B. RISK MANAGEMENT RATIONALE
CAA Regulatory Decision
NSPS: EPA has set NSPS for certain stationary source categories that emit
fluorides on the basis that fluorides can adversely affect public welfare
(primarily effects on teeth and bones of livestock that eat forage
contaminated with fluorides). The source categories regulated include
primary aluminum reduction plants (pot lines and amode bake plants) and five
types of phosphate fertilizer plants. The NSPS are based on best
demonstrated control technology, considering cost and other societal impacts.
As required by section lll(d), States have regulated existing sources of the
same type covered by the NSPS.
Contact: Chief, Pollutant Assessment Branch
FTS/629-5645 or 919/541-5645
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Fluoride: page 6 of 6
V. SUPPLEMENTARY DATA
Chemical: Fluoride
CAS No.: 16984-48-8
Information is not available at this time.
Synonyms: Fluoride (1-); Fluoride Ion; Fluoride Ion (1-); Perfluoride
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Fluridone; CAS No. 59756-60-4 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Fluridone
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: review pending
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: none
V. Supplementary Data: none
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Flurldone: page 2 of 4
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY) DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Fluridone
CAS No.: 59756-60-4 Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Glomerulonephritis
Experimental Doses *
7.7 mg/kg/day (NOAEL)
UF
100
MF
1
RfD
8E-2
mg/kg/day
Rat chronic feeding 25.2 mg/kg/day
study (LOAEL)
Elanco Products Co., 1980
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Elanco Products Co. 1980. MRID 00103251.
Available from EPA. Write to FOI, EPA, Washington D.C. 20460.
A 2-year rat feeding dietary study established a NOAEL for glomeruloneph-
ritis of 9.2 or 7.7 mg fluridone/kg bw/day for females and males, respec-
tively. The effect was observed at 25.2 or 30.1 mg/kg/day in males and
females, respectively. Mortality occurred at a higher dose.
Additional rodent and dog studies described in the CBI Appendix generally
support the specified NOAEL for both kidney and liver effects.
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Flurldone: page 3 of 4
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 100. The 100-fold factor reflects both the expected intra- and
interspecles variability to the toxicity of this chemical in lieu of
specific data.
MF = 1
4. ADDITIONAL COMMENTS
Fluridone does not appear to be teratogenic (CBI), although the data are
limited. Serious reproductive effects have not been reported.
5. CONFIDENCE IN THE RfD
Study: High Data Base: Medium RfD: Medium
The critical study design greatly exceeds minimal requirements in most
respects, and the results are unambiguous. The data base is fairly extensive
and generally supportive of the magnitude of the chosen NOAEL; some differ-
ences in target organ specificity and sensitivity are observed. Overall con-
fidence in the RfD reflects the foregoing discussion, and may be considered
to be slightly greater than medium.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1984. Health and Environmental Effects Profile for Fluridone.
Environmental Criteria and Assessment Office, Cincinnati, OH. ECAO-CIN-P093
AP093.
The ADI in the 1984 Health and Environmental Effects Profile received an
Agency review with the help of two external scientists.
Agency RfD Work Group Review: 11/21/85
Verification Date: 11/21/85
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Fluridone
CAS No.: 59756-60-4
Information is not available at this time.
-------
Fluridone: page 4 of 4
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Fluridone
CAS No.: 59756-60-4
This chemical is among those substances evaluated by the U.S. EPA for
evidence of human carcinogenic potential. This does not imply that this
chemical is necessarily a carcinogen. The evaluation for this chemical is
under review by an inter-office Agency work group. A risk assessment summary
will be included on IRIS when the review has been completed.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Fluridone
CAS No.: 59756-60-4
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Fluridone
CAS No.: 59756-60-4
Information is not available at this time.
V. SUPPLEMENTARY DATA
Chemical: Fluridone
CAS No.: 59756-60-4
Information is not available at this time.
Synonyms: in preparation
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Formic Acid; CAS No. 64-18-6 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Formic Acid
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
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Formic Acid: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) Is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarclnogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) In Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Formic Acid
CAS No.: 64-18-6 Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Solmann (1921) 200 mg/kg/day (NOAEL) 100 1 2
0.2% drinking water mg/kg/day
Rat oral chronic
study 0.5% drinking water
(LOAEL)
Malorny (1969)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Malorny, G. 1969. Acute and chronic toxicity of formic acid and formate.
Z. Ernachrungswiss. 9: 332-339.
Formic acid is a normal component of human tissues and foods and is
important in Intermediary metabolism. Ingested formic acid is rapidly metab-
olized and excreted (Malorny, 1969). The best information on which to base
an RfD is the study of Malorny (1969) In which no adverse effects were
observed in several generations (5) of rats that consumed 150-200 mg/kg/day
(author's estimated range) of formic acid. None of the other information
available suggests that toxic effects would occur at lower levels. Solmann
(1921) reported a series of studies in which rats received 0.25% formic acid
in drinking water (mean dosage of 160 mg/kg) for 15 weeks without showing any
effects on growth or food and water consumption. Solmann (1921) also
reported a study in which men consumed sodium formate in doses of 10 g/day
(150 mg/kg/day) for some time without any harmful effects. On the other
-------
Formic Acid: page 3 of 5
hand, formate doses of 2-3 g several times daily have been reported to cause
nausea and albuminuria in men (von Oettingen, 1969).
The TLV for formic acid vapor in the atmosphere is 5 ppm (ACGIH, 1984),
the same as the OSHA standard (CFR, 1981). Formic acid is "generally recog-
nized as safe" as a synthetic flavoring substance and an indirect food sub-
stance (Guest et al., 1982).
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 100. Based on the information available, the NOEL of 200 mg/kg/day
(Malorny, 1969) can be divided by an uncertainty factor of 100 (10 for
intraspecies extrapolation and 10 for sensitive population) to derive an RfD
of 2 mg/kg/day for protection against adverse human health effects.
MF = 1
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: Medium
Data Base: Medium
RfD: Medium
The study is given a medium confidence because of the extensive length of
testing (i.e., 5 generations) and the fact that several parameters were
measured. The data base is rated medium because several studies are available
that support the choice of NOAEL. A medium rating in the RfD follows.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, August 1985.
U.S. EPA. 1985. Formic Acid: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
Agency RfD Work Group Review: 08/19/85
Verification Date: 08/19/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
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Formic Acid: page 4 of 5
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Formic Acid
CAS No.: 64-18-6
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Formic Acid
CAS No.: 64-18-6
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Formic Acid
CAS No.: 64-18-6
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Formic acid
CAS No.: 64-18-6 Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management
-------
Formic Acid: page 5 of 5
A. RISK MANAGEMENT ACTIONS
Risk Status Risk Considers
Management Management Econ/Tech
Action Date Value Feasibility Reference
Reportable Final 5000 Ibs no 50 FR 13456
Quantity (RQ) 1985 04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity as established under Section
311(b)(4) of the Clean Water Act. Available data indicate that the aquatic
96-Hour Median Threshold Limit for formic acid is between 100 and 175 ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
V. SUPPLEMENTARY DATA
Chemical: Formic Acid
CAS No.: 64-18-6
Information is not available at this time.
Synonyms: ACIDE FORMIQUE (French), ACIDO FORMICO (Italian), AMEISENSAEURE
(German), AMINIC ACID, FORMIC ACID, FORMYLIC ACID, HYDROGEN CARBOXYLIC ACID,
KWAS METANIOWY (Polish), METHANOIC ACID, MIERENZUUR (Dutch), RCRA WASTE NUMBER
U123, UN 1779
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Furan; CAS No. 110-00-9 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code k. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used In these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Furan
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
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Furan: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Furan
CAS No.: 110-00-9 Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Hepatic lesions NOAEL: 2 mg/kg con- 1000 1 1E-3
verted to 1.4 mg/kg/ mg/kg/day
Mouse subchronic oral day on 5 days/7 days
study basis
SRI (1982) LOAEL: 4 mg/kg/day
(rat)
* Dose Conversion Factors & Assumptions: 5 days/week feeding schedule
2. PRINCIPAL AND SUPPORTING STUDIES
SRI (Southern Research Institute). 1982. Subchronic toxicity report on
furan in B6C3F1 mice. Prepared for NTP under Contract No. l-CP-95641-01,
Bethesda, MD.
SRI (1982) performed a 13-week gavage study using mice and rats (10 anl-
mals/sex/group) treated 5 days/week with furan in corn oil at 0-60 mg/kg. In
this study, data on mortality, body weight, organ weight, and clinical and
histopathological signs of toxicity were evaluated.
Clinical signs of toxicity were, for the most part, confined to male and
female rats and female mice in the high-dose (60 mg/kg) group. High-dose
male and female rats and high-dose (30 mg/kg) male mice had treatment-related
reduced rates of body weight gain. In rats, histopathological examination
revealed a dose-related increased severity in liver lesions; lesions observed
-------
Furan: page 3 of 6
at the 4 mg/kg dose level were considered "minimal to mild." Measurement of
relative organ weights revealed a dose-related Increase In liver size in all
treated groups of males and in all but the lowest dose (4 mg/kg) groups of
female rats. In mice, relative organ weight measurements suggest that
treatment-related increases in liver weight occurred in male mice at doses
greater than or equal to 15 mg/kg and in females at doses greater than or
equal to 30 mg/kg. Upon histopathological examination, toxic hepatitis of
dose-related severity was noted in male mice at doses greater than or equal to
8 mg/kg and in female mice at doses greater than or equal to 15 mg/kg.
Examination of the SRI (1982) data indicated that the rat study failed to
define a threshold for toxic hepatitis, the major lesion in the target organ
for the toxicity of furan. The mouse study (SRI, 1982) indicated a threshold
for toxic hepatitis, in that 4 mg/kg was the highest dose in males at which
lesions did not occur; mild lesions of toxic hepatitis occurred at 8 mg/kg.
In females, lesions of toxic hepatitis were absent at 8 mg/kg and present at
15 mg/kg. Since lesions of toxic hepatitis were present in rats at 4 mg/kg,
the highest NOAEL above which no adverse effects occurred is the dose level of
2 mg/kg in male mice. Since treatment was performed 5 days/week, the 2 mg/kg
dose can be transformed to an equivalent dose of 1.4 mg/kg/day. By applying
an uncertainty factor of 1000 to the mouse NOAEL of 1.4 mg/kg/day, an oral RfD
(ADI) of 1 ug/kg/day or 0.1 mg/day for a 70-kg man can be recommended.
3. UNCERTAINTY AND MODIFYING FACTORS
UF « 1000. An uncertainty factor of 1000 was applied: 10 for extrapolation
from subchronic to chronic studies, 10 for interspecies extrapolation and
another factor of 10 to provide added protection for sensitive individuals.
MF - 1
4. ADDITIONAL COMMENTS
Availability of rat and mouse subchronic oral toxicity data provided a
medium level of confidence for the RfD. The National Toxicology Program
(NTP, 1985) is currently evaluating histopathological data of a chronic
gavage bioassay of furan in rats and mice. The data from this study may
change the RfD and the level of confidence.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Low RfD: Medium
The critical study provided toxicological parameters In well-designed
subchronic studies in both rats and mice and, thus, was rated medium; the
data base lacks supporting studies and was rated low; the RfD was based on
multispecies oral studies with adequate toxicity end points, and until addi-
tional data are available a medium confidence is recommended.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1985. Furan: Review and Evaluation of ADI. Environmental Cri-
teria and Assessment Office, Cincinnati, OH. Contract No. 68-03-3228.
ECAO-Cincinnati Internal Review, December 1985.
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Furan: page 4 of 6
Agency RfD Work Group Review: 02/26/86
Verification Date: 02/26/86
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Furan
CAS No.: 110-00-9
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Furan
CAS No.: 110-00-9
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Furan
CAS No.: 110-00-9
Information is not available at this time.
-------
Furan: page 5 of 6
IV. RISK MANAGEMENT SUMMARIES
Chemical: Furan
CAS No.: 110-00-9 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk Status Risk Considers
Management Management Econ/Tech
Action Date Value Feasibility Reference
Reportable Final 100 Ibs no 50 FR 13456
Quantity (RQ) 1985 04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ for furan is based on its ignitability. The boiling point
and flash point for furan are below 100 degrees farenheit.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
V. SUPPLEMENTARY DATA
Chemical: Furan
CAS No.: 110-00-9 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
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Furan: page 6 of 6
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Furan vapors are narcotic (Merck, 1983, p. 613). Acute exposure to furan
by inhalation may involve both reversible and irreversible changes. Acute
exposure by ingestion or skin absorption is associated with high toxicity
(Sax, 1975).
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Vapors are a central nervous system
depressant (Merck, 1976). Symptons include; irritation and burning eyes and
skin, dizziness and suffocation (DOT, 1984, Guide 26).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: C H 0
4 4
Molecular Weight: 68.08
Boiling Point: 90F, 32C at 758 mmHg
Specific Gravity (H20=l): 0.9371 at 19.4C/4C
Vapor Pressure (mmHg): Not Found
Melting Point: -123F, -86C
Vapor Density (AIR=1): 2.3
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: Insoluble; 10 g/liter at 25C
Flash Point [Method Used]: Less than 32F, less than OC [CC]
Flammable Limits:
LEL: 2.3%
UEL: 14.3%
Appearance and Odor: Clear colorless liquid which turns brown upon
standing (Hawley, 1981, p. 483)
Conditions or Materials to Avoid: Do not allow furan to come Into contact
with acids or oxidizing agents (Sax, 1979).
Hazardous Decomposition or Byproducts: Forms of unstable peroxides upon
standing in air (Sax, 1979). Contact with acids can Initiate a violent, heat
producing reaction (Sax, 1979).
Use: Furan is a chemical intermediate for tetrahydrofuran (SRI); used in
the formation of lacquers, as a solvent for resins (Browning, 1965); during
organic synthesis, especially for pyrrole, thiophene (Hawley, 1981).
Synonyms: 1,4-Epoxy-l,3-Butadiene; Divinylene Oxide; Furfuran; NCI-C56202;
Oxacyclopentadiene; Oxole; Tetrole; Axole
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Hexachlorobutadiene; CAS No. 87-68-3 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Hexachlorobutadiene
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: under review
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Hexachlorobutadiene: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Hexachlorobutadiene
CAS No.: 87-68-3 Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Kidney toxicity NOAEL: 0.2 mg/kg/day 100 1 2E-3
ing/kg/day
Rat chronic feeding LOAEL: 2 mg/kg/day
study
Kociba et al. (1977)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Kociba, R.J., D.G. Keyes, G.C. Jersey, et al. 1977. Results of a 2-year
chronic toxicity study with hexachlorobutadiene in rats. Am. J. Ind. Hyg.
Assoc. J. 38: 589-602.
Rats (40/sex/group) were fed diets containing hexachlorobutadiene (HCBD)
at doses equivalent to 0.2, 2.0 or 20 mg/kg bw/day. Untreated controls con-
sisted of 90 animals/sex. Toxicity parameters included hematology, clinical
chemistry urinalysis, gross pathology and histopathology. A LOAEL of 2.0
mg/kg/day was established for kidney toxicity (i.e., excretion of
coproporphyrin was significantly increased at the two higher doses and renal
tubular epithelial hyperplasia was also observed at those same dose levels).
Malignant renal tubular neoplasms were reported at 20 mg/kg/day. No adverse
effects were reported for animals treated at 0.2 mg/kg/day.
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Hexachlorobutadiene: page 3 of 6
3. UNCERTAINTY AND MODIFYING FACTORS
UF — 100. The UF includes uncertainties in interspecies and interhuman
variability to the toxicity of the chemical.
MF = 1
4. ADDITIONAL COMMENTS
A subchronic reproduction study (Schwetz et al., 1977) showed toxic
effects on adult rats fed HCBD at 2 or 20 mg/kg bw/day, but not at 0.2
mg/kg/day. The effects were reduced body weight gain and food consumption;
alterations on neonatal survival and development were also observed. Body
weights of weanlings were slightly reduced at the high dose level.
Other data pertinent to the chronic toxicity of HCBD were not found.
Target organs other than the kidney were not defined.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Low RfD: Low
The critical study appears to be adequate in design but does not warrant
a high confidence rating. Independent supporting data do not exist. Low
confidence is placed in the RfD because of the lack of supporting data and
because the critical effect cannot be clearly dissociated from the carcino-
genic effect.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1982. Toxicity-Based Protective Ambient Water Levels for Various
Carcinogens. Environmental Criteria and Assessment Office, Cincinnati, OH.
ECAO-CIN-431. Internal review draft.
The RfD has been reviewed internally by ECAO-Cin.
Agency RfD Work Group Review: 12/18/85
Verification Date: 12/18/85
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Hexachlorobutadiene
CAS No.: 87-68-3
Information is not available at this time.
-------
Hexachlorobutadiene: page 4 of 6
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Hexachlorobutadiene
CAS No.: 87-68-3
This chemical is among those substances evaluated by the U.S. EPA for
evidence of human carcinogenic potential. This does not imply that this
chemical is necessarily a carcinogen. The evaluation for this chemical is
under review by an Inter-office Agency work group. A risk assessment summary
will be included on IRIS when the review has been completed.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Hexachlorobutadiene
CAS No.: 87-68-3
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Hexachlorobutadiene
CAS No.: 87-68-3 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action In
Appendix E in Service Code 4.
-------
Hexachlorobutadiene: page 5 of 6
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Statutory
1980
Risk
Management
Value
1 Ib
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
2) Marine
Final
1980
0.45 ug/1
no
no
Acute
90 ug/1 (LEL)
Chronic
9.3 ug/1 (LEL)
Acute no
32 ug/1 (LEL)
Chronic
none
45 FR 79318
11/28/80
ibid.
ibid.
B. RISK MANAGEMENT RATIONALE
RQ
The statutory RQ of 1 pound established pursuant to CERCLA Section
102(b) is retained until the assessment of potential carcinogenicity is
complete.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC of 0.45 ug/1 represents a cancer risk level of
IE-6, based on consumption of contaminated organisms and water. A WQC of 50
ug/1 (cancer risk level of 1E-6) has also been established based on
consumption ofcontaminated organisms alone.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value indicates that the
minimum data were not available and the concentration given is not a criteria
value but the lowest effect level found in the literature.
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Hexachlorobutadiene: page 6 of 6
V. SUPPLEMENTARY DATA
Chemical: Hexachlorobutadiene
CAS No.: 87-68-3
Information is not available at this time.
Synonyms: 1,3-Butadiene, Hexachloro-; DOLEN-PUR; GP-40-66:120; HCBD;
Hexachlor-l,3-Butadien (Czech); HeXachlorbutadiene; Hexachlorobutadiene; 1,3-
Hexachlorobutadiene; 1,1,2,3,4,4-Hexachloro-l,3-Butadiene; Perchlorobutadiene;
RCRA Waste Number U128; UN 2279 (DOT)
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Hexachlorocyclopentadiene; CAS No. 77-47-4 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Hexachlorocyclopentadiene
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Hexachlorocyclopentadiene (HCCPD): page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Hexachlorocyclopentadiene (HCCPD)
CAS No.: 77-47-4
Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Stomach lesions
Rat subchronic oral
bioassay
Abdo et al. (1984)
NOAEL: 10 mg/kg bw
(7 mg/kg/day)
LOAEL: 19 mg/kg bw
1000
7E-3
mg/kg/day
* Dose Conversion Factors & Assumptions: 10 mg/kg x 5/7 days = 7 mg/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
Abdo, K.M., C.A. Montgomery, W.M. Kluwe, D.R. Farrell and J.D. Prejean.
1984. Toxicity of hexachlorocyclopentadiene: Subchronic (13-week) adminis-
tration by gavage to F344 rats and B6C3F1 mice. J. Appl. Toxicol. 4: 75-81.
Ten rats/sex were treated by gavage with 0, 10, 19, 38, 75 or 150 mg
hexachlorocyclopentadiene (HCCPD)/kg bw 5 days/week for 13 weeks. Epithe-
lial hyperplasia and focal inflammation of the forestomach was observed in 2
of 8 surviving females only at 19 mg/kg/day. Higher doses were associated
with increased incidence and severity of stomach lesions in both sexes, as
well as a high incidence of toxic nephrosis in females. Toxic nephrosis was
not observed in males. A treatment-related increase in mortality was sug-
gested at the highest dose level.
A mouse study was also conducted (Abdo et al., 1984) in which similar
effects were observed except that 19 mg/kg/day was the NOEL and 38 mg/kg/day
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Hexachlorocyclopentadlene (HCCPD): page 3 of 7
was the LOAEL for mice. Toxic nephrosis was observed only in the female mice.
Mortality was observed in the highest treatment group (300 mg/kg/day), and was
greater for males (10/10) than for females (3/10).
The authors concluded that mice and rats are approximately equally sus-
ceptible to the toxic effects of HCCPD by gavage. Females appeared to be more
susceptible than males. The dose-related kidney injury suggests that the
kidney is a major target organ. The forestomach lesions may result from a
direct biological reaction to high concentrations at this site.
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 1000. A factor of 10 each was applied for uncertainty in the
subchronic NOAEL (since chronic levels were not observed), uncertainty in the
interspecies conversion and uncertainty in the sensitive human subpopulations.
MF = 1
4. ADDITIONAL COMMENTS
The stomach lesions observed in the critical study are consistent with
the general portal effects of this compound. Lung damage and skin lesions
are observed in inhalation and dermal exposures, respectively. However, both
kidney and lung appear to be affected by HCCPD independent of the route of
exposure. One study of an accidental human exposure suggests that the liver
may be another target organ.
A NTP chronic bioassay is in process using F344 rats and B6C3F1 hybrid
mice. The RfD and carcinogenicity values are subject to change pending the
results of this testing. Subchronic results (13 weeks) in rats exposed to
0.5 ppm showed a minimal to mild acute inflammatory response in the respira-
tory tract and minimal squamous metaplasia of the nasal cavity epithelium.
Exposure at the 0.2-ppm level did not produce any clear-cut histopathologic
effects. Mice exposed at 0.5 ppm had moderate to severe subchronic inflamma-
tion of the mucosa of the bronchi and bronchioles as well as squamous meta-
plasia of the larynx, trachea, bronchi and bronchioles. These effects dimin-
ished in severity over the treatment period.
HCCPD was not teratogenic by oral gavage in rats, mice and rabbits.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Low RfD: Low
The critical study, though of short duration, examined a fair number of
toxicity parameters at six dose levels in two species with corroborative
results. No chronic oral toxicological studies on HCCPD can be found in the
available literature. Inhalation studies up to 30 weeks have shown that HCCPD
is much more toxic by that route of administration. Toxicity of HCCPD by der-
mal exposure is also greater than by the oral route. HCCPD toxicity Is
characterized by a steep dose-response curve. Because of these considera-
tions, a low confidence is placed on the RfD.
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Hexachlorocyclopentadiene (HCCPD): page 4 of 7
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1984. Health and Environmental Effects Profile for Hexachloro-
cyclopentadiene. Environmental Criteria and Assessment Office, Cincinnati,
OH. ECAO-CIN-P051.
The ADI in the 1984 Health and Environmental Effects Profile document has
received an Agency review with the help of two external scientists.
Agency RfD Work Group Review: 10/09/86
Verification Date: 10/09/86
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Hexachlorocyclopentadiene
CAS No.: 77-47-4
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Hexachlorocyclopentadiene
CAS No.: 77-47-4
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Hexachlorocyclopentadiene
CAS No.: 77-47-4
Information is not available at this time.
-------
Hexachlorocyclopentadiene (HCCPD): page 5 of 7
Chemical: Hexachlorocyclopentadiene (HCCPD)
CAS No.: 77-47-4
IV. RISK MANAGEMENT SUMMARIES
Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I fie II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E In Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Statutory
1980
Risk
Management
Value
1 Ib
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
1.0 ug/1
no
2) Marine
Clean Air Act
Regulatory
Decision:
(NESHAP or NSPS)
Final
1980
Current
1985
Acute no
7.0 ug/1 (LEL)
Chronic
5.2 ug/1 (LEL)
Acute no
7.0 ug/1 (LEL)
Chronic
none
Decision not
to Regulate
no
45 FR 79318
11/28/80
ibid.
ibid.
50 FR 40154
10/01/85
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Hexachlorocyclopentadlene (HCCPD): page 6 of 7
B. RISK MANAGEMENT RATIONALE
RQ
The statutory RQ of 1 pound established under Section 311(b)(4) of the
Clean Water Act is retained until assessments of chronic toxicity and
degradation characteristics are complete.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: For comparison purposes, two approaches were used to derive
criterion levels for hexachlorocyclopentadiene. Based on available toxicity
data, for the protection of public health, the derived level is 206 ug/1.
Using available organoleptic data, for controlling undesirable taste and odor
quality of ambient water, the estimated level is 1.0 ug/1. It should be
recognized that organoleptic data as a basis for establishing a water quality
criterion have limitations and have no demonstrated relationship to potential
adverse human health effects.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value indicates that the
minimum data were not available and the concentration given is not a criteria
value but the lowest effect level found in the literature.
CAA Regulatory Decision
EPA's assessment of HCCPD as a toxic air pollutant indicated that modeled
ambient concentrations from the largest HCCPD source were very close to the
ACGIH occupational limits for 8 hour and 15 minute time periods. The known
health effects at the levels predicted are irritation to the eyes, nose, and
throat and headaches. The number of sources of HCCPD is very small. Thus,
given the very limited potential for human exposure and the absence of
information suggesting serious health effects at ambient concentrations, EPA
concluded that regulation of HCCPD under the CAA was not warranted. Comment
was solicited on the decision.
Contact: Chief, Pollutant Assessment Branch
FTS/629-5645 or 919/541-5645
V. SUPPLEMENTARY DATA
Chemical: Hexachlorocyclopentadiene
CAS No.: 77-47-4 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
-------
Hexachlorocyclopentadiene (HCCPD): page 7 of 7
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Hexachlorocyclopentadiene is very toxic and may be fatal if inhaled,
swallowed, or absorbed through the skin. The probable human lethal dose is
50-500 mg/kg, or between 1 teaspoon and 1 ounce for a 150-lb. (70-kg) person.
Severe exposure induces pulmonary hyperemia and edema, degenerative and
necrotic changes in brain, heart and adrenal glands and necrosis of liver and
kidney tubules (DOT, 1984; Gosselin, 1984, p. 11-169).
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Inhalation of mist is highly irritating
to mucous membranes, causing tearing, sneezing, and salivation. Eye contact
may result in severe irritation. Contact of liquid with the skin may cause
blistering and burning (CHRIS, 1978). Headaches and throat irritation have
also been reported as a result of exposure to this compound (Clayton and
Clayton, 1981, p. 3751).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: C Cl
5 6
Molecular Weight: 272.77
Boiling Point: 462F, 239C at 753 mmHg
Specific Gravity (H20=l): 1.7019 at 25/4C
Vapor Pressure (mmHg): 0.080 at 25C
Melting Point: 16F, -9C
Vapor Density (AIR-1): 9.4
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: 800 ppb
Flash Point [Method Used]: Non-flammable
Flammable Limits: Not Found
Appearance and Odor: Yellow-green liquid (Weast, 1984) with a pungent
odor (Hawley, 1981)
Conditions or Materials to Avoid: Reacts slowly with water to form
hydrochloric acid; however, the reaction is not hazardous (Weiss, 1980, p.
498). HCCPD will corrode iron and other metals in the presence of moisture
(Weiss, 1980, p. 498).
Hazardous Decomposition or Byproducts: Not Found
Use: Major uses of hexachlorocyclopentadiene include applications as a
chemical intermediate for Insecticides and flame retardants (SRI).
Synonyms: 1,3-Cyclopentadiene, 1,2,3,4,5,5-Hexachloro-; C 56; Graphlox;
HCCPD; Hexachlorocyclopentadien; Hexachloropentadiene; HRS 1655; NCI-C55607;
PCL; Perchlorocyclopentadiene
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Hydrogen Cyanide; CAS No. 74-90-8 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Hydrogen Cyanide
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
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Hydrogen Cyanide: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Hydrogen Cyanide
CAS No.: 74-90-8 Preparation Date: 01/06/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Rat chronic oral 10.8 mg/kg/day CN 100 5 2E-2
study (NOAEL) converted to
11.2 mg/kg/day of
Howard and Hanzal hydrogen cyanide
(1955)
Weight loss, thyroid 30 mg/kg/day CN
effects and myelin (LOAEL)
degeneration (31 mg/kg/day HCN)
Rat subchronic to
chronic oral bioassay
Philbrick et al.
(1979)
* Dose Conversion Factors & Assumptions: molecular weight conversion factor
= 27/26 [ MW HCN = 27; MW CN = 26 ]
2. PRINCIPAL AND SUPPORTING STUDIES
Howard, J.W. and R.F Hanzal. 1955. Chronic toxicity to rats of food treated
with hydrogen cyanide. Agric. Food Chem. 3: 325-329.
Since hydrogen is present in very high levels physiologically, an RfD of
1.5 mg/day is recommended based on cyanide content.
-------
Hydrogen Cyanide: page 3 of 7
In this 2-year dietary study, rats (10/sex/group) were administered food
fumigated with HCN. The average daily concentrations were 73 and 183 mg CN/kg
diet. From the data reported on food consumption and body weight, daily
estimated doses were 4.3 mg and 10.8 mg CN/kg bw. The average food CN
concentrations were estimated based on the authors' data for concentration at
the beginning and end of each food preparation period and by assuming a first-
order rate of loss for the intervening period. There were no treatment-
related effects on growth rate, no gross signs of toxicity, and no histo-
pathological lesions.
Studies by Philbrick et al. (1979) showed decreased weight gain and thy-
roxin levels and myelin degeneration in rats at 30 mg/kg/day CN. Other
chronic studies either gave higher effect levels or used the subcutaneous
route (Crampton et al., 1979; Lessell, 1971; Herthing et al., 1960). Human
data do not provide adequate information from which to derive an RfD because
effective dose levels of chronically ingested CN are not documented.
Therefore, the study of Howard and Hanzel (1955) provides the highest NOAEL,
10.8 mg/kg/day, for CN and is chosen for the derivation of an RfD for CN of
1.5 mg/day or 0.02 mg/kg/day.
Cyanide is metabolized extensively in the liver, indicating that the only
relevant route of administration for quantitative risk assessment in the
derivation of an oral RfD is the oral route of administration.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. According to the U.S. EPA (1985), an uncertainty factor of 100 is
used to derive the RfD (10 for species extrapolation, 10 for sensitive
population).
MF » 5. A modifying factor of 5 is used to account for the apparent tolerance
to cyanide when it is ingested with food rather than when it is administered
by gavage or by drinking water.
4. ADDITIONAL COMMENTS
Decreased protein efficiency ratio was produced by dietary cyanide treat-
ment of rats during gestation, lactation and postweaning growth phase in the
Tewe and Maner (1981a) experiment; the dose level of cyanide (10.6 mg/kg/day)
producing that effect is slightly lower than the currently accepted NOAEL of
10.8 mg/kg/day (U.S. EPA, 1985). Furthermore, Tewe and Maner (1981b) tested
sows. Possible effects observed at about 9.45 mg/kg/day were proliferation
of glomerular cells of the kidneys and reduced activity of the thyroid glands
in the gilts. However, the number of animals in this experiment was very
small. A Japanese study (Amo, 1973) indicated that 0.05 mg/kg/day of cyanide
obtained from drinking water decreased the fertility rate and survival rate
in the Fl generation and produced 100% mortality in the F2 generation in
mice. However, these data are not consistent with the body of available
literature. Thus, until additional chronic studies are available, an RfD of
3.8 mg/day for a 70-kg human is recommended.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD:Medium
The confidence in the study is medium because adequate records of food
consumption and body weight were maintained, and animals of both sexes were
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Hydrogen Cyanide: page 4 of 7
tested at two doses for 2 years. The data base is rated medium because a
small but sufficient number of studies support the chosen study. The confi-
dence in the RfD follows. Additional chronic/reproductive studies are needed
to support a higher level of confidence in the RfD.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, 1985. Limited peer review and Agency-wide
review, 1985.
U.S. EPA. 1985. Cyanides: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. 1984. Health Effects Assessment for Cyanides. Environmental Cri-
teria and Assessment Office, Cincinnati, OH. ECAO-CIN-H011.
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Hydrogen Cyanide
CAS No.: 74-90-8
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Hydrogen Cyanide
CAS No.: 74-90-8
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
-------
Hydrogen Cyanide: page 5 of 7
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Hydrogen Cyanide
CAS No.: 74-90-8
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Hydrogen Cyanide
CAS No.: 74-90-8 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk Status Risk Considers
Management Management Econ/Tech
Action Date Value Feasibility Reference
Reportable Final 10 Ibs no 50 FR 13456
Quantity (RQ) 1985 04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ was based on aquatic toxicity, as established under CWA
Section 311(b)(4). Available data indicate that the aquatic 96-Hour Median
Threshold Limit for hydrogen cyanide is less than 1 ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
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Hydrogen Cyanide: page 6 of 7
V. SUPPLEMENTARY DATA
Chemical: Hydrogen Cyanide
CAS No.: 74-90-8 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Hydrogen cyanide is super toxic. Breathing in a small amount of the gas
or swallowing a very small amount may be fatal (NFPA, 1978; Gosselin, 1976).
Average fatal dose is 50-60 mg. A few minutes of exposure to 300 ppm may
result in death. Exposure to 150 ppm for 1/2 to 1 hour may endanger life
(Merck, 1983, p. 696).
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Exposure to hydrocyanic acid can cause
weakness; headache; confusion; nausea; vomiting; increased rate of
respiration or slow, gasping respiration; and eye and skin irritation
(NIOSH/OSHA, 1978, p. 113). This is followed by collapse, coma, convulsions,
and death (Weiss, 1980, p. 514).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: HCN
Molecular Weight: 27.03
Boiling Point: 78.IF, 25. 6C
Specific Gravity (H20=l): 0.699 (liquid)
Vapor Pressure (mmHg): 630
Melting Point: 7.9F, -13.4C
Vapor Density (AIR=1): 0.901 g/1
Evaporation Rate (Butyl acetate—I): Not Found
Solubility in Water: Miscible with water
Flash Point [Method Used]: OF, -18C (CC)
Flammable Limits:
LEL: 5.6%
UEL: 40.0%
Appearance and Odor: Colorless gas or liquid; bitter almond odor (Merck,
1976; CHRIS, 1978)
Conditions or Materials to Avoid: Hydrocyanic acid solution is sensitive
to light (Hawley, 1977). It may become unstable and subject to explosion if
-------
Hydrogen Cyanide: page 7 of 7
stored for an extended time or exposed to high temperature and pressure
(CHRIS, 1978). Avoid heat, flame or oxidizers (Sax, 1984, p. 1548).
Unstabilized hydrocyanic acid may polymerize spontaneously with explosive
violence (Hawley, 1981). Can polymerize at 50-60C or when catalyzed with
traces of alkali (Sax, 1984, p. 1548). Avoid acetylaldehyde, alkaline
materials, oxidizers, water, steam, acid, and acid fumes (Sax, 1984, p. 1548)
Hazardous Decomposition or Byproducts: Toxic cyanide fumes (Sax, 1984, p.
1548)
Use: Hydrogen cyanide is used as a rodent poison and as a fumigant
(Rossoff, 1974). It Is a chemical intermediate in the manufacture of
acrylates, methacrylates, hexamethylenediamine, nitriles, and other materials
(Patty, 1963). It Is also used in metal polishes, electroplating solutions,
and metallurgical and photographic processes (Gosselin, 1976).
Synonyms: Hydrogen Cyanide; Prussic Acid; Aero Liquid HCN; Cyclon; Cyclone B;
Evercyn; Formic Anammonide; Formonitrile; Zaclondiscoids
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Hydrogen Sulfide; CAS No. 7783-06-4 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Hydrogen Sulfide
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Hydrogen Sulfide: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) Is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Hydrogen Sulfide
CAS No.: 7783-06-4 Preparation Date: 01/10/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
GI disturbance
Pig oral toxicity
3.1 mg/kg/day (NOAEL)
15 mg/kg/day (LOAEL)
1000 1 3E-3
mg/kg/day
study (subchronic)
Watterau et al. (1964-
1965)
* Dose Conversion Factors & Assumptions: 0.200 kg of diet/day x 1210 mg
H2S/kg of diet / 78 kg bw - 3.1 mg/kg bw/day
2. PRINCIPAL AND SUPPORTING STUDIES
Watterau, H., W. Ockert and U.G. Knape. 1964-1965. In: Toxicity of Hydrogen
Sulfide in Animal Feeding. Survey of the literature. (Westermann et al.,
1975. Landwirtsch. Forsch. 28: 70-80)
Data regarding chronic/subchronic toxicity of H2S was limited and H2S is
not scheduled for carcinogenicity testing by the NTP (1985). The oral tox-
icity data (Watterau et al., 1964-1965) may be used to calculate an RfD.
Although lacking In some detail, Watterau et al. (1964-1965) suggested that
adult pigs showed digestive disorders when their diet was replaced by a high
percentage of dried greens containing H2S at an approximate Intake of 15
mg/kg/day. This effect was not reproduced In a second experiment. This dose
may be considered a LOAEL.
Watterau et al. (1964-1965) also tested pigs for 105 days at three lower
doses. An intermediate dose of approximately 3.1 mg/kg/day (determined from
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Hydrogen Sulfide: page 3 of 6
information given in the critical study) was associated with no changes in
body weight gain when compared to controls.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. The uncertainty factor of 1000 represents 10 for interspecies
extrapolation, 10 for sensitive population and 10 for subchronic exposure.
An RfD of 0.003 mg/kg/day may be recommended for adequate protection
against adverse human health effects.
MF = 1
4. ADDITIONAL COMMENTS
Based on epidemiological data (Poda, 1966) the ACGIH (1980) has recom-
mended a TLV-TWA of 10 ppm (13.9 mg/cu. m) for hydrogen sulfide. However,
citing evidence of eye injury, headaches, nausea and insomnia after exposure
to H2S at low concentrations for several hours, NIOSH (1977) adopted a ceil-
ing occupational exposure limit of 10 ppm with a 10-minute maximum exposure
to this concentration. More rigorous epidemiological evidence, however, is
limited. Until further chronic/reproductive data are available, a low
confidence in the RfD is recommended.
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Low RfD: Low
The confidence in the study is rated low because the number of animals/
dose group was unspecified and the study was designed to test for only mini-
mal toxic responses. No oral toxicity data have been located. Low confidence
in the RfD follows.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Interanl Review, August 1985.
U.S. EPA. 1985. Hydrogen Sulfide: Review and Evaluation of ADI. Contract
No. 68-03-3228, Environmental Criteria and Assessment Office, Cincinnati, OH.
Agency RfD Work Group Review: 08/19/85
Verification Date: 08/19/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
-------
Hydrogen Sulfide: page 4 of 6
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Hydrogen SulfIde
CAS No.: 7783-06-4
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Hydrogen Sulfide
CAS No.: 7783-06-4
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Hydrogen Sulfide
CAS No.: 7783-06-4
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Hydrogen sulfide
CAS No.: 7783-06-4 Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent Inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Hydrogen Sulfide: page 5 of 6
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1986
Risk
Management
Value
100 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
51 FR 34534
09/29/86
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity, as established under CWA
Section 311(b)(4), ignitability and reactivity. The available data indicate
the aquatic 96-Hour Median Threshold Limit for hydrogen sulfide is between 1
and 10 ppm. In addition, it has a closed cup flash point below 100 degrees
F, a boiling point above 100 degrees F, and is extremely reactive with water.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
V. SUPPLEMENTARY DATA
Chemical: Hydrogen Sulfide
CAS No.: 7783-06-4 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Exposure to very high concentrations of hydrogen sulfide causes immediate
death (Sax, 1984, p. 1552). Also, death or permanent injury may occur after
very short exposure to small quantities of hydrogen sulfide (Sax, 1975). It
acts directly upon the nervous system resulting in paralysis of respiratory
centers (Casarett, 1975).
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Contact with eyes causes painful
conjunctivitis, sensitivity to light, tearing, and clouding of vision.
Inhalation of low concentrations causes a runny nose with a loss of smelling
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Hydrogen Sulfide: page 6 of 6
sense, labored breathing, and shortness of breath. Direct contact with skin
causes pain and redness. Other symptoms of exposure include profuse
salivation, nausea, vomiting, diarrhea, giddiness, headache, dizziness,
confusion, rapid beathing, rapid heart rate, sweating, weakness, sudden
collapse, unconsciousness and death due to respiratory paralysis (Gosselin
1976).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: H S
2
Molecular Weight: 34.08
Boiling Point: -76.59F, -60.33C
Specific Gravity (H20=l): 0.916 at -60C (Liquid)
1.54 g/L at OC
Vapor Pressure (mmHg): 20 atmospheres at 25.5 C
Melting Point: -121.9F, -85.49C
Vapor Density (AIR-1): 1.19
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: 1 gram dissolves in 242 mL at 20C
Flash Point [Method Used]: Not Found
Flammable Limits:
LEL: 4.3%
UEL: 45%
Appearance and Odor: Colorless gas with the characteristic odor of rotten
eggs (Weast, 1979; Merck, 1976).
Conditions or Materials to Avoid: Avoid physical damage to containers;
sources of ignition; and, storage near nitric acid, strong oxidizing
materials, and corrosive liquids or gases (NFPA, 1978). Hydrogen sulfide is
incompatible with many materials, including strong oxidizers, metals
(NIOSH/OSHA, 1978, p. 112), strong nitric acid, bromine pentafluoride,
chlorine trifluoride, nitrogen triiodide, nitrogen trichloride, oxygen
difluoride and phenyl diazonium chloride (NFPA, 1978).
Hazardous Decomposition or Byproducts: When heated to decomposition, it
emits highly toxic fumes of oxides of sulfur (Sax, 1984, p. 1552).
Use: Used in the manufacturing of chemicals; in metallurgy; as an
analytical reagent; as an agricultural disinfectant, as an intermediate for
sulfuric acid, elemental sulfur, sodium sulfide, and other inorganic
sulfides; as an additives in extreme pressure lubricants and cutting oils;
and as an intermediate for organic sulfur compounds (Merck, 1976; Encyc
Occupat Health and Safety, 1971; SRI). Not registered as a pesticide in the
U.S. (USEPA/Pesticide Index, 1985).
Synonyms: Dihydrogen Monosulfide; Dihydrogen Sulfide; Hydrogen Sulphide;
Hydrosulfuric Acid; Sewer Gas; Stink Damp; Sulfur Hydride; Sulfureted Hydrogen
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Isophorone; CAS No. 78-59-1 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Isophorone
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: review pending
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Isophorone: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Isophorone
CAS No.: 78-59-1
Preparation Date: 07/31/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
None
Dog, subchronic oral
bioassay
Rohm & Haas, 1972
150 mg/kg bw/day
(NOEL)
1000
1.5E-1
mg/kg/day
Transitory weight
loss
Rat, subchronic
bioassay
3000 ppm of diet
(150 mg/kg/ bw/day)
(NOAEL)
Kidney pathology
Rat, chronic gavage
bioassay
NTP Final Technical
Report (1986)
179 mg/kg/day
(LOAEL)
* Dose Conversion Factors & Assumptions: rat food consumption = 5% bw/day.
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Isophorone: page 3 of 6
2. PRINCIPAL AND SUPPORTING STUDIES
Rohm and Haas. 1972. Pesticide Petition No. 2F1224.
Available from EPA. Write to FOI, EPA, Washington D.C. 20460.
National Toxicology Program (NTP). 1986. Draft Technical Report. NIH
Publication No. 84-2547, NTP-83-168
Experimental groups of four male and four female beagle dogs were fed
gelatin capsules containing 0, 35, 75 or 150 mg isophorone/kg bw/day for 90
days (Rohm & Haas, 1982). All animals survived the study with no signs of
ill-health. There were no treatment-related changes in hematology, blood
chemistry, urinalysis or organ weight and gross appearance. In tissues
examined (28 tissues selected from the control and high-dose group, liver and
kidney from all groups) there was no evidence of cellular change. The same
group of researchers fed isophorone in the diet at levels of 0, 750, 1500 and
3000 ppm to groups of 20 male and 20 female CFE weanling rats for 90 days.
The only effect noted was decreased body weight for males of the highest
treatment group for several weeks. Body weights were not different from
controls by the end of the study. The highest dose was approximately
equivalent to 150 mg/kg bw/day using a conservative estimate for rat food
consumption (5% of body weight per day).
Data reported in the 1986 Final Technical Report of an NTP 2-year bio-
assay are supportive of the RfD. Both rats and mice treated with 500 mg/kg,
5 times/week by gavage experienced decreased body weight (5-8%) as compared
to controls. Male F344/N rats treated with 250 mg/kg, 5 times/week (or
approximately 179 mg/kg/day) showed signs of kidney pathology, including epi-
thelial hyperplasia of the renal pelvis and increased mineralization of
medullary collecting ducts. An RfD based on this study would be 0.2 mg/kg/day
with the use of a 1000-fold UF (i.e., LOAEL to NOAEL extrapolation,
interspecies variation and protection of sensitive humans).
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. Factors of 10 each were applied for use of a subchronic study,
to account for interspecies variation and for protection of sensitive human
subpopulations.
MF = 1
4. ADDITIONAL COMMENTS
There was no evidence of teratogenicity or fetotoxicity in Fischer 344
rats or CD-I mice exposed by inhalation on days 6-15 of gestation to 25, 50
or 115 ppm isophorone. Both rat and mouse dams exposed to 115 ppm isophorone
experienced lower body weights as compared to controls on days 12-15 or 18 of
gestation.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
Since there were sufficient numbers of animals of two species and multiple
biological end points measured, the study confidence may be rated as medium;
the subchronic nature of the assay and the lack of an observed adverse effect
preclude a higher rating. Since the RfD is supported by results of the NTP
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Isophorone: page 4 of 6
bioassay, confidence in the data base and the overall confidence in the RfD
are rated medium.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1980. Ambient Water Quality Criteria Document for Isophorone.
Environmental Criteria and Assessment Office, Cincinnati, OH. EPA
440/5-80-056. NTIS PB 81-117673.
The ADI in the 1980 Ambient Water Quality Criteria Document was extensively
reviewed by the Agency and was reviewed by the public.
Agency RfD Work Group Review: 12/02/85, 02/05/86, 05/15/86
Verification Date: 05/15/86
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Isophorone
CAS No.: 78-59-1
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Isophorone
CAS No.: 78-59-1
This chemical is among those substances evaluated by the U.S. EPA for
evidence of human carcinogenic potential. This does not imply that this
chemical is necessarily a carcinogen. The evaluation for this chemical is
under review by an inter-office Agency work group. A risk assessment summary
will be included on IRIS when the review has been completed.
-------
Isophorone: page 5 of 6
III. DRINKING WATER HEALTH ADVISORIES
Chemical:
CAS No.:
Isophorone
78-59-1
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical:
CAS No.:
Isophorone
78-59-1
Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated In the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment Information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
5000 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
5.2 mg/1
no
2) Marine
Final
1980
Acute no
117,000 ug/1 (LEL)
Chronic
none
Acute no
12,900 ug/1 (LEL)
Chronic
none
45 FR 79318
11/28/80
ibid.
ibid.
-------
Isophorone: page 6 of 6
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ for isophorone is based on aquatic toxicity. The available
data indicate that the aquatic 96-Hour Median Threshold Limit for isophorone
is between 100 and 500 ppm.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC of 5.2 mg/1 is based on consumption of contaminated
aquatic organisms and water. A WQC of 520 mg/1 has also been established
based on consumption of contaminated aquatic organisms alone.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value indicates that the
minimum data were not available and the concentration given is not a criteria
value but the lowest effect level found in the literature.
Chemical: Isophorone
CAS No.: 78-59-1
V. SUPPLEMENTARY DATA
Information is not available at this time.
Synonyms: in preparation
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Lindane; CAS No. 58-89-9 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxlcity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Lindane
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: review pending
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Lindane: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Lindane
CAS No.: 58-89-9 Preparation Date: 04/28/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Liver and kidney
toxicity
4 ppm diet 0 . 3 mg/kg
bw/day (females)
(NOAEL)
1000 1
3E-4
ing/kg/day
Rat, subchronic oral
bioassay 20 ppm diet 1.55
mg/kg bw/day (males)
RCC (1983) (LOAEL)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Research and Consulting Co., Ltd. 1983. Ace. Nos. 250340-250342.
Available from EPA. Write to FOI, EPA, Washington D.C. 20460.
Twenty male and 20 female Wistar KFM-Han (outbred) SPF rats/treatment
group were administered 0, 0.2, 0.8, 4, 20 or 100 ppm lindane (99.85%) in the
diet. After 12 weeks, 15 animals/sex/group were sacrificed. The remaining
rats were fed the control diet for an additional 6 weeks before sacrifice.
No treatment-related effects were noted on mortality, hematology, clinical
chemistry or urinalysis. Rats receiving 20 and 100 ppm lindane were observed
to have greater-than-control incidence of the following: liver hypertrophy,
kidney tubular degeneration, hyaline droplets, tubular distension, inter-
stitial nephritis and basophilic tubules. Since these effects were mild or
rare in animals receiving 4 ppm, this represents a NOAEL. The reviewers of
the study calculated the dose to be 0.29 mg/kg/day for males and 0.33
mg/kg/day for females, based on measured food intake.
-------
Lindane: page 3 of 7
In a 2-year feeding study (Fitzhugh, 1950), 10 Wistar rats/sex/group were
exposed to 5, 10, 50, 100, 400, 800 or 1600 ppm lindane. Slight liver and
kidney damage and increased liver weights were noted at the 100 ppm level.
If a food intake equal to 5% body weight is assumed, a NOAEL of 2.5 mg/kg
bw/day (50 ppm) can be determined from this assay. In a 2-year bioassay
(Rivett et al., 1978), four beagle dogs/sex/group were administered 0, 25, 50
or 100 ppm lindane in the diet. Treatment-related effects noted in the
animals of the 100 ppm group were increased serum alkaline phosphatase and
enlarged dark friable livers. A NOAEL was determined to be 50 ppm (1.6 mg/kg
bw/day).
Use of the NOAEL derived from the RCC (1983) study is most appropriate, in
keeping with the practice of utilizing data from the most sensitive species
(or strain) as a surrogate for humans when human data are lacking.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. A factor of 10 each was employed for use of a subchronic vs. a
lifetime assay, to account for interspecies variation and to protect
sensitive human subpopulations.
MF - 1
4. ADDITIONAL COMMENTS
Data on reproductive effects of lindane are inconclusive. Most reports
indicate that hexachlorocyclohexane isomers are nonteratogenic.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The RCC (1983) study used an adequate number of animals and measured mul-
tiple end points. Since there are other reported chronic and subchronic
studies, confidence in the study, data base and RfD is considered medium.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1985. Drinking Water Criteria Document for Lindane. Office of
Drinking Water, Washington, DC.
The RfD in the Drinking Water Criteria Document has been extensively reviewed
by U.S. EPA scientists and selected outside experts.
Agency RfD Work Group Review: 01/22/86
Verification Date: 01/22/86
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
-------
Llndane: page 4 of 7
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Lindane
CAS No.: 58-89-9
Information is not available at this time.
Chemical:
CAS No.:
II. RISK ESTIMATES FOR CARCINOGENS
Llndane
58-89-9
This chemical Is among those substances evaluated by the U.S. EPA for
evidence of human carcinogenic potential. This does not imply that this
chemical is necessarily a carcinogen. The evaluation for this chemical is
under review by an inter-office Agency work group. A risk assessment summary
will be included on IRIS when the review has been completed.
III. DRINKING WATER HEALTH ADVISORIES
Chemical:
CAS No.:
Lindane
58-89-9
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical:
CAS No.:
Lindane
58-89-9
Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Lindane: page 5 of 7
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Status Risk Considers
Management Econ/Tech
Date Value Feasibility
Reference
Reportable
Quantity (RQ)
Water Quality
Criteria (WQC):
a. Human Health
b. Aquatic Toxicity
1) Freshwater
2) Marine
Statutory
1980
Final
1980
Final
1980
1 Ib no
18 . 6 ng/1 no
Acute no
2.0 ug/1
Chronic
0.080 ug/1
Acute no
0.16 ug/1
Chronic
none
50 FR 13456
04/04/85
45 FR 79318
11/28/80
45 FR 79318
11/28/80
ibid.
Pesticide Active
Ingredient:
a. Registration
Standard
b. Special
Review
Current
1985
various
Termination P.O. 1
of RPAR
1983
no
no
Reg. Std.
Sept. 1985
42 FR 9816
02/18/77
P.O.
P.O.
2/3
4
yes
yes
45 FR 45362
07/03/80
48 FR 48512
09/30/83
B. RISK MANAGEMENT RATIONALE
RQ
The statutory RQ of 1 pound established pursuant to CERCLA Section
102(b) is retained until the assessment of potential carcinogenicity is
complete.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC of 18.6 ng/1 represents a cancer risk level of
IE-6 based on consumption of contaminated organisms and water. A WQC of
62.5 ng/1 has been established based on consumtion of contaminated aquatic
organisms alone.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
-------
Lindane: page 6 of 7
variety of aquatic organisms. The data are assumed to be statistically
representative and are used to calculate concentrations which will not have
significant short or long term effects on 95% of the organisms exposed.
Recent criteria (1985 and later) contain duration and frequency stipulations:
the acute criteria maximum concentration is a 1-hour average and the chronic
criteria continuous concentration is a 4-day average which are not to be
exceeded more than once every three years, on the average (see Stephen et al.
1985). Earlier criteria (1980-1984) contained instantaneous acute and
24-hour average chronic concentrations which were not to be exceeded. (FR 45:
79318: November 28, 1980). The freshwater chronic WQC is a 24-hour average.
Pesticide Active Ingredient
a. Regulation Standard: Lindane Pesticide Registration Standard.
September 1985. Registration Support and Emergency Response Branch,
Office of Pesticide Programs.
Contact: Office of Pesticides Programs
202/557-7760 or FTS/557-7760
b. Special Review: Negotiated settlements have been made for Lindane in dog
dips [49 FR 26282 (06/27/84)] and in smoke bombs [50 FR 5424 (02/08/85)].
Contact: Office of Pesticides Programs, Special Review Branch
202/557-7420 or FTS/557-7420
V. SUPPLEMENTARY DATA
Chemical: Lindane
CAS No.: 58-89-9 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
In Service Code 4. The user Is urged to read the background document for
this section (Appendix E In Service Code 4) for further Information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Lindane is a stimulant of the nervous system, causing violent convulsions
that are rapid in onset and generally followed by death or recovery with 24
hours (Hayes, 1982, p. 218). The probable human oral lethal dose is 50-500
mg/kg, or between 1 teaspoon and 1 ounce for a 150-lb (70-kg) person
(Gosselin, 1984, p. 11-286).
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Lindane in contact with the eyes or skin
may produce irritation (DASE, 1980, p. 529). Vomiting, faintness, tremor,
restlessness, muscle spasms, unsteady gait, and convulsions may occur as a
result of exposure. Elevated body temperature and pulmonary edema have been
-------
Lindane: page 7 of 7
reported in children. Coma, respiratory failure and death can result.
Exposure to vapors of this compound, or its thermal decomposition products,
may lead to headache, nausea, vomiting, and Irritation of the eyes, nose, and
throat (Gosselin, 1984, pp. III-240, 241).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: C H Cl
666
Molecular Weight: 290.83
Boiling Point: 614F, 323.4C; Decomposes
Specific Gravity (H20=l): 1.9
Vapor Pressure (mmHg): 9.4 x 10-6 at 20C
Melting Point: 234.5F, 112.5C
Vapor Density (AIR=1): Not Found
Evaporation Rate (Butyl acetate=l): Not Found
Solubility In Water: Insoluble
Flash Point [Method Used]: Not Found
Flammable Limits: Not Found
Appearance and Odor: Colorless solid with a musty odor; pure material is
odorless (NIOSH/OSHA, 1978, p. 120).
Conditions or Materials to Avoid: Not Found
Hazardous Decomposition or Byproducts: Thermal decomposition products may
include chlorine, hydrochloric acid, and phosgene (Sax, 1984, p. 366).
Use: Lindane is used as a pesticide (Hawley, 1981, p. 617) and scabicide
(Hayes, 1982, p. 221).
Synonyms: (NIOSH/RTECS 1983 Synonyms, Volume 1, p. 1,000): Cyclohexane,
1,2,3,4,5,6-Hexachloro-, Gamma-Isomer; Aalindan; Aficide; Agrisol G-20;
Agrocide; Agrocide 2; Agrocide 7; Agrocide 6G; Agrocide III; Agrocide WP;
Agronexit; Ameisenatod; Ameisenmittel Merck; Aparasln; Aphtiria; Aplidal;
Arbitex; BBH; Ben-Hex; Bentox 10; Benzene Hexachloride-gamma-isomer;
gamma-Benzene Hexachloride; Bexol; BHC; gamma-BHC; Celanex; Chloresene;
Codechine; DBH; Detmol-Extrakt; Detox 25; Devoran; Dol Granule; Drill
Tox-Spezial Aglukon; Ent 7,796; Entomoxan; Exagama; Forlin; Gallogama; Gamacid
Gamaphex; Gamene; Gammahexa; Gammahexane; Gammalin; Gammalin 20; Gammaterr;
Gammex; Gammexane; Gammopaz; Gexane; HCCH; HCH; gamma-HCH; Heclotox; Hexa;
Hexachloran; gamma-Hexachloran; Hexachlorane; gamma- Hexachlorane;
gamma-Hexachlorobenzene; 1-alpha,2-alpha,3-beta,4-alpha,
5-alpha,6-beta-Hexachlorocyclohexane; gamma-Hexachlorocyclohexane; gamma-
1,2,3,4,5,6-Hexachlorocyclohexane; Hexachlorocyclohexane, gamma-Isomer;
1,2,3,4,5,6-Hexachlorocyclohexane, gamma-Isomer; Hexatox; Hexaverm; Hexicide;
Hexyclan; HGI; Hortex; Inexit; Isotox; Jacutin; Kokotine; Kwell; Lendine;
Lentox; Lidenal; LIndafor; Lindagam; Lindagrain; Lindagranox; gamma-Lindane;
Lindane (DOT); LIndapoudre; Lindatox; LIndosep; Lintox; Lorexane; Milbol 49;
Mszychol; NCI-C00204; NEO-Scabicidol; Nexen FB; Nexit; Nexit-Stark; Nexol-E;
Nicochloran; Novigam; Omnitox; Ovadziak; Owadzlak; Pedraczak; Pflanzol;
Quellada; Sang gamma; Silvanol; Spritz-Rapidin; Spruehpflanzol; Streunex; Tap
85; TRI-6; Viton
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
MCPA; CAS No. 94-74-6 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR MCPA
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
MCPA: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: MCPA
CAS No.: 94-74-6 Preparation Date: 01/06/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Kidney and liver
toxicity
1.0 mg/kg/day (NOEL)
3.0 mg/kg/day (LOAEL)
1000 1 1E-3
mg/kg/day
Dog subchronic oral
bioassay
Diamond Shamrock, 1980
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Diamond Shamrock Agricultural Chemicals. 1980. MRID 00106595.
Available from EPA. Write to FOI, EPA, Washington D.C. 20460.
Two 13-week dog studies were reported by Diamond Shamrock Agricultural
Chemicals (1980). Collectively, five doses were given to groups of four
dogs/sex. A clinical syndrome which included Icterus, diarrhea, corneal
ulcers, severe dermatitis, dehydration and severe weight loss led to the death
or humane kill of 7/8 high-dose dogs. Elevated blood creatinine and urea
nitrogen were observed in a dose-related fashion at the three highest doses,
suggesting impaired kidney function. (The lowest of these doses was 3.0
mg/kg/day.) The two lowest doses showed no effects outside normal limits.
(The highest of these doses was 1.0 mg/kg/day.)
-------
MCPA: page 3 of 5
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 1000. The uncertainty factor of 1000 reflects 10 for both intraspecies
and Interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation of a subchronic effect level to its
chronic equivalent.
MF = 1
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
Confidence in the chosen study is medium because the study appears to be
well conducted with four beagle dogs/sex in each of five dose groups. Con-
fidence in the data base is medium because the CBI study for the derivation
of the RfD is moderately well supported by studies in the open literature.
Medium confidence in the RfD follows.
6. DOCUMENTATION AND REVIEW
The ADI in the 1984 Health and Environmental Effects Profile has received a
limited Agency review with the help of two external scientists.
U.S. EPA. 1984. Health and Environmental Effects Profile for MCPA and
MCPB. Environmental Criteria and Assessment Office, Cincinnati, OH.
ECAO-CIN-P082AP.
Agency RfD Work Group Review: 07/22/85
Verification Date: 07/22/85
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: MCPA
CAS No.: 94-74-6
Information is not available at this time.
-------
MCPA: page 4 of 5
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: MCPA
CAS No.: 94-74-6
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: MCPA
CAS No.: 94-74-6
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: MCPA
CAS No.: 94-74-6 Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
MCPA: page 5 of 5
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Status Risk Considers
Management Econ/Tech
Date Value Feasibility
Reference
Pesticide Active
Ingredient:
a. Registration Final
Standard 1982
b. Special none
Review
no
MCPA Reg. Std.
June, 1982
B. RISK MANAGEMENT RATIONALE
Pesticide Active Ingredient
a. Registration Standard: MCPA Registration Standard. June 1982.
Registration Support and Emergency Response Branch, Office of Pesticide
Programs.
Contact: Office of Pesticide Programs
202/557-7760 or FTS/557-7760
b. Special Review: none
V. SUPPLEMENTARY DATA
Chemical: MCPA
CAS No.: 94-74-6
Information is not available at this time.
Synonyms: (4-CHLORO-2-METHYLPHENOXY)-ACETIC ACID, AGRITOX, AGROXON, AGROXONE,
ANICON KOMBI, ANICON M, BH MCPA, BORDERMASTER, BROMINAL M & PLUS, B-SELEKTONON
M, CHIPTOX, 4-CHLORO-o-CRESOXYACETIC ACID, (4-CHLORO-2-METHYLPHENOXY)ACETIC
ACID, 4-CHLORO-o-TOLOXYACETIC ACID, ((4-CHLORO-o-TOLYL)OXY)ACETIC ACID,
CHWASTOX, CORNOX-M, DED-WEED, DICOPUR-M, DICOTEX, DIKOTES, DIKOTEX, DOW MCP
AMINE WEED KILLER, EMCEPAN , EMPAL, HEDAPUR M 52, HEDAREX M, HEDONAL M,
HERBICIDE M, HORMOTUHO, HORNOTUHO, KILSEM, 4K-2M, KREZONE, LEGUMEX DB, LEUNA
M, LEYSPRAY, LINORMONE, M 40, 2M-4C, 2M-4CH, MCP, MCPA, 2,4-MCPA, MEPHANAC,
METAXON , METHOXONE, 2-METHYL-4-CHLOROPHENOXYACETIC ACID,
2-METHYL-4-CHLORPHENOXYESSIGSAEURE (German), 2M-4KH, NETAZOL, OKULTIN M,
PHENOXYLENE PLUS, PHENOXYLENE SUPER, RAPHONE, RAZOL DOCK KILLER, RHOMENC,
RHOMENE, RHONOX, SHAMROX, SEPPIC MMD, SOVIET TECHNICAL HERBICIDE 2M-4C,
TRASAN, U 46, U 46 M-FLUID, USTINEX, VACATE, VESAKONTUHO MCPA, VERDONE,
WEEDAR, WEEDAR MCPA CONCENTRATE, WEEDONE, WEEDONE MCPA ESTER, WEED-RHAP
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
MCPP; CAS No. 93-65-2 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR MCPP
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: none
V. Supplementary Data: none
-------
2(2-Methyl-4-Chlorophenoxy)Propionic Acid (MCPP): page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: 2(2-Methyl-4-Chlorophenoxy)Propionic Acid (MCPP)
CAS No.: 93-65-2 Preparation Date: 05/12/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Increased kidney/ 2.5 mg/kg/day (NOAEL) 1000 1 3E-3
body weight ratio mg/kg/day
20 mg/kg/day (LOAEL)
Rat, subchronic, oral
bioassay
Verschuuren et al.
(1975)
* Dose Conversion Factors & Assumptions: 50 ppm MCPP = 50 mg MCPP/kg diet
x 0.05 kg diet/kg bw/day =2.5 mg/kg bw/day
2. PRINCIPAL AND SUPPORTING STUDIES
Verschuuren, H.G., R. Kores and E.M. Den Tonkelar. 1975. Short-term oral
and dermal toxicity of MCPA and MCPP. The Toxicologist. 3: 349-359.
This study utilized four experimental groups of 10 male and 10 female
rats each. Animals were fed 0, 50, 400 or 3200 ppm MCPP in the diet (equiva-
lent to 0, 2.5, 20 or 160 mg/kg bw/day for 90 days. The NOAEL of 2.5 mg/kg
bw/day was set upon observation of increased relative kidney weights at the
higher doses. Male rats had decreased hematocrits at 2.5 and 160 but not at
20 mg/kg/day, indicating that the effect at the lowest feeding level was not
dose-related. These results are corroborated by a longer-term study in which
groups of 10 rats were fed MCPP diethanolamine for 7 weeks. Increased rela-
tive kidney weights were observed at all doses (3.4, 13.4, 33.5 and 83.8
mg/kg bw/day) (Gurd et al., 1965).
-------
2(2-Methyl-4-Chlorophenoxy)Propionlc Acid (MCPP): page 3 of 5
3. UNCERTAINTY AND MODIFYING FACTORS
UF - LOGO. Uncertainty factors of 10 each were used for extrapolation from
animal data, for use of a subchronic study, and for protection of sensitive
human subpopulations.
MF - 1
4. ADDITIONAL COMMENTS
No teratogenicity data for MCPP have been reported.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Low RfD: Low
As the numbers of animals were adequate and there was a reasonable range
of doses and measured end points, confidence in this study is rated as medium.
While there are two corroborating studies, both were done in the same animal
species, and there are no other data in the published literature. Confidence
in the data base is, therefore, low, and the overall confidence in the RfD is
low. Data included in a CBI Appendix, but described in the KEEP, are suppor-
tive of the derived RfD.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1984. Health and Environmental Effects Profile for 2(2-Methyl-4-
chlorophenoxy)Propionic Acid (MCPP). Environmental Criteria and Assessment
Office, Cincinnati, OH. ECAO-CIN-P083,
Schoeny, R. and M.L. Dourson. 1985. U.S. EPA, Cincinnati, OH, memorandum to
RfD Work Group, U.S. EPA, Washington, DC, October 22.
The RfD was reviewed by the ADI work group at their meetings on October 9 and
November 6, 1985.
Agency RfD Work Group Review: 10/09/86, 11/06/85
Verification Date: 11/06/85
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: MCPP
CAS No.: 93-65-2
Information is not available at this time.
-------
2(2-Methyl-4-Chlorophenoxy)Propionic Acid (MCPP): page 4 of 5
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: MCPP
CAS No.: 93-65-2
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: MCPP
CAS No.: 93-65-2
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: MCPP
CAS No.: 93-65-2
Information is not available at this time.
V. SUPPLEMENTARY DATA
Chemical: MCPP
CAS No.: 93-65-2
Information is not available at this time.
Synonyms: Acide 2-(4-Chloro-2-Methyl-Phenoxy)Propionique (French); Acido
2-(4-Chloro-2-Metilfenossi)-Propionico (Italian); BHMercoprop;
2-(4-Chloor-2-Methyl-Fenoxy)-Propionzuur (Dutch);
2-(4-Chlor-2-Methyl-Phenoxy)-Propionsaeure (German);
4-Chloro-2-Methylphenoxy-alpha-Propionic Acid;
(+)-alpha-(4-Chloro-2-Methylphenoxy) Propionic Acid;
2-(4-Chloro-2-Methylphenoxy)Propionic Acid;
2-(4-Chlorophenoxy-2-methyl)Propionic Acid; 2-(p-Chloro-o-Tolyloxy)Propionic
-------
2(2-Methyl-4-Chlorophenoxy)Propionic Acid (MCPP): page 5 of 5
Acid; Chipco Turf Herbicide MCPP; CMPP; Compitox; Hedonal MCPP; Iso-cornox;
Kilprop; Liranox; 2M-4CP; MCPP; 2-MCPP; Mecopeop; Mecoper; Mecopex; Mecoprop;
Mecoturf; Mecprop; Mepro; Methoxone; alpha-(2-Methyl-4-Chlorophenoxy)Propionic
Acid; 2-(2-Methyl-4-Chlorophenoxy)Propionic Acid;
2-Methyl-4-Chlorophenoxy-alpha-Propionic Acid; 2M 4KHP; N.B. Mecoprop; Propal;
Propionic Acid, 2-(4-Chloro-2-Methylphenoxy)-; Propionic Acid,
2-(4-Chloro-2-Methylphenoxy); Propionic Acid, 2-(2-Methyl-4-Chlorophenoxy)-;
Proponex-Plus; Rankotex; Runcatex; RD 4593; U 46; VI-PAR; VI-PEX
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Methylene Chloride; CAS No. 75-09-2 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Methylene Chloride
I. Chronic Systemic Toxicity: Noncarcinogenlc Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: under review
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Methylene Chloride: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Methylene Chloride
CAS No.: 75-09-2 Preparation Date: 06/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Liver toxicity NOAEL: 5.85 and 6.47 100 1 6E-2
mg/kg/day for males mg/kg/day
2-year rat drinking and females,
water bioassay respectively
National Coffee LOAEL: 52.58 and
Association (1982) 58.32 mg/kg/day for
males and females,
respectively
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
National Coffee Association. 24-Month chronic toxicity and oncogenicity
study of methylene chloride in rats. Final Report. Prepared by Hazleton
Laboratories America, Inc., Vienna, VA, August 11, 1982.
The chosen study appears to have been very well conducted, with 85 rats/
sex at each of four dose groups. A high-dose recovery group of 25 rats/sex,
as well as two control groups of 85 and 50 rats/sex, was also tested. Many
effects were monitored.
The supporting data base is limited. A NOAEL of 87 mg/cu. m was reported
in one inhalation study (Haun et al., 1972). [The equivalent oral dose is
about 28 mg/kg bw/day (i.e., 87 mg/cu. m x 0.5 x 0.223 cu. m/day/0.35 kg;
these exposure values are for rats).]
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Methylene Chloride: page 3 of 6
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 100. (lOa x lOh) The 100-fold factor accounts for both the expected
intra- and interspecies variability to the toxicity of this chemical in lieu
of specific data.
MF = 1
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: High Data Base: Medium RfD: Medium
The study is given a high confidence rating because a large number of
animals of both sexes were tested in four dose groups, with a large number of
controls. Many effects were monitored and a dose-related increase in severity
was observed. The data base is rated medium to low because only a few studies
support the NOAEL. Medium confidence in the RfD follows.
6. DOCUMENTATION AND REVIEW
U.S. EPA. Drinking Water Criteria Document for Methylene Chloride. Office
of Drinking Water, Washington, DC. (1985)(Draft)
The ADI has been reviewed by the U.S. EPA's ADI (RfD) Work Group.
Agency RfD Work Group Review: 06/24/85, 07/08/85, 11/06/85
Verification Date: 11/06/85
7. U.S. EPA CONTACTS
Primary: K. Khanna FTS/382-7588 or 202/382-7588
Office of Drinking Water
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Methylene Chloride
CAS No.: 75-09-2
Information is not available at this time.
-------
Methylene Chloride: page 4 of 6
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Methylene Chloride
CAS No.: 75-09-2
This chemical is among those substances evaluated by the U.S. EPA for
evidence of human carcinogenic potential. This does not imply that this
chemical is necessarily a carcinogen. The evaluation for this chemical is
under review by an inter-office Agency work group. A risk assessment summary
will be included on IRIS when the review has been completed.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Methylene Chloride
CAS No.: 75-09-2
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Methylene Chloride
CAS No.: 75-09-2 Preparation Date: 10/16/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Methylene Chloride: page 5 of 6
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
1000 Ibs.
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
2) Marine
Final
1980
Clean Air Act (CAA)
Regulatory Decision:
Nat. Emissions Current
Standards for 1985
Hazardous Air
Pollutants (NESHAP)
Hazardous Waste Final
Constituent 1985
(App. VIII)
0.19 ppb no
Acute no
11,000 ug/1
Chronic
none
Acute no
12,000 ug/1
Chronic
6,400 ug/1
Under no
development
Listed no
45 FR 79318
11/13/80
ibid.
ibid.
FR
10/17/85
40 CFR Part 261
App. VIII
B. RISK MANAGEMENT RATIONALE
RQ
The final adjusted RQ of 1000 pounds is based upon a chronic toxicity
score of 10. This substance has recently been identified for assessment of
carcinogenicity, and the RQ will be reevaluated when that assessment is
completed.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: Methylene chloride is classified as a carcinogen, and under
the assumption of no threshold for a carcinogen, the recommended WQC is zero.
However, if zero cannot be obtained and exposure is via ingestion of water
and aquatic organisms, 0.19 ug/1 is associated with an upper-bound excess
lifetime risk of l.OE-6 [other risk levels to consider: l.OE-5 (1.9 ug/1) and
l.OE-7 (0.019 ug/1)]. If exposure is only via ingestion of aquatic
organisms, the WQC associated with an upper-bound excess lifetime risk of
l.OE-6 is 15.7 ug/1. The criteria are based on halomethanes as a class.
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Methylene Chloride: page 6 of 6
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value indicates that the
minimum data were not available and the concentration given is not a criteria
value but the lowest effect level found in the literature. The values are
based on halomethanes as a class - no specific chemicals are cited.
V. SUPPLEMENTARY DATA
Chemical: Methylene Chloride
CAS No.: 75-09-2
Information is not available at this time.
Synonyms: Methane, dichloro- (8CI9CI); Aerothene MM; Chlorure de methylene
(French); Dichlormethan, uvasol; Dichloromethane; DCM; Freon 30; Methane
dichloride; Methylene bichloride; Methylene chloride (ACN); Methylene
dichloride; Metylenu chlorek (Polish); Narkotil; NCI-C50102; R 30; Solaesthin;
Solmethine; WLN: GIG; 1,1-Dichloromethane.
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Methyl Ethyl Ketone; CAS No. 78-93-3 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Methyl Ethyl Ketone
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Methyl Ethyl Ketone (MEK): page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) Is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Methyl Ethyl Ketone
CAS No.: 78-93-3 Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Rat inhalation
subchronic study
NOAEL: 235 ppm 1000
(693 mg/ cu.m) converted
to 46 mg/kg/day
1
5E-2
mg/kg/day
LaBelle and Brieger
(1955)
Fetotoxicity in rats LOAEL: 130.5 mg/kg/day
(estimated)
Schwetz et al. (1974)
* Dose Conversion Factors & Assumptions: 7 hour/24 hour, 5 days/7 days,
0.223 cu. m/day/0.35 kg (rat breathing rate/rat body weight) 0.5 absorption
rate; thus, 693 mg/cu. m x 7 hour/24 hour x 5 days/7 days x 0.223 cu. m/day
/ 0.35 kg x 0.5 - 46 mg/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
LaBelle, W. and H. Brieger. 1955. The vapor toxicity of a composite solvent
and its principal components. Am. Med. Assoc. Arch. Ind. Health. 12: 623-627.
Schwetz, B.A., B.K.J. Leong and P.J. Gehring. 1974. Embryo- and fetotoxicity
of inhaled carbon tetrachloride, 1,1-dichloroethane and methyl ethyl ketone in
rats. Toxicol. Appl. Pharmacol. 28(3): 452-464.
Adequate chronic toxicity testing has not been performed with methyl
ethyl ketone. Although several more recent subchronic studies have been con-
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Methyl Ethyl Ketone (MEK): page 3 of 5
ducted (Freddi et al., 1982; Cavender et al., 1983; Takeuchi et al., 1983),
only the NOAEL of the LaBelle and Brieger (1955) study provides the lowest and
most protective dose for deriving an RfD. In this study, 25 rats were exposed
to 235 ppm of methyl ethyl ketone for 7 hours/day, 5 days/week for 12 weeks.
No effects were observed, but only a few parameters were measured. Methyl
ethyl ketone has also been tested for teratogenicity (Schwetz et al., 1974;
Deacon et al., 1981) and the observed LOAELs for fetotoxicity are higher than
the NOAELs of LaBelle and Brieger (1955).
The route extrapolation raises a level of uncertainty due to differences
in pharmacokinetic parameters, notably, absorption and elimination.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. The uncertainty factor of 1000 reflects 10 for both intraspecies
and interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation of a subchronic effect level to its
chronic equivalent.
MF - 1
4. ADDITIONAL COMMENTS
No oral chronic studies are available at this time.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The study is given medium to low confidence because only 25 rats were
exposed to only one dose, and the sex, strain and amount of control animals
were unspecified. The data base is given a medium rating because four dif-
ferent studies lend some support to the chosen NOAEL. Medium to low confi-
dence in the RfD follows.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1985. Methyl Ethyl Ketone: Review and Evaluation of ADI. Con-
tract No. 68-03-3228. Environmental Criteria and Assessment Office, Cin-
cinnati, OH.
ECAO-Cincinnati Internal Review, May 1985.
Agency RfD Work Group Review: 06/24/85, 07/08/85
Verification Date: 07/08/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
-------
Methyl Ethyl Ketone (MEK): page 4 of 5
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Methyl Ethyl Ketone
CAS No.: 78-93-3
Information Is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Methyl Ethyl Ketone
CAS No.: 78-93-3
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Methyl Ethyl Ketone
CAS No.: 78-93-3
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Methyl ethyl ketone
CAS No.: 78-93-3 Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Methyl Ethyl Ketone (MEK): page 5 of 5
A. RISK MANAGEMENT ACTIONS
Risk Status Risk Considers
Management Management Econ/Tech
Action Date Value Feasibility Reference
Reportable Final 5000 Ibs no 50 FR 13456
Quantity (RQ) 1985 04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final 5000-pound RQ takes into consideration the natural
biodegradation of this hazardous substance. The lowest primary criteria RQ
for methyl ethyl ketone (1000, pounds based on chronic toxicity and
ignitability/reactivity) has been adjusted upward one RQ level.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
V. SUPPLEMENTARY DATA
Chemical: Methyl Ethyl Ketone
CAS No.: 78-93-3
Information is not available at this time.
Synonyms: aethylmethylketon (German); butanone; butanone 2 (French); ethyl
methyl cetone (French); ethylmethylketon (Dutch); ethyl methyl ketone; ketone,
ethyl methyl; meetco; MEK; methyl acetone; metiletilchetone (Italian);
metyloetyloketon (Polish); RCRA waste number U159; UN 1193 ; UN 1232
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Methyl Mercury; CAS No. 22967-92-6 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Methyl Mercury
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: \
II. Risk Estimates for Carcinogens:
III. Drinking Water Health Advisories:
IV. Risk Management Summaries:
V. Supplementary Data:
none
none
none
none
none
-------
Methyl Mercury: page 2 of 4
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Methyl Mercury
CAS No.: 22967-92-6 Preparation Date: 05/12/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
CNS effects NOAEL: None 10 1 3E-4
mg/kg/day
Several studies 200 ng Hg/mL of blood
reporting human (LOAEL) associated
poisonings with earliest detected
effects equivalent to
0.003 mg/kg/day.
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
The earliest effects in man are at blood concentrations between 200 and
500 ng Hg/mL, for both pre- and postnatal exposures. Blood concentrations
correspond to body burdens in the range of 30-50 mg Hg/70 kg, and are equiva-
lent to intakes in the range of 3-7 ug/kg/day (WHO, 197$).
The LOAEL is associated with CNS effects such as ataxia, paresthesia,
etc. (Clarkson et al., 1973). See also Nordberg and Strangert (1976) for a
discussion of dose-response.
-------
Methyl Mercury: page 3 of 4
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 10. A 10-fold factor is used to adjust the LOAEL to what is expected
to be a NOAEL. Since the effects are seen in sensitive individuals for
chronic exposure, no additional factors are deemed necessary.
MF = 1
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The blood level associated with minimal effects (WHO, 1976) is well
supported by more recent data (U.S. EPA, 1980). Confidence is not higher
than medium in both the chosen studies and supporting data base, however,
because of the lack of a NOEL. A medium confidence in the RfD follows.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1980. Ambient Water Quality Criteria Document for Mercury.
1980. Environmental Criteria and Assessment Office, Cincinnati, OH. EPA
440/5-80-058. p. C-95 to C-96. NTIS PB 81-117699.
The ADI had an extensive Agency review during the 1980 Red Border review of
the AWQC and was also reviewed by the public.
Agency RfD Work Group Review: 12/02/85
Verification Date: 12/02/85
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Methyl Mercury
CAS No.: 22967-92-6
Information is not available at this time.
-------
Methyl Mercury: page 4 of 4
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Methyl Mercury
CAS No.: 22967-92-6
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Methyl Mercury
CAS No.: 22967-92-6
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Methyl Mercury
CAS No.: 22967-92-6
Information is not available at this time.
V. SUPPLEMENTARY DATA
Chemical: Methyl Mercury
CAS No.: 22967-92-6
Information is not available at this time.
Synonyms: Mercury (1+), Methyl-(9C1); Methylmercury; Methylmercury (1+);
Methylmercury (II) Cation; Methylmercury Ion; Methylmercury Ion (1+); Mercury
(1+), Methyl-, Ion
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Nitrate; CAS No. 14797-55-8 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Nitrate
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Nitrate: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action In humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Nitrate
CAS No.: 14797-55-8
Preparation Date: 04/14/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF MF
RfD
Methemoglobinemia
Infant chronic expo-
sure drinking water
Walton (1951)
10 ppm of drinking
water or 10 mg/L
(NOEL) converted to
1.0 mg/kg/day
11-20 ppm (LOAEL)
1 1 1EO
mg/kg/day
* Dose Conversion Factors & Assumptions: 1 L water consumed/day 10 kg
child; thus, 10 mg/L x 1 L/day/10 kg - 1.0 mg/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
Walton, G. 1951. Survey of literature relating to infant methemoglobinemia
due to nitrate-contaminated water. Am. J. Public Health. 41: 986-996.
This is an epidemlologic study on the incidence of methemoglobinemia in
infants who routinely consumed formula prepared from water containing various
levels of nitrate. The study analyzed all cases of infant methemoglobinemia
occurlng in 37 U.S. states irrespective of date of occurrence or type of
water supply. Nitrate (nitrogen) content ranged from 10 ppm to greater than
100 ppm. No incidences of methemoglobinemia were found to occur in drinking
water containing less than 10 ppm (10 mg/L) nitrate (nitrogen). Therefore, a
NOEL of 10 ppm (10 mg/L) was derived.
Several more recent epidemiological studies support Walton's (1951)
threshold for infant methemoglobinemia (NAS, 1977; Winton, 1971; Calabrese,
1978).
-------
Nitrate: page 3 of 5
Nitrate toxicity is due to its conversion to nitrites, which results in
the oxidation of hemoglobin to methemoglobin in humans. Animals are not a
good model for methemoglobin formation because many species lack nitrate-
reducing bacteria. Infants are, however, particularly susceptible due to
their high gut content of nitrate-reducing bacteria, their lower enzymatic
capacity to reduce methemoglobin to hemoglobin and finally to the presence of
hemoglobin F, which is more susceptible to oxidation.
An RfD of 1.0 mg/kg/day (U.S. EPA, 1985) for nitrate/nitrogen was derived
based on the NOEL of 10 mg/L (Walton, 1951).
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1. No uncertainty factor was used in the derivation of the RfD because
the NOEL was of the critical toxic effect (i.e., methemoglobinemia) in the
sensitive human population (i.e., infants). The length of exposure
encompassed both the critical effect and the sensitive population.
MF = 1
4. ADDITIONAL COMMENTS
A RfD of 2 mg/kg/day could be calculated from the Walton (1951) study
using the body weight of 4 kg and fluid consumption of 0.64 L/day for infants.
The lower value of 1 mg/kg/day is maintained, however, due to the
uncertainties in the changing fluid consumption and body weight as a neonate
(4 kg) ages to a 2-year-old child (10 kg). While there are some data to the
contrary, it is most likely that older children do not respond with increased
methemoglobin to nitrate in drinking water. For example, Craun et al. (1981)
reported that 64 children, aged 1-8, consuming water with nitrate nitrogen
concentrations of 22-111 mg/L had an average methemoglobin concentration of
1.13%. This is not considered to be elevated and was in fact no different
from the level (0.98%) observed in 38 children who drank water containing less
than 10 rug nitrate/L.
5. CONFIDENCE IN THE RfD
Study: High Data Base: High RfD: High
Confidence in the study, data base and RfD are all considered high
because the NOEL is determined in the known sensitive human population. The
data base contains several recent supporting epidemiological studies.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1985. Nitrogen Dioxide: Review and Evaluation of ADI. Contract
No. 68-03-3228. Environmental Criteria and Assessment, Cincinnati, OH.
ECAO-Cincinnati Internal Review, August 1985.
Agency RfD Work Group Review: 11/21/85, 02/05/86, 02/26/86
Verification Date: 02/26/86
-------
Nitrate: page 4 of 5
7. U.S. EPA CONTACTS
Primary: K.L. Bailey FTS/382-5535 or 202/382-5535
Office of Drinking Water
Secondary: R.S. Schoeny FTS/684-7814 or 513/569-7814
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Nitrate
CAS No.: 14797-55-8
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Nitrate
CAS No.: 14797-55-8
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Nitrate
CAS No.: 14797-55-8
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Nitrate
CAS No.: 14797-55-8
Information is not available at this time.
-------
Nitrate: page 5 of 5
V. SUPPLEMENTARY DATA
Chemical: Nitrate
CAS No.: 14797-55-8
Information is not available at this time.
Synonyms: in preparation
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Nitric Oxide; CAS No. 10102-43-9 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A and B in Service Code 4. The other sections are
supplementary information which may be useful in particular risk management
situations, but have not yet undergone comprehensive U.S. EPA review. The
risk management numbers (Section V) may not be based on the most current risk
assessment, or may be based on a current, but unreviewed, risk assessment,
and may take into account factors other than health effects (e.g., treatment
technology). When considering the use of risk management numbers for a
particular situation, note the date of their development, the date of the
most recent risk assessment, and whether technological factors were
considered. For a more detailed description of procedures used in these
assessments and the development of risk management numbers, see Appendix E in
Service Code 4.
STATUS OF DATA FOR Nitric Oxide
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Nitric Oxide: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Nitric Oxide
CAS No.: 10102-43-9 Preparation Date: 06/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Methemoglobinemia 10 ppm of drinking 1 10 1E-1
water or 10 mg/L mg/kg/day
Infant chronic (NOAEL) converted to
exposure via drinking 1.0 mg/kg/day
water
11-20 ppm (LOAEL)
Walton (1951)
* Dose Conversion Factors & Assumptions: 1 L drinking water/day for a 10-kg
child assumed
2. PRINCIPAL AND SUPPORTING STUDIES
Walton, G. Survey of literature relating to infant methemoglobinemia due to
nitrate-contaminated water. American Journal of Public Health 41: 986-996
(1951).
This is an epidemiological study on the formation of methemoglobinemia in
infants routinely fed milk prepared from nitrate-contaminated water. This
study analyzed all known cases of infant methemoglobinemia occurring in 37
U.S. states irrespective of date or type of water supply. Nitrate (nitrogen)
content ranged from 10 ppm to over 100 ppm. No incidences of
methemoglobinemia were found to occur in drinking water containing greater
than 10 ppm (10 mg/L) nitrate (nitrogen). A NOAEL of 10 mg/L was derived from
these studies.
Nitric oxide in water generates N02 (nitrite). Methemoglobinemia is
formed by the oxidation of hemoglobin to methemoglobin by nitrite.
Infants are particularly susceptible to the formation of methemoglobin.
-------
Nitric Oxide: page 3 of 7
Several more recent studies support Walton's (1951) 10 mg/L NOAEL for
infant methemoglobinemia (NAS, 1977; Winton, 1971; Calabrese, 1978).
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1. An uncertainty factor of one was used in the derivation of the RfD
because the NOAEL was of the critical toxic effect (i.e., methemoglobinemia)
in the sensitive human population (i.e., infants). The length of exposure
encompassed both the critical effect and the sensitive population.
MF - 10. A modifying factor of 10 was applied because of the direct
toxlcity of nitrite.
4. ADDITIONAL COMMENTS
An RfD of 0.2 mg/kg/day could be calculated using the body weight of 4 kg
and fluid consumption of 0.64 L/day from the Walton (1951) study. The lower
value of 0.1 mg/kg/day is maintained, however, due to the uncertainties in the
changing fluid consumption and body weight as a neonate (4 kg) ages to a
2-year-old child (10 kg), and the varying lengths of weaning time among
families.
5. CONFIDENCE IN THE RfD
Study: High Data Base: High RfD: High
Confidence in the study, data base and RfD are all considered high because
the NOEL is determined in the known sensitive human population. The data base
contains several recent supporting epidemiological studies.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1985. Nitric Oxide: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinna-.i, OH.
ECAO-Cincinnati Internal Review, August 1985.
Agency RfD Work Group Review: 08/19/85, 02/26/86
Verification Date: 02/26/86
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
-------
Nitric Oxide: page 4 of 7
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Nitric Oxide
CAS No.: 10102-43-9
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Nitric Oxide
CAS No.: 10102-43-9
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Nitric Oxide
CAS No.: 10102-43-9
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Nitric Oxide
CAS No.: 10102-43-9 Preparation Date: 07/02/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Nitric Oxide: page 5 of 7
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Status
Date
Risk Considers
Management Econ/Tech
Value Feasibility
Reference
Reportable
Quantity (RQ)
Final
1985
10 Ibs.
no
50 FR 13456
04/04/85
40 CFR Parts
117 & 302
04/04/85
National Ambient
Air Quality
Standard (NAAQS)
Final
1985
0.053 ppm no
(ann. aver.)
50 FR 25532
06/19/85
40 CFR
Part 50.11
B. RISK MANAGEMENT RATIONALE
RQ
The adjusted final RQ of 10 pounds is based upon reactivity. An RQ
assignment based upon available mammalian acute toxicity data or aquatic
toxicity could have produced an RQ in excess of 10 pounds.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
5. NAAQS
Retention of the current primary annual standard of 0.053 ppm is
necessary to protect public health against chronic effects with an adequate
margin of safety, and provides some measure of protection against possible
short-term health effects. Sensitive populations (young children and
asthmatics) were considered in this decision.
Contact: Chief, Ambient Standards Branch
FTS/629-5565 or 919/541-5565
V. SUPPLEMENTARY DATA
Chemical:
CAS No.:
Nitric Oxide
10102-43-9
Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
-------
Nitric Oxide: page 6 of 7
A. ACUTE HEALTH HAZARD INFORMATION
Nitric oxide can cause death or permanent injury after a very short
exposure to small quantities (Sax, 1975). Nitric oxide is an irritant of
eyes, nose, and throat, and can cause unconsciousness (NIOSH/OSHA, 1978, pp.
138-139). Nitric oxide forms acids in the respiratory system which are
irritating and cause congestion in the lungs. Concentrations of 60-150 ppm
cause immediate irritation of the nose and throat with coughing and burning
in the throat and chest. Six to 24 hours after exposure, labored breathing
and unconsciousness may result. Nitric oxide can cause death due to blockage
of gas exchange in lungs. Concentrations of 100-150 ppm are dangerous for
short exposure of 30-60 minutes. Concentrations of 200-700 ppm may be fatal
after very short exposure (Sax, 1984, p. 2004).
Medical Conditions Generally Aggravated By Exposure: Not Found
Signs and Symptoms of Exposure: Initially, symptoms include slight
coughing, fatigue and nausea at high concentrations, coughing, choking,
headache, nausea, abdominal pain and shortness of breath. Latent symptoms
are uneasiness, restlessness, rapid and shallow breathing, bluing of skin,
lips and fingernail beds, anxiety, mental confusion, and finally loss of
consciousness (Gosselin, 1976).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: NO
Molecular Weight: 30.01
Boiling Point: -241.IF, -151.7C
Specific Gravity (H20-1): 1.27 at -150.2C
Vapor Pressure (mmHg): 26,000 at 20C
Melting Point: -262.5F, -163.6C
Vapor Density (AIR«=1) : 1.04
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: 7.34 mL/100 mL at OC
Flash Point [Method Used]: Not Found
Flammable Limits: Not Found
Appearance and Odor: Colorless gas; deep blue when liquid; bluish-white
snow when solid (Merck, 1976). Colorless gas with sharp, sweet odor; brown
at high concentrations in air (NIOSH/OSHA, 1978, pp. 138-139).
Conditions or Materials to Avoid: Avoid storage in direct sunlight, or
areas of high fire hazard (Sax, 1975). Avoid aluminum, boron, carbon
disulfide, hypo- chlorite, chromium, fluorine, fuels, hydrocarbons, nitrogen
trichloride, ozone, phosphorus, uns-dimethyl hydrazine, uranium, acetic
anhydride, ammonia, barium oxide, boron trichloride, methyl chloride,
1,2-dichloroethane, dichloroethylene, ethylene, iron, magnesium, manganese,
olefins, potassium, propylene, sodium, sulfur, trichloroethylene,
1,1,1-trichloroethane, uns-tetrachloroethane (Sax, 1984, p. 2004); and
reducing agents (Sax, 1975).
Hazardous Decomposition or Byproducts: When heated to decomposition,
highly toxic fumes of nitrogen oxides are emitted. Nitric oxide reacts with
water or steam to produce heat and corrosive fumes (Sax, 1975). It also
reacts with oxygen to form poisonous nitrogen dioxide (Student, 1981, p.
368).
-------
Nitric Oxide: page 7 of 7
Use: Nitric oxide is used in the manufacture of nitric acid, in bleaching
of rayon, as a stabilizer for propylene and methyl ether (Merck, 1976), and
in the preparation of nitrosyl carbonyls (Hawley, 1977).
Synonyms: Nitrogen oxide (NO) (8CI9CI); Bioxyde d'azote (French); Nitric oxide
(DOT); Nitric oxide (NO); Nitrogen monoxide; Nitrogen oxide, natural; Nitrosyl
radical; WLN: .N-0; WLN: N 0.
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Nitrite; CAS No. 14797-65-0 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Nitrite
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Nitrite: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Nitrite
CAS No.: 14797-65-0 Preparation Date: 04/14/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Methemoglobinemia 10 ppm of drinking 1 10 1E-1
water or 10 mg/L mg/kg/day
Infant chronic expo- (NOEL) converted to
sure to drinking water 1.0 mg/kg/day
Walton (1951) 11-20 ppm (LOAEL)
* Dose Conversion Factors & Assumptions: 1 L drinking water/day 10 kg
child; thus, 10 mg/L x 1 L/day / 10 kg - 1.0 mg/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
Walton, G. 1951. Survey of literature relating to infant methemoglobinemia
due to nitrate-contaminated water. Am. J. Public Health. 41: 986-996.
This is an epidemiological study on the incidence of methemoglobinemia in
infants routinely fed formula prepared from nitrate-contaminated water. This
study analyzed all known cases of infant methemoglobinemia occurring in 37
U.S. states irrespective of date or type of water supply. Nitrate (nitrogen)
content ranged from 10 ppm to over 100 ppm. No incidences of methemoglobi-
nemia were found to occur in drinking water containing greater than 10 ppm
(10 mg/L) nitrate (nitrogen). A NOEL of 10 mg/L was derived from these
studies.
Nitrite exposure to hemoglobin results in its oxidation to methemoglobin.
Animals do not provide a good model for methemoglobin formation because many
-------
Nitrite: page 3 of 5
species lack nitrate-reducing bacteria. Infants are, however, particularly
susceptible due to their high gut content of nitrate reducing bacteria, their
lower enzymatic capacity to reduce methemoglobin to hemoglobin and finally to
the presence of hemoglobin F, which is more susceptible to oxidation.
Several more recent studies support Walton's (1951) 10 mg/L NOAEL for
infant methemoglobinemia (NAS, 1977; Winton, 1971; Calabrese, 1978).
Using the NOAEL from the Walton study, the RfD for nitrite was calculated
(U.S. EPA, 1985) for a 10-kg child drinking 1 L of water/day and a modifying
factor of 10. An RfD of 0.1 mg/kg/day or 1 mg/day was, therefore, derived
for nitric oxide.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1. No uncertainty factor was used in the derivation of the RfD because
the NOEL was of the critical toxic effect (i.e., methemoglobinemia) in the
sensitive human population (i.e., infants). The length of exposure
encompassed both the critical effect and the sensitive population.
MF - 10. A modifying factor of 10 was applied because of the direct
toxicity of nitrite.
4. ADDITIONAL COMMENTS
An RfD of 0.2 mg/kg/day could be calculated from the Walton (1951) study
using the body weight of 4 kg and fluid consumption of 0.64 L/day for
infants. The lower value of 0.1 mg/kg/day Is maintained, however, due to the
uncertainties in the changing fluid consumption and body weight as a neonate
(4 kg) ages to a 2-year-old child (10 kg). While there are some data to the
contrary, it is most likely that older children do not respond witli increased
methemoglobin to nitrate in drinking water. For example, Craun et al. (1981)
reported that 64 children aged 1-8, consuming water with nitrate nitrogen
concentrations of 22-111 mg/L, had an average methemoglobin concentration of
1.13%. This is not considered to be elevated and was in fact no different
from the level (0.98%) observed in 38 children who drank water contaminated
with less than 10 mg nitrate/L.
5. CONFIDENCE IN THE RfD
Study: High Data Base: High RfD: High
Confidence in the study, data base and RfD are all considered high
because the NOEL is determined in the known sensitive human population. The
data base contains several recent supporting epidemiological studies.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1985. Nitric Oxide: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
ECAO-Cincinnati Internal Review, August 1985.
-------
Nitrite: page 4 of 5
Agency RfD Work Group Review: 11/21/85, 02/05/86, 02/26/86
Verification Date: 02/26/86
7. U.S. EPA CONTACTS
Primary: K.L. Bailey FTS/382-5535 or 202/382-5535
Office of Drinking Water
Secondary: R.S. Schoeny FTS/684-7814 or 513/569-7814
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Nitrite
CAS No.: 14797-65-0
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Nitrite
CAS No.: 14797-65-0
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Nitrite
CAS No.: 14797-65-0
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Nitrite
CAS No.: 14797-65-0
Information is not available at this time.
-------
Nitrite: page 5 of 5
V. SUPPLEMENTARY DATA
Chemical: Nitrite
CAS No.: 14797-65-0
Information is not available at this time.
Synonyms: Nitrous acid, ion(l-)
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Nitrobenzene; CAS No. 98-95-3 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Nitrobenzene
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: review pending
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Nitrobenzene: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime, RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Nitrobenzene
CAS No.: 98-95-3
Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Hematologic, adrenal, NOAEL: None
renal and hepatic
lesions
Rat/mice subchronic
inhalation study
CUT (1984)
25 mg/cu. m (mice)
converted to 4.6
mg/kg/day LOAEL)
10,000
5E-4
mg/kg/day
* Dose Conversion Factors & Assumptions: 6 hour/24 hour, 5 days/7 days,
0.039 cu. m/day/0.03 kg (mice breathing rate/body weight) and 0.8
absorption factor; thus, 25 mg/cu. m x 6 hour/24 hour x 5 days/7 days x
0.039 cu. m/day / 0.03 kg x 0.8 = 4.6 mg/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
CUT (Chemical Industry Institute of Toxicology). 1984. Ninety-day inhala-
tion toxicity study of nitrobenzene in F344 rats and B6C3F1 mice. Research
Triangle Park, NC. FYI-OTS-0874-0333.
The CUT study provides the most appropriate data currently available to
derive an RfD. Ten animals/sex/species/dose group were administered nitro-
benzene at 1 of 3 doses in a 90-day inhalation study. Other than increased
incidence of hemolytic anemia in rats at 25 mg/cu. m and vacuolization of
adrenal cortical cells in female mice at 25 mg/cu. m and higher, adverse
effects of nitrobenzene exposure in mice and rats were comparable to unex-
-------
Nitrobenzene: page 3 of 7
posed controls at this dose. Mice and rats exposed to nitrobenzene at 81
mg/cu. m showed increased incidence and severity of liver and kidney lesions.
Environ, Inc. (1984) recommended an RfD of 0.057 mg/kg/day or 4 mg/day,
which is based on the TLV of 1 ppm, a predicted level to protect workers
against cyanogenic and hematologic effects. An absorption coefficient of 0.8
and a dermal-to-inhalation absorption ratio of 7:18, based on the
pharmacokinetic data of Piotrowski (1967, 1977) and Salmowa et al. (1963),
were employed to derive the daily exposure level of nitrobenzene.
Data regarding the effects of nitrobenzene in humans are limited to
symptoms and observations in workers, including headaches, vertigo and
methemoglobinemia (ACGIH, 1980). The RfD derived from the TLV appears
adequate to protect workers from above adverse effects; however, the effects
of occupational exposure to nitrobenzene on the liver and/or kidneys have not
been adequately evaluated. The CUT (1984) study indicates that the liver and
kidney may be target organs of chronic/subchronic nitrobenzene exposure, and
the RfD based on the TLV may not be protective for the toxic effects of
nitrobenzene on the liver and/or kidney. Therefore, until more definitive
chronic data are available, the RfD of 0.0005 mg/kg/day is recommended to
protect against adverse health effects of nitrobenzene.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 10,000. The uncertainty factor of 1000 represents two 10-fold factors
for both intra- and interspecies variability to the toxicity of this
chemical in lieu of specific data, a 10-fold factor for estimating a chronic
effect level from its subchronic equivalent and a 10-fold factor for
estimating a RfD from a LOAEL rather than a NOAEL.
MF - 1
4. ADDITIONAL COMMENTS
A subchronic animal inhalation study (CUT, 1984) provided adequate data
over the recommended TLV (ACGIH, 1985) to derive an RfD. Further Chronic
studies are needed to recommend an RfD at a higher level of confidence.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
Medium confidence in the study is recommended because a limited number of
animals/sex/dose was tested and a NOEL for the critical toxic effect (i.e.,
adrenal toxicity) was not determined; however, two species were used and many
parameters were measured. Medium confidence in the data base is recommended
because many unpublished studies support the chosen LOAEL. Medium confidence
in the RfD follows.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, May 1985.
U.S. EPA. 1985. Health and Environmental Effects Profile for Nitrobenzene.
Environmental Criteria and Assessment Office, Cincinnati, OH. ECAO-CIN-P145.
-------
Nitrobenzene: page 4 of 7
U.S. EPA. 1985. Nitrobenzene: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
Agency RfD Work Group Review: 06/24/85, 07/08/85, 11/06/85
Verification Date: 07/08/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Nitrobenzene
CAS No.: 98-95-3
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Nitrobenzene
CAS No.: 98-95-3
This chemical is among those substances evaluated by the U.S. EPA for
evidence of human carcinogenic potential. This does not imply that this
chemical is necessarily a carcinogen. The evaluation for this chemical is
under review by an inter-office Agency work group. A risk assessment summary
will be included on IRIS when the review has been completed.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Nitrobenzene
CAS No.: 98-95-3
Information is not available at this time.
-------
Nitrobenzene: page 5 of 7
IV. RISK MANAGEMENT SUMMARIES
Chemical:
CAS No.:
Nitrobenzene
98-95-3
Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
1000 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
30 ug/1
no
2) Marine
Final
1980
Acute no
27,000 ug/1 (LEL)
Chronic
none
Acute no
6,680 ug/1 (LEL)
Chronic
none
45 FR 79318
11/28/80
ibid.
ibid.
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity as established under Section
311(b)(4) of the Clean Water Act. The available data indicate that the
aquatic 96-Hour Median Threshold Limit for nitrobenzene is between 10 and 100
ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
-------
Nitrobenzene: page 6 of 7
WQC
a. Human health: The WQC of 30 ug/1 is based upon organoleptic effects
(taste and odor thresholds). However, organoleptic end-points have limited
value in setting water quality standards as there is no demonstrated
relationship between taste/odor effect and adverse health effects. The
concentration of 19.8 mg/1 was derived from available toxicity data.
b. Aquatic toxicity: Generic(LEL)
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
V. SUPPLEMENTARY DATA
Chemical: Nitrobenzene
CAS No.: 98-95-3 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Nitrobenzene can cause death due to respiratory failure (Arena, 1974). It
is classified as extremely toxic. The mean lethal oral dose is probably
between 1 and 5 grams. Systemic effects to nitrobenzene may be delayed for a
few hours (Gosselin, 1984, p. 11-214). This compound is rapidly absorbed
through the skin (Merck, 1983, p. 945). It is a powerful methemoglobin
former (Patty, 1963).
Medical Conditions Generally Aggravated by Exposure: Ethyl alcohol
aggravates intoxication caused by nitrobenzene exposure (Gosselin, 1984, p.
11-214).
Signs and Symptoms of Exposure: Common symptoms include euphoria, flushed
face, headache, weakness, dizziness, nausea, vomiting, disturbed vision,
lightheadedness, incoordination, shortness of breath, labored breathing, and
an alarming bluing of skin, lips, and fingernail bed. Severe exposures can
cause stupor, coma and death due to respiratory failure (Hamilton, 1974;
Arena, 1974).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: C H NO
652
-------
Nitrobenzene: page 7 of 7
Molecular Weight: 123.11
Boiling Point: 411.4F, 210.8C
Specific Gravity (H20=l): 1.2037 at 20C/4C
Vapor Pressure (nunHg) : 1 at 44.4C
Melting Point: 42F, 5 . 7C
Vapor Density (AIR=1): 4.3
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: Soluble in about 500 parts water
Flash Point [Method Used]: 88C [CC]
Flammable Limits:
LEL: 1.8%
UEL: Not Found
Appearance and Odor: Greenish-yellow crystals or yellow, oily liquid
(Hawley, 1977) with an odor of volatile oil almond (Merck, 1976).
Conditions or Materials to Avoid: Avoid sunlight (Sax, 1975), physical
damage to container, freezing, and intense heat (NFPA, 1984, pp. 49-67).
Avoid contact with aluminum trichloride, aniline, gycerol, sulfuric acid,
oxidants, phosphorus pentachloride, potassium and potassium hydroxide (Sax,
1984, p. 2010).
Hazardous Decomposition or Byproducts: Not Found
Use: Nitrobenzene is used as a solvent for cellulose ethers; in the
modifying esterification of cellulose acetate; as an ingredient of metal
polishes (Hawley, 1977); in soaps and shoe polishes; for refining lubricating
oils; in manufacturing of pyroxylin compound (Merck, 1976); as a preservative
in spray paints; as a constituent of floor polishes; as a substitute for
almond essence; in perfume industry (Browning, 1965); and, as a chemical
intermediate for aniline and dichloroanilines (SRI). It is registered as an
insecticide for use on cadavers (USEPA/Pesticide Index, 1985).
Synonyms: Benzene, Nitro-; Essence of Mirbane; Essence of Myrbane; Mirbane
Oil; NCI-C60082; Nitrobenzol; Oil of Mirbane; Oil of Myrbane
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Nitrogen Dioxide; CAS No. 10102-44-0 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A and B in Service Code 4. The other sections are
supplementary information which may be useful in particular risk management
situations, but have not yet undergone comprehensive U.S. EPA review. The
risk management numbers (Section V) may not be based on the most current risk
assessment, or may be based on a current, but unreviewed, risk assessment,
and may take into account factors other than health effects (e.g., treatment
technology). When considering the use of risk management numbers for a
particular situation, note the date of their development, the date of thr
most recent risk assessment, and whether technological factors were
considered. For a more detailed description of procedures used In these
assessments and the development of risk management numbers, see Appendix E In
Service Code 4.
STATUS OF DATA FOR Nitrogen Dioxide
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Nitrogen Dioxide: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Nitrogen Dioxide
CAS No.: 10102-44-0 Preparation Date: 04/16/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Methemoglobinemia 10 ppm of drinking 11 1
water or 10 mg/L mg/kg/day
Infant chronic (NOEL) converted to
exposure drinking 1.0 mg/kg/day
water
11-20 ppm (LOAEL)
Walton (1951)
* Dose Conversion Factors & Assumptions: 1 L water consumed/day 10 kg
child; thus, 10 mg/L x 1 L/day / 10 kg - 1.0 mg/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
Walton, G. 1951. Survery of literature relating to infant methemoglobinemia
due to nitrate-contaminated water. Am. J. Public Health. 41: 986-996.
This is an epldemiologic study on the formation of methemoglobinemia in
infants who routinely consumed milk prepared from water containing various
levels of nitrate. The study analyzed all cases of infant methemoglobinemia
occuring in 37 U.S. states irrespective of date of occurrence or type of
water supply. Nitrate (nitrogen) content ranged for 10 ppm to greater than
100 ppm. No incidences of methemoglobinemia were found to occur In drinking
waters containing <10 ppm (10 mg/1) nitrate (nitrogen). Therefore, a NOEL of
10 ppm (10 mg/1) was derived.
Several more recent epidemiologlcal studies support Walton's (1951)
threshold for infant methemoglobinemia (NAS, 1977; Winton, 1971; Calabrese,
1978).
-------
Nitrogen Dioxide: page 3 of 7
Nitrogen dioxide in water dissociates to form nitrates and nitrite.
Nitrate toxicity appears to be due to its conversion to nitrites, which
results in the oxidation of hemoglobin to methemoglobin in humans. Animals
are not a good model for methemoglobin formation because of interspecies
variations in the response. Infants are, however, particularly susceptible
due to their high nitrate-reducing bacteria content, their lower enzymatic
capacity to reduce methemoglobin to hemoglobin, and finally to the presence of
hemoglobin F, which is more susceptible to oxidation.
An RfD of 1.0 mg/kg/day (U.S. EPA, 1985) for nitrate/nitrogen was derived
based on the NOEL of 10 mg/1 (Walton, 1951).
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 1. No uncertainty factor was used in the derivation of the RfD because
the NOEL was of the critical toxic effect (i.e., methemoglobinemia) in the
sensitive human population (i.e., infants). The length of exposure
encompassed both the critical effect and the sensitive population.
MF - 1
4. ADDITIONAL COMMENTS
A RfD of 2 mg/kg/day could be calculated using the body weight of 4 kg
and fluid consumption of 0.64 L/day from the Walton (1951) study. The lower
value of 1 mg/kg/day is maintained, however, due to the uncertainties in the
changing fluid consumption and body weight as a neonate (4 kg) ages to a
2-year-old child (10 kg). While there are some data to the contrary, it is
most likely that older children do not respond with increased methemoglobin
to nitrate in drinking water. For example, Craun et al. (1981) reported that
64 children, aged 1-8, consuming water with nitrate nitrogen concentrations
of 22-111 mg/1 had an average methemoglobin concentration of 1.13%. This is
not considered to be elevated and was, in fact, no different from the level
(0.98%) observed in 38 children who drank water with <10 mg nitrate/1.
5. CONFIDENCE IN THE RfD
Study: High Data Base: High RfD: High
Confidence in the study, data base and RfD are all considered high
because the NOEL is determined in the known sensitive human population. The
data base contains several recent supporting epidemiological studies.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, August 1985.
U.S. EPA. 1985. Nitrogen Dioxide: Review and Evaluation of ADI. Contract
No. 68-03-3228. Environmental Criteria and Assessment, Cincinnati, OH.
Agency RfD Work Group Review: 08/19/85, 02/26/86
Verification Date: 02/26/86
-------
Nitrogen Dioxide: page 4 of 7
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Nitrogen Dioxide
CAS No.: 10102-44-0
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Nitrogen Dioxide
CAS No.: 10102-44-0
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Nitrogen Dioxide
CAS No.: 10102-44-0
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Nitrogen Dioxide
CAS No.: 10102-44-0 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
-------
Nitrogen Dioxide: page 5 of 7
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
National Ambient
Air Quality
Standard (NAAQS)
Status
Date
Final
1985
Final
1985
Risk
Management
Value
10 Ibs
0.053 ppm
Considers
Econ/Tech
Feasibility
no
no
Reference
50 FR 13456
04/04/85
50 FR 25532
06/19/85
40 CFR 50.11
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on reactivity. Nitrogen oxide is a strong
oxidizer, may cause other materials to ignite, and will sustain their
combustion.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
5. NAAQS
EPA reviewed the primary (health-based) and secondary (welfare-related)
NAAQS for N02, originally set in 1971, and decided to retain them at 0.053
ppm, annual average. Retention of the primary standard is necessary and
prudent to protect public health against chronic health effects with an
adequate margin of safety, and provides some protection against possible
short-term health effects. Sensitive populations (children and asthmatics)
were considered in this decision. A decision on a separate short-term
standard was deferred pending completion of ongoing research. The secondary
standard set at the same level is adequate to protect against adverse welfare
effects (visibility impairment and vegetation and materials damage).
Contact: Chief, Ambient Standards Branch
FTS/629-5565 or 919/541-5565
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Nitrogen Dioxide: page 6 of 7
V. SUPPLEMENTARY DATA
Chemical: Nitrogen Dioxide
CAS No.: 10102-44-0 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Severe exposures to nitrogen dioxide may be fatal (DASE, 1980, p. 685).
It can cause death by asphyxiation. Contact may cause burns to skin and
eyes. Contact with liquid may cause frostbite (DOT, 1984, Guide 20). This
compound was reported to react with blood to form methemoglobin (Gosselin,
1978). The lowest lethal human inhalation dose has been reported at 200
ppm/1 min (NIOSH/RTECS, 1985).
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Symptoms include coughing, frothy thick
sputum, shortness of breath, labored breathing, chest pain, bluing of lips
and nail beds, rapid breathing, rapid heart beat, abdominal pain, fatigue,
restlessness, mental confusion and pulmonary edema (NIOSH/OSHA, 1978, p. 141,
Weiss, 1980, p. 664, DASE, 1980, p. 685).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: NO
2
Molecular Weight: 46.01
Boiling Point: 70.07F, 21.15C
Specific Gravity (H20=l): 1.448 at 20C/4C
Vapor Pressure (mmHg): 720 at 20C
Melting Point: 15.3F, -9.3C
Vapor Density (AIR=1): 1.58
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: Soluble; decomposes
Flash Point [Method Used]: Not Found
Flammable Limits: Does not burn
Appearance and Odor: Colorless solid, yellow liquid (Weast, 1979).
Reddish-brown gas, liquid below 21.15C, has an irritating odor (Merck, 1976).
Conditions or Materials to Avoid: Avoid moisture and physical damage to
storage container (NFPA, 1978). Nitrogen dioxide is incompatible with
combustible matter, chlorinated hydrocarbons, ammonia, carbon disulfide
-------
Nitrogen Dioxide: page 7 of 7
(NIOSH/OSHA, 1978, p. 171). It reacts with alkalies to form nitrates and
nitrites (Merck, 1976) and reacts violently with cyclohexane, fluorine,
formaldehyde, alcohols, nitrobenzene, petroleum, and toluene (Sax, 1984, p.
2023).
Hazardous Decomposition or Byproducts: Nitrogen dioxide decomposes in
water forming nitric acid and nitric oxide (Merck, 1976)
Use: It is used in bleaching flour; in initiation of organic compounds
and explosives; in the manufacture of oxidized cellulose for acrylates
(Hawley, 1977); as a chemical intermediate (captive) for nitric acid; and as
a catalyst for sulfurlc acid (SRI).
Synonyms: Nitrlto; Nitro; Nitrogen Dioxide (liquid); Nitrogen Oxide (N02);
Nitrogen Peroxide; Nitrogen Tetroxide
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
N-Nitrosopyrrolidine; CAS No. 930-55-2 (Revised 12/24/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR N-Nitrosopyrrolidine
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: none
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: available
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: in preparation
V. Supplementary Data: none
-------
N-Nitrosopyrrolidine: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: N-Nitrosopyrrolidine
CAS No.: 930-55-2
Information is not available at this time.
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: N-Nitrosopyrrolidine
CAS No.: 930-55-2
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: N-Nitrosopyrrolidine
CAS No.: 930-55-2 Preparation Date: 12/24/86
A. U.S. EPA CLASSIFICATION AND BASIS
Classification: B2, probable human carcinogen. Tumors at more than one
site have been observed in two rodent species administered
nitrosopyrrolidine orally.
1. HUMAN DATA
None. Human exposure to nitrosamines results from contact with mixtures
containing these compounds (e.g., cutting oils, tobacco products). Because
of potential confounding by the other substances in these mixtures, data is
of limited use in the evaluation of carcinogenicity of individual nitro-
samines .
2. ANIMAL DATA
There is a large data base on the carcinogenicity of nitrosamines, most
of which pertains to structure-activity relationships rather than to dose-
response. Nitrosopyrrolidine produced a 100% incidence of liver carcinomas
in MRC rats given an oral dose of 16 mg/kg/day. Male rats also developed
papillary mesotheliomas of the testes (Greenblatt and Lijinsky, 1972a).
Exposure in drinking water of 0.25 mg (7-8 mg/kg/day) induced a low incidence
of lung adenomas in male and female Swiss mice (Greenblatt and Lijinsky,
1972b). Druckrey (1967) noted hepatocarcinogenicity in BD rats fed 10-20
mg/kg/day in the diet.
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N-Nitrosopyrrolidine: page 3 of 5
Equal numbers (12-31) of male and female Sprague-Dawley rats were
maintained on water formulated to deliver 0, 0.3, 1, 3 or 10 mg/kg bw/day
nitrosopyrrolidine (Preussmann et al., 1977). Animals remained on treatment
until they died or became moribund. There was no statistically significant
increase in numbers of tumors in the lowest dose group. Dose-related
increases in hepatocellular carcinomas and adenomas were observed. Latency
periods were also diminished with increasing dose.
3. SUPPORTING DATA
N-nitrosopyrrolidine is mutagenic for Salmonella typhimurium upon addi-
tion of mammalian metabolic enzymes (Montesano and Bartsch, 1976). It is
structurally related to carcinogenic nitrosamines.
B. ORAL QUANTITATIVE ESTIMATE
Slope Factor = 2.1/mg/kg/day
1. UNIT RISK SUMMARY TABLE
Water Concentrations Producing Risk Levels
E-4 E-5 E-6
Unit Risk
Model
1.5
ug/1
1.5E-1
ug/1
1.5E-2
ug/1
6.1E-5
/ug/1
LM
extra risk
2. DOSE RESPONSE DATA
Study reference :
Species/strain;
Tumor type ; Route
Preussmann et al., 1977:
Rat/Sprague -Dawley, male and
female; hepatocellular
carcinoma and adenoma; diet
Admin .
Dose
(mg/kg/day)
0
0.3
1.0
3.0
10.0
Human Equiv.
Dose
(mg/kg/day)
0
0.051
0.17
0.51
1.70
Tumor
Incidence
0/61
3/60
17/62
31/38
14/24
3. ADDITIONAL COMMENTS
There was increased mortality due to pneumonia in the highest dose group.
Preussmann et al. (1977) indicated that increased susceptibility to respira-
tory infection may have been due to cumulative nitrosopyrrolidine toxicity.
As incidence of benign and malignant growths were added it is not possible to
ascertain whether any animals were counted more than once. The unit risk
should not be used if water concentrations exceed 160 ug/1 as above this
concentration the slope factor may differ from that stated above.
-------
N-Nitrosopyrrolidine: page 4 of 5
4. STATEMENT OF CONFIDENCE
Tumor incidence was shown to be dependent on the nitrosopyrrolidine dose
in one study. As adequate numbers of animals were treated at several doses,
confidence in the risk estimate is rated medium.
C. INHALATION QUANTITATIVE ESTIMATE
Slope Factor = 2.1/mg/kg/day
1. UNIT RISK SUMMARY TABLE
Air Concentrations Producing
E-4
1.5E-1
ug/cu.m
E-5
1.5E-2
ug/cu.m
Risk Levels
E-6
1.5E-3
ug/cu . m
Unit Risk
6.1E-4
/ug/cu . m
Model
LM
extra risk
2. DOSE RESPONSE DATA
The inhalation risk estimates were calculated from the oral exposure data,
3. ADDITIONAL COMMENTS
The unit risk should not be used if air concentrations exceed 16 ug/cu.m.
as above this concentration the slope factor may differ from that stated
above.
4. STATEMENT OF CONFIDENCE
This inhalation risk estimate based on oral data can be rated only low
to medium.
D. DOCUMENTATION AND REVIEW
1. REFERENCES
U.S. EPA. 1980. Ambient Water Quality Criteria Document for Nitrosamines
Environmental Criteria and Assessment Office, Cincinnati, OH. EPA
440/5-80-064. NTIS PB 81-117756.
Preussmann, R., D. Schmahl and G. Eisenbrand. 1977. Carcinogenicity of
N-nitrosopyrrolidine: Dose-response study in rats. Z. Krebsforsch. 90:
161-166.
-------
N-Nitrosopyrrolidine: page 5 of 5
2. REVIEW
The values in the Ambient Water Quality Criteria Document for Nitros-
amines (U.S. EPA, 1980) received extensive peer and public review.
Agency CRAVE Work Group Review: 07/23/86, 10/14/86
Verification Date: 10/14/86
3. U.S. EPA CONTACTS
Primary: J. Holder (202/FTS) 382-5721
Office of Research and Development
Secondary: R.E. McGaughy (202/FTS) 382-5898
Office of Research and Development
III. DRINKING WATER HEALTH ADVISORIES
Chemical: N-Nitrosopyrrolidine
CAS No.: 930-55-2
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: N-Nitrosopyrrolidine
CAS No.: 930-55-2
in preparation
V. SUPPLEMENTARY DATA
Chemical: N-Nitrosopyrrolidine
CAS No.: 930-55-2
Information is not available at this time.
Synonyms: pyrrolidine, 1-nitroso-; 1-nitrosopyrrolidine; NO-pyr; N-N-pyr;
NPYR; Pyrrole, tetrahydro-N-nitroso-; RCRA waste number U180
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Pentachlorobenzene; CAS No. 608-93-5 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Pentachlorobenzene
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Pentachlorobenzene: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Pentachlorobenzene
CAS No.: 608-93-5
Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Liver and kidney
toxicity
Subchronic rat oral
NOAEL:
LOAEL:
day
None
8.3 mg/kg/
10,000 1 8E-4
nig/kg/day
bioassay (including
weanlings)
Linder et al. (1980)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Linder, R., T. Scotti, J. Goldstein, K. McElroy and D. Walsh. 1980. Acute
and subchronic toxicity of pentachlorobenzene. J. Environ. Pathol. Toxicol.
4: 183-196.
This study utilized eight experimental groups (3 male, 5 female) of 10
rats each. A statistically significant increase in kidney weights, a
decreased heart weight, and an increase in hyaline droplets in proximal
kidney tubules was noted in rats receiving 8.3 mg/kg/day. Female rats
receiving the next highest dose, 18 mg/kg/day, and their offspring showed
increased liver/body weight ratios. At higher doses (up to 72 mg/kg/day)
animals of both sexes showed hepatocellular enlargement, increase in adrenal
and kidney weights, increased WBC counts and lowered RBC indices. Suckling
pups of dams receiving 18 mg/kg/day and higher doses of pentachlorobenzene
developed tremors. The lowest dose of 8.3 mg/kg/day is considered a LOAEL.
-------
Pentachlorobenzene: page 3 of 6
Linder et al. (1980) report a chart on estimated dietary dosage of penta-
chlorobenzene from which a figure of 8.3 mg/kg/day was estimated for male
rats receiving 125 ppm in the diet. The 1985 Health Assessment Document for
Chlorinated Benzenes reports an estimated dosage of approximately 11 mg/kg/
day calculated from the same data.
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 10,000. The composite uncertainty factor of 10,000 represents 10 each
for the expected interspecies and interhuman variability to the toxicity of
this compound in lieu of specific data, 10 to extrapolate a subchronic effect
level to its chronic counterpart, and 10 to drop the LOAEL into the expected
range of a NOAEL.
MF = 1
4. ADDITIONAL COMMENTS
An ADI of 0.0167 mg/kg was reported in the 1980 Ambient Water Quality
Criteria for Chlorinated Benzenes. This was based on a paper by Khera and
Villaneuve (1975) dealing with reproductive effects of short-term (10 days)
feeding in rats.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Low RfD: Low
The study rates a medium confidence because several effects were mon-
itored, and both adult and neonates were tested. The study does not rate
higher than medium because a NOAEL was not established and only a moderate
number of animals was used. The data base rates a low confidence because few
data exist to support this analysis. A low to medium confidence in the RfD
follows.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1983. Health and Environmental Effects Profile for Pentachloro-
benzene. Environmental Criteria and Assessment Office, Cincinnati, OH.
(Draft)
U.S. EPA. 1985. Health Assessment Document for Chlorinated Benzenes.
Office of Health and Environmental Assessment, Washington, DC. EPA
600/8-84-015F.
The ADI in the 1983 Health and Environmental Effects Profile document has
received an Agency review with the help of two external scientists.
Agency RfD Work Group Review: 10/09/85
Verification Date: 10/09/85
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
-------
Pentachlorobenzene: page 4 of 6
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Pentachlorobenzene
CAS No.: 608-93-5
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Pentachlorobenzene
CAS No.: 608-93-5
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Pentachlorobenzene
CAS No.: 608-93-5
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Pentachlorobenzene
CAS No.: 608-93-5 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
-------
Pentachlorobenzene: page 5 of 6
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Status
Date
Risk
Management
Value
Considers
Econ/Tech
Feasibility
Reference
Reportable Final
Quantity (RQ) 1985
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
2) Marine
Clean Air Act
Regulatory
Decision:
(NESHAP or NSPS)
Final
1980
Final
1985
10 Ibs
74 ug/1
no
no
Acute no
250 ug/1 (LEL)
Chronic
50 ng/1 (LEL)
Acute no
160 ug/1 (LEL)
Chronic
129 ug/1 (LEL)
Decision not
to regulate
no
50 FR 13456
04/04/85
45 FR 79318
11/28/80
ibid.
ibid.
50 FR 32628
06/13/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity. The available data indicate
that the aquatic 96-Hour Median Threshold Limit for pentachlorobenzene Is
between 0.1 and 1 ppm.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC of 74 ug/1 is based on consumption of contaminated
aquatic organisms and water. A WQC of 85 ug/1 has also been established
based on consumption of contaminated aquatic organisms alone.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value indicates that the
-------
Pentachlorobenzene: page 6 of 6
minimum data were not available and the concentration given is not a criteria
value but the lowest effect level found in the literature. The values given
represent chlorinated solvents as a class - no specific chemicals were
mentioned.
CAA Regulatory Decision
EPA concluded that the available health information on the chloro-
benzenes (including pentachlorobenzene) at concentrations measured or
estimated to occur in the ambient air is insufficient to warrant specific
Federal regulation of routine pentachlorobenzene emissions under the CAA at
this time.
Contact: Chief, Pollutant Assessment Branch
FTS/629-5645 or 919/541-5645
V. SUPPLEMENTARY DATA
Chemical: Pentachlorobenzene
CAS No.: 608-93-5
Information is not available at this time.
Synonyms: BENZENE, PENTACHLORO-; PENTACHLOROBENZENE; QCB; RCRA WASTE NUMBER
U183
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Pentachlorophenol; CAS No. 87-86-5 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Pentachlorophenol
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: review pending
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Pentachlorophenol: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Pentachlorophenol
CAS No.: 87-86-5
Preparation Date: 06/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Liver and kidney
pathology
Rat oral chronic
study
Schwetz et al. (1978)
3 mg/kg/day (NOAEL)
10 mg/kg/day (LOAEL)
100
3E-2
ing/kg/day
•>'< Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Schwetz, B.A., J.F. Quast, P.A. Keelev, C,G. Humiston and R.J. Kociba.
Results of 2-year toxicity and reproduction studies on pentachlorophenol in
rats. In: Pentachlorophenol: Chemistry, Pharmacology and Environmental
Toxicology, K.R. Rao, Ed. Plenum Press, NY. p. 301 (1978).
Only one chronic study regarding oral exposure (Schwetz et al., 1978) was
located in the available literature. Twenty-five rats/sex were administered 1
of 3 doses in the diet. At the 30 mg/kg/day level of treatment, a reduced
rate of body weight gain and increased specific gravity of the urine were
observed in females. Pigmentation of the liver and kidneys was observed in
females exposed at 10 mg/kg/day or higher levels and in males exposed to 30
mg/kg/day. Tne 3 mg/kg/day level of exposure was reported as a chronic NOEL.
A number of studies that have investigated the teratogenicity of orally
administered pentachlorophenol in rodents are available in the literature.
-------
Pentachlorophenol: page 3 of 7
Although these studies (Larsen et al., 1975; Schwetz and Gehring, 1973;
Schwetz et al., 1978; Hinkle, 1973) did not reveal teratogenic effects,
feto-maternal toxicity was seen at 30 mg/kg/day (Schwetz and Gehring, 1973).
Since pentachlorophenol apparently does not cross the placental barrier, the
observed fetotoxicity may be a reflection of maternal toxicity (Larsen et al.,
1975). The NOAEL in these studies was concluded to be 3.0 mg/kg/day (U.S.
EPA, 1984), which is the same as for the chronic study reported earlier.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. The 100-fold factor accounts for the expected intra- and inter-
species variability to the toxicity of this chemical in lieu of specific data.
MF = 1
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: High Data Base: Medium RfD: Medium
The confidence in the chosen study is rated high because a moderate number
of animals/sex were used in each of three doses, a comprehensive analysis of
parameters was conducted, and a reproductive study was also run. Confidence
in the supporting data base is rated medium because only one chronic study is
available. Other subchronic studies provide adequate but weaker supporting
data. The confidence in the RfD is medium. More chronic/reproductive studies
are needed to provide a higher confidence in the RfD.
6. DOCUMENTATION AND REVIEW
U.S. EPA. Health Effects Assessment for Pentachlorophenol. Environmental
Criteria and Assessment Office, Cincinnati, OH. ECAO-CIN-H043 (1984).
Limited Peer Review and Agency-wide Internal Review, 1984.
U.S. EPA. Drinking Water Criteria Document for Pentachlorophenol. Office of
Drinking Water, Washington, DC. (1985).
Two external peer reviews and an Agency internal review.
Agency RfD Work Group Review: 05/20/85
Verification Date: 05/20/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
-------
Pentachlorophenol: page 4 of 7
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Pentachlorophenol
CAS No.: 87-86-5
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Pentachlorophenol
CAS No.: 87-86-5
This chemical is among those substances evaluated by the U.S. EPA for
evidence of human carcinogenic potential. This does not imply that this
chemical is necessarily a carcinogen. The evaluation for this chemical is
under review by an inter-office Agency work group. A risk assessment summary
will be included on IRIS when the review has been completed.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Pentachlorophenol CAS No.: 87-86-5
Information is not available at this time.
=£======
IV. RISK MANAGEMENT SUMMARIES
Chemical: Pentachlorophenol
CAS No.: 87-86-5 Preparation Date: 10/15/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I ft II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Pentachlorophenol: page 5 of 7
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
10 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
40 CFR parts
117 & 302
04/04/85
Water Quality
Criteria (WQC):
a . Human Health
b. Aquatic Toxicity
1) Freshwater
2) Marine
Final
1980
Proposed
1986
Proposed
1986
Acute
1.01 mg/1
Chronic
30.0 ug/1
Acute
55 ug/1
Chronic
32 ug/1
Acute
53 ug/1
Chronic
34 ug/1
Hazardous Waste Final
Constituent 1985
(App. VIII)
Pesticide Active
Ingredient:
a. Registration n.a.
Standard
b. Special Final
Review 1984
Listed
Position
Document 1
P.O. 2/3
no
no
no
no
no
yes
45 FR 79318
11/28/80
51 FR 8361
03/11/86
ibid.
40 CFR Part 261
(App. VIII)
43 FR 48443
10/18/78
46 FR 13020
10/31/84
B. RISK MANAGEMENT RATIONALE
RQ
CERCLA statutory RQ subject to adjustment when assessment of
carcinogenicity is completed.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC necessary for the protection of public health is
1.01 mg/1. Its basis is a NOAEL of 3 mg/kg in a mammalian study, safety
-------
Pentachlorophenol: page 6 of 7
factor of 100 and an assumption of daily ingestion of 2L of water and 6.5g of
fish. The WQC of 30.0 ppb is based upon organoleptic effects (taste and odor
thresholds). However, organoleptic end points have limited value in setting
water quality standards, since there is no demonstrated relationship between
taste/odor effect and adverse health effects.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The data are assumed to be statistically
representative and are used to calculate concentrations which will not have
significant short or long term effects on 95% of the organisms exposed.
Recent criteria (1985 and later) contain duration and frequency stipulations:
the acute criteria maximum concentration is a 1-hour average and the chronic
criteria continuous concentration is a 4-day average which are not to be
exceeded more than once every three years, on the average (see Stephen et al.
1985) . Earlier criteria (1980-1984) contained instantaneous acute and
24-hour average chronic concentrations which were not to be exceeded. (FR 45:
79318: November 28, 1980).
Pesticide Active Ingredient
a. Registration Standard: none
b. Special Review: For specific details on the Special Review process for
this active ingredient please check the references listed.
Contact: Office of Pesticide Programs, Special Review Branch
202/557-7420 or FTS/557-7420
V. SUPPLEMENTARY DATA
Chemical: Pentachlorophenol
CAS No.: 87-86-5 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4, The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Pentachlorophenol is poisonous if swallowed or inhaled (DOT, 1984). It is
very toxic: the probable oral lethal dose being (human) 50-500 mg/kg (1
teaspoon to 1 ounce) for 70-kg person (150 Ibs.) (Gosselin, 1976). Lethal
oral doses in humans have been reported at 29 mg/kg (NIOSH, 1985). It causes
lung, liver, and kidney damage, and contact dermatitis (Merck, 1976).
Inhalation results in acute poisoning centering in the circulatory system
with accompanying heart failure. Also, visual damage, scotoma, inflammation
of conjuctiva, cornea opacity, cornea numbness and slight pupil dilation are
experienced (ACGIH, 1980).
-------
Pentachlorophenol: page 7 of 7
Medical Conditions Generally Aggravated by Exposure: Kidney and liver
diseases (Clayton and Clayton, 1982).
Signs and Symptoms of Exposure: Ingestion causes increased then decreased
respiration, blood pressure, and urinary output; fever; increased bowel
action; motor weakness; collapse with convulsions; and death (Merck, 1976).
Inhalation of dust and mist causes violent sneezing and coughing (USEPA, AWQC
1980). Liquid or solid dermal contact causes smarting of skin and
first-degree burns on short exposure; it may cause secondary burns on long
exposure (CHRIS, 1978).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: C HC1 0
6 5
Molecular Weight: 266.35
Boiling Point: 588F, 309C
Specific Gravity (H20=l): 1.978 at 22C/4C
Vapor Pressure (mmHg): 0.0002 at 20C
Melting Point: 374F, 190C
Vapor Density (AIR=1): 9.20
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: 0.002 g/100 ml at 30C
Flash Point [Method Used]: Not Found
Flammable Limits: This material may burn but may not ignite readily
Under normal conditions it is not flammable
Appearance and Odor: Needle-like crystals (Merck, 1983). Colorless
crystals (pure); dark greyish powder or flakes (crude product) (Spencer,
1982). Phenolic odor (Spencer, 1982) and also a very pungent odor when hot
(Merck, 1976).
Conditions or Materials to Avoid: Prolonged heating above 200C produces
trace amounts of octachlorodibenzo-para-dioxin (IARC, 1972-1985). Contact
with strong oxidizers may cause fires or explosions (NIOSH/OSHA, 1981).
Hazardous Decomposition or Byproducts: When heated to decomposition,
pentachlorophenol emits highly toxic fumes of chlorides (Sax, 1975).
Hydrogen chloride, chlorinated phenols, and carbon monoxide may be released
upon decomposition (NIOSH/OSHA, 1981).
Use: Pentachlorophenol is used as a. wood preservative; as a soil fumigant
for termites; as an herbicide, fungicide, slimicide, alglcide; and as an
antibacterial agent in disinfectants and cleaners (SRI).
Synonyms: Phenol, pentachloro-; Chem-Tol; Chlorophen; Cryptogil OL; Dowicide
EC-7; Dowicide G; Dowicide 7; Durotox; DP-2, technical; EP 30; Fungifen; Glazd
penta; Grundier arbezol; Lauxtol; Lauxtol A; Liroprem; NCI-C54933; NCI-C55378;
NCI-C55389; NCI-C56655; Penchlorol; Penta; Penta-KIl; Pentachloorfenol
(Dutch); Pentachlorofenol; Pentachlorofenolo; Pentachlorophenate;
Pentachlorphenol (German); Pentaclorofenolo (Italian); Pentacon; Pentasol;
Penwar; Peratox; Permacide; Permagard; Permasan; Permatox; Permatox penta;
Permatox DP-2; Permlte; Preventol P; Priltox; PGP; Santobrite; Santophen;
Santophen 20; Sinituho; Term-i-trol; Thompson's wood fix; Weedone; WLN: QR BG
CG DG EG FG; 1-Hydroxy- 2,3,4,5,6-pentachlorobenzene;
2,3,4,5,6-Pentachlorophenol.
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Phenol; CAS No. 108-95-2 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Phenol
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
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Phenol: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) Is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carclnogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, It Is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenlcity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Phenol
CAS No.: 108-95-2 Preparation Date: 01/07/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Kidney and liver NOAEL: None 1000 1 4E-2
pathology mg/kg/day
LOAEL: 50 mg/kg/day
Rat oral subchronic 5 days per week
study (converted to 35.7 mg/kg/day)
Dow Chemical (1945)
* Dose Conversion Factors & Assumptions: dosing schedule adjustment = 5/7
2. PRINCIPAL AND SUPPORTING STUDIES
Dow Chemical Co. 1945. Unpublished Report.
Available from EPA. Write to FOI, EPA, Washington D.C. 20460.
Groups of 10 rats were gavaged with 0, 50 or 100 mg/kg of phenol, 5
days/week (0, 35.7, or 71.4 mg/kg/day on a 7-day basis) until 135 or 136 doses
were administered, after which surviving animals were killed for histopath-
ological examination. The animals receiving 71.4 mg/kg/day of phenol showed a
marked temporary drop in body weight gain, but rapidly recovered. Surviving
animals (6/10) in this group showed a very slight amount of cloudy swelling of
the liver, while four animals had some kidney damage. In the animals (6/10)
that survived treatment with 35.7 mg/kg/day phenol, two showed a slight amount
of kidney damage. Mortality was not treatment related. The low dose (35.7
mg/kg/day) was judged a LOAEL.
No effects on liver, kidneys or any other organs were observed in 90-day
studies in rats (780 mg/kg/day of phenol) and mice (1700 mg/kg/day of phenol)
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Phenol: page 3 of 7
which received various doses of phenol in the drinking water (NCI, 1980). The
NCI (1980) also exposed rats and mice to phenol for 103 weeks and observed the
animals for a subsequent 2 weeks. Rats and mice treated with 153 and 313
mg/kg/day phenol, respectively, showed decreased weight gain and reduced water
intake. In addition, male and female rats at the 344-mg/kg/day dosed had
significantly increased incidences of chronic kidney inflammation.
The difference in LOAELs of the NCI (1980) study (344 mg/kg) and the Dow
Chemical (1945) study (37.5 mg/kg) are plausibly attributed to differences in
mode of administration with the gavage study of Dow Chemical producing the
lowest LOAEL.
Diechmann and Oespar (1940) noted no effects on water consumption and
weight gain at phenol concentrations as high as 1600 mg/1. Further, in
studies using rats and spanning 3-5 generations, Heller and Purcell (1938)
observed normal growth and reproduction at phenol concentrations up to 5000
mg/L. Taking the drinking water consumption data provided by Deichmann and
Oesper (1940) for the 1600 mg/1 group, this NOEL represents an average dose
of 49 mg/kg/day which is equivalent to that used in the derivation of the ADI.
Consideration of all these factors suggest that the previously estimated
ADI of 7 mg/day (U.S. EPA, 1980) based on the LOAEL of 50 mg/kg/day from the
Dow Chemical (1976) study should provide adequate protection.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. An overall uncertainty factor of 1000 was considered sufficient to
account for all the uncertainties involved (animals to man, the range of human
sensitivity, subchronic to chronic exposure, LOAEL to NOAEL). A UF of 10,000
was not considered necessary because of the minimally severe effects observed
at the low dose.
MF = 1
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The 6-month oral subchronic study incorporated adequate toxicological end
points, but doses were inadequate to provide a NOEL and thus, a medium
confidence was recommended. The data base contained well-designed subchronic
and reproductive studies which provided considerable information on the
toxicity of phenol, thus a medium confidence was recommended. The RfD was
based on a subchronic LOAEL, so that further chronic studies are needed to
support a confidence level higher than medium.
6. DOCUMENTATION AND REVIEW
Extensive Agency-wide and limited peer review, 1985. ECAO-Cin review, 1986.
-------
Phenol: page 4 of 7
U.S. EPA. 1985. Health and Environmental Effects Profile for Phenol.
Errata, 1986. Prepared by the Environmental Criteria and Assessment Office,
Cincinnati, OH for the Office of Solid Waste and Emergency Response,
Washington, DC.
Agency RfD Working Group Review: 08/05/85
Verification Date: 10/28/86
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Phenol
CAS No.: 108-95-2
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Phenol
CAS No.: 108-95-2
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Phenol
CAS No.: 108-95-2
Information is not available at this time.
-------
Phenol: page 5 of 7
IV. RISK MANAGEMENT SUMMARIES
Chemical:
CAS No.:
Phenol
108-95-2
Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1986
Risk
Management
Value
1000 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
51 FR 34534
09/29/86
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
0.3 mg/1
no
2) Marine
Clean Air Act
Regulatory
Decision:
(NESHAP or NSPS)
Final
1980
Current
1986
Acute no
10,200 ug/1 (LEL)
Chronic
2,560 ug/1 (LEL)
Acute no
5,800 ug/1 (LEL)
Chronic
none
Decision not
to Regulate
no
45 FR 79318
11/28/80
ibid.
ibid.
51 FR 22854
06/23/86
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Phenol: page 6 of 7
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ takes into account the natural biodegradation and photolysis
of this hazardous substance. The lowest primary criteria RQ for phenol (100
pounds based on chronic toxicity) has been adjusted upward one RQ level.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC of 0.3 mg/1 is based upon organoleptic effects
(taste and odor thresholds). However, organoleptic end-points have limited
value in setting water quality standards as there is no demonstrated
relationship between taste/odor effect and adverse health effects. If there
is significant chlorination of water containing phenol, reference should be
made the criteria for 2-chlorophenol and 2,4-dichlorophenol.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value indicates that the
minimum data were not available and the concentration given is not a criteria
value but the lowest effect level found in the literature.
CAA Regulatory Decision
EPA concluded that the available health information on phenol at
concentrations measured or estimated to occur in the ambient air is
insufficient to warrant specific Federal regulation of routine phenol
emissions under the CAA at this time.
Contact: Chief, Pollutant Assessment Branch
FTS/629-5645 or 919/541-5645
V. SUPPLEMENTARY DATA
Chemical: Phenol
CAS No.: 108-95-2 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Phenol's toxic hazard rating is very toxic. The probable oral lethal dose
(human) is 50-500 mg/kg (Gosselin, 1976). Ingestion of 1 gram has been
-------
Phenol: page 7 of 7
lethal to humans (Encyc Occupat Health and Safety, 1971). Lethal amounts may
be absorbed through skin or inhaled (NFPA, 1978).
Medical Conditions Generally Aggravated by Exposure: Persons affected
with hepatic or kidney diseases are at a greater risk (Clayton and Clayton,
1981-82).
Signs and Symptoms of Exposure: Symptoms include burning pain in the
mouth and throat, bloody diarrhea, pallor, sweating, weakness, headache,
dizziness, ringing in the ears, shock, profound fall in body temperature.
Oral exposure signs and symptoms include sonorous breathing, and frothing at
the mouth and nose. Skin exposure may cause pain followed by numbness
(Gosselin, 1976).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: C H 0
6 6
Molecular Weight: 94.11
Boiling Point: 359.IF, 181.75C
Specific Gravity (H20=l): 1.0722 at 20/4C
Vapor Pressure (mmHg): 0.3513 at 25C
Melting Point: 109F, 43C
Vapor Density (AIR=1): 3.24
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: 93 g/liter at 25C
Flash Point [Method Used]: 79C (CC)
Flammable Limits:
LEL: 1.7%
UEL: 8.6%
Appearance and Odor: Colorless crystals or white crystalline mass (Merck,
1976), with aromatic, somewhat sickening sweet and acrid odor (Clayton and
Clayton, 1981-82). It is liquefied by mixing with about 8% water (Merck,
1983, p. 1043).
Conditions or Materials to Avoid: Phenol decomposes slowly on air contact
(Merck, 1976). Avoid contact with strong oxidizing agents (CHRIS, 1978),
aluminum chloride/nitrobenzene mixture, peroxodisulfuric acid,
peroxomonosulfuric acid (Bretherick, 1979), and strong oxidizing agents
(CHRIS, 1978).
Hazardous Decomposition or Byproducts: Not Found
Use: Used as a disinfectant, antiseptic and bactericide (Merck, 1976);
as a chemical intermediate for phenolic resins, medicinals, and many other
chemicals; and as a solvent for petroleum refining (SRI).
Synonyms: Benzenol; Carbolic Acid; Hydroxybenzene; Izal; Monohydroxybenzene;
Monophenol; NCI-C50124; Oxybenzene; Phenic Acid; Phenyl Alcohol; Phenyl
Hydrate; Phenyl Hydroxide; Phenylic Acid; Phenylic Alcohol
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
m-Phenylenediamine; CAS No. 108-45-2 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR m-Phenylenediamine
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: review pending
III. Drinking Water Health Advisories: none
IV, Risk Management Summaries: none
V. Supplementary Data: none
-------
m-Phenylenediamine: page 2 of 4
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: m-Phenylenediamine
CAS No.: 108-45-2 Preparation Date: 05/12/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Increased relative
and absolute liver
weights and degener-
ative liver lesions
Experimental Doses *
6.0 mg/kg/day (NOEL)
18.0 mg/kg/day
(LOAEL)
UF MF RfD
1000 1 6E-3
mg/kg/day
Rat oral subchronic
study
Hofer and Hruby
(1982)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Hofer, H. and R. Hruby. 1982. Ninety-day toxicity study with m-pheny-
lenediamine on rats. Oestrr. Forschungszent. Seibersdorf (Ber.) OEFZS Ber.
No. 4155. p. 50.
In the Hofer and Hruby (1982) study, groups of rats (20/sex/dose) were
treated with 0, 2, 6 or 18.0 mg/kg/day m-phenylenediamine. The compound was
administered orally as an aqueous solution for 90 days. No effect was
observed on body weight, food consumption, ophthalmology, hematology or blood
and urine biochemistry of treated rats. A significant increase in relative
and absolute liver weight accompanied by an increased incidence of degenera-
tive liver lesions occurred in rats treated with 18.0 mg/kg/day m-phenylene-
-------
m-Phenylenedlamlne: page 3 of 4
diamine. Female rats treated at the 18 mg/kg/day dose also had significantly
increased relative kidney weights. Based on these findings, a NOEL of 6.0
mg/kg/day and a LOAEL of 18.0 mg/kg/day was established and an ADI of 0.006
mg/kg/day was derived.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. An uncertainty factor of 1000 was applied: 10 for interspecies
variability, 10 for intraspecies variability and 10 for the use of subchronic
data.
MF = 1
4. ADDITIONAL COMMENTS
Teratogenic studies of m-phenylenediamine in mice and rats have been con-
ducted by a number of investigators (Burnett et al., 1976; Hruby et al., 1981;
Picciano et al., 1983) with equivocal results.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Low RfD: Low
The critical study was well designed and established a clear NOEL and
LOAEL; however, testing was done in only one species for a subchronic period
of time. Thus, the study was assigned a medium level of confidence. The
data base contains no other subchronic or chronic oral toxicity studies and
no epidemiological data and, therefore, a low confidence was assigned to the
data base. Until further chronic/reproductive studies are conducted, a low
confidence in the RfD is recommended.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1986. m-Phenylenediamine: Review and Evaluation of ADI. Contract
No. 68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. 1985. Health and Environmental Effects Profile for Phenylene-
diamine. Environmental Criteria and Assessment Office, Cincinnati, OH.
ECAO-CIN-P112.
The Health and Environmental Effects Profile has received extensive Agency-
wide and external review.
Agency RfD Work Group Review: 02/26/86
Verification Date: 02/26/86
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
-------
m-Phenylenediamine: page 4 of 4
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: m-Phenylenediamine
CAS No.: 108-45-2
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: m-Phenylenediamine
CAS No.: 108-45-2
This chemical is among those substances evaluated by the U.S. EPA for
evidence of human carcinogenic potential. This does not imply that this
chemical is necessarily a carcinogen. The evaluation for this chemical is
under review by an inter-office Agency work group. A risk assessment summary
will be included on IRIS when the review has been completed.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: m-Phenylenediamine
CAS No.: 108-45-2
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: m-Phenylenediamine
CAS No.: 108-45-2
Information is not available at this time.
V. SUPPLEMENTARY DATA
Chemical: m-Phenylenediamine
CAS No.: 108-45-2
Information is not available at this time.
Synonyms: m-aminoaline; 3-aminoaniline; APCO 2330; m-benzenediamine;
1,3-benzenediamine; C.I. 76025; developer 11; developer c; developer h;
developer m; m-diaminobenzene; 1,3-diaminobenzene; direct brown br; direct
brown gg; m-fenylendiamin (Czech); metaphenylenediamine; 1,3-
phenylenediamine; UN 1673
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Phenylmereuric Acetate; CAS No. 62-38-4 (Revised 04/10/1987)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix D in Service Code 4.
STATUS OF DATA FOR Phenylmercuric Acetate
I. Chronic Systemic Toxicity: Noncarcinogenlc Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Fhenyl Mercuric Acetate: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Phenylmercurie Acetate
CAS No.: 62-38-4 Preparation Date: 04/10/87
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Renal damage 0.1 ppm Hg diet or 100 1 8E-5
0.0084 mg/kg/day mg/kg/day
Rat oral chronic phenyl mercuric
study acetate (NOAEL)
Fitzhugh et al. 0.5 ppm Hg or 0.042
(1950) mg/kg/day phenyl
mercuric acetate
(LOAEL)
* Dose Conversion Factors & Assumptions: Food consumption 5% bw/day,
molecular weight PMA/Hg is 337/201; thus, 0.1 mg/kg of diet (ppm) x 0.05
kg of diet/kg bw/day x 337/201 - 0.0084 mgAg bw/day
2. PRINCIPAL AND SUPPORTING STUDIES
Fitzhugh, 0.6, A.A. Nelson, E.P. Laug and I.M. Kunze. 1950. Chronic oral
toxicities of mercuric phenyl and mercuric salts. Arch. Ind. Hyg. Occup.
Med. 2: 433-442.
Phenyl mercuric acetate was administered to rats (10-24/group/sex) at
levels of 0, 0.1, 0.5, 2.5, 10, 40 and 160 mercury in their diet for 2 years.
Detailed microscopic examinations of the liver and kidney were performed at 1
and 2 years of age. Microscopic examination of the viscera was also per-
formed at the 2-year mark. As little as 0.5 ppm mercury as phenyl mercuric
acetate resulted in detectable kidney damage in females after 2 years. No
-------
Phenyl Mercuric Acetate: page 3 of 6
differences were seen between controls and females receiving 0.1 ppm mer-
cury. At higher doses (greater than 2.5 ppm), renal lesions were observed in
both males and females. A NOEL of 0.1 ppm was determined from these results.
Fitzhugh et al. (1950) is the only chronic study regarding the oral tox-
icity of phenyl mercuric acetate. Therefore, assuming that the rat consumed
the equivalent of 5% of its body weight in food/day, the 0.1 ppm Hg NOEL is
equivalent to 0.005 mg/kg/day Hg or 0.0084 mg/kg bw phenyl mercuric acetate.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. An ADI of 0.08 ug/kg/day or 6 ug/kg/day for a 70-kg human was
derived by dividing the NOEL by an uncertainty factor of 100 to account for
species extrapolation and differences in human sensitivity.
MF = 1
4. ADDITIONAL COMMENTS
The data base contains very little information on the oral toxicity of
phenyl mercuric acetate. Some subchronic testing has been conducted.
Limited data are available on the mutagenic and teratogenic effects of this
compound. No relevant carcinogenic data are available.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Low RfD: Medium
The chosen study is given a medium confidence rating because a moderate
number of animals/sex were tested at each of six doses; several parameters
were measured. The data base is given a low confidence rating because little
or no supporting data exist. Medium confidence in the RfD follows.
•
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, August 1985.
U.S. EPA. 1985. Phenyl Mercuric Acetate: Review and Evaluation of ADI.
Contract No. 68-03-3228. Environmental Criteria and Assessment Office, Cin-
cinnati, OH.
Agency RfD Work Group Review: 08/19/85
Verification Date: 08/19/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
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Phenyl Mercuric Acetate: page 4 of 6
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Phenyl Mercuric Acetate
CAS No.: 62-38-4
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Phenyl Mercuric Acetate
CAS No.: 62-38-4
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Phenyl Mercuric Acetate
CAS No.: 62-38-4
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Phenyl mercuric acetate
CAS No.: 62-38-4 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Phenyl Mercuric Acetate: page 5 of 6
A. RISK MANAGEMENT ACTIONS
Risk Status Risk Considers
Management Management Econ/Tech
Action Date Value Feasibility Reference
Reportable Final 100 Ibs no 51 FR 34534
Quantity (RQ) 1986 09/29/86
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on chronic toxicity. RQ assignments based on
chronic toxicity reflect two primary attributes of the hazardous substance,
the minimum effective dose (MED) levels for chronic exposure (mg/day for 70-
kg man) and the type of effect (liver necrosis, teratogenicity, etc). In
accordance with the methodology described in the Agency's "Technical
Background Document to Support Rulemaking Pursuant to CERCLA Section 102,
Volume 1" of March 1985 and 50 FR 13468 (04/04/85), a composite score is
determined from an evaluation of these two attributes. Phenyl mercuric
acetate was determined to have a composite score between 21 and 40,
corresponding to a chronic toxicity RQ of 100 pounds.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
V. SUPPLEMENTARY DATA
Chemical: Phenylmercuric Acetate
CAS No.: 62-38-4 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Phenylmercuric acetate is rated as extremely toxic. The probable oral
lethal dose for humans is 5-50 mg/kg, between 7 drops and 1 teaspoonful
for a 70-kg (150-lb.) person (Gosselin, 1984, p. 11-137).
Medical Conditions Generally Aggravated by Exposure: Not Found
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Phenyl Mercuric Acetate: page 6 of 6
Signs and Symptoms of Exposure: Symptoms arising from acute exposure may
occur at varying intervals up to several weeks following exposure. Ingestion
of mercurial fungicide treated grain resulted in gastrointestinal
irritation with nausea, vomiting, abdominal pain, and diarrhea.
Alkylmercurials produce severe neurologic toxicity, such as loss of feeling
in lips, tongue, and extremities, confusion, hallucinations, irritability,
sleep disturbances, staggering walk, memory loss, slurred speech, auditory
defects, emotional instability, and inability to concentrate. It is also a
strong skin irritant; erythema and blistering may result 6-12 hours after
exposure (Rumack, 1975 to Present). Phenylmercury acetate, at sufficient
concentration, is expected to be injurious to the eye externally (Grant,
1974).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: C H HgO
88 2
Molecular Weight: 336.75
Boiling Point: Not Found
Specific Gravity (H20=l): Not Found
Vapor Pressure (mmHg): 9 x 10-6 at 35C
Melting Point: 300F, 149C
Vapor Density (AIR=1): Not Found
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: 1 g/180 ml; soluble in about 600 parts
water
Flash Point [Method Used]: Above 100F (OC)
Flammable Limits: Not Found
Appearance and Odor: White to creamy white crystalline powder or small
white prisms or leaflets. Odorless (Osol, 1980).
Conditions or Materials to Avoid: Phenylmercuric ion is incompatible with
halides, with which precipitates are formed (Osol, 1980).
Hazardous Decomposition or Byproducts: When heated to decomposition, very
toxic mercuric fumes may be given off (Sax, 1984, p. 100).
Use: Used as an antiseptic, fungicide, herbicide; mildewcide for paints;
and slimicide in paper mills (Hawley, 1977). It was also used in
contraceptive gels and foams (Osol, 1980).
Synonyms: (Acetoxymercuri)Benzene; Acetic Acid, Phenylmercury Deriv;
Acetoxyphenylmercury; Agrosan GN 5; Algimycin; Antimucin WDR; Bufen; Ceresan
Universal; Contra Creme; Dyanacide; Femma; FMA; Fungitox OR; Gallotox; HL-331;
Hostaquick; Kwiksan; Leytosan; LIquiphene; Mercury(II) Acetate, Phenyl-;
Mercury, (Acetato)Phenyl-; Mersolite; Mersolite 8; Metasol 30; Norforms;
Phenmad; Phenomercuric Acetate; Phenylmercuriacetate; Phenylmercuric Acetate;
Phix; PMA; PMAC; PMacetate; PMAL; PMAS; Programin; Purasan-SC-10; Puraturf 10;
Quicksan 20; Sanitized SPG; SC-110; Shimmerex; Spor-Kil; TAG; Trigosan;
Ziarnik; Mercury,(Acetato-O)Phenyl-
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Phosphine; CAS No. 7803-51-2 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Phosphine
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Phosphlne: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Phosphine
CAS No.: 7803-51-2
Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Body weight and
clinical parameters
Rat chronic oral
study
Hackenburg (1972)
0.51 mg/kg food
converted to 0.026
mg/kg/day (NOEL)
LOAEL: None
100
3E-4
nig/kg/day
* Dose Conversion Factors & Assumptions: Food consumption of 5% bw/day;
thus, 0.51 mg/kg of diet x 0.05 kg of diet/kg bw/day - 0.026 mg/kg bw/day
2. PRINCIPAL AND SUPPORTING STUDIES
Hackenburg, U. 1972. Chronic ingestion by rats of standard diet treated
with aluminum phosphate. Toxicol. Appl. Pharmacol. 23(1): 147-153.
This study reported a no effects dose level for rats fed diet fumigated
with phastoxin over a 2-year period. The mean phosphine concentration during
that time period was 0.51 mg/kg of feed. Based on an average 5% food con-
sumption and average rat body weight of 610.4 g (reported in the study), the
phosphine dose can be calculated as 0.026 mg/kg bw/day. Hackenburg (1972)
found a slight, but statistically insignificant, tendency for test females to
gain weight faster than their control counterparts. There were no other dif-
ferences between controls and treated rats in hemoglobin content, hematocrit,
differential white blood cell count, glucose levels, SGPT, serum urea, pro-
thrombin time, organ weights or tissue histopathology. Survival rates and
tumor incidences were similar between controls and experimental animals.
-------
Phosphine: page 3 of 5
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 100. Application of an uncertainty factor of 100 (10 for intraspecies
extrapolation and 10 for sensitive population) to the rat NOEL of 0.026 mg/kg
yields an RfD of 0.02 mg/day.
MF
4. ADDITIONAL COMMENTS
The ACGIH (1984) has recommended a TLV of 0.3 ppm (0.42 mg/cu. m) for
phosphine, based principally on an epidemiological study by Jones (1964).
In this study, workers exposed intermittently to about 10 ppm phosphine gas
experienced GI, cardiorespiratory and CNS symptomatology. Based on the TLV,
an RfD of 0.021 mg/kg/day can be recommended. However, the Hackenburg (1972)
study was a 2-year study in rats which explored a number of functional and
morphological end points. This study forms a better basis for an RfD.
5. CONFIDENCE IN THE RfD
Study: High Data Base: High RfD: High
The confidence in the study was rated high because of the moderate number
of animals/dose, the extensive methodology employed to assure proper admin-
istration of the test compound, and the extensive number of parameters mea-
sured. The data base was rated high because of the effectiveness and safety
of this chemical has been long reported. The overall rating for the RfD is,
thus, high.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1985. Phosphine: Review and Evaluation of ADI. Contract No.
68-03-3228, Environmental Criteria and Assessment Office, Cincinnati, OH.
ECAO-Cincinnati Internal Review, August 1985.
Agency RfD Work Group Review: 08/19/85
Verification Date: 08/19/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Phosphine
CAS No.: 7803-51-2
Information is not available at this time.
-------
Phosphlne: page 4 of 5
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Phosphine
CAS No.: 7803-51-2
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Phosphine
CAS No.: 7803-51-2
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Phosphine
CAS No. : 7803-51-2 Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (In this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent Inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Phosphine: page 5 of 5
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Status
Date
Risk
Management
Value
Considers
Econ/Tech
Feasibility
Reference
Reportable
Quantity (RQ)
Final
1985
100 Ibs
No
50 FR 13456
04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on ignitability and acute toxicity. Phosphine is a
flammable gas with a boiling point well below 100 degrees F. Available data
indicate that the inhalation LC50 for rats is between 4 and 40 ppm (exposure
time = 4 hours).
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
V. SUPPLEMENTARY DATA
Chemical: Phosphine
CAS No.: 7803-51-2
Information is not available at this time.
Synonyms: CELPHOS, DELICIA, DETIA, DETIA GAS EX-B, FOSFOROWODOR (Polish),
GAS-EX-B, HYDROGEN PHOSPHIDE, PHOSPHINE , PHOSPHORUS TRIHYDRIDE,
PHOSPHORWASSERSTOFF (German), RCRA WASTE NUMBER P096, UN 2199
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Potassium Cyanide; CAS No. 151-50-8 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & 6 in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Potassium Cyanide
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
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Potassium Cyanide: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Potassium Cyanide
CAS No.: 151-50-8
Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Rat chronic oral
study
Howard and Hanzal
(1955)
10.8 mg/kg/day CN
(NOAEL) converted to
27.0 mg/kg/day of
potassium cyanide
100
5E-2
mg/kg/day
Weight loss, thyroid
effects and myelin
degeneration
Rat subchronic to
chronic oral bioassay
Philbrick et al.
(1979)
30 mg/kg/day CN
(LOAEL)
(75 mg/kg/day KCN)
* Dose Conversion Factors & Assumptions: molecular weight conversion factor
= 65/26 [ Mtf KCN =65; MW CN = 26 ]
2. PRINCIPAL AND SUPPORTING STUDIES
Howard, J.W. and R.F. Hanzal. 1955. Chronic toxicity to rats of food
treated with hydrogen cyanide. Agric. Food Chem. 3: 325-329.
Potassium cyanide is soluble in water and dilute acid (which includes the
gastric environment) and is readily hydrolyzed to 1 molar equivalent of
cyanide and 1 molar equivalent of potassium (Hartung, 1982).
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Potassium Cyanide: page 3 of 7
Since potassium is present in very high levels in food and the environ-
ment; an RfD of 3.8 rag/day for potassium cyanide, based on cyanide content, is
recommended.
In this 2-year dietary study, rats (10/sex/group) were administered food
fumigated with HCN. The average daily concentrations were 73 and 183 mg CN/kg
diet. From the data reported on food consumption and body weight, daily
estimated doses were 4.3 mg and 10.8 mg CN/kg bw. The average food CN
concentrations were estimated based on the authors' data for concentration at
the beginning and end of each food preparation period and by assuming a first-
order rate of loss for the intervening period. There were no treatment-
related effects on growth rate, no gross signs of toxicity, and no histo-
pathological lesions.
Studies by Philbrick et al. (1979) showed decreased weight gain and thy-
roxin levels and myelin degeneration in rats at 30 mg/kg/day CN. Other
chronic studies either gave higher effect levels or used the subcutaneous
route (Crampton et al., 1979; Lessell, 1971; Herthing et al., 1960). Human
data do not provide adequate information from which to derive an RfD because
effec- tive dose levels of chronically ingested CN are not documented.
Therefore, the study of Howard and Hanzel (1955) provides the highest NOAEL,
10.8 mg/kg/day for CN, and is chosen for the derivation of an RfD for CN of
1.5 mg/day or 0.02 mg/kg/day.
Cyanide is metabolized extensively in the liver, indicating that the only
relevant route of administration for quantitative risk assessment in the
derivation of an oral RfD is the oral route of administration.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. According to the U.S. EPA (1985), an uncertainty factor of 100 is
used to derive the RfD (10 for species extrapolation, 10 for sensitive
population).
MF = 5. A modifying factor of 5 is used to account for the apparent tolerance
to cyanide when it is ingested with food rather than when it is administered
by gavage or by drinking water.
4. ADDITIONAL COMMENTS
Decreased protein efficiency ratio was produced by dietary cyanide treat-
ment of rats during gestation, lactation and postweaning growth phase in the
Tewe and Maner (1981a) experiment; the dose level of cyanide (10.6 mg/kg/day)
producing that effect is slightly lower than the currently accepted NOAEL of
10.8 mg/kg/day (U.S. EPA, 1985). Furthermore, Tewe and Maner (1981b) tested
sows. Possible effects observed at about 9.45 mg/kg/day were proliferation
of glomerular cells of the kidneys and reduced activity of the thyroid glands
in the gilts. However, the number of animals in this experiment was very
small. A Japanese study (Amo, 1973) indicated that 0.05 mg/kg/day of cyanide
obtained from drinking water decreased the fertility rate and survival rate
in the Fl generation and produced 100% mortality in the F2 generation in
mice. However, these data are not consistent with the body of available
literature. Thus, until additional chronic studies are available, an RfD of
3.8 mg/day for a 70-kg human is recommended.
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Potassium Cyanide: page 4 of 7
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD:Medium
The confidence in the study is medium because adequate records of food
consumption and body weight were maintained, and animals of both sexes were
tested at two doses for 2 years. The data base is rated medium because a
small but sufficient number of studies support the chosen study. The confi-
dence in the RfD follows. Additional chronic/reproductive studies are needed
to support a higher level of confidence In the RfD.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, 1985. Limited peer review and Agency-wide
review, 1985.
U.S. EPA. 1985. Cyanides: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. 1984. Health Effects Assessment for Cyanides. Environmental Cri-
teria and Assessment Office, Cincinnati, OH. ECAO-CIN-H011.
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Potassium Cyanide
CAS No.: 151-50-8
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Potassium Cyanide
CAS No.: 151-50-8
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
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Potassium Cyanide: page 5 of 7
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Potassium Cyanide
CAS No.: 151-50-8
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Potassium Cyanide
CAS No.: 151-50-8 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk Status Risk Considers
Management Management Econ/Tech
Action Date Value Feasibility Reference
Reportable Final 10 Ibs no 50 FR 13456
Quantity (RQ) 1985 04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ was based on aquatic toxicity, as established under CWA
Section 311(b)(4). Available data indicate that the aquatic 96-Hour Median
Threshold Limit for potassium cyanide is between .1 and 1 ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
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Potassium Cyanide: page 6 of 7
V. SUPPLEMENTARY DATA
Chemical: Potassium Cyanide
CAS No.: 151-50-8 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Potassium cyanide is classified as super toxic. The probable oral lethal
dose in humans is less than 5 mg/kg or less than a taste (7 drops) for a
150-lb. person (Gosselin, 1976). It is an eye and skin irritant (Grant,
1974, Encyc Occupat Health and Safety, 1971). Poisonous in very small
quantities; a taste is lethal (Gosselin, 1984).
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Exposure to potassium cyanide can cause
weakness, headache, confusion, nausea, vomiting, increased rate of
respiration or slow, gasping respiration, scarlet rash, itching, blindness,
odor of bitter almonds, rise in blood pressure, irregular pulse, giddiness,
and anxiety (Clayton and Clayton, 1981-82, Gosselin, 1976, Encyc Occupat
Health and Safety, 1971, Grant, 1979).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: KCN
Molecular Weight: 65.11
Boiling Point: Not Found
Specific Gravity (H20=l): 1.52 at 16C
Vapor Pressure (mmHg): Not Found
Melting Point: 1173F, 634C
Vapor Density (AIR=1): Not Found
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: Soluble in 2 parts cold water or 1 part boiling
water.
Flash Point [Method Used]: Not flammable
Flammable Limits: Not Found
Appearance and Odor: White granular powder or lumps with faint odor of
bitter almonds (Merck, 1976; Hawley, 1977)
Conditions or Materials to Avoid: Avoid contact with acids (see Section
III above). Reacts with acids to produce hydrogen cyanide gas (NFPA, 1978).
-------
Potassium Cyanide: page 7 of 7
Reacts with strong oxidizers such as nitrates and chlorates (NIOSH/OSHA,
1978, p. 74); nitrogen trichloride; perchloryl fluoride; sodium nitrate;
acids; alkaloids; chloral hydrate; and iodine (Sax, 1984, p. 2273).
Hazardous Decomposition or Byproducts: When heated to decomposition, it
emits very toxic fumes of cyanide and nitrogen oxides (Sax, 1984, p. 2273).
Use: Potassium cyanide is used for electroplating, steel hardening,
extraction of gold and silver from ores, manufacture of some chemicals, and
fumigation (Encyc Occupat Health and Safety, 1971).
Synonyms: Cyanide of Potassium; Hydrocyanic Acid, Potassium Salt; Potassium
Cyanide (KCN)
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Potassium Silver Cyanide; CAS No. 506-61-6 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Potassium Silver Cyanide
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Potassium Silver Cyanide: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Potassium Silver Cyanide
CAS No.: 506-61-6
Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Weight loss, thyroid 10.8 mg/kg/day CN
100
effects and myelin
degeneration
Rat chronic oral
study
Howard and Hanzal
(1955)
Rat subchronic to
chronic oral bioassay
Philbrick et al.
(1979)
(NOAEL) converted to
82.7 mg/kg/day
potassium silver
cyanide
30.0 mg/kg/day CN
(LOAEL)
2E-1
mg/kg/day
* Dose Conversion Factors & Assumptions: molecular weight conversion factor
= 199/26 [ MW KAg(CN) =199; MW CN - 26 ]
2
2. PRINCIPAL AND SUPPORTING STUDIES
Howard, J.W. and R.F. Hanzal. 1955. Chronic toxicity to rats of food
treated with hydrogen cyanide. Agric. Food Chem. 3: 325-329.
Because potassium silver cyanide dissociates to form potassium, cyanide
and silver cyanide, only 1 molar equivalent of cyanide is generated (Windholz,
-------
Potassium Silver Cyanide: page 3 of 6
1983). Based on free cyanide liberated by the dissociation of potassium
silver cyanide, an RfD of 12 mg/day for a 70-kg man is recommended.
In this 2-year dietary study, rats (10/sex/group) were administered food
fumigated with HCN. The average daily concentrations were 73 and 183 mg
CN/kg diet. From the data reported on food consumption and body weight,
daily estimated doses were 4.3 mg and 10.8 mg CN/kg bw. The average food CN
concentrations were estimated based on the authors' data for concentration at
the beginning and end of each food preparation period and by assuming a first-
order rate of loss for the intervening period. There were no treatment-
related effects on growth rate, no gross signs of toxicity, and no histo-
pathological lesions.
Studies by Philbrick et al. (1979) showed decreased weight gain and thy-
roxin levels and myelin degeneration in rats at 30 mg/kg/day CN. Other
chronic studies either gave higher effect levels or used subcutaneous route
(Crampton et al., 1979; Lessell, 1971; Herthing et al., 1960). Human data do
not provide adequate information from which to derive an RfD because effec-
tive dose levels of chronically ingested CN are not documented. Therefore,
the study of Howard and Hanzel (1955) provides the highest NOAEL, 10.8 mg/kg/
day for CN, and is chosen for the derivation of an RfD for CN of 1.5 mg/day or
0.02 mg/kg/day.
Cyanide is metabolized extensively in the liver, indicating that the only
relevant route of administration for quantitative risk assessment in the
derivation of an oral RfD is the oral route of administration.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. According to the U.S. EPA (1985), an uncertainty factor of 100 is
used to derive the RfD (10 for species extrapolation, 10 for sensitive
population).
MF = 5. A modifying factor of 5 was used to account for the apparent
tolerance to cyanide when it is ingested with food rather than when it is
administered by gavage or by drinking water.
4. ADDITIONAL COMMENTS
Decreased protein efficiency ratio was produced by dietary cyanide treat-
ment of rats during gestation, lactation and postweaning growth phase in the
Tewe and Maner (1981a) experiment: the dose level of cyanide (10.6 mg/kg/
day) producing that effect is slightly lower than the currently accepted
NOAEL of 10.8 mg/kg/day (U.S. EPA, 1985). Furthermore, Tewe and Maner
(1981b) tested sows. Possible effects observed at about 9.45 mg/kg/day were
proliferation of glomerular cells of the kidneys and reduced activity of the
thyroid glands in the gilts. However, the number of animals in this experi-
ment was very small. A Japanese study (Amo, 1973) indicated that 0.05 mg/kg/
day of cyanide obtained from drinking water decreased the fertility rate and
survival rate in the Fl generation and produced 100% mortality in the F2 gen-
eration in mice. However, these data are not consistent with the body of
available literature. Thus, until additional chronic studies are available,
an RfD of 12 mg/day for a 70-fkg man is recommended.
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Potassium Silver Cyanide: page 4 of 6
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The confidence in the study is medium because adequate records of food
consumption and body weight were maintained and animals of both sexes were
tested at two doses for 2 years. The data base is rated medium because a
small but sufficient number of studies support the chosen study. The confi-
dence in the RfD follows. Additional chronic/reproductive studies are needed
to support a higher level of confidence in the RfD.
6. DOCUMENTATION AND REVIEU
ECAO-Cincinnati Internal Review, July 1985.
U.S. EPA. 1985. Cyanides: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Potassium Silver Cyanide
CAS No.: 506-61-6
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Potassium Silver Cyanide
CAS No.: 506-61-6
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
-------
Potassium Silver Cyanide: page 5 of 6
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Potassium Silver Cyanide
CAS No.: 506-61-6
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Potassium Silver Cyanide
CAS No.: 506-61-6 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Ratiorale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
1 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity. Available data indicate that
the 96-Hour Median Threshold Limit for potassium silver cyanide is less than
0.1 ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
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Potassium Silver Cyanide: page 6 of 6
V. SUPPLEMENTARY DATA
Chemical: Potassium Silver Cyanide
CAS No.: 506-61-6
Information is not available at this time.
Synonyms: KYANOSTRIBRNAN DRASELNY (Czech), RCRA WASTE NUMBER P099, SILVER
POTASSIUM CYANIDE, POTASSIUM SILVER CYANIDE
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Selenious Acid; CAS No. 7783-00-8 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Selenious Acid
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Selenious Acid: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Selenious Acid
CAS No.: 7783-00-8
Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Selenosis
Human epidemic-
logical study
Yang et al. (1983)
0.750 mg/day (NOAEL)
3.2 mg/day or 0.046
mg/kg/day (LOAEL)
10 1.5 3E-3
ing/kg/day
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Yang, G., S. Wang, R. Zhou and S. Sun.
of humans in China. Am. J. Clin. Nutr.
1983. Endemic selenium intoxication
37: 872-881.
In solution, selenium from selenious acid and selenite salts is present
predominantly as the biselenite ion (NAS, 1976). The toxicity of selenite
salts and selenious acid would therefore be expected to be similar at sub-
lethal doses. It would thus be appropriate to derive a selenious acid RfD by
analogy to selenium.
The effects of oral selenium exposure have been relatively thoroughly
studied in experimental animals and man. The NAS (1980) has determined an
adequate and safe range for selenium intake of 0.05-0.2 mg/day for an adult
man.
The effects of selenium deficiency are potentially as serious as those of
selenium toxicity. Selenosis has been reported in high-selenium areas where
-------
Selenious Acid: page 3 of 6
the average intake was 5 mg/day (range 3.2-6.7), but no selenosis occurred
when the average intake was 0.750 mg/day (range 0.240-1.51) (Yang et al.,
1983). Therefore, care must be exercised in deriving an RfD to insure that
minimum dietary requirements are met.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 10. An uncertainty factor of 10 for the LOAEL for selenosis (3.2 mg/day)
was applied to derive an RfD of 0.2 mg selenious acid/day for adequate
protection against adverse health effects in humans. Since the LOAEL is from
a large population of humans, the usual uncertainty factor of 10 for
interhuman variability is not thought to be necessary.
MF = 1.5. A modifying factor of 1.5 is used based on information suggesting
that selenium in water is absorbed more efficiently than selenium in food
(U.S. EPA, 1985).
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: High RfD: High
Confidence in the chosen study is medium because doses are given as
ranges. Confidence in the data base and RfD are both high because many sup-
porting animal studies (reviewed by NAS, 1977) and epidemiological studies
exist.
6. DOCUMENTATION AND REVIEW
Office of Drinking Water and ECAO-Cincinnati Internal Reveiw, 1985.
U.S. EPA. 1985. Health Effects Assessment for Selenium (and Compounds).
Environmental Criteria and Assessment Office, Cincinnati, OH. ECAO-CIN-H058.
Agency RfD Work Group Review: 08/19/85
Verification Date: 08/19/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
-------
Selenious Acid: page 4 of 6
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Selenious Acid
CAS No.: 7783-00-8
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Selenious Acid
CAS No.: 7783-00-8
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Selenious Acid
CAS No.: 7783-00-8
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Selenious acid
CAS No.: 7783-00-8 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Selenious Acid: page 5 of 6
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1986
Risk
Management
Value
10 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
51 FR 34534
09/29/86
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on chronic toxicity. RQ assignments based on
chronic toxicity reflect two primary attributes of the hazardous substance,
the minimum effective dose (MED) levels for chronic exposure (mg/day for 70-
kg man) and the type of effect (liver necrosis, teratogenicity, etc). In
accordance with the methodology described in the Agency's "Technical
Background Document to Support Rulemaking Pursuant to CERCLA Section 102,
Volume 1" of March 1985 and 50 FR 13468 (04/04/85), a composite score is
determined from an evaluation of these two attributes. Selenious acid was
determined to have a composite score between 41 and 80, corresponding to a
chronic toxicity RQ of 10 pounds.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
V. SUPPLEMENTARY DATA
Chemical: Selenious Acid
CAS No.: 7783-00-8 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Selenous acid and its salts are capable of penetrating the skin and can
produce acute poisonings (Rumack, 1975 to Present). It causes irritations
and burns of the skin (Friberg, 1979). It is highly toxic orally.
Inorganic selenium compounds may cause dermatitis (Sax, 1984, p. 2390).
Medical Conditions Generally Aggravated by Exposure: Not Found
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Selenious Acid: page 6 of 6
Signs and Symptoms of Exposure: Toxic effects are similar to those of
selenium and other selenium compounds. Garlic odor of breath is a common
symptom. Pallor, nervousness, depression, and digestive disturbances have
been reported in cases of chronic exposure (Sax, 1984, p. 2390). The most
common industrial injuries are irritations and burns of the skin (Friberg,
1979).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: H 0 Se
2 3
Molecular Weight: 128.98
Boiling Point: Not Found
Specific Gravity (H20=l): 3.004 at 15/4C
Vapor Pressure (mmHg): 2 at 15C
Melting Point: Decomposes at 158F, 70C
Vapor Density (AIR=1): Not Found
Evaporation Rate (Butyl acetate-1): Not Found
Solubility in Water: 90 parts/100 parts at 32F, OC
Flash Point [Method Used]: 88C (CC)
Flammable Limits:
LEL: 1.8%
UEL: Not Found
Appearance and Odor: Colorless solid (Merck, 1976, Weast, 1979);
transparent, colorless crystals (Sax, 1984, p. 2390)
Conditions or Materials to Avoid: Avoid heating (Sax, 1984, p. 2390).
Hazardous Decomposition or Byproducts: When heated to decomposition it
emits toxic fumes of selenium (Sax, 1984, p. 2390)
Use: It is used as a reagent for alkaloids and as an oxidizing agent
(Merck, 1976). Isotope is used in labeling radiopharmaceuticals (Nuclear
Medicine Communication 3(4)247, 1982).
Synonyms: Monohydrated Selenium Dioxide; Selenious Acid
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Selenourea; CAS No. 630-10-4 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Selenourea
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
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Selenourea: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) Is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Selenourea
CAS No.: 630-10-4
Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Selenosis
Experimental Doses *
0.750 rag/day (NOAEL)
UF
10
MF
1.5
RfD
5E-3
mg/kg/day
Human epidemiological
study
Yang et al. (1983)
3.2 mg/day Se or
0.046 mg/kg/day con-
verted to 0.072 mg/
kg/day equivalent
exposure of seleno-
urea by analogy to
selenium (LOAEL)
* Dose Conversion Factors & Assumptions: Molecular weight of Se(NH2)2/Se(-
2) is 123.03/78.96; thus, 0.046 mg/kg/day x 123.03/78.96 = 0.072 mg/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
Yang, G., S. Wang, R. Zhou and S. Sun.
of humans In China. Am. J. Clin. Nutr.
1983. Endemic selenium intoxication
37: 872-881.
There is little information regarding the toxicity of selenourea. Cummins
and Kimura (1971) reported a rat oral LD50 of 50 mg/kg, compared with 7 mg/kg
for sodium selenite. It was postulated that the lower toxicity of selenourea
was probably due to its lower water solubility and consequent poorer GI
absorption compared with sodium selenite. Because of the lack of data
regarding the toxicity of selenourea, the best approach in deriving an RfD
for selenourea is by analogy to selenium.
The NAS (1980) has determined an adequate and safe range for selenium
intake of 50-200 ug/day for an adult man. The effects of selenium deficiency
-------
Selenourea: page 3 of 5
are potentially as serious as those of selenium toxicity. Selenosis has been
reported in high-selenium areas where the average intake was 5 mg/day (range
3.2-6.7), but no selenosis occurred when the average intake was 0.75 mg/day
(range 0.24-1.51; Yang et al., 1983). U.S. EPA (1985) recommended an RfD of
0.21 mg/day for selenium by applying an uncertainty factor of 15 to the LOAEL
of 3.2 mg/day (Yang et al., 1983). This RfD was derived on the intake of
selenium in drinking water, and an uncertainty factor of 15 rather than 10
was applied because of Information that selenium in water is absorbed more
efficiently than selenium in food.
This RfD should be adjusted for differences in molecular weight between
selenourea (123.03) and selenium (78.96) and, thus, an RfD of 0.005 mg/kg/day
(0.003 mg Se x 1.6) or 0.33 mg/day for selenourea is recommended to provide
adequate protection against adverse health effects.
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 10. An uncertainty factor of 10 for the LOAEL for selenosis (3.2
mg/day) was applied to derive an RfD of 0.2 mg selenious acid/day for
adequate protection against adverse health effects in humans. Since the
LOAEL Is from a large population of humans, the usual uncertainty factor of
10 for interhuman variability is not thought to be necessary.
MF = 1.5. A modifying factor of 1.5 is used based on information suggesting
that selenium in water Is absorbed more efficiently than selenium in food
(U.S. EPA, 1985).
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: High RfD: High
Confidence in the chosen study is medium because doses are given as
ranges. Confidence in the data base and RfD are both high because many sup-
porting animal studies (reviewed by NAS, 1977) and epidemiological studies
exist.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, August 1985.
U.S. EPA. 1985. Selenourea: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. 1985. Health Effects Assessment for Selenium (and Compounds).
Environmental Criteria and Assessment Office, Cincinnati, OH. ECAO-CIN-H058.
Agency RfD Work Group Review: 08/19/85
Verification Date: 08/19/85
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Selenourea: page 4 of 5
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Selenourea
CAS No.: 630-10-4
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Selenourea
CAS No.: 630-10-4
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Selenourea
CAS No.: 630-10-4
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Selenourea
CAS No.: 630-10-4 Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
-------
Selenourea: page 5 of 5
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk Status Risk Considers
Management Management Econ/Tech
Action Date Value Feasibility Reference
Reportable Final 1000 Ibs No 51 FR 34i34
Quantity (RQ) 1986 09/29/66
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on acute toxicity. Available data indicate that
selenourea has an oral LD50 for rats of between 10 and 100 mg/kg.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
V. SUPPLEMENTARY DATA
Chemical: Selenourea
CAS No.: 630-10-4
Information is not available at this time.
Synonyms: RCRA WASTE NUMBER P103, SELENOUREA
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Silver; CAS No. 7440-22-4 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Silver
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Sliver: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Silver
CAS No.: 7440-22-4
Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses
UF
MF
RfD
argyria
1-3 year therapeu-
tic treatments in
humans
Gaul and Stand
(1935)
Blumberg and Carey
(1934)
East et al. (1980)
NOAEL: None
3E-3
mg/kg/day
1.0 g (total i.v.
dose) (LOAEL)
6.4 g (total oral
dose) (LOAEL)
7.2 g (total oral
dose estimated)
(LOAEL)
Average dose =
0.0052 mg/kg/day
Dose Conversion Factors & Assumptions:
1000 mg x 1/0.18 x 1/70 kg x 1/25,500 days = 0.0031 mg/kg day;
6400 mg/32.7 kg/25,500 days = 0.0077 mg/kg/day;
7200 mg/58.6 kg/25,500 days = 0.0048 mg/kg/day;
Average = 0.0052 mg/kg/day
-------
Silver: page 3 of 7
2. PRINCIPAL AND SUPPORTING STUDIES
Gaul, L.E. and A.N. Stand. 1935. Clinical spectroscopy. Seventy cases of
generalized argyria following organic and colloidal silver medication. J.
Am. Med. Assoc. 104: 1387-1390.
Blumberg, H. and T.N. Carey. 1934. Argyremia: Detection of unsuspected and
obscure argyria by the spectrographic demonstration of high blood silver. J.
Am. Med. Assoc. 103: 1521-1524.
East, B.W., K. Boddy, E.D. Williams, D. Maclntyre and A.L.C. McLay. 1980.
Silver retention, total body silver and tissue silver concentrations in
argyria associated with exposure to an anti-smoking remedy containing silver
acetate. Clin. Exp. Dermatol. 5: 305-311.
In Gaul and Staud (1935), the LOAEL of 1.0 g was representative of the
lowest total doses (0.9-1.5 g) of silver associated with argyria in humans.
The doses were administered i.v. over a 2- to 3-year period as silver
arsphenamine. No body weight data were reported.
Blumberg and Carey (1934) estimated the total dose from a dosing schedule
for silver nitrate taken orally for 1 year as 6.4 g. The subject was an
emaciated adult female (32.7 kg).
East et al. (1980) estimated the total body content of silver In one
individual with argyria to be 6.4 (plus or minus 2) g. The subject ingested
an unknown quantity of silver acetate over a period of 2.5 years. Symptoms
of argyria appeared after the first 6 months of exposure. This subject
retained 18% of a single dose of orally-administered silver in a separate
30-week experiment. Body weight was given as 58.6 kg.
Argyria is considered adverse beyond its cosmetic effect since it is
irreversible and can be clinically mistaken for cyanosis.
Total dose is the most appropriate parameter because argyria is a cumula-
tive effect of silver. The i.v. to oral conversion factor of 1/0.18 is based
on the East et al. (1980) retention study. Pharmacokinetic studies in ani-
mals suggest that this value (18%) is high and should be considered a conser-
vative estimate. Human body weight defaults to 70 kg in the absence of
reported values. The total body burden of silver reported in East et al.
(1980) was adjusted for the time of onset of argyria and then converted to an
oral dose In the following manner:
6.4 g x 6 months/30 months = 1.3 g body burden; 1.3 g/0.18 = 7.2 g.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 2. The standard UF of 10 for the intraspecies (human) variability
is not considered appropriate because the affected subjects are of generally
poor health and are considered to be sensitive elements of the population.
A UF of 2 is used for the LOAEL because the critical effect is considered to
be minimally severe.
MF = 1
-------
Silver: page 4 of 7
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The human studies rate a medium confidence; they are reasonably good,
with some quantitative dosing data. The data base confidence is medium;
supporting animal data suggest that the RfD based on the human data should
not be lower. Medium confidence in the RfD follows.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1985. Drinking Water Criteria Document for Silver. Office of
Drinking Water, Washington, DC. (External Review Draft)
The 1985 Office of Drinking Water document has received Agency review and has
been reviewed by several outside experts.
Agency RfD Work Group Review: 10/09/85, 02/05/86, 10/09/85
Verification Date: 10/09/85
7. U.S. EPA CONTACTS
Primary: S. Goldhaber FTS/382-7583 or 202/382-7583
Office of Drinking Water
Secondary: L. Erdreich FTS/684-7573 or 513/569-7573
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Silver
CAS No.: 7440-22-4
Information is not available at this time.
-------
Silver: page 5 of 7
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Silver
CAS No.: 7440-22-4
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Silver
CAS No.: 7440-22-4
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Silver
CAS No.: 7440-22-4 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (In sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Silver: page 6 of 7
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
1000 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Water Quality
Criteria (WQC):
a. Human Health
Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
2) Marine
Final
50 ug/1 no
Acute no
varies with
hardness
Chronic
0.12 ug/1 (LEL)
Acute no
45 FR 79318
11/28/80
ibid.
ibid.
1980
2.3 ug/1
Chronic
none
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on chronic toxlcity. RQ assignments based on
chronic toxicity reflect two primary attributes of the hazardous substance,
the minimum effective dose (MED) levels for chronic exposure (mg/day for 70-
kg man) and the type of effect (liver necrosis, teratogenicity, etc). In
accord- ance with the methodology described in the Agency's "Technical
Background Document to Support Rulemaking Pursuant to CERCLA Section 102,
Volume 1" of March 1981 and 50 FR 13468 (04/04/85), a composite score is
determined from an evaluation of these two attributes. Silver was
determined to have a composite score between 6 and 20, corresponding to a
chronic toxicity RQ of 1000 pounds.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: This value is the same as the drinking water standard and
approximates a safe level assuming consumption of contaminated organisms and
water.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value indicates that the
-------
Silver: page 7 of 7
minimum data were not available and the concentration given is not a criteria
value but the lowest effect level found in the literature. The freshwater
acute criterion varies with water hardness. For freshwater aquatic life the
concentration (in ug/1) of total recoverable silver should not exceed the
numerical value given by the equation "e**(1.72 [In (hardness)]-6.52)" (**
indicates exponentiation; hardness is in mg/1). For example, at a hardness
of 50 mg/1, the acute WQC would be 1.2 and, at a hardness of 100 mg/1, the
criterion would be 4.1 mg/1
V. SUPPLEMENTARY DATA
Chemical: Silver
CAS No.: 7440-22-4
Information is not available at this time.
Synonyms: SILVER; ARGENTUM; C.I. 77820; L-3; SHELL SILVER; SILBER (German);
SILVER (ACGIH); SILVER ATOM; SILVER, COLLOIDAL; ARGENTUM CREDE; COLLARGOL
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Silver Cyanide; CAS No. 506-64-9 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Silver Cyanide
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Silver Cyanide: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Silver Cyanide
CAS No.: 506-64-9
Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Rat chronic oral
study
Howard and Hanzal
(1955)
10.8 mg/kg/day CN
(NOAEL) converted to
55.7 mg/kg/day of
silver cyanide
100
1E-1
mg/kg/day
Weight loss, thyroid
effects and myelin
degeneration
Rat subchronic to
chronic oral bioassay
Philbrick et al.
(1979)
30 mg/kg/day CN
(LOAEL)
(155 mg/kg/day AgCN)
* Dose Conversion Factors & Assumptions: molecular weight conversion factor
= 134/26 [ MW AgCN = 134; Mtf CN = 26 ]
2. PRINCIPAL AND SUPPORTING STUDIES
Howard, J.W. and R.F. Hanzal. 1955. Chronic toxicity for rats by food
treated with hydrogen cyanide. Agric. Food Chem. 3: 325-329.
Silver cyanide is not soluble in water or dilute acid (tfindholz, 1983).
Currently the data base does not provide any toxicity information on silver
-------
Silver Cyanide: page 3 of 6
cyanide. It is, therefore, recommended that an RfD of 8 mg/day for a 70-kg
human based on cyanide will provide adequate protection against an adverse
health effects. Note that this is a conservative protective assumption in
light of silver cyanide's lack of solubility.
In this 2-year dietary study, rats (10/sex/group) were administered food
fumigated with HCN. The average daily concentrations were 73 and 183 mg CN/kg
diet. From the data reported on food consumption and body weight, daily
estimated doses were 4.3 mg and 10.8 mg CN/kg bw. The average food CN
concentrations were estimated based on the authors' data for concentration at
the beginning and end of each food preparation period and by assuming a first-
order rate of loss for the intervening period. There were no treatment-
related effects on growth rate, no gross signs of toxicity, and no histo-
pathological lesions.
Studies by Philbrick et al. (1979) showed decreased weight gain and thy-
roxin levels and myelin degeneration in rats at 30 mg/kg/day CN. Other
chronic studies either gave higher effect levels or used the subcutaneous
route (Crampton et al., 1979; Lessell, 1971; Berthing et al., 1960). Human
data do not provide adequate Information from which to derive an RfD because
effec- tive dose levels of chronically Ingested CN are not documented.
Therefore, the study of Howard and Hanzel (1955) provides the highest NOAEL,
10.8 mg/kg/ day for CN, and is chosen for the derivation of an RfD for CN of
1.5 mg/day or 0.02 mg/kg/day.
Cyanide Is metabolized extensively in the liver, indicating that the only
relevant route of administration for quantitative risk assessment in the
derivation of an oral RfD is the oral route of administration.
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 100. According to the U.S. EPA (1985), an uncertainty factor of 100 is
used to derive the RfD (10 for species extrapolation, 10 for sensitive
population).
MF - 5. A modifying factor of 5 is used to account for the apparent tolerance
to cyanide when It is ingested with food rather than when it is administered
by gavage or by drinking water.
4. ADDITIONAL COMMENTS
Decreased protein efficiency ratio was produced by dietary cyanide treat-
ment of rats during gestation, lactation and postweaning growth phase In the
Tewe and Maner (1981a) experiment; the dose level of cyanide (10.6 mg/kg/day)
producing that effect is slightly lower than the currently accepted NOAEL of
10.8 mg/kg/day (U.S. EPA, 1985). Furthermore, Tewe and Maner (1981b) tested
sows. Possible effects observed at about 9.45 mg/kg/day were proliferation
of glomerular cells of the kidneys and reduced activity of the thyroid glands
in the gilts. However, the number of animals in this experiment was very
small. A Japanese study (Amo, 1973) Indicated that 0.05 mg/kg/day of cyanide
obtained from drinking water decreased the fertility rate and survival rate
in the Fl generation and produced 100% mortality in the F2 generation in
mice. However, these data are not consistent with the body of available
literature. Thus, until additional chronic studies are available, an RfD of
3.8 mg/day for a 70-kg human is recommended.
-------
Silver Cyanide: page 4 of 6
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Low RfD: Medium
The confidence in the study is medium because adequate records of food
consumption and body weight were maintained, and animals of both sexes were
tested at two doses for 2 years. The data base is rated low because this
chemical has not been tested. The confidence in the RfD is low becauese it is
based on analogy. Chronic/reprocutive studies are needed to support a higher
level of confidence in the RfD.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, 1985. Limited peer review and Agency-wide
review, 1985.
U.S. EPA. 1985. Cyanides: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. 1984. Health Effects Assessment for Cyanides. Environmental Cri-
teria and Assessment Office, Cincinnati, OH. ECAO-CIN-H011.
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Silver Cyanide
CAS No.: 506-64-9
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Silver Cyanide
CAS No.: 506-64-9
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
-------
Silver Cyanide: page 5 of 6
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Silver Cyanide
CAS No.: 506-64-9
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Silver Cyanide
CAS No.: 506-64-9 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
1 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity. Available data indicate that
the 96-Hour Median Threshold Limit for silver cyanide is less than 0.1 ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
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Silver Cyanide: page 6 of 6
V. SUPPLEMENTARY DATA
Chemical: Silver Cyanide
CAS No.: 506-64-9
Information is not available at this time.
Synonyms: CYANURE D'ARGENT (French), KYANID STRIBRNY (Czech), RCRA WASTE
NUMBER P104 , SILVER CYANIDE , UN 1684
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Sodium Cyanide; CAS No. 143-33-9 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Sodium Cyanide
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
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Sodium Cyanide: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Sodium Cyanide
CAS No.: 143-33-9
Preparation Date: 01/08/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Rat chronic oral
study
Howard and Hanzal
(1955)
10.8 mg/kg/day CN
(NOAEL) converted to
20.4 mg/kg/day of
sodium cyanide
100
4E-2
ing/kg/day
Weight loss, thyroid
effects and myelin
degeneration
Rat subchronic to
chronic oral bioassay
Philbrick et al.
(1979)
30 mg/kg/day CN
(LOAEL)
(56 mg/kg/day NaCN)
* Dose Conversion Factors & Assumptions: molecular weight conversion factor
= 49/26 [ MW NaCN =49; MW CN - 26 ]
2. PRINCIPAL AND SUPPORTING STUDIES
Howard, J.W. and R.F. Hanzal. 1955. Chronic toxicity for rats of food
treated with hydrogen cyanide. Agric. Food Chem. 3: 325-329.
Since sodium is present in very high levels physiologically, an RfD for
sodium cyanide of 0.04 mg/kg/day or 3 mg/day can be calculated based on the
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Sodium Cyanide: page 3 of 7
maximum molar equivalents (1) of cyanide generated in aqueous solution or
dilute acids.
In this 2-year dietary study, rats (10/sex/group) were administered food
fumigated with HCN. The average daily concentrations were 73 and 183 mg CN/kg
diet. From the data reported on food consumption and body weight, daily
estimated doses were 4.3 mg and 10.8 mg CN/kg bw. The average food CN
concentrations were estimated based on the authors' data for concentration at
the beginning and end of each food preparation period and by assuming a first-
order rate of loss for the intervening period. There were no treatment-
related effects on growth rate, no gross signs of toxicity, and no histo-
pathological lesions.
Studies by Philbrick et al. (1979) showed decreased weight gain and thy-
roxin levels and myelin degeneration in rats at 30 mg/kg/day CN. Other
chronic studies either gave higher effect levels or used the subcutaneous
route (Crampton et al., 1979; Lessell, 1971; Berthing et al., 1960). Human
data do not provide adequate information from which to derive an RfD because
effec- tive dose levels of chronically ingested CN are not documented.
Therefore, the study of Howard and Hanzel (1955) provides the highest NOAEL,
10.8 mg/kg/ day for CN, and is chosen for the derivation of an RfD for CN of
1.5 mg/day or 0.02 mg/kg/day.
Cyanide is metabolized extensively in the liver, indicating that the only
relevant route of administration for quantitative risk assessment in the
derivation of an oral RfD is the oral route of administration.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. According to the U.S. EPA (1985), an uncertainty factor of 100 is
used to derive the RfD (10 for species extrapolation, 10 for sensitive
population).
MF = 5. A modifying factor of 5 is used to account for the apparent tolerance
to cyanide when it is ingested with food rather than when it is administered
by gavage or by drinking water.
4. ADDITIONAL COMMENTS
Decreased protein efficiency ratio was produced by dietary cyanide treat-
ment of rats during gestation, lactation and postweaning growth phase in the
Tewe and Maner (1981a) experiment; the dose level of cyanide (10.6 mg/kg/day)
producing that effect is slightly lower than the currently accepted NOAEL of
10.8 mg/kg/day (U.S. EPA, 1985). Furthermore, Tewe and Maner (1981b) tested
sows. Possible effects observed at about 9.45 mg/kg/day were proliferation
of glomerular cells of the kidneys and reduced activity of the thyroid glands
in the gilts. However, the number of animals in this experiment was very
small. A Japanese study (Amo, 1973) indicated that 0.05 mg/kg/day of cyanide
obtained from drinking water decreased the fertility rate and survival rate
In the Fl generation and produced 100% mortality in the F2 generation in
mice. However, these data are not consistent with the body of available
literature. Thus, until additional chronic studies are available, an RfD of
3.8 mg/day for a 70-kg human is recommended.
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Sodium Cyanide: page 4 of 7
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD:Medium
The confidence in the study is medium because adequate records of food
consumption and body weight were maintained, and animals of both sexes were
tested at two doses for 2 years. The data base is rated medium because a
small but sufficient number of studies support the chosen study. The confi-
dence in the RfD follows. Additional chronic/reproductive studies are needed
to support a higher level of confidence in the RfD.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, 1985. Limited peer review and Agency-wide
review, 1985.
U.S. EPA. 1985. Cyanides: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. 1984. Health Effects Assessment for Cyanides. Environmental Cri-
teria and Assessment Office, Cincinnati, OH. ECAO-CIN-H011.
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Sodium Cyanide
CAS No.: 143-33-9
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Sodium Cyanide
CAS No.: 143-33-9
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
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Sodium Cyanide: page 5 of 7
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Sodium Cyanide
CAS No.: 143-33-9
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Sodium Cyanide
CAS No.: 143-33-9 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
10 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ was based on aquatic toxicity, as established under CWA
Section 311(b)(4). Available data indicate that the aquatic 96-Hour Median
Threshold Limit for sodium cyanide is between .1 and 1 ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
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Sodium Cyanide: page 6 of 7
V. SUPPLEMENTARY DATA
Chemical: Sodium Cyanide
CAS No.: 143-33-9 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Sodium cyanide is super toxic; the probable oral lethal dose in humans is
less than 5 mg/kg or a taste (less than 7 drops) for a 70-kg (150-lb.)
person (Gosselin, 1976). Sodium cyanide is poisonous and may be fatal if
inhaled, swallowed or absorbed through the skin. Contact with sodium
cyanide may cause burns to skin and eyes (DOT, 1984).
Medical Conditions Generally Aggravated by Exposure: Individuals with
chronic diseases of the kidneys, respiratory tract, skin, or thyroid are at
greater risk of developing toxic cyanide effects (Encyc Occupat Health and
Safety, 1983).
Signs and Symptoms of Exposure: Sodium cyanide produces all typical
symptoms of other sources of cyanide ion. Acute symptoms can be produced by
inhalation, skin absorption, and ingestion (Clayton and Clayton, 1981-82).
Massive doses may produce sudden loss of consciousness and prompt death from
respiratory arrest. Smaller doses may still be lethal but Illness may be
prolonged for 1-2 hours. Upon ingestion, a bitter, acrid, burning taste is
sometimes noted, followed by a feeling of constriction or numbness in the
throat (Gosselin, 1976).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: NaCN
Molecular Weight: 49.01
Boiling Point: 2725F, 1496C
Specific Gravity (H20=l): Not Found
Vapor Pressure (mmHg): 1 at 817C
Melting Point: 1047F, 564C
Vapor Density (AIR=1): Not Found
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: 82 g/100 cc at 35C
Flash Point [Method Used]: Not combustible
Flammable Limits:
Appearance and Odor: White solid in form of granules, flakes, or eggs
(resembling chicken eggs) (NFPA, 1978); colorless cubes (Weast, 1979);
-------
Sodium Cyanide: page 7 of 7
odorless when perfectly dry but emits odor of hydrogen cyanide when damp
(Merck, 1983)
Conditions or Materials to Avoid: Avoid contact with acids (NFPA, 1978).
Aqueous solutions rapidly decompose (Hawley, 1977). Avoid strong oxidizers
such as nitrates and chlorates; acids and acid salts (NIOSH/OSHA, 1978, p.
74)
Hazardous Decomposition or Byproducts: Hydrogen cyanide (NFPA, 1978)
Use: Sodium cyanide is used as a fumigant (Merck, 1983), a rodenticide
(Morgan, 1982), in cleaning metals, in the manufacturing of dyes and
pigments, as a chelating compound (Hawley, 1977), as a component of
electroplating solutions, as a component of salts for case hardening steel,
and as an agent for extraction of gold and silver from ores (SRI).
Synonyms: Cyanide of Sodium; Cyanogran; Cymag; Hydrocyanic Acid, Sodium salt;
Sodium Cyanide, Solid (DOT)
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Sodium Diethyldithiocarbamate; CAS No. 148-18-5 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Sodium Diethyldithiocarbamate
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: none
V. Supplementary Data: none
-------
Sodium Diethyldithiocarbamate (Dithiocarb): page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Sodium Diethyldithiocarbamate (Dithiocarb)
CAS No.:
148-18-5
Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses
UF
MF
RfD
Reduced body weight
Rat subchronic oral
study
Sunderman et al.
(1967)
NOEL: 30 mg/kg/day
LOAEL: 100 mg/kg/day
1000 1 3E-2
mg/kg/day
Reduced body weight
and cataracts in
females
Chronic rat bio-
assay
NCI (1979)
NOEL: None
LOAEL: 1250 ppm diet
(62.5 mg/kg/day)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Sunderman, F.W., O.E. Paynter and R.B. George. 1967. The effects of the
protracted administration of the chelating agent, sodium diethyldithiocarba-
mate (dithiocarb). Am. J. Med. Sci. 254: 46-56.
NCI (National Cancer Institute). 1979. Bioassay of sodium diethyldithio-
carbamate for possible carcinogenicity. NCI Carcinogenesis Tech. Rep. Ser.
No. 172. DHEW(NIH) 79-1728.
-------
Sodium Diethyldithiocarbamate (Dithiocarb): page 3 of 5
Albino rats (25/sex/group) were dosed p.o. with 0, 30, 100 or 300 mg
dithiocarb/kg bw/day for 90 days (Sunderman et al., 1967). A dose-related
decrease in weight gain was observed for all treatment groups, but was
statistically significant only for the 100 and 300 mg/kg/day groups. Food
consumption was not reported. Red blood cell counts were reduced and related
end points were affected for animals in the highest dose group. Histopatho-
logical analysis showed evidence of mild kidney effects at 300 mg/kg/day.
Beagle dogs (2/sex/group) were treated according to the same protocol
(Sunderman et al., 1967). Effects were noted for the high dose (300 mg/kg/
day) group only. These animals exhibited slight body weight loss, hemato-
logic effects and mortality (one animal died at day 70).
F344 rats (50/sex/group) were fed dithiocarb at 0, 1250 or 2500 ppm for 2
years. Reduced body weights were observed for females at both doses (about
10% less than controls) and males at the high dose only. A statistically
significant increase in the incidence of cataracts was observed in the
treated females, but not in males. The rats are assumed to consume 5% of
body weight/day during the 2-year exposure of the NCI (1979) study.
Short-term administrations of slightly higher doses have been associated
with central nervous system lesions in rabbits and neonatal lambs, with con-
siderable mortality in the latter species. Dithiocarb has been reported to
cause pancreatic damage in rabbits.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. The uncertainty factor of 1000 reflects 10 for both intraspecies
and interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation of a subchronic effect level to its
chronic equivalent.
MF = 1
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: High Data Base: Medium RfD: Medium
The critical study was well designed and adequately reported; the two
subchronic studies are mutually supportive, with similar effects observed.
Support for chronic effects is lacking, and hematologic end points were not
examined in the NCI study. The confidence in the RfD can be considered to be
medium to low because of the lack of adequate chronic data.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1984. Health and Environmental Effects Profile for Sodium
Diethyldithiocarbamate. Environmental Criteria and Assessment Office,
Cincinnati, OH. ECAO-CIN-P016.
The ADI in the Health and Environmental Effects Profile document has received
an Agency-wide review with the help of two external scientists.
-------
Sodium Diethyldithiocarbamate (Dithiocarb): page 4 of 5
Agency RfD Work Group Review: 10/09/85
Verification Date: 10/09/85
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Sodium Diethyldithiocarbamate
CAS No.: 148-18-5
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Sodium Diethyldithiocarbamate
CAS No.: 148-18-5
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Sodium Diethyldithiocarbamate
CAS No.: 148-18-5
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Sodium Diethyldithiocarbamate
CAS No.: 148-18-5
Information is not available at this time.
-------
Sodium Diethyldithiocarbamate (Dithiocarb): page 5 of 5
V. SUPPLEMENTARY DATA
Chemical: Sodium Diethyldithiocarbamate
CAS No.: 148-18-5
Information is not available at this time.
Synonyms: CARBAMIC ACID, DIETHYLDITHIO-, SODIUM SALT; CARBAMODITHIOIC ACID,
DIETHYL-, SODIUM SALT (9CI); CUPRAL; DDC; DEDC; DEDK; DIETHYLCARBAMODITHIOIC
ACID, SODIUM SALT; DIETHYLDITHIOCARBAMATE SODIUM; DIETHYLDITHIOCARBAMIC ACID
SODIUM; DIETHYLDITHIOCARBAMIC ACID, SODIUM SALT; DIETHYL SODIUM
DITHIOCARBAMATE; DITHIOCARB; DITHIOCARBAMATE; NCI C02835; SODIUM DEDT; SODIUM
DIETHYLDITHIOCARBAMATE; SODIUM N,N-DIETHYLDITHIOCARBAMATE; SODIUM SALT of N,N-
DIETHYLDITHIOCARBAMIC ACID; THIOCARB; USAF EK-2596
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Strychnine; CAS No. 57-24-9 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take Into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used In these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Strychnine
I. Chronic Systemic Toxlclty: Noncarcinogenlc Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
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Strychnine: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) Is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Strychnine
CAS No.: 57-24-9
Preparation Date: 01/12/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Toxicity/histo-
pathology
Rat oral short-term
to subchronic study
Seidl and Zbinden
(1982)
NOAEL: None
2.5 mg/kg/day
LOAEL/FEL
10,000
3E-4
mg/kg/day
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Seidl, I. and G. Zbinden. 1982. Subchronic oral toxicity of strychnine in
rats. Arch. Toxicol. 51(3): 267-271.
This is the only oral short-term or subchronic study reported, in which
rats received daily doses of 0 - 10 mg/kg of strychnine by gavage for 28
days. Data recorded for the surviving animals included blood cell counts,
electrocardiograms, eye examinations, urine chemistry, weight gain, tissue
histology, organ weights, behavioral tests and food and water consumption.
Mortality was observed in 5/12 male rats receiving 10 mg/kg, 1/12 in each of
the 5 mg and 2.5 mg/kg groups. All deaths occurred 0.5-6 hours after oral
doses. While one rat that died in the 2.5-mg/kg/day group showed signs of
poisoning, no symptoms were exhibited by survivors, nor did any of the
survivors differ from controls histologically or in any of the parameters
monitored. The systemic level of this rapidly degradable toxicant [based on
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Strychnine: page 3 of 7
pharmacokinetic data, Sgaragli and Mannaion (1973)] was probably much higher
than in normal oral intake with food and water because it was administered all
at once by gavage. Thus, 2.5 mg/kg/day could be considered a short-term to
subchronic LOAEL for rats.
Additional studies (Gritzelmann et al., 1978) reported that a 6-month-old
human patient received strychnine doses of 0.3-1.1 mg/kg/day over an 18-month
period without any adverse effects. However, the patient may have had a
higher strychnine tolerance as a result of nonketotic hyperglycinemia. The
Oil and Hazardous Materials-Technical Assistance Data Systems (1984) reported
that "adults may safely drink daily 0.078-0.25 gallons of water containing 10
mg/L of strychnine" (equivalent to 2.9-9.5 mg/day). This corresponds to
0.041-0.136 mg/kg.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 10,000. An RfD of 0.0003 mg/kg/day or 0.02 mg/day for a 70-kg man is
derived from the Seidl and Zbinden (1982) short-term to subchronic study by
applying an uncertainty factor of 1000. This factor accounts for
extrapolation from a less-than-chronic to a chronic exposure study,
extrapolation from animals to humans and differences in sensitivity among the
human population. An additional 10 is used because a LOAEL/FEL (2.5
mg/kg/day) was utilized in the estimation of the RfD instead of a NOAEL. In
view of this concern and the limitations in the data base, the derived RfD
should be viewed as an interim estimate. Despite the limitations of the data
base, the additional factor of 10 should result in a sufficiently protective
level.
MF - 1
4. ADDITIONAL COMMENTS
The data base contained only one rat short-term to subchronic study for
RfD with supportive clinical data. Until further chronic/reproductive studies
are available, a low confidence in the RfD is recommended.
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Low RfD: Low
Confidence in the chosen study is low because a small number of animals
was tested, a NOEL was not established, and the study was extremely short.
Confidence in the data base is low because of the limited supporting studies.
Low confidence in the RfD follows.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, July 1985.
U.S. EPA. 1985. Strychnine: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
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Strychnine: page 4 of 7
7. U.S. EPA CONTACTS
Primary:
C.T. DeRosa
Office of
Secondary: M.L. Dourson
Office of
FTS/684-7534 or 513/569-7534
FTS/684-7544 or 513/569-7544
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Strychnine
CAS No.: 57-24-9
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Strychnine
CAS No.: 57-24-9
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Strychnine
CAS No.: 57-24-9
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Strychnine
CAS No.: 57-24-9
Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
-------
Strychnine: page 5 of 7
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Status
Date
Risk
Management
Value
Considers
Econ/Tech
Feasibility
Reference
Reportable Final
Quantity (RQ) 1985
Pesticide Active
Ingredient:
a. Registration none
Standard
10 Ibs
No
50 FR 13456
04/04/85
b. Special
Review
Final P.O.
1983
P.O.
P.O.
1
2,3
4
No
Yes
Yes
42 FR 2713
01/13/77
45 FR 73602
11/05/80
48 FR 48523
10/19/83
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxlcity, as established under Section
311(b)(4) of the Clean Water Act. Available data indicate that the aquatic
96-Hour Median Threshold Limit for strychnine and salts is between 0.1 and 1
ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
Pesticide Active Ingredient
a. Registration Standard: None
b. Special Review: For specific details on the Special Review process for
this active ingredient please check the references provided.
Contact: Office of Pesticide Programs, Special Review Branch
202/557-7420 or FTS/557-7420
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Strychnine: page 6 of 7
V. SUPPLEMENTARY DATA
Chemical: Strychnine
CAS No.: 57-24-9 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Strychnine is super toxic; the probable oral lethal dose in humans is
less than 5 mg/kg, a taste (less than 7 drops) for a 70-kg (150-lb.) person.
It causes violent generalized convulsions. Death results from respiratory
arrest as the respiratory muscles are in sustained spasm (Gosselin, 1976).
The lowest lethal oral dose reported for humans is 30 mg/kg (NIOSH/RTECS,
1985).
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Within 15 to 30 minutes after ingestion,
signs and symptoms include violent convulsions, restlessness, apprehension,
heightened acuity of perception, abrupt movements, hyperreflexia, and
muscular stiffness of the face and legs. Minor sensory stimulus may trigger
a violent generalized convulsion lasting 0.5 to 2 minutes (Gosselin, 1976).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: C H N 0
21 22 2 2
Molecular Weight: 334.40
Boiling Point: 518F, 270C at SmmHg
Specific Gravity (H20=l): 1.36 at 20C/4C
Vapor Pressure (mmHg): Not Found
Melting Point: 514-554F, 268-290C
Vapor Density (AIR=1): Not Found
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: 1 g in 6400 ml
Flash Point [Method Used]: Not Found
Flammable Limits: Material may burn but does not ignite readily.
Appearance and Odor: Colorless, transparent crystals or white
crystalline powder; odorless (Osol, 1980).
Conditions or Materials to Avoid: Protect from light (Merck, 1983)
Use: Material (and its salts) is used for destroying rodents and
predatory animals and for trapping fur-bearing animals (Merck, 1983).
-------
Strychnine: page 7 of 7
Synonyms: Certox; Dolco Mouse Cereal; Kwik-Kil; Mole Death; Mouse-Nots;
Mouse-Rid; Mouse-Tox; Pied Piper Mouse Seed; Ro-Dex; Sanaseed; Strychnos;
Strychnidin-10-one; Strychnin
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Styrene; CAS No. 100-42-5 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Styrene
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: review pending
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Styrene: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Styrene
CAS No.: 100-42-5 Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Red blood cell and 200 mg/kg/day (NOAEL) 1000 1 2E-1
liver effects mg/kg/day
400 mg/kg/day (LOAEL)
Dog subchronic oral
study
Quast et al. (1979)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Quast, J.F., C.G. Humiston, R.Y. Kalnins, et al. 1979. Results of a tox-
icity study of monomeric styrene administered to beagle dogs by oral intuba-
tion for 19 months. Toxicology Research Laboratory, Health and Environmental
Sciences, DOW Chemical Co., Midland, MI. Final Report.
Four beagle dogs/sex were gavaged with doses of 0, 200, 400 or 600 mg
styrene/kg bw/day in peanut oil for 560 days. No adverse effects were
observed for dogs administered styrene at 200 mg/kg/day. Effects in the
higher dose groups were increased numbers of Heinz bodies in the red blood
cells (RBCs), decreased packed cell volume and sporadic decreases in hemo-
globin and RBC counts; increased iron deposits and elevated numbers of Heinz
bodies were found in the livers. Marked individual variations in blood cell
parameters were noted for animals at the same dose level. Other parameters
examined were body weight, organ weights, urinalyses and clinical chemistry.
-------
Styrene: page 3 of 5
Long-term studies (120 weeks) in rats and mice (Ponomarkov and Tomatis,
1978) showed liver, kidney and stomach lesions for rats (dosed weekly with
styrene at 500 mg/kg) and no significant effects for mice (dosed weekly with
300 mg/kg). Rats receiving an average daily oral dose of 95 mg styrene/kg bw
for 185 days showed no adverse effects, while those receiving 285 or 475
mg/kg/day showed reduced growth and increased liver and kidney weights (Wolf
et al., 1956). Other subchronic rat feeding studies found LOAELs in the
350-500 mg/kg/day range and NOAELs in the range of 100-400 mg/kg/day.
The lifetime studies in rats and mice (Ponomarkov and Tomatis, 1978) are
not appropriate for risk assessment of chronic toxicity because of the dosing
schedule employed. The Wolf et al. (1956) study is of insufficient duration
to be considered chronic.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. The uncertainty factor of 1000 reflects 10 for both intraspecies
and interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation of a subchronic effect level to its
chronic equivalent.
MF = 1
4, ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The critical study appears to be well done and the effect levels seem
reasonable, but the small number of animals/sex/dose prevents a higher confi-
dence at this time. The data base offers strong support but lacks only a
bona fide full-term chronic study; thus, it is also considered to have medium
confidence. Medium confidence in the RfD follows.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1985. Drinking Water Criteria Document for Styrene. Office of
Drinking Water, Washington, DC.
U.S. EPA. 1984. Health and Environmental Effects Profile for Styrene.
Environmental Criteria and Assessment Office, Cincinnati, OH. ECAO-CIN-P103.
The ADI in the 1984 Health and Environmental Effects Profile document has
received an Agency review with the help of two external scientists.
Agency RfD Work Group Review: 10/09/85, 11/06/85, 10/09/85
Verification Date: 10/09/85
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Styrene: page 4 of 5
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: W. Marcus FTS/382-7580 or 202/382-7580
Office of Drinking Water
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Styrene
CAS No.: 100-42-5
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Styrene
CAS No.: 100-42-5
This chemical is among those substances evaluated by the U.S. EPA for
evidence of human carcinogenic potential. This does not imply that this
chemical is necessarily a carcinogen. The evaluation for this chemical is
under review by an inter-office Agency work group. A risk assessment summary
will be included on IRIS when the review has been completed.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Styrene
CAS No.: 100-42-5
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Styrene
CAS No.: 100-42-5 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
-------
Styrene: page 5 of 5
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
1000 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity (as established under Section
311(b)(4) of the Clean Water Act), ignitability and reactivity. The
available data indicate that the aquatic 96-Hour Median Threshold Limit for
styrene is between 10 and 100 ppm. In addition, styrene is easily
combustible when exposed to heat or flame and can react vigorously with
oxidizing materials.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
V. SUPPLEMENTARY DATA
Chemical: Styrene
CAS No.: 100-42-5
Information is not available at this time.
Synonyms: STYRENE; BENZENE, VINYL-; CINNAMENE; CINNAMENOL; CINNAMOL; DIAREX
HF 77; ETHENYLBENZENE; ETHYLENE, PHENYL-; NCI-C02200; PHENETHYLENE;
PHENYLETHENE; PHENYLETHYLENE; STIROLO (Italian); STYREEN (Dutch); STYREN
(Czech); STYRENE, MONOMER (ACGIH); STYRENE MONOMER, inhibited (DOT); STYROL
(German); STYROLE; STYROLENE; STYRON; STYROPOL; STYROPOR; UN 2055 (DOT);
VINYLBENZEN (Czech); VINYLBENZENE; VINYLBENZOL
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
1,2,4,5-Tetrachlorobenzene; CAS No. 95-94-3 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR 1,2,4,5-Tetrachlorobenzene
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
1,2,4,5-Tetrachlorobenzene: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: 1,2,4,5-Tetrachlorobenzene
CAS No.: 95-94-3 Preparation Date: 05/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Kidney lesions
Rat oral subchronic
5.0 ppm of diet or
0.34 mg/kg/day
(NOAEL)
1000 1 3E-4
mg/kg/day
study
50 ppm of diet or 3.4
Chu et al. (1984) mg/kg/day (LOAEL)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Chu, I., D.C. Villeneuve, V.E. Valli and V.E. Secours. 1984. Toxicity of
1,2,3,4-, 1,2,3,5- and 1,2,4,5-tetrachlorobenzene in the rat: Results of a
90-day feeding study. Drug Chem. Toxicol. 7: 113-127.
Groups of 15/sex weanling Sprague-Dawley rats were fed diets containing
0, 0.5, 5.0, 50 and 500 ppm of 1,2,4,5-tetrachlorobenzene (TCB) for 13
weeks. The corresponding dose range in mg/kg bw/day was given as 0.034-34.
Dose-related increases in the frequency and severity of kidney lesions for
male rats were observed at 1,2,4,5-TCB dose levels of 5.0 ppm and greater.
The severity of effects was considered significant only at the 50 and 500 ppm
levels because of a high incidence of mild kidney lesions in the controls.
Liver lesions were observed for female rats at 500 ppm.
A 28-day feeding study of 1,2,4,5-TCB in rats (10/sex/group) showed dose-
related effects for liver and kidney pathology at 3.4 and 32 mg/kg bw/day (Chu
-------
1,2,4,5-Tetrachlorobenzene: page 3 of 6
et al., 1983). Liver lesions were reported as mild to moderately severe,
while kidney lesions were judged to be mild. Relative liver weight was sig-
nificantly increased (20-30%) at 32 mg/kg/day. Hepatic microsomal enzymes
were induced 2- to 12-fold at 32 mg/kg/day. Males were more susceptible than
females for all criteria. Adverse effects were not observed at two lower
doses (0.04 and 0.4 mg/kg/day).
Higher doses (50, 100 and 200 mg/kg/day) were associated with mortality
(200 mg/kg/day only), elevated serum cholesterol, increased organ weights and
liver enzyme induction when administered to pregnant rats for 10 days
[Ruddick et al., 1981 (Abstr.)].
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. The uncertainty factor of 1000 reflects 10 for both intraspecies
and interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation of a subchronic effect level to its
chronic equivalent.
MF = 1
4. ADDITIONAL COMMENTS
Braun et al. (1978) reported a NOAEL for dogs of 5 mg/kg bw/day for
1,2,4,5-TCB administered in the diet for 2 years. Increased serum alkaline
phosphatase activity and increased liver weights were reported at 10 mg/kg
bw/day in a separate 144-day dog study referred to in Braun et al. (1978).
Both studies were unpublished and were judged inadequate for risk assess-
ment. The 2-year study was designed for other purposes and did not employ
adequate controls or timely histopathological analysis.
A Russian study (Fomenko, 1964) reported impaired liver function and
learning response for rats and rabbits dosed orally for 8 months with
1,2,4,5-TCB at 0.005 or 0.05 mg/kg bw/day. A NOAEL of 0.001 mg/kg/day was
established. The study was judged unsuitable because of the lack of itemized
data and detailed study protocol.
NTP testing is in progress.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The critical study, although of short duration, is excellent in most
respects (dose range, toxicological criteria, data presentation, range of
effects) except for the high incidence of kidney lesions in the control ani-
mals and a subsequent uncertainty in interpretation of effects. Thus, the
confidence in the study is rated at medium. The principal supporting study is
of similar high quality, although shorter in duration. Effect levels are
mutually supportive. However, the data base lacks a bona fide chronic study.
Thus, the data base also rates a medium confidence. Medium confidence in the
RfD follows.
6. DOCUMENTATION AND REVIEW
The ADI in the 1980 Ambient Water Quality Criteria document was not verified
by the RfD Work Group review on 10/09/85.
-------
1,2,4,5-Tetrachlorobenzene: page 4 of 6
This verified RfD has only been reviewed by the RfD Work Group. See notes of
Work Group Meeting for 10/09/65 and 11/06/85 for details.
Agency RfD Work Group Review: 10/09/85, 11/06/85
Verification Date: 11/06/85
7. U.S. EPA CONTACTS
Primary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
Secondary: W.B. Peirano FTS/684-7525 or 513/569-7525
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: 1,2,4,5-Tetrachlorobenzene
CAS No.: 95-94-3
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: 1,2,4,5-Tetrachlorobenzene
CAS No.: 95-94-3
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: 1,2,4,5-Tetrachlorobenzene
CAS No.: 95-94-3
Information is not available at this time.
-------
1,2,4,5-Tetrachlorobenzene: page 5 of 6
IV. RISK MANAGEMENT SUMMARIES
Chemical: 1,2,4,5-Tetrachlorobenzene
CAS No.: 95-94-3
Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
5000 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
2) Marine
Clean Air Act
Regulatory
Decision:
(NESHAP or NSPS)
Final
1980
Final
1985
30 ug/1 no
Acute no
250 ug/1
Chronic
129 ug/1
Acute no
160 ug/1
Chronic
none
Decision not no
to regulate
45 FR 79318
11/28/80
ibid.
ibid.
50 FR 32628
06/13/85
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1,2,4,5-Tetrachlorobenzene: page 6 of 6
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on chronic toxicity. RQ assignments based on
chronic toxicity reflect two primary attributes of the hazardous substance,
the minimum effective dose (MED) levels for chronic exposure (mg/day for 70-
kg man) and the type of effect (liver necrosis, teratogenicity, etc). In
accordance with the methodology described in the Agency's "Technical
Background Document to Support Rulemaking Pursuant to CERCLA Section 102,
Volume 1" of March 1981 and 50 FR 13468 (04/04/85), a composite score is
determined from an evaluation of these two attributes. 1,2,4,5-
Tetrachlorobenzene was determined to have a composite score between 1 and 5,
corresponding to a chronic toxicity RQ of 5000 pounds.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC of 38 ug/1 is based on consumption of contaminated
based on consumption of contaminated aquatic organisms alone.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The data are assumed to be statistically
representative and are used to calculate concentrations which will not have
significant short or long term effects on 95% of the organisms exposed.
Recent criteria (1985 and later) contain duration and frequency stipulations:
the acute criteria maximum concentration is a 1-hour average and the chronic
criteria continuous concentration is a 4-day average which are not to be
exceeded more than once every three years, on the average (see Stephen et al.
1985). Earlier criteria (1980-1984) contained instantaneous acute and
24-hour average chronic concentrations which were not to be exceeded. (FR 45:
79318: November 28, 1980).
CAA Regulatory Decision
EPA concluded that the available health information on the chloro-
benzenes (including 1,2,4,5-Tetrachlorobenzene) at concentrations measured or
estimated to occur in the ambient air is insufficient to warrant specific
Federal regulation of routine tetrachlorobenzene emissions under the CAA at
this time.
Contact: Chief, Pollutant Assessment Branch
FTS/629-5645 or 919/541-5645
V. SUPPLEMENTARY DATA
Chemical: 1,2,4,5-Tetrachlorobenzene
CAS No.: 95-94-3
Information is not available at this time.
Synonyms: BENZENE, 1,2,4,5-TETRACHLORO-; RCRA WASTE NUMBER U207
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Tetrachloroethylene; CAS No. 127-18-4 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Tetrachloroethylene
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: review pending
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Tetrachloroethylene: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Tetrachloroethylene
CAS No.: 127-18-4
Preparation Date: 06/13/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Kidney and liver
changes
Rat inhalation, 7
months at 8 hours/
day, 5 days/week
Carpenter (1937)
NOAEL: 70 ppm
inhalation con-
verted to an oral
dose of 19.4
mg/kg/day
LOAEL: 230 ppm
1,000
2E-2
mg/kg/day
* Dose Conversion Factors & Assumptions: 70 ppm = 475 mg/cu. m x 1 cu.
m/hour (assumed ventilation rate) x 8 hours/day x 5 days/7 days x 0.5
(assumed inhalation retention factor)/70 kg (assumed human body weight)
19.4 mg/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
Carpenter, C.P. 1937. The chronic toxicity of tetrachloroethylene. J. Ind.
Hyg. and Toxicol. 19:323-336.
Carpenter (1937) exposed groups of 24 rats (12/sex) to 1 of 3 doses by
inhalation for 8 hours/day, 5 days/week for 7 months. No significant changes
were observed at the low dose of 70 ppm. At 230 ppm, renal congestion and
swelling were noted. At 470 ppm, the liver also was congested and exhibited
cloudy swelling, which remained for 46 days after termination of exposure.
The kidney showed increased secretion, cloudy swelling and desquamation; the
spleen was congested and showed an increase in pigment content.
-------
Tetrachloroethylene: page 3 of 6
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1,000. The uncertainty factor of 1,000 reflects 10 for both intraspecies
and interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation of a subchronic effect level to its
chronic equivalent.
MF = 1
4. ADDITIONAL COMMENTS
Adequate oral data could not be found.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: High RfD: Medium
Confidence in the chosen study is medium because, while only a small
number of animals/sex were tested at each dose, the number of parameters
measured was large and a good dose-response relationship was observed.
Confidence in the supporting data base is high to medium because several
inhalation studies support the chosen effect level. Medium to high confidence
in the RfD normally would follow, but medium is chosen because the data are
from inhalation exposures.
6. DOCUMENTATION AND REVIEW
U.S. EPA. Drinking Water Criteria Document for Tetrachloroethylene. Office
of Drinking Water, Washington, DC. (1985).
Extensive internal (i.e., Red Border) and Steering Committee review. Public
comment period was June 12 to September 15, 1984.
Agency RfD Work Group Review: 05/20/85
Verification Date: 05/20/85
7. U.S. EPA CONTACTS
Primary: P. Fenner-Crisp FTS/382-7589 or 202/382-7589
Office of Drinking Water
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Tetrachloroethylene
CAS No.: 127-18-4
Information is not available at this time.
-------
Tetrachloroethylene: page 4 of 6
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Tetrachloroethylene
CAS No.: 127-18-4
This chemical is among those substances evaluated by the U.S. EPA for
evidence of human carcinogenic potential. This does not imply that this
chemical is necessarily a carcinogen. The evaluation for this chemical is
under review by an inter-office Agency work group. A risk assessment summary
will be included on IRIS when the review has been completed.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Tetrachloroethylene
CAS No.: 127-18-4
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Tetrachloroethylene
CAS No.: 127-18-4 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are Indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Tetrachloroethylene: page 5 of 6
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Status
Date
Risk
Management
Value
Considers
Econ/Tech
Feasibility
Reference
Reportable Statutory
Quantity (RQ) 1980
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
2) Marine
Final
1980
Clean Air Act
Regulatory
Decision:
Nat. Emissions
Standards for
Hazardous Air
Pollutants (NESHAP)
Current
1985
1 Ib. no
0.80 ppb no
Acute no
5280 ug/1
Chronic
840 ug/1
Acute no
10,280 ug/1
Chronic
450 ug/1
Under no
development
50 FR 13456
04/04/85
45 FR 79318
11/28/80
ibid.
ibid.
50 FR 52880
12/26/85
B. RISK MANAGEMENT RATIONALE
RQ
The CERCLA statutory RQ is subject to adjustment when assessment of
carcinogenicity is completed.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: Tetrachloroethylene is classified as a carcinogen, and
under the assumption of no threshold for a carcinogen, the recommended WQC is
zero. However, if zero cannot be obtained and exposure is via ingestion of
water and aquatic organisms, 0.8 ug/1 is associated with an upper-bound
excess lifetime risk of l.OE-6 [other upper bound risk levels to consider:
l.OE-5 (8.0 ug/1) and l.OE-7 (0.08 ug/1)]. If exposure is only via ingestion
of aquatic organisms, the WQC associated with an excess lifetime risk of
l.OE-6 is 8.85 ug/1.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The data are assumed to be statistically
-------
Tetrachloroethylene: page 6 of 6
representative and are used to calculate concentrations which will not have
significant short or long term effects on 95% of the organisms exposed.
Recent criteria (1985 and later) contain duration and frequency stipulations:
the acute criteria maximum concentration is a 1-hour average and the chronic
criteria continuous concentration is a 4-day average which are not to be
exceeded more than once every three years, on the average (see Stephen et al.
1985). Earlier criteria (1980-1984) contained instantaneous acute and
24-hour average chronic concentrations which were not to be exceeded. (FR 45:
79318: November 28, 1980).
CAA Regulatory Decision
NESHAP
Tetrachloroethylene (perchloroethylene or perc) is a probable human
carcinogen (EPA Group B2) and according to EPA's preliminary risk assessment
from ambient air exposures, public health risks are significant (5.3 cancer
cases per year and maximum lifetime individual risks of 1.5 x 10-4). Thus,
EPA indicated that it intends to add perc to the list of hazardous air
pollutants for which it intends to establish emission standards under section
112(b)(l)(A) of the Clean Air Act. The EPA will decide whether to add perc
to the list only after studying possible techniques that might be used to
control emissions and further assessing the public health risks. The EPA
will add perc to the list if emission standards are warranted.
Contact: Chief, Pollutant Assessment Branch
919/541-5645 or FTS/629-5645
V. SUPPLEMENTARY DATA
Chemical: Tetrachloroethylene
CAS No.: 127-18-4
Information is not available at this time.
Synonyms: Ethene, tetrachloro- (9CI); Ethylene, tetrachloro- (SCI);
Ankilostin; Antisal 1; Antisol 1; Carbon bichloride; Carbon dichloride;
Czterochloroetylen (Polish); Dee-Solv; Didakene; Didokene; Dow-Per; Dowclene
EC; Ethylene tetrachloride; ENT 1,860; ENT 1860; Fedal-Un; Nema (VAN); Nema,
veterinary; NCI-C04580; NEMA; Perawin; Perchloorethyleen, per (Dutch);
Perchlor; Perchloraethylen, per (German); Perchlorethylene; Perchlorethylene,
per (French); Perchloroethylene; Perclene; Percloroetilene (Italian);
Percosolv; Percosolve; Perklone; Persec; PerSec; PCE; PER; PERC; PERK; Tetlen;
Tetracap; Tetrachlooretheen (Dutch); Tetrachloraethen (German);
Tetrachlorethylene; Tetrachloroethene; Tetrachloroethylene (ACN);
Tetracloroetene (Italian); Tetraguer; Tetraleno; Tetralex; Tetravec;
Tetroguer; Tetropil; WLN: GYGUYGG; 1,1,2,2-Tetrachloroethylene.
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
2,3,4,6-Tetrachlorophenol; CAS No. 58-90-2 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR 2,3,4,6-Tetrachlorophenol
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
2,3,4,6-Tetrachlorophenol: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: 2,3,4,6-Tetrachlorophenol
CAS No.: 58-90-2 Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Liver necrosis
Rat oral short-term
10 mg/kg/day (NOEL)
50 mg/kg/day (LOAEL)
1000 1 1E-2
mg/kg/day
to subchronic study
Hattula et al. (1981)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Hattula, M.L., V.M. Wasenius, R. Krees, A.N. Arstila and M. Kihlstrom. 1981.
Acute and short-term toxicity of 2,3,4,6-tetrachlorophenol in rats. Bull.
Environ. Contain. Toxicol. 26: 795-800.
The reported study is a short-term toxicity study in which body weight
changes and organ histopathology were observed. Concern existed about the
short duration of exposure (55 days), but this was mitigated by the compound's
rapid rate of urinary elimination, precluding the possibility of accumulation.
Based on the data, the 10 mg/kg/day was considered a NOEL, and application of
an uncertainty factor of 1000 (10 for subchronic study, 10 for interspecies
conversion and 10 for sensitive population) was used to derive the ADI of
0.01 mg/kg/day. Additional data are presented to substantiate the above
ADI.
Schwetz et al. (1974) performed an acute range finding toxicity study
which resulted in the selection of an MTD of 30 mg/kg/day for the reproduc-
-------
2,3,4,6-Tetrachlorophenol: page 3 of 5
tion study. The lower dose (10 mg/kg) was a NOAEL, since subcutaneous edema
in exposed fetuses was considered a chance-alone incidence. The subcu-
taneous edema was not observed in the high-dose group. High dose exposure (30
mg/kg) caused significant delayed ossification of the skull bones; however,
this anomaly normally occurs in all control populations. No other maternal or
fetal toxicity was reported in any of the doses tested in this study. Since
subcutaneous edema was a chance-alone incidence, it is recommended that the
10-mg/kg dose may be used as a NOEL.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. The uncertainty factor of 1000 reflects 10 for both intraspecies
and interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation of a subchronic effect level to its
chronic equivalent.
MF = 1
4. ADDITIONAL COMMENTS
Chronic studies are not available. Subchronic and reproductive studies
provided adequate data for a RfD of medium level confidence.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
Medium confidence in the critical study is selected because, although only
a few animals were tested/dose and sex was unspecified, dosing was conducted
7 days/week, and several parameters were measured. Medium confidence in the
data base is selected since two bioassays are available that support the
chosen NOEL. Medium confidence in the RfD follows.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, May 1985.
U.S. EPA. 1985. 2,3,4,6-Tetrachlorophenol: Review and Evaluation of ADI.
Contract No. 68-03-3228. Environmental Criteria and Assessment Office, Cin-
cinnati, OH.
Agency RfD Work Group Review: 06/24/85, 07/08/85
Verification Date: 07/08/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
-------
2,3,4,6-Tetrachlorophenol: page 4 of 5
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: 2,3,4,6-Tetrachlorophenol
CAS No.: 58-90-2
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: 2,3,4,6-Tetrachlorophenol
CAS No.: 58-90-2
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: 2,3,4,6-Tetrachlorophenol
CAS No.: 58-90-2
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: 2,3,4,6-Tetrachlorophenol
CAS No.: 58-90-2 Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
2,3,4,6-Tetrachlorophenol: page 5 of 5
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Water Quality
Criteria (WQC) :
a. Human Health
b. Aquatic Toxic ity
Status
Date
Final
1985
Final
1980
Risk
Management
Value
10 Ibs
1 ug/1
none
Considers
Econ/Tech
Feasibility
no
no
Reference
50 FR 13456
04/04/85
45 FR 79318
11/28/80
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity. Available data indicate that
the aquatic 96-Hour Median Threshold Limit for 2,3,4,6-Tetrachlorophenol is
between 0.1 and 1 ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
WQC
a. Human health: The WQC of 1 ug/1 is based upon organoleptic effects (taste
and odor thresholds). However, organoleptic end-points have limited value in
setting water quality standards as there is no demonstrated relationship
between taste/odor effect and adverse health effects.
b. Aquatic toxicity: none
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
V. SUPPLEMENTARY DATA
Chemical: 2,3,4,6-Tetrachlorophenol
CAS No.: 58-90-2
Information is not available at this time.
Synonyms: PHENOL, 2,3,4,6-TETRACHLORO-; DOWICIDE 6; RCRA WASTE NUMBER U212;
TCP; 2,3,4,6-TETRACHLOROPHENOL; 2,4,5,6-TETRACHLOROPHENOL
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Tetraethyl Lead; CAS No. 78-00-2 (Revised 04/10/1987)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxieity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix D in Service Code 4.
STATUS OF DATA FOR Tetraethyl Lead
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Tetraethyl Lead: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Tetraethyl Lead
CAS No.: 78-00-2 Preparation Date: 04/10/87
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Histopathology of
liver and thymus
Experimental Doses *
NOAEL: None
UF
10.000
MF
1
RfD
IE- 7
mg/kg/day
1.7 ug/kg/day (LOAEL)
Rat subchronic converted to 1.2 ug/
study/gavage 5 days/7 kg/day
days
Schepers (1964)
* Dose Conversion Factors & Assumptions: 5 days/7 days; thus, 1.7 ug/kg/
day x 5 days/7 days - 1.2 ug/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
Schepers, G.V. 1964. Tetraethyl and tetramethyl lead. Arch. Environ.
Health. 8: 277-295.
In a 20-week study, Schepers (1964) administered tetraethyl lead in pea-
nut oil by gavage to groups of 12 CD rats (6/sex) at 1.7 and 170 ug/kg/bw 5
days/week. Gross observations revealed swollen livers and fatty plaques in
the thymus at both dose groups. Histological preparations revealed hepato-
cyte vacuolization, cytoplasmic degeneration and neuronal damage among low-
dose rats. Rats exposed to the higher dose developed similar, but more
severe, histopathologies. Based on these findings, a LOAEL of 1.2 ug/kg/day
(1.7 ug/kg/day x 5 days/7 days) was determined.
A subchronic inhalation study by Davis et al. (1963) in rats and dogs
supports these findings. However, the equivalent oral doses derived from
-------
Tetraethyl Lead: page 3 of 6
this study are substantially higher than the LOAEL derived from the Schepers
(1964) study. Therefore, a human RfD of 0.0001 ug/kg/day was derived based
on the LOAEL of 1.2 ug/kg/day from Schepers (1964) and on a standard scaling
factor of 10,000.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 10,000. The uncertainty factor of 10,000 represents 10 to extrapolate
from animal to human, 10 to convert subchronic to chronic exposure and 10 to
protect for sensitive humans, and an additional factor of 10 to convert a
LOAEL to a NOAEL.
MF = 1
4. ADDITIONAL COMMENTS
The data base contained limited long-term oral studies, as well as
limited subchronic inhalation and oral data. Reproductive, carcinogenic and
teratogenic data are available but inconclusive. Limited epidemiologlcal
data are also available.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The chosen study is given medium confidence because, although only a few
animals/sex/dose were tested, a good histopathology was conducted and a
dose-severity was observed. The data base was considered to have medium to
low confidence because some supporting information was available. Medium
(tending to low) confidence in the RfD follows.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, July 1985.
U.S. EPA. 1985. Tetraethyl Lead: Review and Evaluation of ADI. Contract
No. 68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
-------
Tetraethyl Lead: page 4 of 6
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Tetraethyl Lead
CAS No.: 78-00-2
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Tetraethyl Lead
CAS No.: 78-00-2
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Tetraethyl Lead
CAS No.: 78-00-2
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Tetraethyl lead
CAS No.: 78-00-2 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Tetraethyl Lead: page 5 of 6
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1986
Risk
Management
Value
10 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
51 FR 34534
09/29/86
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on chronic toxicity. RQ assignments based on
chronic toxicity reflect two primary attributes of the hazardous substance,
the minimum effective dose (MED) levels for chronic exposure (mg/day for 70-
kg man) and the type of effect (liver necrosis, teratogenicity, etc). In
accordance with the methodology described in the Agency's "Technical
Background Document to Support Rulemaking Pursuant to CERCLA Section 102,
Volume 1" of March 1985 and 50 FR 13468 (04/04/85), a composite score is
determined from an evaluation of these two attributes. Tetraethyl lead was
determined to have a composite score between 41 and 80, corresponding to a
chronic toxicity RQ of 10 pounds.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
V. SUPPLEMENTARY DATA
Chemical: Tetraethyl Lead
CAS No.: 78-00-2 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Tetraethyl lead is extremely poisonous; it may be fatal if inhaled,
swallowed, or absorbed from the skin. Contact may cause burns to skin and
eyes (DOT, 1984). Most symptoms of poisoning are due to the effects of
tetraethyl lead on the nervous system (Oilman, 1980).
Medical Conditions Generally Aggravated by Exposure: Not Found
-------
Tetraethyl Lead: page 6 of 6
Signs and Symptoms of Exposure: Major symptoms of exposure to
tetraethyl lead are due to interaction with the central nervous system. The
victim suffers from insomnia, nightmares, anorexia, nausea, vomiting,
headache, weakness, and emotional instability. Subjective central nervous
system symptoms such as irritability, restlessness, and anxiety are next
evident. In the case of intense acute exposure, central nervous system
symptoms progress to delusions, uncoordinated and exaggerated muscle
movements, and finally a maniacal state (Oilman, 1980).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: C H Pb
8 20
Molecular Weight: 323.45
Boiling Point: About 392F, 200C; decomposes between 110
and 200C
Specific Gravity (H20=l): 1.653 at 20C
Vapor Pressure (mmHg): 0.2 at 20C
Melting Point: -202F, -130C
Vapor Density (AIR-1): 8.6 (NFPA 1984, p. 325M-86) (SUSPECT)
Evaporation Rate (Butyl acetate-1): Not Found
Solubility in Water: Insoluble
Flash Point [Method Used]: 200F [no method given]
Flammable Limits:
LEL: 1.8 percent by volume
UEL: Not Found
Appearance and Odor: Colorless liquid with a pleasant odor (Hawley, 1981,
p. 1006)
Conditions or Materials to Avoid: Tetraethyl lead decomposes slowly at
room temperature and more rapidly at elevated temperatures (IARC, 1972-
1985).
Hazardous Decomposition or Byproducts: Not Found
Use: Virtually all of the tetraethylead produced in the USA is used as an
antiknock additive for gasolines (IARC, 1972-1985).
Synonyms: Lead, Tetraethyl-; NCI-C54988; Plumbane, Tetraethyl-; TEL;
Tetraethyl Lead, Liquid; Tetraethyl Lead; Tetraethylplumbane
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Thallic Oxide; CAS No. 1314-32-5 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Thallic Oxide
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Thallic Oxide: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical:
CAS No.:
Thallic Oxide
1314-32-5
Preparation Date: 01/08/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Increased kidney
weight, alopecia
Rat subchronic
feeding
Downs et al. (1960)
5 ppm in diet thal-
lium acetate (NOEL)
converted to 0.39
mg/kg/day as thal-
lium or 0.43 mg/kg/
day thallic oxide
15 ppm in diet as
thallium acetate
(LOAEL) converted to
1.16 mg/kg/day
thallium or 1.30
mg/kg/day thallic
oxide
1000
4E-4
* Dose Conversion Factors & Assumptions: Young rat food consumption assumed
to be 10% bw/day; molecular weight conversion factor (for equimolar Tl) =
456/(2 x 263) [MW Tl 0 - 456; MW TIC 0 H = 263]
23 223
2. PRINCIPAL AND SUPPORTING STUDIES
Downs, W.L., J.K Scott, L.T. Steadman and E.A. Maynard. 1960. Acute and
subacute toxicity studies of thallium compounds. Am. Ind. Hyg. Assoc. 21:
399-406.
Groups of rats (5/sex/dose) were fed diets containing nominal concentra-
tions of thallium acetate of 0, 5, 15 or 50 ppm. An additional group (30 ppm)
-------
Thallic Oxide: page 3 of 7
was added partway through (time not specified). Animals were allowed ad
libidum access to these diets for 15 weeks. The 50-ppm level resulted in 100%
mortality by week 5. The 30-ppm level resulted in 100% mortality by week 9.
Four of 10 control animals died (2/sex) by week 15, making interpretation of
survival in the remaining dose groups difficult (15 ppm 3/5 males died, 1/5
females; 5 ppm 2/6 males died, 0/4 females). At termination, the only gross
finding was alopecia in the 15- and 30-ppm groups. The authors stated that
there was a slight increase in kidney weight (doses not specified, data not
shown). The authors reported that histopathological evaluations did not
indicate treatment-related pathology. In addition, other groups of rats
(10/sex/dose) were fed thallic oxide at dietary levels of 20, 35, 50, 100 and
500 ppm for 15 weeks. All animals fed greater than or equal to 50 ppm died.
Increased mortality was seen at 35 ppm. At 20 ppm, males showed weight
depression, and both sexes showed alopecia and increased kidney weight. These
data indicate that the toxicity of thallic oxide is substantially similar to
that of thallium acetate. Unfortunately, lower feeding levels corresponding
to a NOAEL were not utilized for this salt. It is proposed that the NOEL for
thallium acetate, 5 ppm (0.39 mg/kg/day as thallium), be used to calculate an
RfD for thallic oxide. A feeding level of 0.43 mg/kg/day thallic oxide would
provide an equivalent thallium intake.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. The uncertainty factor of 1000 reflects 10 for both intraspecies
and interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation of a subchronlc effect level to Its
chronic equivalent.
MF = 1
4. ADDITIONAL COMMENTS
Downs et al. (1960) is the only subchronic study available for the oral
route. There appear to be no chronic data. An abstract of a Russian study
was located which reported administration of thallium sulfate or carbonate by
i.p. or s.c. Injection. However, in the absence of data for oral absorption
efficiency, it is difficult to compare these doses. Further chronic/repro-
ductive toxicity data are needed for a higher level of confidence In the RfD.
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Low RfD: Low
Confidence in the chosen study Is low. This study Is flawed by small
group sizes, mortality in the control group, failure to monitor food consump-
tion and lack of detail in the reported results. However, four doses were
tested and were preceded by a short-term bioassay that tested six doses.
Confidence In both the data base and the RfD Is low because no supporting
data are available.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, July 1985.
U.S. EPA. 1985. Thallium Compounds: Review and Evaluation of ADI. Contract
No. 68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
-------
Thallic Oxide: page 4 of 7
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Thallic Oxide
CAS No.: 1314-32-5
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Thallic Oxide
CAS No.: 1314-32-5
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Thallic Oxide
CAS No.: 1314-32-5
Information is not available at this time.
-------
Thallic Oxide: page 5 of 7
IV. RISK MANAGEMENT SUMMARIES
Chemical: Thallic oxide
CAS No.: 1314-32-5 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk Status Risk Considers
Management Management Econ/Tech
Action Date Value Feasibility Reference
Reportable Final 100 Ibs no 51 FR 34534
Quantity (RQ) 1986 09/29/86
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on chronic toxicity. RQ assignments based on
chronic toxicity reflect two primary attributes of the hazardous substance,
the minimum effective dose (MED) levels for chronic exposure (mg/day for 70-
kg man) and the type of effect (liver necrosis, teratogenicity, etc). In
accordance with the methodology described in the Agency's "Technical
Background Document to Support Rulemaklng Pursuant to CERCLA Section 102,
Volume 1" of March 1985 and 50 FR 13468 (04/04/85), a composite score is
determined from an evaluation of these two attributes. Thallic oxide was
determined to have a composite score between 21 and 40, corresponding to a
chronic toxicity RQ of 100 pounds.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
-------
Thallic Oxide: page 6 of 7
V. SUPPLEMENTARY DATA
Chemical: Thallic Oxide
CAS No.: 1314-32-5 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Thallic oxide attacks the retinal ganglion cells, nerve fibers and optic
nerves (Grant, 1974). It causes degeneration of the central nervous system.
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Signs and symptoms similar to other
thallium compounds. When large doses are taken, the first symptoms are
hemorrhage of the gastrointestinal tract, stomach cramps, rapid heartbeat
and headaches, usually occurring within the first 12 hours. Other symptoms
include abdominal pain, vomiting, constipation, and diarrhea. When smaller
doses are taken the predominant symptoms are tingling sensations and
unsteadiness. The tingling is usually more severe in the lower extremities
and may progress to weakness and muscular atrophy (Clayton and Clayton,
1981-82).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: Tl 0
2 3
Molecular Weight: 456.78
Boiling Point: 1607F, 875C (loses two oxygens)
Specific Gravity (H20=l): 9.65
Vapor Pressure (mmHg): Not Found
Melting Point: 1323F, 717C
Vapor Density (AIR=1): Not Found
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: Insoluble
Flash Point [Method Used]: Not Found
Flammable Limits: Not Found
Appearance and Odor: Colorless to brown powder (Weast, 1979; Merck,
1976)
Conditions or Materials to Avoid: A mixture of thallic oxide and
antimony sulfide or sulfur explodes when ground in a mortar (NFPA, 1978) .
Thallic oxide is decomposed by hydrogen chloride with evolution of chlorine
-------
Thallic Oxide: page 7 of 7
(Merck, 1976). Dry hydrogen sulflde ignites and sometimes feebly explodes,
over thallium oxide (Bretherick, 1979).
Hazardous Decomposition or Byproducts: When heated to decomposition,
toxic fumes of thallium are emitted (Sax, 1984, p. 2555).
Use: Not Found
Synonyms: Dithallium Trioxide; Thallium Oxide (Tl 203); Thallium Peroxide;
Thallium Sesquioxide; Thallium(3+) Oxide; Thallium(III) Oxide
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Thallium Acetate; CAS No. 563-68-8 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Thallium Acetate
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Thallium Acetate: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Thallium Acetate
CAS No.: 563-68-8 Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Increased kidney 5 ppm in diet (NOEL) 1000 1 5E-4
weight, alopecia converted to 0.5 mg/kg/day
mg/kg/day
Rat subchronic
feeding study 15 ppm in diet
(LOAEL) converted to
Downs et al. (1960) 1.5 mg/kg/day
* Dose Conversion Factors & Assumptions: Young rat food consumption = 10%
bw/day (assumed)
2. PRINCIPAL AND SUPPORTING STUDIES
Downs, W.L., J.K Scott, L.T. Steadman and E.A. Maynard. 1960. Acute and
subacute toxicity studies of thallium compounds. Am. Ind. Hyg. Assoc. 21:
399-406.
Groups of rats (5/sex/dose) were fed diets containing nominal
concentrations of thallium acetate of 0, 5, 15 or 50 ppm. An additional group
(30 ppm) was added partway through (time not specified). Animals were allowed
ad libidum access to these diets for 15 weeks. The 50-ppm level resulted in
100% mortality by week 5. The 30-ppm level resulted in 100% mortality by week
9. Four of 10 control animals died (2/sex) by week 15, making interpretation
of survival in the remaining dose groups difficult (15 ppm 3/5 males, 1/5
females died; 5 ppm 2/6 males , 0/4 females died). At termination, the only
-------
Thallium Acetate: page 3 of 5
gross finding was alopecia in the 15- and 30-ppm groups. The authors stated
that there was a slight increase in kidney weight (doses not specified, data
not shown); histopathological evaluations did not indicate treatment-related
pathology.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. The uncertainty factor of 1000 reflects 10 for both intraspecies
and interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation of a subchronic effect level to its
chronic equivalent.
MF = 1
4. ADDITIONAL COMMENTS
Downs et al. (1960) is the only subchronic study available for the oral
route. There appear to be no chronic data. An abstract of a Russian study
was located which reported administration of thallium sulfate or carbonate by
i.p. or s.c. injection. However, in the absence of data for oral absorption
efficiency, it is difficult to compare these doses. Further chronic/repro-
ductive toxicity data are needed for a higher level of confidence in the RfD.
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Low RfD: Low
Confidence in the chosen study is low. This study is flawed by small
group sizes, mortality in the control group, failure to monitor food consump-
tion and lack of detail in the reported results. However, four doses were
tested and were preceded by a short-term bioassay that tested six doses.
Confidence in both the data base and the RfD is low because no supporting
data are available.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, July 1985.
U.S. EPA. 1985. Thallium Compounds: Review and Evaluation of ADI. Contract
No. 68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
-------
Thallium Acetate: page 4 of 5
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Thallium Acetate
CAS No.: 563-68-8
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Thallium Acetate
CAS No.: 563-68-8
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Thallium Acetate
CAS No.: 563-68-8
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Thallium Acetate
CAS No.: 563-68-8 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Thallium Acetate: page 5 of 5
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1986
Risk
Management
Value
100 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
51 FR 34534
09/29/86
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on chronic toxicity. RQ assignments based on
chronic toxicity reflect two primary attributes of the hazardous substance,
the minimum effective dose (MED) levels for chronic exposure (mg/day for 70-
kg man) and the type of effect (liver necrosis, teratogenicity, etc). In
accordance with the methodology described in the Agency's "Technical
Background Document to Support Rulemaking Pursuant to CERCLA Section 102,
Volume 1" of March 1985 and 50 FR 13468 (04/04/85), a composite score is
determined from an evaluation of these two attributes. Thallium acetate was
determined to have a composite score between 21 and 40, corresponding to a
chronic toxicity RQ of 100 pounds.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
V. SUPPLEMENTARY DATA
Chemical: Thallium Acetate
CAS No.: 563-68-8
Information is not available at this time.
Synonyms: RCRA WASTE NUMBER U214, THALLIUM ACETATE, THALLIUM(1+) ACETATE,
THALLIUM(I) ACETATE, THALLIUM MONOACETATE, THALLOUS ACETATE
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Thallium Carbonate; CAS No. 6533-73-9 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Thallium Carbonate
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Thallirun Carbonate: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Thallium Carbonate
CAS No.: 6533-73-9
Preparation Date: 01/08/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Increased kidney
weight, alopecia
Rat subchronic
feeding study
Downs et al. (1960)
5 ppm in diet as
thallium acetate
(NOEL) converted to
0.39 mg/kg/day
thallium or 0.446
mg/kg/day thallium
carbonate
15 ppm in diet
(LOAEL) converted to
1.2 mg/kg/day as
thallium or 1.3 mg/
kg/day thallium
carbonate
1000
4E-4
mg/kg/day
* Dose Conversion Factors & Assumptions: Young rat food consumption assumed
to be 10% bw/day; molecular weight conversion factor (for equimolar Tl) -
469/(2 x 263) [MW Tl CO =469; MW TIC 0 H = 263]
23 223
2. PRINCIPAL AND SUPPORTING STUDIES
Downs, W.L., J.K Scott, L.T. Steadman and E.A. Maynard. 1960. Acute and
subacute toxicity studies of thallium compounds. Am. Ind. Hyg. Assoc. 21:
399-406.
Groups of rats (5/sex/dose) were fed diets containing nominal concentra-
tions of thallium acetate of 0, 5, 15 or 50 ppm. An additional group (30 ppm)
-------
Thallium Carbonate: page 3 of 7
was added partway through (time not specified). Animals were allowed ad
libidum access to these diets for 15 weeks. The 50-ppm level resulted in 100%
mortality by week 5. The 30-ppm level resulted in 100% mortality by week 9.
Four of 10 control animals died (2/sex) by week 15, making interpretation of
survival in the remaining dose groups difficult (15 ppm 3/5 males died, 1/5
females; 5 ppm 2/6 males died, 0/4 females). At termination, the only gross
finding was alopecia in the 15- and 30-ppm groups. The authors stated that
there was a slight increase in kidney weight (doses not specified, data not
shown). The authors reported that histopathological evaluations did not
indicate treatment-related pathology.
Data concerning the toxicity of thallium carbonate per se were not
located. The toxicity of thallium acetate and thallium carbonate should be
substantially similar. This assumes that gastrointestinal absorption of the
two compounds is also substantially similar. An interim RfD is proposed by
analogy to thallium acetate based on the feeding level of 5 ppm thallium
acetate, which corresponds to a NOEL. This feeding level provided a thallium
equivalent of 0.39 mg/kg/day, corresponding to a feeding level of
0.44 mg/kg/day thallium carbonate.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. The uncertainty factor of 1000 reflects 10 for both intraspecies
and interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation of a subchronic effect level to its
chronic equivalent.
MF = 1
4. ADDITIONAL COMMENTS
Downs et al. (1960) is the only subchronic study available for the oral
route. There appear to be no chronic data. An abstract of a Russian study
was located which reported administration of thallium sulfate or carbonate by
i.p. or s.c. injection. However, in the absence of data for oral absorption
efficiency, it is difficult to compare these doses. Further chronic/repro-
ductive toxicity data are needed for a higher level of confidence in the RfD.
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Low RfD: Low
Confidence in the chosen study is low. This study is flawed by small
group sizes, mortality in the control group, failure to monitor food consump-
tion and lack of detail in the reported results. However, four doses were
tested and were preceded by a short-term bioassay that tested six doses.
Confidence in both the data base and the RfD are low because no supporting
data are available.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, July 1985.
U.S. EPA. 1985. Thallium Compounds: Review and Evaluation of ADI. Contract
No. 68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
-------
Thallium Carbonate: page 4 of 7
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Thallium Carbonate
CAS No.: 6533-73-9
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Thallium Carbonate
CAS No.: 6533-73-9
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Thallium Carbonate
CAS No.: 6533-73-9
Information is not available at this time.
-------
Thallium Carbonate: page 5 of 7
IV. RISK MANAGEMENT SUMMARIES
Chemical: Thallium Carbonate
CAS No.: 6533-73-9 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1986
Risk
Management
Value
100 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
51 FR 34534
09/29/86
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on chronic toxicity. RQ assignments based on
chronic toxicity reflect two primary attributes of the hazardous substance,
the minimum effective dose (MED) levels for chronic exposure (mg/day for 70-
kg man) and the type of effect (liver necrosis, teratogenicity, etc). In
accordance with the methodology described in the Agency's "Technical
Background Document to Support Rulemaking Pursuant to CERCLA Section 102,
Volume 1" of March 1985 and 50 FR 13468 (04/04/85), a composite score is
determined from an evaluation of these two attributes. Thallium carbonate
was determined to have a composite score between 21 and 40, corresponding to
a chronic toxicity RQ of 100 pounds.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
-------
Thallium Carbonate: page 6 of 7
V. SUPPLEMENTARY DATA
Chemical: Thallous Carbonate
CAS No.: 6533-73-9 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Thallium is a digestive tract irritant and nervous system toxicant
(Doull, 1980, p. 457). It is classified as extremely toxic. The probable
oral lethal dose (humans) is 5-50 mg/kg, or between 7 drops and 1 teaspoon
for 70-kg person (150 Ibs.) (Gosselin, 1976).
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Symptoms appear within 12-24 hours after a
single toxic dose or after several weeks of small daily doses. In acute
poisoning dominant symptoms include severe stomach cramps, vomiting and
diarrhea. In severe cases nervous system damage may be indicated by
tremors, delirium, convulsions, paralysis, and coma, culminating in death.
Symptoms of subacute poisonings include stomach cramps, nausea, vomiting,
diarrhea, leg pains, tremors, and tingling sensations in the hands and feet.
Damage to nervous system may be permanent (Gosselin, 1976).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: Tl 0
2 3
Molecular Weight: 468.78
Boiling Point: Not Found
Specific Gravity (H20=l): 7.1
Vapor Pressure (mmHg): Not Found
Melting Point: 522F, 272C
Vapor Density (AIR=1): Not Found
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: Soluble in 24 parts water, 3.7 parts boiling water
Flash Point [Method Used]: Not Found
Flammable Limits: Not Found
Appearance and Odor: Heavy, shiny, colorless or white crystals (Hawley,
1977)
Conditions or Materials to Avoid: Not Found
-------
Thallium Carbonate: page 7 of 7
Hazardous Decomposition or Byproducts: When heated to decomposition, it
emits toxic fumes of thallium (Sax, 1984, p. 2556).
Use: Used in the manufacture of imitation diamonds (Merck, 1976). Also
used in analysis to test for carbon disulfide (Hawley, 1977) . Used as a
fungicide (Venugopal, 1978).
Synonyms: Thallium(I) Carbonate(2:1); Dithallium Carbonate; Carbonic Acid,
Dithallium (1+) Salt; Thallium Carbonate; Thallium Carbonate (T12C03)
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Thallium Chloride; CAS No. 7791-12-0 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Thallium Chloride
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Thallium Chloride: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Thallium Chloride
CAS No.: 7791-12-0 Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Increased kidney NOEL: 5 ppm Tl acetate 1000 1 4E-4
weight, alopecia in diet; converted to mg/kg/day
0.45 mg/kg/day of
Rat subchronic thallium chloride
feeding study
LOAEL: 15 ppm Tl acetate
Downs et al. (1960) in diet; converted to
1.36 mg/kg/day of
thallium chloride
* Dose Conversion Factors & Assumptions: Young rat food consumption assumed
to be 10% bw/day; molecular weight conversion factor (for equimolar Tl) =
239/263 [MW T1C1 = 239; Mtf TIC 0 H = 263]
223
2. PRINCIPAL AND SUPPORTING STUDIES
Downs, W.L. , J.K Scott, L.T. Steadman and E.A. Maynard. 1960. Acute and
subacute toxicity studies of thallium compounds. Am. Ind. Hyg. Assoc. 21:
399-406.
Groups of rats (5/sex/dose) were fed diets containing nominal concentra-
tions of thallium acetate of 0, 5, 15 or 50 ppm. An additional group (30 ppm)
was added partway through (time not specified). Animals were allowed ad
libidum access to these diets for 15 weeks. The 50-ppm level resulted in 100%
-------
Thallium Chloride: page 3 of 7
mortality by week 5. The 30-ppm level resulted in 100% mortality by week 9.
Four of 10 control animals died (2/sex) by week 15, making interpretation of
survival in the remaining dose groups difficult (15 ppm 3/5 males died, 1/5
females; 5 ppm 2/6 males died, 0/4 females). At termination, the only gross
finding was alopecia in the 15- and 30-ppm groups. The authors stated that
there was a slight increase in kidney weight (doses not specified, data not
shown). The authors reported that histopathological evaluations did not
indicate treatment-related pathology.
Data concerning the toxicity of thallium chloride per se were not located.
The toxicity of thallium acetate and thallium chloride should be substantially
similar. This assumes that gastrointestinal absorption of the two compounds
is also substantially similar. An interim RfD is proposed by analogy to
thallium acetate based on the feeding level of 5 ppm thallium acetate, which
corresponds to a NOEL. This feeding level provided a thallium equivalent of
0.39 mg/kg/day, corresponding to a feeding level of 0.45 mg/kg/day thallium
chloride.
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 1000. The uncertainty factor of 1000 reflects 10 for both intraspecies
and interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation of a subchronic effect level to its
chronic equivalent.
MF = 1
4. ADDITIONAL COMMENTS
Downs et al. (1960) is the only subchronic study available for the oral
route. There appear to be no chronic data. An abstract of a Russian study
was located which reported administration of thallium sulfate or carbonate by
i.p. or s.c. injection. However, in the absence of data for oral absorption
efficiency, it is difficult to compare these doses. Further chronic/repro-
ductive toxicity data are needed for a higher level of confidence In the RfD.
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Low RfD: Low
Confidence in the chosen study is low. This study is flawed by small
group sizes, mortality in the control group, failure to monitor food consump-
tion and lack of detail in the reported results. However, four doses were
tested and were preceded by a short-term bioassay that tested six doses.
Confidence in both the data base and the RfD are low because no supporting
data are available.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, July 1985.
U.S. EPA. 1985. Thallium Compounds: Review and Evaluation of ADI. Contract
No. 68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
-------
Thallium Chloride: page 4 of 7
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Thallium Chloride
CAS No.: 7791-12-0
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Thallium Chloride
CAS No.: 7791-12-0
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Thallium Chloride
CAS No.: 7791-12-0
Information is not available at this time.
-------
Thallium Chloride: page 5 of 7
IV. RISK MANAGEMENT SUMMARIES
Chemical: Thallium Chloride
CAS No.: 7791-12-0 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk Status Risk Considers
Management Management Econ/Tech
Action Date Value Feasibility Reference
Reportable Final 100 Ibs no 51 FR 34534
Quantity (RQ) 1986 09/29/86
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on chronic toxicity. RQ assignments based on
chronic toxicity reflect two primary attributes of the hazardous substance,
the minimum effective dose (MED) levels for chronic exposure (mg/day for 70-
kg man) and the type of effect (liver necrosis, teratogenicity, etc). In
accordance with the methodology described in the Agency's "Technical
Background Document to Support Rulemaking Pursuant to CERCLA Section 102,
Volume 1" of March 1985 and 50 FR 13468 (04/04/85), a composite score is
determined from an evaluation of these two attributes. Thallium chloride
was determined to have a composite score between 21 and 40, corresponding to
a chronic toxicity RQ of 100 pounds.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
-------
Thallium Chloride: page 6 of 7
V. SUPPLEMENTARY DATA
Chemical: Thallium Chloride
CAS No.: 7791-12-0 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
(Non-Specific -- Thallium Salts) Compound is poisonous if swallowed.
Inhalation of dust is poisonous (DOT, 1984, Guide 53).
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: When large doses of thallium compounds
are taken, first symptoms are hemorrhage of the gastrointestinal tract,
stomach cramps, rapid heartbeat, and headache within the first 12-24 hours.
Other symptoms include abdominal pain, vomiting, constipation, and diarrhea.
When smaller doses are taken, the predominant symptoms are tingling
sensation and unsteadiness in the extremities. The tingling sensation is
generally more severe in the lower limbs and may progress to weakness and
muscular atrophy (Clayton and Clayton, 1981-82). Chronic thallous ion
intoxication in the first three months of pregnancy has caused deformities
in newborn babies. If intoxication takes place after the third month of
pregnancy the central nervous system of the baby is damaged (Venupogal,
1978).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: T1C1
Molecular Weight: 239.82
Boiling Point: 1328F, 720C
Specific Gravity (H20=l): 7.0
Vapor Pressure (mmHg): Not Found
Melting Point: 806F, 430C
Vapor Density (AIR-1): Not Found
Evaporation Rate (Butyl acetate-1): Not Found
Solubility in Water: Soluble in 260 parts cold water
Flash Point [Method Used]: Not Found
Flammable Limits: Not Found
-------
Thallium Chloride: page 7 of 7
Appearance and Odor: White, crystalline powder (Merck, 1976); becomes
violet on exposure to light (Hawley, 1977).
Conditions or Materials to Avoid: Thallium(I) chloride is vigorously
attacked by cold fluorine (Bretherick, 1979). A mixture of potassium and
thallous chloride produces a weak explosion on impact (NFPA, 1978).
Hazardous Decomposition or Byproducts: Not Found
Use: Used as a catalyst in chlorinations (Merck, 1976) and in suntan
lamps (Hawley, 1977).
Synonyms: Thallium Chloride; Thallium Chloride (T1C1); Thallium Monochloride;
Thallium (1+) Chloride; Thallium (I) Chloride
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Thallium Nitrate; CAS No. 10102-45-1 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Thallium Nitrate
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Thallium Nitrate: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Thallium Nitrate
CAS No.: 10102-45-1
Preparation Date: 01/08/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Increased kidney
weight, alopecia
Rat subchronic
feeding study
Downs et al. (1960)
5 ppm in diet as
thallium acetate
(NOEL) converted to
0.39 mg/kg/day
thallium or 0.51
mg/kg/day thallium
nitrate
15 ppm in diet
(LOAEL) converted to
1.16 mg/kg/day as
thallium or 1.52
mg/kg/day thallium
nitrate
1000
5E-4
mg/kg/day
* Dose Conversion Factors & Assumptions: Young rat food consumption assumed
to be 10% bw/day; molecular weight conversion factor (for equimolar Tl) -
266/263 [MW T1NO = 266; MW TIC 0 H - 263]
3 223
2. PRINCIPAL AND SUPPORTING STUDIES
Downs, W.L., J.K Scott, L.T. Steadman and E.A. Maynard. 1960. Acute and
subacute toxicity studies of thallium compounds. Am. Ind. Hyg. Assoc. 21:
399-406.
Groups of rats (5/sex/dose) were fed diets containing nominal concentra-
tions of thallium acetate of 0, 5, 15 or 50 ppm. An additional group (30 ppm)
-------
Thallium Nitrate: page 3 of 6
was added partway through (time not specified). Animals were allowed ad
libitum access to these diets for 15 weeks. The 50-ppm level resulted in 100%
mortality by week 5. The 30-ppm level resulted in 100% mortality by week 9.
Four of 10 control animals died (2/sex) by week 15, making interpretation of
survival in the remaining dose groups difficult (15 ppm 3/5 males died, 1/5
females; 5 ppm 2/6 males died, 0/4 females). At termination, the only gross
finding was alopecia in the 15- and 30-ppm groups. The authors state that
there was a slight increase in kidney weight (doses not specified, data not
shown). The authors reported that histopathological evaluations did not
indicate treatment-related pathology.
No data were located concerning the toxicity of thallium nitrate per se.
The toxicity of thallium nitrate and thallium acetate should be substantially
similar. This presumes that absorption of these compounds from the GI tract
is similar. By analogy, an RfD for thallium nitrate may be calculated from
the NOEL for thallium acetate. The thallium nitrate feeding level equivalent
to the NOEL dose was 5 ppm. This corresponds to 0.39 mg/kg/day thallium,
which would be equivalent (in terms of thallium content) to 0.51 mg/kg/day
thallium nitrate.
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 1000. The uncertainty factor of 1000 reflects 10 for both intraspecies
and interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation of a subchronic effect level to its
chronic equivalent.
MF = 1
4. ADDITIONAL COMMENTS
Downs et al. (1960) is the only subchronic study available for the oral
route. There appear to be no chronic data. An abstract of a Russian study
was located which reported administration of thallium sulfate or carbonate by
i.p. or s.c. injection. However, in the absence of data for oral absorption
efficiency, it is difficult to compare these doses. Further chronic/repro-
ductive toxicity data are needed for a higher level of confidence in the RfD.
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Low RfD: Low
Confidence in the chosen study is low. This study is flawed by small
group sizes, mortality in the control group, failure to monitor food consump-
tion, and lack of detail in the reported results. However, four doses were
tested and were preceded by a short-term bioassay that tested six doses.
Confidence in both the data base and the RfD is low because no supporting data
are available.
6. DOCUMENTATION AND REVIEW
Limited in-house review by ECAO-Cincinnati, July 1985.
U.S. EPA. 1985. Thallium Compounds: Review and Evaluation of ADI. Contract
No. 68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
-------
Thallium Nitrate: page 4 of 6
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Thallium Nitrate
CAS No.: 10102-45-1
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Thallium Nitrate
CAS No.: 10102-45-1
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Thallium Nitrate
CAS No.: 10102-45-1
Information is not available at this time.
-------
Thallium Nitrate: page 5 of 6
IV. RISK MANAGEMENT SUMMARIES
Chemical: Thallium Nitrate
CAS No.: 10102-45-1 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk Status Risk Considers
Management Management Econ/Tech
Action Date Value Feasibility Reference
Reportable Final 100 Ibs no 51 FR 34534
Quantity (RQ) 1986 09/29/86
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on chronic toxicity. RQ assignments based on
chronic toxicity reflect two primary attributes of the hazardous substance,
the minimum effective dose (MED) levels for chronic exposure (mg/day for 70-
kg man) and the type of effect (liver necrosis, teratogenicity, etc). In
accordance with the methodology described in the Agency's "Technical
Background Document to Support Rulemaking Pursuant to CERCLA Section 102,
Volume 1" of March 1985 and 50 FR 13468 (04/04/85), a composite score is
determined from an evaluation of these two attributes. Thallium nitrate was
determined to have a composite score between 21 and 40, corresponding to a
chronic toxicity RQ of 100 pounds.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
-------
Thallium Nitrate: page 6 of 6
V. SUPPLEMENTARY DATA
Chemical: Thallium Nitrate
CAS No.: 10102-45-1
Information is not available at this time.
Synonyms: THALLIUM(1+) SALT NITRIC ACID, RCRA WASTE NUMBER U217, THALLIUM
MONONITRATE, THALLIUM NITRATE, THALLOUS NITRATE, UN 2727
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Thallium Selenite; CAS No. 12039-52-0 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Thallium Selenite
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Thallium Selenite: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD Is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical:
CAS No.:
Thallium Selenite
12039-52-0
Preparation Date: 01/08/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Increased kidney
weight, alopecia
Rat subchronic
feeding study
Downs et al. (1960)
5 ppm in diet as
thallium acetate
(NOEL) converted to
0.39 mg/kg/day
thallium or 0.54
mg/kg/day thallium
selenite
15 ppm in diet
(LOAEL) converted to
1.16 mg/kg/day
thallium or 1.61
mg/kg/day thallium
selenite
1000
5E-4
mg/kg/day
* Dose Conversion Factors & Assumptions: Young rat food consumption assumed
to be 10% bw/day; molecular weight conversion factor (for equimolar Tl) —
283/263 [MW TISe - 283; MW TIC OH- 263]
223
2. PRINCIPAL AND SUPPORTING STUDIES
Downs, W.L., J.K Scott, L.T. Steadman and E.A. Maynard. 1960. Acute and
subacute toxicity studies of thallium compounds. Am. Ind. Hyg. Assoc. 21:
399-406.
Groups of rats (5/sex/dose) were fed diets containing nominal concentra-
tions of thallium acetate of 0, 5, 15 or 50 ppm. An additional group (30 ppm)
-------
Thallium Selenlte: page 3 of 5
was added partway through (time not specified). Animals were allowed ad
libitum access to these diets for 15 weeks. The 50-ppm level resulted in 100%
mortality by week 5. The 30-ppm level resulted in 100% mortality by week 9.
Four of 10 control animals died (2/sex) by week 15, making interpretation of
survival in the remaining dose groups difficult (15 ppm 3/5 males died, 1/5
females; 5 ppm 2/6 males died, 0/4 females). At termination, the only gross
finding was alopecia in the 15- and 30-ppm groups. The authors state that
there was a slight increase in kidney weight (doses not specified, data not
shown). The authors reported that histopathological evaluations did not
indicate treatment-related pathology.
No toxicological data were located concerning thallium selenite per se.
It is possible to develop an RfD based on equivalent thallium exposure from
data concerning thallium acetate. However, this extrapolation is considered
more uncertain than extrapolations among the simple thallium salts.
The no-effect feeding level for thallium acetate was 5 ppm, which
contributed 0.39 mg/kg/day thallium. The dietary thallium selenite intake
which would provide an equivalent thallium intake is 0.54 mg/kg/day thallium
selenite. The exposure to selenium from this compound, based upon the
proposed interim RfD of 38 ug/day, should be well below the toxic range for
selenium alone.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. The uncertainty factor of 1000 reflects 10 for both intraspecies
and interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation of a subchronic effect level to its
chronic equivalent.
MF = 1
4. ADDITIONAL COMMENTS
Downs et al. (1960) is the only subchronic study available for the oral
route. There appear to be no chronic data. An abstract of a Russian study
was located which reported administration of thallium sulfate or carbonate by
i.p. or s.c. injection. However, in the absence of data for oral absorption
efficiency, it is difficult to compare these doses. Further chronic/repro-
ductive toxicity data are needed for a higher level of confidence in the RfD.
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Low RfD: Low
Confidence in the chosen study is low. This study is flawed by small
group sizes, mortality in the control group, failure to monitor food consump-
tion, and lack of detail in the reported results. However, four doses were
tested and were preceded by a short-term bioassay that tested six doses.
Confidence in both the data base and the RfD is low because no supporting data
are available.
6. DOCUMENTATION AND REVIEW
Limited in-house review by ECAO-Cincinnati, July 1985.
-------
Thallium Selenite: page 4 of 5
U.S. EPA. 1985. Thallium Compounds: Review and Evaluation of ADI. Contract
No. 68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Thallium Selenite
CAS No.: 12039-52-0
Information Is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Thallium Selenite
CAS No.: 12039-52-0
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Thallium Selenite
CAS No.: 12039-52-0
Information is not available at this time.
-------
Thallium Selenite: page 5 of 5
IV. RISK MANAGEMENT SUMMARIES
Chemical: Thallium Selenite
CAS No.: 12039-52-0 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1986
Risk
Management
Value
1000 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
51 FR 34534
09/29/86
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on acute toxicity. Available data indicate that
the oral LD50 for rats is between 10 and 100 mg/kg.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
V. SUPPLEMENTARY DATA
Chemical: Thallium Selenite
CAS No.: 12039-52-0
Information is not available at this time.
Synonyms: RCRA WASTE NUMBER P114, THALLIUM MONOSELENIDE, THALLIUM SELENIDE
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Thallium (I) Sulfate; CAS No. 7446-18-6 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Thallium (I) Sulfate
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Thallium (I) Sulfate: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Thallium (I) Sulfate
CAS No.: 7446-18-6
Preparation Date: 01/08/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF MF
RfD
Increased kidney
weight, alopecia
Rat subchronic
feeding study
Downs et al. (1960)
5 ppm in diet as
thallium acetate
(NOEL) converted to
0.39 mg/kg/day thal-
lium or 0.48 mg/kg/
day thallium sulfate
15 ppm in diet (LOEL)
converted to 1.16
mg/kg/day thallium or
1.44 mg/kg/day
thallium sulfate
1000 1 5E-4
mg/kg/day
* Dose Conversion Factors & Assumptions: Young rat food consumption assumed
to be 10% bw/day; molecular weight conversion factor (for equimolar Tl) =
505/(2 x 263) [MW Tl SO = 505; Mtt TIC 0 H = 263]
24 223
2. PRINCIPAL AND SUPPORTING STUDIES
Downs, W.L., J.K Scott, L.T. Steadman and E.A. Maynard. 1960. Acute and
subacute toxicity studies of thallium compounds. Am. Ind. Hyg. Assoc. 21:
399-406.
Groups of rats (5/sex/dose) were fed diets containing nominal concentra-
tions of thallium acetate of 0, 5, 15 or 50 ppm. An additional group (30 ppm)
-------
Thallium (I) Sulfate: page 3 of 7
was added partway through (time not specified). Animals were allowed ad
libitum access to these diets for 15 weeks. The 50-ppm level resulted in 100%
mortality by week 5. The 30-ppm level resulted in 100% mortality by week 9.
Four of 10 control animals died (2/sex) by week 15, making interpretation of
survival in the remaining dose groups difficult (15 ppm 3/5 males died, 1/5
females; 5 ppm 2/6 males died, 0/4 females). At termination, the only gross
finding was alopecia in the 15- and 30-ppm groups. The authors state that
there was a slight increase in kidney weight (doses not specified, data not
shown). The authors reported that histopathological evaluations did not
indicate treatment-related pathology.
No data concerning the toxicity of thallium sulfate per se were located.
The toxicity of thallium sulfate and thallium acetate should be substantially
similar. This presumes that gastrointestinal absorption is substantially
similar. An RfD for thallium sulfate may be estimated by analogy to thallium
acetate. The no-effect feeding level for thallium acetate was 5 ppm, which
provided 0.39 mg/kg/day thallium. A thallium sulfate intake providing a cor-
responding thallium intake would be 0.48 mg/kg/day.
3. UNCERTAINTY AND MODIFYING FACTORS
UF •= 1000. The uncertainty factor of 1000 reflects 10 for both intraspecies
and interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation of a subchronic effect level to its
chronic equivalent.
MF = 1
4. ADDITIONAL COMMENTS
Downs et al. (1960) is the only subchronic study available for the oral
route. There appear to be no chronic data. An abstract of a Russian study
was located which reported administration of thallium sulfate or carbonate by
i.p. or s.c. injection. However, in the absence of data for oral absorption
efficiency, it is difficult to compare these doses. Further chronic/repro-
ductive toxicity data are needed for a higher level of confidence in the RfD.
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Low RfD: Low
Confidence in the chosen study is low. This study is flawed by small
group sizes, mortality in the control group, failure to monitor food consump-
tion, and lack of detail in the reported results. However, four doses were
tested and were preceded by a short-term bioassay that tested six doses.
Confidence in both the data base and the RfD is low because no supporting data
are available.
6. DOCUMENTATION AND REVIEW
Limited in-house review by ECAO-Cincinnati, July 1985.
U.S. EPA. 1985. Thallium Compounds: Review and Evaluation of ADI. Contract
No. 68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
-------
Thallium (I) Sulfate: page 4 of 7
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Thallium (I) Sulfate
CAS No.: 7446-18-6
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Thallium (I) Sulfate
CAS No.: 7446-18-6
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Thallium (I) Sulfate
CAS No.: 7446-18-6
Information is not available at this time.
-------
Thallium (I) Sulfate: page 5 of 7
IV. RISK MANAGEMENT SUMMARIES
Chemical:
CAS No.:
Thallium Sulfate
7446-18-6
Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Status
Date
Risk
Management
Value
Considers
Econ/Tech
Feasibility
Reference
Reportable Final
Quantity (RQ) 1986
Pesticide Active
Ingredient:
a. Registration n.a.
Standard
b. Special Final
Review 1972
100 Ibs
no
51 FR 34534
09/29/86
n.a.
yes
Reg. Standard
03/09/72
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on chronic toxicity. RQ assignments based on
chronic toxicity reflect two primary attributes of the hazardous substance,
the minimum effective dose (MED) levels for chronic exposure (mg/day for 70-
kg man) and the type of effect (liver necrosis, teratogenicity, etc). In
accordance with the methodology described in the Agency's "Technical
Background Document to Support Rulemaking Pursuant to CERCLA Section 102,
Volume 1" of March 1985 and 50 FR 13468 (04/04/85), a composite score is
determined from an evaluation of these two attributes. Thallium sulfate was
determined to have a composite score between 21 and 40, corresponding to a
chronic toxicity RQ of 100 pounds.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
-------
Thallium (I) Sulfate: page 6 of 7
Pesticide Active Ingredient
a. not available
b. Special Review: For specific details on the Special Review process for
this active ingredient please check the references listed.
Contact: Office of Pesticide Programs, Special Review Branch
202/557-7420 or FTS/557-7420
V. SUPPLEMENTARY DATA
Chemical: Thallium (I) Sulfate
CAS No.: 7446-18-6 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Thallium (I) sulfate is rated as extremely toxic. The probable oral
lethal dose in humans is 5 to 50 mg/kg, or between 7 drops and 1 teaspoon
for a 150-pound person (Gosselin, 1984, p. 11-139). The mean lethal dose
in an adult is probably about 1 gm of thallium sulfate (Gosselin, 1984, p.
Ill 380). Repeated exposure causes hair loss starting 10 days after
exposure and complete baldness in about a month (Clayton and Clayton,
1981-82, p. 1922).
Medical Conditions Generally Aggravated by Exposure: Not Found
Signs and Symptoms of Exposure: Can cause death due to shock. Dominant
effects include severe abdominal pain, vomiting and diarrhea. Blood in
vomitus and stools are often seen. In severe cases, tremors, delirium,
convulsions, paralysis, coma and even death may occur (Gosselin, 1984, p.
III-381).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: Tl SO
2 4
Molecular Weight: 504.80
Boiling Point: Decomposes
Specific Gravity (H20=l): 6.77
Vapor Pressure (mmHg): Inappreciable
Melting Point: 1170F, 632C
Vapor Density (AIR=1): Not Found
-------
Thallium (I) Sulfate: page 7 of 7
Evaporation Rate (Butyl acetate-1): Not Found
Solubility in Water: 4.87 g/100 ml at 20C, 19.14 g/100 ml at 100C
Flash Point [Method Used]: Not Found
Flammable Limits: Not Found
Appearance and Odor: White rhomboid prisms to a colorless dense powder;
odorless (Hayes, 1982, p. 25; Merck, 1983, p. 1325; Hawley, 1981, p. 1013)
Conditions or Materials to Avoid: Not Found
Hazardous Decomposition or Byproducts: When heated to decomposition, it
emits very toxic fumes of thallium and sulfur oxides (Sax, 1984, p. 2557).
Use: Used as a rat poison, as ant bait and as a reagent in analytical
chemistry (Merck, 1983, p. 1325). Also used for analysis (testing for
iodine in the presence of chlorine); ozonometry; as a rodenticide; and as a
pesticide (Hawley, 1981, p. 1013). Not registered as a pesticide in the
U.S. (USEPA/Pesticide Index, 1985).
Synonyms: (NIOSH/RTECS 1983 SYNONYMS, VOLUME 3, p. 706)
Thallium(I)Sulfate(2:l); C.F.S.; CSF-Giftweizen; Dithallium Sulfate;
Dithallium(l+) Sulfate; M7-Giftkoerner; Rattengiftkonserve; Sulfuric Acid,
Dithallium(l+) Salt; Sulfuric Acid, Thallium(l+) Salt (1:2); Thallium Sulfate;
Thallium(I) Sulfate
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Toluene; CAS No. 108-88-3 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Toluene
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Toluene: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Toluene
CAS No.: 108-88-3
Preparation Date: 01/08/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Clinical chemistry
and hematological
parameters
Rat chronic inha-
lation study
CITT (1980)
300 ppm (1130 mg/ cu.
m) converted to 29
mg/kg/day (NOAEL)
LOAEL: None
100
3E-1
mg/kg/day
* Dose Conversion Factors & Assumptions: 5 days/7 days, 6 hour/24 hour;
0.5 absorption factor, 20 cu. m human breathing rate; 70 kg; thus, 1130
mg/cu. m x 5 day/7 days x 6 hours/24 hours x 0.5 x 20 cu. m/day / 70 kg •
28.8 mg/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
CUT (Chemical Industry Institute of Toxicology). 1980. A 24-month
inhalation toxicology study in Fischer-344 rats exposed to atmospheric
toluene. CUT, Research Triangle Park, NC.
Toluene is most likely a potential source of respiratory hazard. The only
chronic toxicity study on toluene was conducted for 24 months in male and
female F344 rats (CUT, 1980). Toluene was administered by inhalation at 30,
100 or 300 ppm (113, 377 or 1130 mg/cu. m) to 120 male and 120 female F344
rats for 6 hours/day, 5 days/week. The same number of animals (120 males and
120 females) was used as a control. Clinical chemistry, hematology and
-------
Toluene: page 3 of 6
urinalysis testing was conducted at 18 and 24 months. All parameters measured
at the termination of the study were normal except for a dose-related
reduction in hematocrit values in females exposed to 100 and 300 ppm toluene.
Based on these findings, a NOAEL of 300 ppm or 1130 mg/cu. m was derived.
An oral RfD of 20 mg/day can be derived using route-to-route extrapolation.
This was done by expanding the exposure from 6 hours/day, 5 days/week to con-
tinuous exposure and multiplying by 20 cu. m/day and 0.5 to reflect a 50%
absorption factor.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. An uncertainty factor of 100 (10 for sensitive individuals and 10
for intraspecies extrapolation was also applied.
MF = 1
4. ADDITIONAL COMMENTS
The only oral study found in the data base (Wolf et al., 1956) contains
subchronic data in which no adverse effects of toluene were reported at the
highest dose tested (590 mg/kg/day).
5. CONFIDENCE IN THE RfD
Study: High
Data Base: Medium
RfD: Medium
Confidence in the critical study is high because a large number of
animals/sex were tested in each of three dose groups and many parameters were
studied. Interim kills were performed. The data base is rated medium because
several studies support the chosen effect level. The confidence of the RfD is
not higher than medium because the critical study was by the inhalation route.
6. DOCUMENTATION AND REVIEW
Limited Peer Review and Agency-wide Internal Review, 1984.
U.S. EPA. 1985. Drinking Water Criteria Document for Toluene.
Drinking Water, Washington, DC.
Agency RfD Work Group Review: 05/20/85, 08/05/85, 08/05/86
Verification Date: 05/20/85
Office of
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
-------
Toluene: page 4 of 6
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Toluene
CAS No.: 108-88-3
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Toluene
CAS No.: 108-88-3
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Toluene
CAS No.: 108-88-3
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Toluene
CAS No.: 108-88-3 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Toluene: page 5 of 6
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
1000 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
14.3 mg/1
no
2) Marine
Final
1980
Acute no
17,500 ug/1 (LEL)
Chronic
none
Acute no
6,300 ug/1 (LEL)
Chronic
5,000 ug/1 (LEL)
45 FR 79318
11/28/80
ibid.
ibid.
Clean Air Act
Regulatory
Decision:
(NESHAP or NSPS)
Final
1984
Decision not no
to Regulate
49 FR 22195
05/25/84
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity, as established under Section
311(b)(4) of the Clean Water Act, ignitability and chronic toxicity.
Available data indicate that the aquatic 96-Hour Median Threshold Limit for
Toluene is between 10 and 100 ppm. Its closed cap flash point is less than
100 degrees F and its boiling point is greater than 100 degrees F. RQ
assignments based on chronic toxicity reflect two primary attributes of the
hazardous substance, the minimum effective dose (MED) levels for chronic
exposure (mg/day for 70-kg man) and the type of effect (liver necrosis,
teratogenicity, etc). In accordance with the methodology described in the
Agency's "Technical Background Document to Support Rulemaking Pursuant to
CERCLA Section 102, Volume 1" of March 1985 and 50 FR 13468 (04/04/85), a
composite score is determined from an evaluation of these two attributes.
Toluene was determined to have a composite score between 6 and 20,
corresponding to a chronic toxicity RQ of 1000 pounds.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC of 14.3 mg/1 is based on consumption of
contaminated aquatic organisms and water. A WQC of 424 mg/1 has also been
established based on consumption of contaminated aquatic organisms alone.
-------
Toluene: page 6 of 6
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value indicates that the
minimum data were not available and the concentration given is not a criteria
value but the lowest effect level found in the literature.
CAA Regulatory Decision
EPA concluded that current information does not indicate that toluene
endangers public health at ambient concentrations (excluding emergency
releases), and thus no regulation directed specifically at toluene is
necessary at this time under the CAA.
Contact: Chief, Pollutant Assessment Branch
FTS/629-5645 or 919/541-5645
V. SUPPLEMENTARY DATA
Chemical: Toluene
CAS No.: 108-88-3
Information is not available at this time.
Synonyms: ANTISAL la, METHYL-BENZENE, METHACIDE, PHENYL-METHANE,
METHYLBENZENE, METHYLBENZOL, NCI-C07272, PHENYLMETHANE, RCRA WASTE NUMBER
U220, TOLUEEN (Dutch), TOLUEN (Czech), TOLUENE , TOLUOL, TOLUOLO (Italian),
TOLU-SOL, UN 1294
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
1,2,4-Trichlorobenzene; CAS No. 120-82-1 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR 1,2,4-Trichlorobenzene
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
1,2,4-Trtchlorobenzene: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) Is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: 1,2,4-Trichlorobenzene
CAS No.: 120-82-1 Preparation Date: 05/12/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Increased liver-to- 20 mg/kg/day (NOAEL) 1000 1 2E-2
body weight ratio mg/kg/day
40 mg/kg/day (LOEL)
Rat oral subchronic
study
Carlson and Tardiff
(1976)
* Dose Conversion Factors & Assumptions: none
2. PRINCIPAL AND SUPPORTING STUDIES
Carlson, G.P. and R.G. Tardiff. 1976. Effect of chlorinated benzenes on the
metabolism of foreign organic compounds. Toxicol. Appl. Pharmacol. 36:
383-394.
Pertinent data on the chronic toxicity or carcinogenicity of this com-
pound are not available in the current data base. Based on several sub-
chronic inhalation studies, the ACGIH (1984) has recommended a TLV of 5 ppm
(37 mg/cu. m). This could be used to derive an RfD of 13 mg/kg/day; however,
results of several subchronic oral studies, taken together, would support the
calculations of an RfD for oral exposure.
-------
1,2,4-Trichlorobenzene: page 3 of 7
The effect of oral dosing of male CD rats (6 animals/group) at 0, 10, 20
or 40 mg/kg/day with 1,2,4-trichlorobenzene In corn oil on weight gain, liver
weight, hemoglobin, hematocrit, and indicators of xenobiotic mechanism, such
as cytochrome C\reductase, o-ethyl-o-p-nitrophenyl phenylphosphothionate (EPN)
detoxification, cytochrome P-450, glucoronyl transferase, benzopyrene
hydroxylase, and azoreductase activities in liver were evaluated. The lowest
dose tested, 10 mg/kg/day, was sufficient to induce some of the enzymes
assayed, but no effect on liver-to-body weight ratio, blood hemoglobin level
or hematocrit was reported. More pronounced evidence of enzyme Induction was
obtained at 20 mg/kg/day, but other parameters remained unaffected. The
highest dose tested, 40 mg/kg/day, was the most effective for enzyme Induc-
tion and also increased liver-to-body weight ratios; these changes persisted
throughout a 30-day "recovery period," while the enzyme induction and liver
weight changes seen at the two lower doses were unremarkable. Although enzyme
induction is a very sensitive end point for this chemical, it is not
necessarily an adverse effect. The 20 mg/kg/day dose Is considered a NOAEL,
and by applying an uncertainty factor of 1000 to this NOAEL, an RfD of 0.02
mg/kg/day or 1.4 mg/day for a 70-kg person is derived. Because data are
available for a variety of toxicological end points In two species (Smith et
al., 1978; Robinson et al., 1981), the U.S. EPA (1983) suggested an uncer-
tainty factor of 100 and derived an RfD of 7 mg/day. However, current evi-
dence was inadequate to judge whether trichlorinated benzene toxicity follow-
ing low exposure was independent of exposure duration. It is, therefore,
recommended to that an uncertainty factor of 1000 be used to derive the RfD
from the above subchronic rodent study.
3. UNCERTAINTY AND MODIFYING FACTORS
UF - 1000. An uncertainty factor of 1000 was applied; 10 for interspecies,
10 for intraspecies variability and 10 for the use of subchronic data.
MF = 1
4. ADDITIONAL COMMENTS
The critical study discussed above provided a NOEL and LOEL of the com-
pound which can be supported by other subchronic studies. Robinson et al.
(1981) reported NOAELs (14.8 and 8.9 mg/kg/day, respectively, for females and
males) In their multigeneratIon reproduction study, and Carlson (1977) in his
120-day study observed porphyria in rats exposed to greater than or equal to
50 mg 1,2,4-trichlorobenzene/kg/day (LOAEL). Robinson et al. (1981) reported
both NOAELs and LOAELs; however, the control and FO and Fl, but not F2,
exposed animals shared adrenal hyperplasia, which could not be explained.
Carlson (1977) demonstrated porphyria in rats exposed to different doses of
trichlorobenzene. Porphyria is one of the toxicological parameters strongly
associated with chlorinated compounds. This study reported no NOAELs; how-
ever, the LOAEL (50 mg/kg/day) was in good agreement with the LOAELs of both
the Robinson et al. (1981) and Carlson and Tardiff (1976) studies (33.0
mg/kg/day and 40 mg/kg/day for male rats, respectively).
-------
1,2,4-Trichlorobenzene: page 4 of 7
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The referenced subchronic study provided both a NOEL and LOEL, and
incorporated several biochemical and biological end points; therefore, a med-
ium level of confidence was assigned. The data base did not provide any
chronic oral or inhalation studies; however, several subchronic studies pro-
vided supportive data. Therefore, a medium level of confidence was assigned
to the data base. Oral chronic studies are needed to support a higher-than-
medium confidence in the RfD.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1986. 1,2,4-Trichlorobenzene: Review and Evaluation of ADI. Con-
tract NO. 68-03-3228. Environmental Criteria and Assessment Office, Cincin-
nati, OH.
U.S. EPA. 1985. Health Assessment Document for Chlorinated Benzenes. Envi-
ronmental Criteria and Assessment Office, Cincinnati, OH. EPA 600/8-84-015F.
U.S. EPA. 1983. Hazard Profile for 1,2,4-Trichlorobenzene. Environmental
Criteria and Assessment Office, Cincinnati, OH.
ECAO-Cin internal review, January 1986 and an extensive Agency-wide and peer
review, 1985.
Agency RfD Work Group Review: 02/26/86
Verification Date: 02/26/86
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: 1,2,4-Trichlorobenzene
CAS No.: 120-82-1
Information is not available at this time.
-------
1,2,4-Trichlorobenzene: page 5 of 7
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: 1,2,4-Trichlorobenzene
CAS No.: 120-82-1
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: 1,2,4-Trichlorobenzene
CAS No.: 120-82-1
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: 1,2,4-Trichlorobenzene
CAS No.: 120-82-1 Preparation Date: 09/30/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
1,2,4-Trichlorobenzene: page 6 of 7
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Status
Date
Risk
Management
Value
Considers
Econ/Tech
Feasibility
Reference
Reportable
Quantity (RQ)
Final
1985
Water Quality
Criteria (WQC):
a. Human Health
b. Aquatic Toxicity
1) Freshwater Final
1980
2) Marine
Final
1980
100 Ibs no
none
Acute no
250 ug/1 (LEL)
Chronic
50 ug/1 (LEL)
Acute no
160 ug/1 (LEL)
Chronic
129 ug/1 (LEL)
50 FR 13456
04/04/85
45 FR 79318
11/28/80
ibid.
Clean Air Act
Regulatory
Decision:
(NESHAP or NSPS)
Final
1985
Decision not no
to regulate
50 FR 32628
06/13/85
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity. The available data indicate
that the aquatic 96-Hour Median Threshold Limit for 1,2,4-trichlorobenzene
is between 1 and 10 ppm.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: none
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value indicates that the
minimum data were not available and the concentration given is not a criteria
value but the lowest effect level found in the literature. The values given
represent chlorinated benzenes as a class - no specific chemicals were
mentioned.
-------
1,2,4-TrIchlorobenzene: page 7 of 7
CAA Regulatory Decision
EPA concluded that the available health information on the chloro-
benzenes (including 1,2,4,-Trichlorobenzene) at concentrations measured or
estimated to occur in the ambient air is insufficient to warrant specific
Federal regulation of routine trichlorobenzene emissions under the CAA at
this time.
Contact: Chief, Pollutant Assessment Branch
FTS/629-5645 or 919/541-5645
V. SUPPLEMENTARY DATA
Chemical: 1,2,4-Trichlorobenzene
CAS No.: 120-82-1
Information is not available at this time.
Synonyms: BENZENE, 1,2,4-TRICHLORO-; unsym-TRICHLOROBENZENE; 1,2,4-
TRICHLOROBENZENE; 1,2,4-TRICHLOROBENZENE (ACGIH); 1,2,4-TRICHLOROBENZENE,
liquid (DOT); TROJCHLOROBENZEN (Polish); UN 2321 (DOT)
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Trichloromonofluoromethane; CAS No. 75-69-4 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Trichloromonofluoromethane
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Trlchloromonofluoromethane: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Trichloromonofluoromethane
CAS No.: 75-69-4 Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Survival and histo- NOAEL: None 1000 1 3E-1
pathology mg/kg/day
488 mg/kg/day (LOAEL)
Cancer bioassay converted to 349 mg/
studies in rats and kg/day
mice
NCI (1978)
* Dose Conversion Factors & Assumptions: 5 days/7 days; thus, 488 mg/kg/
day x 5 days/7 days = 349 mg/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
NCI (National Cancer Institute). 1978. Bioassay of trichlorofluoromethane
for possible carcinogenicity. Report. No. 106, PHS/NIH, DHEW Publ. No.
78-1356.
The NCI bioassay was performed on rats and mice exposed to various doses
of trichloromonofluoromethane by gavage over a period of 78 weeks (50 ani-
mals/species/sex/dose for each of two doses with 20 animals/species/sex for
each of two control groups. A statistically significant positive association
between increased dosage and accelerated mortality by the Tarone test in male
and female rats and female mice was observed. In treated rats of both sexes
there were also elevated incidences of pleuritis and pericarditis not seen in
controls. Inhalation studies which employed multispecies exposures to higher
-------
Trichloromonofluoromethane: page 3 of 6
levels of the compound than used by NCI (Leuschner et al . , 1983; Colman et
al., 1981; Hansen et al . , 1984), reported no adverse clinical/pathological
signs of toxicity due to subchronic or short-term exposures.
The LOAEL of 488 mg/kg/day (mortality in rats) was converted to 349
mg/kg/day on a 7-day exposure basis.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. An uncertainty factory of 1000 (10 for LOAEL, 10 for species
conversion, and 10 for sensitive human population), results in an ADI of 0.3
MF
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: High Data Base: High RfD: High
The chosen study is given a high to medium confidence because large
numbers of animals/sex were tested in two doses for chronic exposures . One
difficult was that the study did not establish a NOEL. The data base is given
a high confidence because multi-species inhalation studies provide supporting
data. High to medium confidence in the RfD follows.
6. DOCUMENTATION AND REVIEW
ECAO- Cincinnati Internal Review, May 1985.
U.S. EPA. 1985. Trichloromonofluoromethane: Review and Evaluation of ADI.
Contract No. 68-03-3228. Environmental Criteria and Assessment Office, Cin-
cinnati, OH.
Agency RfD Work Group Review: 05/20/85, 05/31/85
Verification Date: 05/31/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
-------
Trichloromonofluoromethane: page 4 of 6
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Trichloromonofluoromethane
CAS No.: 75-69-4
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Trichloromonofluoromethane
CAS No.: 75-69-4
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic, potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Trichloromonofluoromethane
CAS No.: 75-69-4
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Trichlorofluoromethane
CAS No.: 75-69-4 Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
Trichloromonofluoromethane: page 5 of 6
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1985
Risk
Management
Value
5000 Ibs
Considers
EC on/Tech
Feasibility
no
Reference
50 FR 13456
04/04/85
Water Quality
Criteria (WQC):
a. Human Health Final
1980
b. Aquatic Toxicity
1) Freshwater Final
1980
2) Marine
Final
1980
0.19 ug/1
no
Acute no
11,000 ug/1 (LEL)
Chronic
none
Acute no
12,000 ug/1 (LEL)
Chronic
6,400 ug/1 (LEL)
45 FR 79318
11/28/80
ibid.
ibid.
B. RISK MANAGEMENT RATIONALE
RQ
No data have been found that permit the ranking of this hazardous
substance. The available data for the acute hazards may lie above the upper
limit for the 5000-pound RQ, but since it is a designated hazardous
substance, the largest assignable RQ is 5000 pounds.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC of 0.19 ug/1 represents a cancer risk level of
1E-6, based on consumption of contaminated organisms and water. A WQC of
15.7 ug/1 (cancer risk level of 1E-6) has also been established based on
consumption of contaminated organisms alone. The criteria are based on
halomethanes as a class.
b. Aquatic toxicity: Water quality criteria for the protection of aquatic
life are derived from a minimum data base of acute and chronic tests on a
variety of aquatic organisms. The "(LEL)" after the value indicates that the
minimum data were not available and the concentration given Is not a criteria
value but the lowest effect level found in the literature. The values are
based on halomethanes as a class - no specific chemicals are cited.
-------
Trlchloromonofluoromethane: page 6 of 6
V. SUPPLEMENTARY DATA
Chemical: Trichloromonofluoromethane
CAS No.: 75-69-4
Information is not available at this time.
Synonyms: ALGOFRENE TYPE 1, ARCTON 9, ELECTRO-CF 11, ESKIMON 11, F 11, FC 11,
FLUOROCARBON NO. 11, FLUOROTRICHLOROMETHANE, FLUOROTROJCHLOROMETAN (Polish) ,
FREON 11, FREON 11A, FREON 11B, FREON HE, FREON MF, FRIGEN 11, GENETRON 11,
HALOCARBON 11, ISCEON 131, ISOTRON 11, LEDON 11, MONOFLUOROTRICHLOROMETHANE,
NCI-C04637, RCRA WASTE NUMBER U121, TRICHLOROFLUOROMETHANE,
TRICHLOROMONOFLUOROMETHANE, UCON FLUROCARBON 11, UCON REFRIGERANT 11
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
2,4,5-Trichlorophenol; CAS No. 95-95-4 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR 2,4,5-Trichlorophenol
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
2,4,5-Trichlorophenol: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: 2,4,5-Trichlorophenol
CAS No.: 95-95-4
Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses
UF
MF
RfD
Liver and kidney
pathology
Rat oral subchronic
study
McCollister et al.
(1961)
100 mg/kg/day (1000
ppm) (NOEL)
300 mg/kg/day (3000
ppm) (LOAEL)
1000
1E-1
mg/kg/day
* Dose Conversion Factors & Assumptions: Food consumption 10% of body
weight young adult animals; thus, 1000 mg/kg of diet x 0.1 kg of diet/kg
bw/day = 100 mg/kg/day
2. PRINCIPAL AND SUPPORTING STUDIES
McCollister, D.D., D.T. Lockwood and V.K. Rowe. 1961. Toxicologic informa-
tion on 2,4,5-trichlorophenol. Toxicol. Appl. Pharmacol. 3: 63-70.
This is the only subchronic (98 days) oral study in rodents available in
the literature. Ten rats of each sex were exposed to different levels (from
100 through 10,000 ppm) of 2,4,5-trichlorophenol for 98 days. Mild diuresis
and slight degenerative changes in the liver and kidneys were observed in
rats of both sexes in the 3000 ppm and higher doses. In this study 1000 ppm
(100 mg/kg/day based on food consumption as 10% of body weight in young
adults) was considered to be a NOEL, as judged by behavior, mortality, food
consumption, growth, body and organ weights, and histopathology. Until
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2,4,5-Trichlorophenol: page 3 of 6
further chronic/reproductive studies are available, this RfD, 0.1 mg/kg/day,
is recommended.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 1000. The uncertainty factor of 1000 reflects 10 for both intraspecies
and interspecies variability to the toxicity of this chemical in lieu of
specific data, and 10 for extrapolation of a subchronic effect level to its
chronic equivalent.
MF = 1
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Low RfD: Medium
The confidence in the chosen study is medium because five dose groups
were tested and several parameters were monitored. It is not higher than
medium because only a few animals were tested/dose. Confidence in the data
base is low because little, if any, supporting data exist. Confidence in the
RfD is medium to low. Additional chronic/reproductive toxicity studies are
needed to support a higher confidence in the RfD.
6. DOCUMENTATION AND REVIEW
Limited Peer Review and Agency-wide Internal Review, 1984.
U.S. EPA. 1984. Health Effects Assessment for 2,4,5-Trichlorophenol. Envi-
ronmental Criteria and Assessment Office, Cincinnati, OH. ECAO-CIN-H034.
Agency RfD Work Group Review: 05/20/85
Verification Date: 05/20/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: 2,4,5-Trichlorophenol
CAS No.: 95-95-4
Information is not available at this time.
-------
2,4,5-Trichlorophenol: page 4 of 6
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: 2,4,5-Trichlorophenol
CAS No.: 95-95-4
This chemical is among those substances evaluated by the U.S. EPA for
evidence of human carcinogenic potential. This does not imply that this
chemical is necessarily a carcinogen. The evaluation for this chemical is
under review by an inter-office Agency work group. A risk assessment summary
will be included on IRIS when the review has been completed.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: 2,4,5-Trichlorophenol
CAS No.: 95-95-4
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: 2,4,5-Trichlorophenol
CAS No.: 95-95-4 Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
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2,4,5-Trichlorophenol: page 5 of 6
A. RISK MANAGEMENT ACTIONS
Risk Status Risk Considers
Management Management Econ/Tech
Action Date Value Feasibility Reference
Reportable Statutory 10 Ibs no 50 FR 13456
Quantity (RQ) 1980 04/04/85
Water Quality
Criteria (WQC):
a. Human Health Final 1 ug/1 no 45 FR 79318
1980 11/28/80
b. Aquatic Toxicity none
Pesticide Active
Ingredient:
a. Registration none
Standard
b. Special Draft Final Position no 51 FR 60
Review 1986 Documents 01/20/86
2/3/4
B. RISK MANAGEMENT RATIONALE
RQ
The statutory RQ of 10 pounds established under Section 311(b)(4) of the
Clean Water Act is retained until the assessment of potential careinogenicity
is completed.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
WQC
Contact: Office of Water Regulations and Standards
202-382-5400 or FTS-382-5400
a. Human health: The WQC of 1 ug/1 is based upon organoleptic effects (taste
and odor thresholds). However, organoleptic end-points have limited value in
setting water quality standards as there is no demonstrated relationship
between taste/odor effect and adverse health effects.
b. Aquatic toxicity: none
Pesticide Active Ingredient
a. Registration Standard: None
b. Special Review: For specific details on the Special Review process for
this active ingredient please check the references provided.
Contact: Office of Pesticides Programs, Special Review Branch
202/557-7420 or FTS/557-7420
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2,4,5-Trichlorophenol: page 6 of 6
V. SUPPLEMENTARY DATA
Chemical: 2,4,5-Trichlorophenol
CAS No.: 95-95-4
Information is not available at this time.
Synonyms: Collunosol; Dowicide 2; Dowicide B; NCI-C61187; Nurelle;
Preventol I; RCRA waste number U230
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
2,4,6-Trichlorophenol; CAS No. 88-06-2 (Revised 12/24/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR 2,4,6-Trichlorophenol
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: none
B. Inhalation RfD:
II. Risk Estimates for Carcinogens:
III. Drinking Water Health Advisories:
IV. Risk Management Summaries:
V. Supplementary Data:
none
available
none
in preparation
none
-------
2,4,6-Trichlorophenol: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: 2,4,6-Trichlorophenol
CAS No.: 88-06-2
Information is not available at this time.
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: 2,4,6-Trichlorophenol
CAS No.: 88-06-2
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: 2,4,6-Trichlorophenol
CAS No.: 88-06-2 Preparation Date: 12/24/86
A. U.S. EPA CLASSIFICATION AND BASIS
Classification: B2, probable human carcinogen, based on increased incidence
of lymphomas or leukemias in male rats and hepatocellular
adenomas or carcinomas in male and female mice.
1. HUMAN DATA
None.
2. ANIMAL DATA
2,4,6-Trichlorophenol was added to the diet of 50 each male and female
F344 rats and B6C3F1 mice (NCI, 1979). The diets, containing 5000 or 10,000
ppm trichlorophenol were administered for 106 or 107 weeks. Male mice
received the same concentration of test compound for 105 weeks. Female mice
were initially administered 10,000 or 20,000 ppm. As the animals were
observed to have decreased body weights, these concentrations were lowered
to 2500 and 5000 ppm at week 38 (TWA dose «= 5214 or 10,428 ppm).
In male but not female rats, there were dose-related increases in lym-
phomas or leukemias which were significantly elevated over controls. In
some treated male rats wherein no leukemia occurred, leukocytosis and mono-
cytosis of peripheral blood and hyperplasia of the bone marrow were noted.
Significantly increased incidences of hepatocellular carcinomas or adenomas
-------
2 , 4,6-TrIchlorophenol: page 3 of 5
occurred In both male and female mice.
related.
These Increases were also dose-
A 20% solution of 2,4,6-trIchlorophenol In benzene did not promote skin
tumors in mice initiated with 7,12-dimethylbenz(a)anthracene (Boutwell and
Bosch, 1959). In a study of 120 pesticides, both male and female mice of
two strains were gavaged from day 7-28 of age with 100 mg 2,4,6-trichloro-
phenol/kg bw. This was followed by 18 months of dietary exposure to 260 ppm
(approximately 20-25 mg/kg total). The authors reported results as
inconclusive as to carcinogenicity (Innes, 1969).
3. SUPPORTING DATA
2,4,6-Trichlorophenol was not mutagenic for Salmonella typhimurium
(Rasanen et al., 1977). It was mutagenic for Saccharomyces cerevesiae, but
had no effect on mitotic recombination. It has been reported as mutagenic in
the mouse spot test, but is ranked among the weakest mutagens tested in that
assay (Fahrig, 1978).
B. ORAL QUANTITATIVE ESTIMATE
Slope Factor - 2.OE-2/mg/kg/day
1. UNIT RISK SUMMARY TABLE
Water Concentrations Producing Risk Levels
E-4 E-5 E-6
Unit Risk
Model
1.8E2
1.8E1 1.8
ug/1 ug/1
5.7E-7
/ug/1
LM
extra risk
2. DOSE RESPONSE DATA
Study reference:
Species/strain;
Tumor type; Route
Admin.
Dose
(ppm diet)
Human Equiv.
Dose
(mg/kg/day)
Tumor
Incidence
NCI, 1978:
Mice/B6C3Fl, male; hepato-
cellular carcinomas and
adenomas; diet
0
5,000
10,000
0
650
1350
4/20
32/49
39/47
3. ADDITIONAL COMMENTS
Above human equivalent doses were adjusted for food intake and reported
weight of animals (0.040 kg). While both rodent species showed dose-related
decreases in mean body weight, no Increased mortality nor other toxic signs
were observed. The unit risk value should not be used if the water concen-
tration exceeds 18,000 ug/1 as above this concentration the slope factor may
differ from that stated above.
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2,4,6-Trichlorophenol: page 4 of 5
4. STATEMENT OF CONFIDENCE
Neoplasia were induced in male rats and in mice of both genders. Inci-
dence of hepatocellular adenomas and carcinomas in mice was also elevated in
a dose-dependent fashion. As adequate numbers of animals were observed,
confidence in the risk estimate is rated medium.
C. INHALATION QUANTITATIVE ESTIMATE
Slope Factor = 2.OE-2/mg/kg/day
1. UNIT RISK SUMMARY TABLE
Air Concentrations Producing
E-4
1.8E1
ug/cu.m
E-5
1.8
ug/cu . m
Risk Levels
E-6
1.8E-1
ug/cu . m
Unit Risk
5.7E-6
/ug/cu . m
Model
LM
extra risk
2. DOSE RESPONSE DATA
The inhalation risk estimates were calculated from the oral exposure data.
3. ADDITIONAL COMMENTS
The unit risk value should not be used if the air concentration exceeds
1800 ug/cu.m as above this concentration the slope factor may differ from
that stated above.
4. STATEMENT OF CONFIDENCE
Confidence in this inhalation risk estimate derived from oral data can be
rated no higher than low.
D. DOCUMENTATION AND REVIEW
1. REFERENCES
NCI (National Cancer Institute). 1979. Bioassay of 2,4,6-Trichlorophenol
for Possible Carcinogenicity. U.S. DHEW Publ. No. NCI-CG-TR-155.
U.S. EPA. 1980. Ambient Water Quality Criteria for Chlorinated Phenols.
Environmental Criteria and Assessment Office, Cincinnati, OH. EPA
440/5-80-032.
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2,4,6-Trichlorophenol: page 5 of 5
2. REVIEW
The values in the Ambient Water Quality Criteria Document for Chlori-
nated Phenols (1980) received extensive peer and public review.
Agency CRAVE Work Group Review: 06/26/86, 10/29/86
Verification Date: 10/29/86
3. U.S. EPA CONTACTS
Primary: R. McGaughy (202/FTS) 382-5898
Office of Research and Development
Secondary: C.B. Hiremath (202/FTS) 382-5898
Office of Research and Development
III. DRINKING WATER HEALTH ADVISORIES
Chemical: 2,4,6-Trichlorophenol
CAS No.: 88-06-2
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: 2,4,6-Trichlorophenol
CAS No.: 88-06-2
in preparation
V. SUPPLEMENTARY DATA
Chemical: 2,4,6-Trichlorophenol
CAS No.: 88-06-2
Information is not available at this time.
Synonyms: Phenol, 2,4,6-trichloro-: Dowicide 2S; NCI-C02904; Omal;
phenachlor; RCRA waste number U231
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Triehlorotrifluoroethane (CFC-113); CAS No. 76-13-1 (Revised 04/06/87)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Trichlorotrifluoroethane (CFC-113)
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories; none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
l,l,2-Trichloro-l,2,2-trifluoroethane: page 2 of 5
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: 1,1,2-Trichloro-1,2,2-trifluoroethane (CFC-113)
CAS No.: 76-13-1 Preparation Date: 04/06/87
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect Experimental Doses * UF MF RfD
Psychomotor impair- 5358 mg/cu. m con- 10 1 3E1
ment verted to 273 mg/kg/ mg/kg/day
day (NOAEL)
Epidemiologic study:
Human occupational
exposure
Imbus and Adkins
(1972)
* Dose Conversion Factors & Assumptions: 10 cu. m (8-hour human breathing
volume), 5 days/7 days, 0.5 absorption factor, 70 kg bw; thus, 5358 mg/cu.
m x 10 cu. m x 5 days/7 days x 0.5/70 kg - 273 mg/kg/da7
2. PRINCIPAL AND SUPPORTING STUDIES
Imbus, H.R. and C. Adkins. 1972. Physical examination of workers exposed to
trichlorotrifluoroethane. Arch. Environ. Health. 24(4): 257-261.
Several animal inhalation studies reported negative results in dogs, rab-
bits, and rats chronically exposed to very high concentrations of trichloro-
trifluoroethane (U.S. EPA, 1983). No apparent adverse effects have been
reported in humans occupationally exposed to trichlorotrifluoroethane at
either 500 mg/cu. m levels for 11 years or 5358 mg/cu. m levels for 2.77 years
(Imbus and Adkins, 1972).
Slight impairment of psychomotor performance was reported in male volun-
teers exposed to trichlorotrifluoroethane concentrations of 19,161 mg/cu. m
-------
l,l,2-Trichloro-l,2,2-trifluoroethane: page 3 of 5
for 2.75 hours (Stopps and McLaughlin, 1967). This exposure period was too
brief to consider a NOAEL for chronic exposure. Therefore, the RfD of 30
mg/kg/day is considered protective.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 10. The uncertainty factor of 10 accounts for the expected interhuman
variability to the toxicity of this chemical in lieu of specific data.
MF = 1
4. ADDITIONAL COMMENTS
None.
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Low RfD: Low
Confidence in the chosen study, data base and RfD are all considered low.
Although based on human data, and the fact that several chronic studies in
animals support the human NOEL, uncertainties in both the exposure levels and
route extrapolation preclude a higher confidence rating.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, May 1985.
U.S. EPA. 1985. l,l,2-Trichloro-l,2,2-trifluoroethane: Review and Evalua-
tion of ADI. Contract No. 68-03-3228. Environmental Criteria and Assessment
Office, Cincinnati, OH.
Agency RfD Work Group Review: 06/24/85, 07/08/85
Verification Date: 07/08/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Trichlorotrifluoroethane
CAS No.: 76-13-1
Information is not available at this time.
-------
l,l,2-Trichloro-l,2,2-trifluoroethane: page 4 of 5
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Trichlorotrifluoroethane
CAS No.: 76-13-1
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Trichlorotrifluoroethane
CAS No.: 76-13-1
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: 1,1,2-Trichloro- 1,2,2-Trifluoroethane (CFC-113)
CAS No.: 76-13-1 Preparation Date: 08/28/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
-------
l,l,2-Trichloro-l,2,2-trifluoroethane: page 5 of 5
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Clean Air Act
Regulatory
Status
Date
Final
1985
Risk Considers
Management Econ/Tech
Value Feasibility
Decision not no
to Regulate
Reference
50 FR 24313
06/10/85
Decision:
(NESHAP or NSPS)
B. RISK MANAGEMENT RATIONALE
CAA Regulatory Decision
EPA concluded that current information on health effects at
concentrations measured or estimated to occur in the ambient air as a result
of normal operations of emissions sources does not warrant regulation under
the CAA at this time. This decision did not consider the role of CFC-113 in
reducing stratospheric ozone. This issue is being evaluated separately and
will consider the effect of a number of trace gases on stratospheric ozone.
Contact: Chief, Pollutant Assessment Branch
FTS/629-5645 or 919/541-5645
V. SUPPLEMENTARY DATA
Chemical: Trichlorotrifluoroethane
CAS No.: 76-13-1
Information is not available at this time.
Synonyms: ETHANE, 1,1,2-TRICHLORO-l,2,2-TRIFLUORO-; ARCTON 63; ARKLONE P;
DAIFLON S 3; FLUOROCARBON 113; FREON 113; FREON F113; FREON TF; FREON 113TR-
T; FRIGEN 113a; FRIGEN 113 TR-T; GENETRON 113; HALOCARBON 113; ISCEON 113;
KAISER CHEMICALS 11; KHLADON 113; R 113; REFRIGERANT 113;
TRICHLOROTRIFLUOROETHANE; 1,1,2-TRICHLORO-1,2,2-TRIFLUOROETHANE; 1,1,2-
TRICHLORO-1,2,2-TRIFLUOROETHANE (ACGIH); 1,1,2-TRIFLUORO-l,2,2-
TRICHLOROETHANE; UCON 113; UCON FLUOROCARBON 113; UCON 113/HALOCARBON 113
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Vanadium Pentoxide; CAS No. 1314-62-1 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Vanadium Pentoxide
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: available
-------
Vanadium Pentoxide: page 2 of 7
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Vanadium Pentoxide
CAS No.: 1314-62-1
Preparation Date: 05/12/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Rat chronic oral
study
Stokinger et al.
(1953)
Experimental Doses *
UF
MF
RfD
Decreased hair
cystine
NOAEL: 35.7 ppm
converted to 1.785
mg/kg/day
100 1 2E-2
mg/kg/day
LOAEL: None
* Dose Conversion Factors & Assumptions:
to be 5% bw/day.
Adult rat food consumption assumed
2. PRINCIPAL AND SUPPORTING STUDIES
Stokinger, H.E., W.D. Wagner, J.T. Mountain, F.R. Stacksill, O.J. Dobrogorski
and R.G. Keenan. 1953. Unpublished results. Division of Occupational
Health, Cincinnati, OH. (Cited in Patty's Industrial Hygiene and Toxicology,
3rd ed., 1981)
In this chronic study, an unspecified number of rats were exposed to
dietary levels of 10 or 100 ppm vanadium (about 35.7 or 357 ppm vanadium
pentoxide) for 2.5 years. The results of this unpublished study were sum-
marized by Stokinger et al. (1981). The criteria used to evaluate vanadium
toxicity were growth rate, survival and hair cystine content. The only sig-
nificant change reported was a decrease in the amount of cystine in the hair
of animals ingesting vanadium.
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Vanadium Pentoxtde: page 3 of 7
Of the subchronic and chronic animal studies available, the lower dose
level (35.7 ppm vanadium pentoxide) reported in the Stokinger et al. (1953)
study is the highest oral NOAEL upon which an RfD can be derived. An oral
RfD of 0.02 mg/kg/day (1.0 mg/day for a 70-kg man) can be calculated by
assuming that rats eat food equivalent to 5% of their body weight and by
applying an uncertainty factor of 100.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. An uncertainty factor of 100 was applied, 10 for interspecies
extrapolation and a factor of 10 to provide added protection for unusually
sensitive individuals.
MF = 1
4. ADDITIONAL COMMENTS
In a subchronic feeding study (Mountain et al., 1953), groups of five male
Wistar rats were fed vanadium pentoxide at levels of 0, 25 or 50 ppm for 35
days, after which dietary levels of vanadium were increased to 100 and 150 ppm
and continued for 68 days. There was a decrease in the amount of cystine in
the hair of the high-dosed (50-150 ppm or 2.5-7.5 mg/kg/day, based on food
consumption of 5% bw) rats. A significant decrease was also reported in
erythrocyte and hemoglobin levels of the high dosed-rats. In an abstract of a
subchronic inhalation study (Suguira, 1978), mice and rats exposed to 1-3
mg/cu. m vanadium pentoxide for 3 months, 6 hours/day developed histopatho-
logical changes in their lungs and had a decrease in growth rate. Adverse
effects were not detected in either species similarly exposed at 0.1-0.4
mg/cu. m.
Although several epidemiological studies have been conducted on factory
workers exposed to vanadium pentoxide for several years, the air concentra-
tion levels of vanadium pentoxide were measured only at scattered intervals,
making it impossible to determine a minimum effective dose. Also, in cases of
humans exposed to relatively high atmospheric concentrations of vanadium
pentoxide for short periods of time, all individuals developed respiratory
symptoms that usually subsided within 7-14 days.
5. CONFIDENCE IN THE RfD
Study: Low Data Base: Low RfD: Low
The NTP (1985) has approved vanadium pentoxide for carcinogenicity test-
ing; however, the route of administration has not been determined (i.e.,
oral, inhalation). Because of the lack of details in the reference study and
the scarcity of data available on vanadium pentoxide, low confidence in the
RfD, the data base and the study is recommended.
6. DOCUMENTATION AND REVIEW
U.S. EPA. 1985. Vanadium Pentoxide: Review and Evaluation of ADI. Contract
No 68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
ECAO-Cincinnati Internal Review, November 1985.
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Vanadium Pentoxide: page 4 of 7
Agency RfD Work Group Review: 02/26/86
Verification Date: 02/26/86
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Vanadium Pentoxide
CAS No.: 1314-62-1
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Vanadium Pentoxide
CAS No.: 1314-62-1
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Vanadium Pentoxide
CAS No.: 1314-62-1
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Vanadium Pentoxide
CAS No.: 1314-62-1 Preparation Date: 09/30/86
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Vanadium Pentoxide: page 5 of 7
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1986
Risk
Management
Value
1000 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
FR
in press
B. RISK MANAGEMENT RATIONALE
RQ
The final RQ is based on aquatic toxicity (as established under Section
311(b)(4) of the Clean Water Act), chronic toxicity and acute toxicity. The
available data indicate that the aquatic 96-Hour Median Threshold Limit for
vanadium pentoxide is between 10 and 100 ppm. RQ assignments based on
chronic toxicity reflect two primary attributes of the hazardous substance,
the minimum effective dose (MED) levels for chronic exposure (mg/day for 70-
kg man) and the type of effect (liver necrosis, teratogenicity, etc). In
accordance with the methodology described in the Agency's "Technical
Background Document to Support Rulemaking Pursuant to CERCLA Section 102,
Volume 1" of March 1981 and 50 FR 13468 (04/04/85), a composite score is
determined from an evaluation of these two attributes. Vanadium pentoxide
was determined to have a composite score between 6 and 20, corresponding to
a chronic toxicity RQ of 1000 pounds. In addition, the oral LD50 for rats is
between 10 and 100 mg/kg and the inhalation LClo for rats is between 40 and
400 ppm.
Contact: Office of Emergency and Remedial Response
202\382-2180 or FTS\382-2180
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Vanadium Pentoxide: page 6 of 7
V. SUPPLEMENTARY DATA
Chemical: Vanadium Pentoxide
CAS No.: 1314-62-1 Preparation Date: 11/07/86
USE AND INTERPRETATION OF SUPPLEMENTARY DATA
The Information contained in this section (subsections A and B) has been
extracted from the EPA Chemical Profiles Database, which has been compiled
from a number of secondary sources and has not undergone formal Agency
review. The complete reference listings for the citations below are provided
in Service Code 4. The user is urged to read the background document for
this section (Appendix E in Service Code 4) for further information on the
sources and limitations of the data presented here.
A. ACUTE HEALTH HAZARD INFORMATION
Probable oral lethal dose of vanadium pentoxide for humans Is between 5
and 50 mg/kg or between 7 drops and 1 teaspoonful for a 70-kg (150-lb.)
person (Gosselin, 1984). Toxicity is about the same magnitude as
pentavalent arsenic (Gosselin, 1984, p. 11-148).
Medical Conditions Generally Aggravated by Exposure: Chronic respiratory
disease (Encyc Occupat Health and Safety, 1983).
Signs and Symptoms of Exposure: Can cause death by pulmonary edema.
Contact with eyes and skin causes irritation and redness. Ingestion causes
irritation of mouth and stomach, vomiting, abdominal spasms, and a green
discoloration of the tongue. Inhalation of dust initially Irritates the
nose and throat, causing coughing and shortness of breath followed by
headaches, a greenish discoloration of the tongue, blood in sputum,
bronchospasm and pulmonary edema. Chronic inhalation may cause bronchitis,
emphysema, and bronchial pneumonia (Weiss, 1980, p. 909; DASE, 1980, p. 950;
ACGIH, 1980; Gosselin, 1976; Clayton and Clayton, 1981-82).
B. PHYSICAL-CHEMICAL PROPERTIES
Chemical Formula: V 0
2 5
Molecular Weight: 181.90
Boiling Point: 3182F, 1750C (decomposition)
Specific Gravity (H20=l): 3.357 at 18C
Vapor Pressure (mmHg): Approximately 0 at 20C, 68F
Melting Point: 1274F, 690C
Vapor Density (AIR=1): Not Found
Evaporation Rate (Butyl acetate=l): Not Found
Solubility in Water: 1 g in 125 ml
Flash Point [Method Used]: Not Found
Flammable Limits: Not Flammable
Appearance and Odor: Vanadium pentoxide exists as a yellow-orange powder,
dark gray flakes, or yellow to rust brown crystals (NIOSH/OSHA, 1981; Merck,
1983). It is odorless (CHRIS, 1978)
-------
Vanadium Pentoxide: page 7 of 7
Conditions or Materials to Avoid: Avoid chlorine trifluoride; lithium;
peroxyformic acid; and calcium, sulfur, water complexes (Sax, 1984, p. 2718)
Hazardous Decomposition or Byproducts: When heated to decomposition, it
emits acrid smoke and fumes of vanadium oxides (Sax, 1984, p. 2718).
Use: Vanadium pentoxide is used as a catalyst in the oxidation of sulfur
dioxide to sulfur trioxide, alcohol to acetaldehyde, etc.; for the
manufacture of yellow glass; inhibiting ultraviolet light transmission in
glass; as a depolarizer; as a developer in photography; in form of ammonium
vanadate as mordant in dyeing and printing fabrics and in manufacture of
aniline black (Merck, 1983, p. 1418).
Synonyms: CI 77938; Divanadium Pentaoxide; Divanadium Pentoxide; Vanadic
Anhydride; Vanadium Oxide; Vanadium Pentaoxide
-------
INTEGRATED RISK INFORMATION SYSTEM: Chemical Files
Zinc Cyanide; CAS No. 557-21-1 (Revised 11/16/1986)
USE AND INTERPRETATION OF THE DATA IN IRIS
Health risk assessment information on chemicals is included in IRIS only
after a comprehensive review of chronic toxicity data by work groups
composed of U.S. EPA scientists from several Agency Program Offices. The
summaries presented in Sections I and II represent a consensus reached in
those reviews. The conceptual bases of these risk assessments are described
in Appendices A & B in Service Code 4. The other sections are supplementary
information which may be useful in particular risk management situations, but
have not yet undergone comprehensive U.S. EPA review. The risk management
numbers (Section V) may not be based on the most current risk assessment, or
may be based on a current, but unreviewed, risk assessment, and may take into
account factors other than health effects (e.g., treatment technology). When
considering the use of risk management numbers for a particular situation,
note the date of their development, the date of the most recent risk
assessment, and whether technological factors were considered. For a more
detailed description of procedures used in these assessments and the
development of risk management numbers, see Appendix E in Service Code 4.
STATUS OF DATA FOR Zinc Cyanide
I. Chronic Systemic Toxicity: Noncarcinogenic Health Effects
A. Oral RfD: available
B. Inhalation RfD: none
II. Risk Estimates for Carcinogens: none
III. Drinking Water Health Advisories: none
IV. Risk Management Summaries: available
V. Supplementary Data: none
-------
Zinc Cyanide: page 2 of 6
I. CHRONIC SYSTEMIC TOXICITY: NONCARCINOGENIC HEALTH EFFECTS
INTERPRETATION OF CHRONIC SYSTEMIC TOXICITY DATA
The Reference Dose (RfD) is based on the assumption that thresholds may exist
for certain toxic effects such as cellular necrosis, but may not exist for
other toxic effects such as carcinogenicity. The RfD is considered to be the
level unlikely to cause significant adverse health effects associated with a
threshold mechanism of action in humans exposed for a lifetime. RfDs can
also be derived for the noncarcinogenic health effects of compounds which are
also carcinogens. Therefore, it is essential to refer to section II, and
other sources as well, for risk assessment information pertaining to the
carcinogenicity of this compound. Please refer to the Background Document on
the RfD (Appendix A) in Service Code 4 for an elaboration of these concepts.
A. REFERENCE DOSE (RfD) FOR ORAL EXPOSURE
Chemical: Zinc Cyanide
CAS No.: 557-21-1
Preparation Date: 01/09/86
1. REFERENCE DOSE SUMMARY TABLE
Critical Effect
Experimental Doses *
UF
MF
RfD
Rat chronic oral
study
Howard and Hanzal
(1955)
10.8 mg/kg/day CN
(NOAEL) converted to
24.3 mg/kg/day of
zinc cyanide
100
5E-2
mg/kg/day
Weight loss, thyroid
effects and myelin
degenerat ion
Rat subchronic to
chronic oral bioassay
Philbrick et al.
(1979)
30 mg/kg/day CN
(LOAEL)
(67.5 mg/kg/day ZnCN)
* Dose Conversion Factors & Assumptions: molecular weight conversion factor
= 117/(2 x 26) [ MW Zn(CN) = 117; MW CN = 26 J
2
2. PRINCIPAL AND SUPPORTING STUDIES
Howard, J.W. and R.F. Hanzal. 1955. Chronic toxicity for rats by food
treated with hydrogen cyanide. Agric. Food Chem. 3: 325-329.
Since zinc is present at high levels in foods and is considerably less
toxic than cyanide, an RfD for zinc cyanide of 0.05 mg/kg/day or 3.4 mg/day
-------
Zinc Cyanide: page 3 of 6
can be calculated based on the maximum molar equivalents (2) of cyanide gen-
erated in aqueous solution or dilute acids.
In this 2-year dietary study, rats (10/sex/group) were administered food
fumigated with HCN. The average daily concentrations were 73 and 183 mg CN/kg
diet. From the data reported on food consumption and body weight, daily
estimated doses were 4.3 mg and 10.8 mg CN/kg bw. The average food CN
concentrations were estimated based on the authors' data for concentration at
the beginning and end of each food preparation period and by assuming a first
order rate of loss for the intervening period. There were no treatment
related effects on growth rate, no gross signs of toxicity, and no histo-
pathological lesions.
Studies by Philbrick et al. (1979) showed decreased weight gain and
thyroxin levels and myelin degeneration in rats at 30 mg/kg/day CN. Other
chronic studies either gave higher effect levels or used the subcutaneous
route (Crampton et al., 1979; Lessell, 1971; Herthing et al., 1960). Human
data do not provide adequate information from which to derive an RfD because
effective dose levels of chronically ingested CN are not documented.
Therefore, the study of Howard and Hanzel (1955) provides the highest NOAEL,
10.8 mg/kg/day for CN, and is chosen for the derivation of an RfD for CN of
1.5 mg/day or 0.02 mg/kg/day.
Cyanide is metabolized extensively in the liver, indicating that the only
relevant route of administration for quantitative risk assessment in the
derivation of an oral RfD is the oral route of administration.
3. UNCERTAINTY AND MODIFYING FACTORS
UF = 100. According to the U.S. EPA (1985), an uncertainty factor of 100 is
used to derive the RfD (10 for species extrapolation, 10 for sensitive
population).
MF = 5. A modifying factor of 5 is used to account for the apparent tolerance
to cyanide when it is ingested with food rather than when it is administered
by gavage or by drinking water.
4. ADDITIONAL COMMENTS
Decreased protein efficiency ratio was produced by dietary cyanide treat-
ment of rats during gestation, lactation and postweaning growth phase in the
Tewe and Maner (1981a) experiment: the dose level of cyanide (10.6 mg/kg/
day) producing that effect is slightly lower than the currently accepted
NOAEL of 10.8 mg/kg/day (U.S. EPA, 1985). Furthermore, Tewe and Maner
(1981b) tested sows. Possible effects observed at about 9.45 mg/kg/day were
proliferation of glomerular cells of the kidneys and reduced activity of the
thyroid glands in the gilts. However, the number of animals in this experi-
ment was very small. A Japanese study (Amo, 1973) indicated that 0.05 mg/
kg/day of cyanide obtained from drinking water decreased the fertility rate
and survival rate in the Fl generation and produced 100% mortality in the F2
generation in mice. However, these data are not consistent with the body of
available literature. Thus, until additional chronic studies are available,
an RfD of 3 mg/day for a 70-kg man is recommended.
-------
Zinc Cyanide: page 4 of 6
5. CONFIDENCE IN THE RfD
Study: Medium Data Base: Medium RfD: Medium
The confidence in the study is medium because adequate records of food
consumption and body weight were maintained and animals of both sexes were
tested at two doses for 2 years. The data base is rated medium because a
small but sufficient number of studies support the chosen study. The confi-
dence in the RfD follows. Additional chronic/reproductive studies are needed
to support a higher level of confidence in the RfD.
6. DOCUMENTATION AND REVIEW
ECAO-Cincinnati Internal Review, July 1985.
U.S. EPA. 1985. Cyanides: Review and Evaluation of ADI. Contract No.
68-03-3228. Environmental Criteria and Assessment Office, Cincinnati, OH.
Agency RfD Work Group Review: 08/05/85
Verification Date: 08/05/85
7. U.S. EPA CONTACTS
Primary: C.T. DeRosa FTS/684-7534 or 513/569-7534
Office of Research and Development
Secondary: M.L. Dourson FTS/684-7544 or 513/569-7544
Office of Research and Development
B. REFERENCE DOSE (RfD) FOR INHALATION EXPOSURE
Chemical: Zinc Cyanide
CAS No.: 557-21-1
Information is not available at this time.
II. RISK ESTIMATES FOR CARCINOGENS
Chemical: Zinc Cyanide
CAS No.: 557-21-1
This chemical has not been evaluated by the U.S. EPA for evidence of human
carcinogenic potential.
-------
Zinc Cyanide: page 5 of 6
III. DRINKING WATER HEALTH ADVISORIES
Chemical: Zinc Cyanide
CAS No.: 557-21-1
Information is not available at this time.
IV. RISK MANAGEMENT SUMMARIES
Chemical: Zinc Cyanide
CAS No.: 557-21-1 Preparation Date: 10/06/86
INTERPRETATION OF RISK MANAGEMENT DATA
EPA risk assessments may be continuously updated as new data are published
and as assessment methodologies evolve. Risk management (RM) decisions are
frequently not updated at the same time. Carefully read the dates for the
risk management actions (in this section) and the verification dates for the
risk assessments (in sections I & II), as this may explain apparent inconsis-
tencies. Also note that some risk management decisions consider factors not
related to health risk, such as technical or economic feasibility. Such
considerations are indicated in the table below (Considers Econ/Tech
Feasibility). Please direct any questions you may have concerning the use of
risk assessment information in making a risk management decision to the
contact listed in Part B of this section (Risk Management Rationale). Users
are strongly urged to read the background information on each RM action in
Appendix E in Service Code 4.
A. RISK MANAGEMENT ACTIONS
Risk
Management
Action
Reportable
Quantity (RQ)
Status
Date
Final
1986
Risk
Management
Value
10 Ibs
Considers
Econ/Tech
Feasibility
no
Reference
51 FR 34534
09/29/86
B. RISK MANAGEMENT RATIONALE
Final 10 Ibs no FR
RQ
The final RQ was based on aquatic toxicity, as established under CWA
Section 311(b)(4). Available data indicate that the aquatic 96-Hour Median
Threshold Limit for zinc cyanide is between .1 and 1 ppm.
Contact: RCRA/Superfund Hotline
800-424-9346 or 382-3000 (202 area/FTS)
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Zinc Cyanide: page 6 of 6
V. SUPPLEMENTARY DATA
Chemical: Zinc Cyanide
CAS No.: 557-21-1
Information is not available at this time.
Synonyms: CYANURE DE ZINC (French), RCRA WASTE NUMBER P121, UN 1713 , ZINC
CYANIDE , ZINC DICYANIDE
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