United States
Environmental Protection
Agency
500ECAOCING008
&EPA Research and
Development
HEALTH AND ENVIRONMENTAL EFFECTS DOCUMENT
FOR SELECTED NITRILES
Prepared for
OFFICE OF SOLID WASTE AND
EMERGENCY RESPONSE
Prepared by
Environmental Criteria and Assessment Office
Office of Health and Environmental Assessment
U.S. Environmental Protection Agency
Cincinnati, OH 45268
DRAFT: DO NOT CITE OR QUOTE
NOTICE
This document Is a preliminary draft. It has not been formally released
by the U.S. Environmental Protection Agency and should not at this stage be
construed to represent Agency policy. It1 Is being circulated for comments
on Its technical accuracy and policy Implications.
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DISCLAIMER
This report 1s an external draft for review purposes only and does not
constitute Agency policy. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
U.S. Environmental Protection
Region 5. library (PL-12J)
f"foulevard, 12th
60604-3590
11
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PREFACE
Health and Environmental Effects Documents (HEEDs) are prepared for the
Office of Solid Waste and Emergency Response (OSWER). This document series
1s Intended to support listings under the Resource Conservation and Recovery
Act (RCRA) as well as to provide health-related limits and goals for emer-
gency and remedial actions under the Comprehensive Environmental Response,
Compensation and Liability Act (CERCLA). Both published literature and
Information obtained from Agency Program Office files are evaluated as they
pertain to potential human health, aquatic life and environmental effects of
hazardous waste constituents. The literature searched for 1n this document
and the dates searched are Included In "Appendix: Literature Searched."
Literature search material 1s current up to 8 months previous to the final
draft date listed on the front cover. Final draft document dates (front
cover) reflect the date the document 1s sent to the Program Officer (OSWER).
Several quantitative estimates are presented provided sufficient data
are available. For systemic toxicants, these Include Reference doses (RfDs)
for chronic and subchronlc exposures for both the Inhalation and oral
exposures. The subchronlc or partial lifetime RfD, Is an estimate of an
exposure level that would not be expected to cause adverse effects when
exposure occurs during a limited time Interval, for example, one that does
not constitute a significant portion of the Hfespan. This type of exposure
estimate has not been extensively used, or rigorously defined as previous
risk assessment efforts have focused primarily on lifetime exposure
scenarios. Animal data used for subchronlc estimates generally reflect
exposure durations of 30-90 days. The general methodology for estimating
subchronlc RfDs 1s the same as traditionally employed for chronic estimates,
except that subchronlc data are utilized when available.
In the case of suspected carcinogens, RfDs are not estimated. A
carcinogenic potency factor, or q-j* (U.S. EPA, 1980), Is provided Instead.
These potency estimates are derived for both oral and Inhalation exposures
where possible. In addition, unit risk estimates for air and drinking water
are presented based on Inhalation and oral data, respectively.
Reportable quantities (RQs) based on both chronic toxldty and carclno-
genldty are derived. The RQ 1s used to determine the quantity of a hazar-
dous substance for which notification 1s required 1n the event of a release
as specified under the CERCLA. These two RQs (chronic toxldty and carclno-
genlclty) represent two of six scores developed (the remaining four reflect
1gn1tab1l1ty, reactivity, aquatic toxldty, and acute mammalian toxldty).
Chemical-spedf 1c RQs reflect the lowest of these six primary criteria. The
methodology for chronic toxldty and cancer-based RQs are defined 1n U.S.
EPA, 1984 and 1986, respectively.
111
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EXECUTIVE SUMMARY
Nlcotlnonltrlle Is a solid; sucdnonltrlle Is a colorless, waxy solid;
and methacrylonltrlle Is a 'clear, colorless liquid at room temperature
(Hawley, 1981). These compounds are expected to undergo reactions typical
of nitrlles. They are soluble In many common organic solvents and are
slightly soluble In water (Dean, 1985; Hawley, 1981; Wlndholz, 1983). The
1985 Directory of Chemical Producers (SRI, 1985) reports that Nepera Inc. 1n
Harrlman, NY, and Rellly Tar and Chemical Corp. In Indianapolis, IN, are the
only current domestic manufacturers of n1cot1non1tr1le and that R.S.A. Corp.
1n Ardsley, NY, Is the only current domestic manufacturer of sucdnonltrlle.
Nlcotlnonltrlle 1s used as a chemical Intermediate and succlnonltrlle 1s
used In organic synthesis {Kuney, 1985; Hawley, 1981; Hlndholz, 1983).
Methacrylonltrlle Is used as a vinyl nltMle monomer and as a copolymer with
chemicals such as styrene and butadiene (Hawley, 1981).
If released to the atmosphere, these compounds are expected to exist.
almost entirely In the vapor phase (Elsenreich et al., 1981). The half-
lives for nlcotlnonltrlle, sucdnonltrlle and methacrylonltrlle vapor react-
ing with photochemlcally generated hydroxyl radicals have been estimated to
be 2 days, 1 hour and 5 hours, respectively (U.S. EPA, 1987b). Small
amounts of methacrylonltrlle may react with ozone (estimated half-life,
1 day) (U.S. EPA, 1987b). Small amounts of these compounds may be removed
from the atmosphere by wet deposition. If released to water, nlcotlno-
nltrlle, sucdnonltrlle and methacrylonltrlle may be susceptible to chemical
hydrolysis (Lyman et al., 1982). Volatilization of methacrylonltrlle from
water appears to be an Important removal process (half-life 1n a typical
river, 2 days) although volatilization of nlcotlnonltrlle or sucdnonltrlle
1v
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1s not expected to be significant. Adsorption to sediments or suspended
solids In water and bloaccumulatlon In aquatic organisms are not expected to
be significant. Results of two blodegradatlon screening studies Indicate
that sucdnonltrlle 1s resistant to blodegradatlon under aerobic conditions.
If released to soil, the selected nltrlles are expected to be very highly
mobile and readily leach through most soil. These compounds may be suscep-
tible to hydrolysis In moist soil. Evaporation of methacrylonltrlle from
moist or dry soil surfaces 1s expected to be significant.
Monitoring data pertaining to human exposure by Inhalation (succlno-
nltrlle and methacrylonltrlle), Ingestlon or dermal contact could not be
located 1n the available literature as dted 1n Appendix A. N1cot1non1tr1le
has been Identified as a component of tobacco smoke (Schmeltz et al., 1979),
which suggests that a significant number of people would be exposed to this
compound by Inhalation.
There 1s potential that these selected nltrlles could be released to the
environment 1n the effluent or In fugitive emissions from production and use
facilities.
Pertinent data regarding toxldty of the selected nltrlles to aquatic
organisms could not be located 1n the available literature as cited 1n
Appendix A.
Pertinent data regarding the rate and extent of absorption of the
nltrlles were not located, but the demonstrated toxldty of these chemicals
(Chapter 6) Indicates that methacrylonltrlle Is absorbed after Inhalation
exposure 1n dogs and rats, and after oral exposure In rats and mice, and
that sucdnonltrlle and nlcotlnonltrlle are absorbed following oral exposure
In rats and mice. Methacrylonltrlle was UpophHlc and distributed rapidly
to various organs of the rat (Haguenoer et al., 1976). The metabolism of
succlnonltrlle has been studied _Ui vivo and Ui vitro 1n experimental animals
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(mice, rats and rabbHs), and the primary metabolic pathway appears to be
liberation of free HCN from the parent compound (WIllhHe and Smith, 1981;
Contessa and Santl, 1973; Floreanl et al., 1980, 1981; Tanll and Hashimoto,
1985). Liberation of free cyanide also appears to be the primary pathway of
methacrylonltrlle metabolism In vivo and in vitro In experimental animals
(Tanll and Hashimoto, 1984a,b, 1986; Peter and Bolt, 1985; Pozzanl et al.,
1968; Haguenoer et al., 1976). Succlnonltrlle administered Intravenously to
humans (Lodl et al., 1973) or 1ntraper1toneally or Intravenously to
experimental animals (Cavanna and Pocch1ar1, 1972; Curry, 1974, 1975;
Contessa et al., 1978; Contessa and Santl, 1973) Is excreted 1n the urine
primarily as the parent compound and thlocyanate 1on. Methacrylon1tr1le
administered Intraperltoneally to rats was excreted 1n the urine as the
parent compound, free cyanide and bound cyanide 1n the form of thlocyanate
1on (Haguenoer et al., 1976).
One study was located regarding the toxlclty of methacrylonltrlle by
subchronlc Inhalation exposure (Pozzanl et al., 1968). In this study,
exposure of rats to concentrations >52.6 ppm (>144 mg/m3), but not 19.3
ppm (53 mg/m3) for 7 hours/day, 5 days/week for 91 days resulted 1n
Increased liver weight and death. Exposure of dogs for 7 hours/day, 5
days/week for 90 days resulted In transiently elevated SGOT and SGPT levels
at 8.8 ppm (24 mg/m3) and loss of motor control of hind limbs and hlsto-
pathologlcal brain lesions at 13.5 ppm (37 mg/m3). No effects were
observed 1n dogs at 3.2 ppm (9 mg/m3).
The acute toxlclty of the nltrlles appears to be due to release of
cyanide during metabolism of the parent compound (Marlgo and Pappalardo,
1966; Haguenoer et al., 1976; Pozzanl et al., 1968).
v1
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Information regarding the carclnogenlcHy of succlnonHrlle, nlcotlno-
nltrlle and methacrylonHMle, and the mutagenlclty of methacrylonUrlle and
succlnonltrUe were not located. One study Indicated that n1cot1non1tr1le
was not mutagenlc In S. typhlmuMum (Florin et al., 1980).
A study by Doherty et al. (1983) Indicated that succlnonltrUe was
teratogenlc 1n hamsters treated Intraperltoneally at >4.56 mmol/kg. No
Information was located regarding the teratogenldty of either nlcotlno-
nltrlle or methacrylonHMle.
Based on the NOEL 1n dogs of 3.2 ppm (9 mg/m3), 7 hours/day, 5 days/
week for 90 days, a subchronlc Inhalation RfD of 0.02 mg/m3 or 0.4 mg/day,
a chronic Inhalation RfD of 0.002 mg/m3 or 0.04 mg/day, a subchronlc oral
RfD of 0.003 mg/kg/day or 0.2 mg/day and a chronic oral RfD of 0.0003
mg/kg/day or 0.02 mg/day were derived for methacrylonltrlle. Uncertainty
factors of 100 (10 for Interspedes extrapolation and 10 to protect the most
sensitive Individuals) for the subchronlc RfDs and 1000 (an additional
factor of 10 for the use of a subchronlc s.tudy) for the chronic RfDs were
used. Because the critical study was well-conducted, medium confidence was
placed 1n the Inhalation RfDs. Low confidence was placed 1n the oral RfDs,
however, because the study used Inhalation exposure. An RQ of 100 was
derived for methacrylonltrlle based on the dose-response data for loss of
motor control and brain lesions In dogs exposed by Inhalation 1n the study
by Pozzanl et al. (1968). Data were Insufficient to derive risk assessment
values for succlnonltrUe and n1cot1non1tr1le.
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TABLE OF CONTENTS
1. INTRODUCTION 1
1.1. STRUCTURE AND CAS REGISTRY NUMBER 1
1.2. PHYSICAL AND CHEMICAL PROPERTIES 1
1.3. PRODUCTION DATA 1
1.4. USE DATA 4
1.5. SUMMARY 4
2. ENVIRONMENTAL FATE AND TRANSPORT 5
2.1. AIR 5
2.1.1. Reaction with Hydroxyl Radicals 5
2.1.2. Reaction with Ozone 5
2.1.3. Photolysis 6
2.1.4. Physical Removal 6
2.2. WATER 6
2.2.1. Hydrolysis 6
2.2.2. Photolysis 6
2.2.3. Mlcroblal Degradation 6
2.2.4. Bloaccumulatlon 7
2.2.5. Adsorption 7
2.2.6. Volatilization 7
2.3. SOIL 7
2.3.1. Chemical Degradation 7
2.3.2. Mlcroblal Degradation 8
2.3.3. Adsorption 8
2.3.4. Volatilization 8
2.4. SUMMARY 8
3. EXPOSURE 10
4. AQUATIC TOXICITY 11
5. PHARMACOKINETCS 12
5.1. ABSORPTION 12
5.2. DISTRIBUTION 12
5.3. METABOLISM 13
5.4. EXCRETION 15
5.5. SUMMARY 16
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TABLE OF CONTENTS (cont.)
Page
6. EFFECTS 17
6.1. SYSTEMIC TOXICITY 17
6.1.1. Inhalation Exposures 17
6.1.2. Oral Exposures 18
6.1.3. Other Relevant Information 18
6.2. CARCINOGENICITY 19
6.2.1. Inhalation 19
6.2.2. Oral 19
6.2.3. Other Relevant Information 19
6.3. MUTAGENICITY 21
6.4. TERATOGENICITY 21
6.5. OTHER REPRODUCTIVE EFFECTS 22
6.6. SUMMARY 22
7. EXISTING GUIDELINES AND STANDARDS 24
7.1. HUMAN 24
7.2. AQUATIC 24
8. RISK ASSESSMENT 25
8.1. CARCINOGENICITY 25
8.2. SYSTEMIC TOXICITY 25
8.2.1. Inhalation Exposure 25
8.2.2. Oral Exposure 26
9. REPORTABLE QUANTITIES 28
9.1. BASED ON SYSTEMIC TOXICITY 28
9.2. BASED ON CARCINOGENICITY 31
10. REFERENCES 35
APPENDIX A: LITERATURE SEARCHED 44
APPENDIX B: SUMMARY TABLE FOR METHACRYLONITRILE 47
1x
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LIST OF TABLES
No. Title Page
1-1 CAS Registry Number, Synonyms and Structure of Selected
NHrlles 2
1-2 Relevant Physical Properties of Selected NHrlles 3
6-1 LOso or LCso Values for Methacrylonltrlle 20
9-1 Inhalation Toxlclty Summary for Methacrylonltrlle 29
9-2 Inhalation Composite Scores for Methacrylonltrlle 30
9-3 Methacrylonltrlle: Minimum Effective Dose (MED) and
Reportable Quantity (RQ) 32
9-4 Succlnonltrlle: Minimum Effective Dose (MEO) and
Reportable Quantity (RQ) 33
9-5 Nlcotlnonltrlle: Minimum Effective Dose (MED) and
Reportable Quantity (RQ) 34
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LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
BCF B1oconcentrat1on factor
BUN Blood urea nitrogen
CNS Central nervous system
CS Composite score
Koc Soil sorptlon coefficient
Kow Octanol/water partition coefficient
Concentration lethal to 50% of recipients
Dose lethal to 50% of recipients
LOAEL Lowest-observed-adverse-effect level
MED Minimum effective dose
NOEL No-observed-effect level
ppm Parts per million
RfD Reference dose
RQ Reportable quantity
RV(j Dose-rating value
RVe Effect-rating value
SGOT Serum glutamlc oxaloactlc transamlnase
SGPT Serum glutamlc pyruvlc transamlnase
TLV Threshold limit value
TOD Theoretical oxygen demand
TWA Time-weighted average
UV Ultraviolet
x1
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1. INTRODUCTION
1.1. STRUCTURE AND CAS REGISTRY NUMBER
The synonyms, structure, CAS Registry number, empirical formula and
molecular weight of nlcotlnonltrlle, succlnonltrlle and methacrylonltrlle
are provided In Table 1-1.
1.2. PHYSICAL AND CHEMICAL PROPERTIES
Nltrlles are extremely versatile reactants and can be used to prepare
amines, amides, carboxyllc acids and esters, aldehydes, ketones, Imlnes,
heterocycles and other compounds (Smiley, 1981). Nlcotlnonltrlle, suc-
clnonltrlle and methacrylonltrlle are expected to undergo reactions typical
of nltrlles. Nlcotlnonltrlle Is a solid; succlnonltrlle 1s a colorless,
waxy solid; and methacrylonltrlle Is a clear, colorless liquid at room
temperature (Hawley, 1981). These compounds are soluble In many common
organic solvents (Dean, 1985; Hawley, 1981; Wlndholz, 1983). Relevant
physical properties are listed In Table 1-2.
1.3. PRODUCTION DATA
The 1985 Directory of Chemical Producers (SRI, 1985) reports that Nepera
Inc. in Harrlman, NY, and Rellly Tar and Chemical Corp. 1n Indianapolis, IN,
are the only current domestic manufacturers of nlcotlnonltrlle and that
R.S.A. Corp. In Ardsley, NY, Is the only current domestic manufacturer of
succlnonltrlle. The 1987 OPD Chemical Buyers Directory (CMR, 1986) lists
three suppliers for nlcotlnonltrlle, five suppliers for succlnonltrlle and
four suppliers for methacrylonltrlle. Nlcotlnonltrlle can be prepared by
the ammoxldatlon or ammonodehydrogenatlon of an alkylpyrldlne, primarily
3-methylpyrldlne or 2-methyl-5-ethylpyr1d1ne (Offermanns et al., 1984);
succlnonltrlle can be prepared from ethylene dlbromlde and potassium cyanide
In alcohol (Wlndholz, 1983); and methacrylonltrlle can be prepared by the
ammoxldatlon of Isobutylene (Nemec and Kirch, 1981).
0033d -1 - 09/08/87
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1.4. USE DATA
NkotinonltMle Is used as an Intermediate In the preparation of nlacln
and nladnamlde (Kuney, 1985); succlnonltrlle Is used In organic synthesis
(Hawley, 1981); and methacrylonltrlle Is used as a vinyl nltrlle monomer, as
a copolymer with chemicals such as styrene and butadiene, and as an In-
termediate In the manufacture of elastomers, coatings, plastics, acids,
amides, amines, esters and nltrlles (Hawley, 1981; Wlndholz, 1983).
1.5. SUMMARY
N1cot1non1tr1le Is a solid; succlnonHrlle Is a colorless, waxy solid;
and methacrylonltrlle Is a clear, colorless liquid at room temperature
(Hawley, 1981). These compounds are expected to undergo reactions typical
of nltrlles. They are soluble In many common organic solvents and are
slightly soluble In water (Dean, 1985; Hawley, 1981; Wlndholz, 1983). The
1985 Directory of Chemical Producers (SRI, 1985) reports that Nepera Inc. In
Harrlman, NY, and Rellly Tar and Chemical Corp. In Indianapolis, IN, are the
only current domestic manufacturers of nlcotlnonltrlle and that R.S.A. Corp.
In Ardsley, NY, 1s the only current domestic manufacturer of succlnonltrlle.
Nlcotlnonltrlle Is used as a chemical Intermediate and succlnonltrlle Is
used 1n organic synthesis (Kuney, 1985; Hawley, 1981; Hlndholz, 1983). Met-
hacrylonltrlle 1s used as a vinyl nltrlle monomer and as a copolymer with
chemicals such as styrene and butadiene (Hawley, 1981).
0033d -4- 09/08/87
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2. ENVIRONMENTAL FATE AND TRANSPORT
Very limited data pertaining to the environmental fate and transport of
nlcotlnonltrlle, sucdnonHrlle or methacrylonltMle were located In the
available literature as cited In Appendix A. When possible, Information
concerning fate and transport of these chemicals was derived from physical
property data or molecular structure.
2.1. AIR
Based on the vapor pressures listed 1n Table 1-1, these compounds are
expected to exist almost entirely 1n the vapor phase 1n the atmosphere
(E1senre1ch et al., 1981).
2.1.1. Reaction with Hydroxyl Radicals. The half-lives for
nlcotlnonltrlle, succlnonltMle and methacrylonltrUe vapor reacting with
photochemically generated hydroxyl radicals 1n the atmosphere have been
estimated to be 2 days, 1 hour and 5 hours, respectively, using an ambient
hydroxyl radical concentration of S.OxlO5 molecules/cm3 and reaction
rate constants of S.OxlO'12, 2.4xlO~10 and S.OxlO'11 cmVmole-
cule-sec at 25°C (U.S. EPA, 1987b). The hydroxyl radical-Initiated
photooxldatlon of methacrylonltrlle 1n the presence of nitrogen monoxide
resulted 1n the formation of formaldehyde and acetyl cyanide as primary
products (Hashimoto et al., 1984).
2.1.2. Reaction with Ozone. Nlcotlnonltrlle and succlnonltrUe are not
susceptible to oxidation by ozone (U.S. EPA, 1987b). The half-life for
methacrylonltrlle vapor reacting with ozone 1n the atmosphere has been
estimated to be -1 day, using an ambient ozone concentration of dxlO11
molecules/cm3 and an estimated reaction rate constant of 1.3xlO~17
cm3/molecule-sec at 25°C (U.S. EPA, 1987b).
0033d -5- 09/09/87
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2.1.3. Photolysis. N1cot1non1tMle 1n methanol absorbs very little UV
light of wavelengths In the environmentally significant range >290 nm
(Sadtler, 1961). Therefore, direct photolysis of this compound 1n the
atmosphere may not be significant.
2.1.4. Physical Removal. Based on the water solubilities listed 1n Table
1-2, potentially significant amounts of these compounds could be removed
from the atmosphere by wet deposition; however, rapid reaction with hydroxyl
radicals would limit the Importance of wet deposition as a removal process.
2.2. WATER
2.2.1. Hydrolysis. Because organic compounds containing the nltrlle
group are potentially susceptible to hydrolysis 1n water under environmental
conditions (Lyman et al., 1982), nlcotlnonltrlle, succ1non1tr1le and
methacrylon1tr1le may be susceptible to hydrolysis; however, no quantitative
rate data for these reactions that would permit estimation of half-lives
were available 1n the literature.
2.2.2. Photolysis. Nlcotlnonltrlle In methanol does not significantly
absorb UV light 1n the environmentally significant range (wavelengths >290
nm) (Sadtler, 1961), which Indicates that potential for photolysis of this
compound 1n water may not be significant.
2.2.3. M1crob1al Degradation. Based on TOD, 500 mg/j, succlnonltrlle
Incubated 1n activated sludge under aerobic conditions for 24 hours
underwent 3.8X degradation (Nalaney and Gerhold, 1969). When Incubated for
72 hours 1n activated sludge samples obtained from three different
wastewater treatment facilities 1n Tennessee, an Initial concentration of
500 mg/j, succ1non1tr1le was found to be resistant to biological oxidation
(Lutln, 1970), which Indicates that these compounds may be resistant to
blodegradatlon In natural waters.
0033d -6- 09/09/87
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2.2.4. B1oaccumulat1on. Using the water solubilities listed 1n Table 1-2
and the following linear regression equation (Lyman et al., 1982): log BCF =
2.791 - 0.564 log S, BCF values of <2 have been estimated for the selected
nltrHes. Based on these BCF values, bloaccumulatlon of these compounds 1n
aquatic organisms Is not expected to be significant.
2.2.5. Adsorption. Based on estimated K values of 7-16 (Section
2.3.3.), the selected nltMles are not expected to adsorb significantly to
suspended solids or sediments 1n water.
2.2.6. Volatilization. Henry's Law constant for nlcotlnonltrlle has been
estimated to be 2xlO~9 atm-mVmol at 25°C using an estimated vapor
pressure of 0.0016 mm Hg (Neely and Blau, 1985) and a water solubility of
109,000 mg/l (Offermanns et al., 1984). Based on a method of group con-
tributions to Intrinsic hydrophlllc character (Mine and Mookerjee, 1975),
Henry's Law constant for succ1non1tr1le has been estimated to be 3.3xlO~»
atm-mVmol at 25°C. Volatilization of nlcotlnonltrlle and sucdnonHrlle
from water can be considered Insignificant based on these values of Henry's
Law constant (Lyman et al., 1982). Based on a method of bond contributions
to Intrinsic hydrophlllc character (H1ne and Mookerjee, 1975), Henry's Law
constant for methacrylonltrlle has been estimated to be 1.5xlO~5 atm-m3/
mol at 25°C. Based on this value of Henry's Law constant and following the
method of Lyman et al. (1982), the volatilization half-life from water 1 m
deep, flowing at a speed of 1 m/sec, with a wind speed of 3 m/sec has been
estimated to be 2 days.
2.3. SOIL
2.3.1. Chemical Degradation. Since nltrlles are potentially susceptible
to hydrolysis In water under environmental conditions (Lyman et al., 1982),
they may also be susceptible to hydrolysis In moist soils.
0033d -7- 09/08/87
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2.3.2. Mlcroblal Degradation. Nocardla rhodochrous strain LL100-21
Isolated from soil was found to use sucdnonltrlle as Us sole nitrogen and
carbon source (DIGeronlmo and Antolne, 1976). It 1s difficult to predict
the blotlc fate of these nltrlles 1n natural soils from this experiment.
Based on the conclusions regarding their blodegradablHty In water (see
Section 2.2.3.), blodegradatlon of these compounds In soils may be a slow
process.
2.3.3. Adsorption. Using the water solubilities listed 1n Table 1-2 and
the following linear regression equation (Lyman et a!., 1982): log K =
-0.55 log S + 3.64, soil adsorption coefficients of 7, 7 and 16 have been
estimated for nlcotlnonltrlle, sucdnonltrlle and methacrylonltrlle, res-
pectively. These K values suggest that these compounds would be highly
mobile and would leach readily through most soil (Swann et al., 1983).
2.3.4. Volatilization. The relatively high vapor pressure of met-
hacrylon1tr1le (60 mm Hg at 21.5°C (Perry and Green, 1984)) suggests that
volatilization of this compound from dry soil surfaces may be significant.
Evaporation from moist soil surfaces may also be significant since this
compound does not have a tendency to adsorb to soil and apparently
evaporates rapidly from water (see Section 2.3.3. and 2.2.6.).
2.4. SUMMARY
If released to the atmosphere, these compounds are expected to exist
almost entirely In the vapor phase (E1senre1ch et al., 1981). The
half-lives for nlcotlnonltrlle, sucdnonltrlle and methacrylonltrlle vapor
reacting with photochemically generated hydroxyl radicals have been
estimated to be 2 days, 1 hour and 5 hours, respectively (U.S. EPA, 1987b).
Small amounts of methacrylonltrlle may react with ozone (estimated
half-life, 1 day) (U.S. EPA, 1987b). Small amounts of these compounds may
0033d -8- 09/10/87
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be removed from the atmosphere by wet deposition. If released to water,
nicotlnonltrlle, succlnonltrlle and methacrylonHrlle may be susceptible to
chemical hydrolysis (Lyman et al., 1982). Volatilization of
methacrylonHrlle from water appears to be an Important removal process
(half-life In a typical river, 2 days) although volatilization of
nicotlnonltrlle or succlnonltrlle 1s not expected to be significant.
Adsorption to sediments or suspended solids In water and bloaccumulatlon In
aquatic organisms are not expected to be significant. Results of two
blodegradatlon screening studies Indicate that succlnonltrlle 1s resistant
to blodegradatlon under aerobic conditions. If released to soil, the
selected nltrlles are expected to be highly mobile and leach readily through
most soil. These compounds may be susceptible to hydrolysis 1n moist soil.
Evaporation of methacrylonHrlle from moist or dry soil surfaces 1s expected
to be significant.
0033d -9- 09/10/87
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3. EXPOSURE
Monitoring data pertaining to human exposure by inhalation (suc-
cinonitrlle and methacrylonitrile), ingest ion or dermal contact could not be
located in the available literature as cited in Appendix A. Nicotmonitr ilo
has been identified as a component of tobacco smoke (Schmcltz et al. 1979),
which suggests that a significant number of people would be exposed to this
compound by inhalation.
The selected nHriles could potentially be released to the environment
in the effluent or in fugitive emissions from production and use facilities.
0033d 10- 09/08/87
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4. AQUATIC TOXICITY
Pertinent data regarding toxlclty of the selected nltrlles to aquatic
organisms could not be located 1n the available literature as dted In
Appendix A.
0033d -11- 05/26/87
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5. PHARMACOKINETICS
5.1. ABSORPTION
MethacrylonltMle Is absorbed after Inhalation exposure, as Indicated by
the finding of cyanide liberated from methacrylonltrlle 1n the blood of dogs
exposed by Inhalation to methocrylonltrlle (Pozzanl et a!., 1968) and by
symptoms of cyanide poisoning 1n rats exposed by Inhalation to
methacrylonltrlle (Peter and Bolt, 1985) (Chapter 6). The only data that
Indicate absorption of methacrylonltrlle after oral exposure In rats and
mice Is Information regarding oral LD5_ values (Anonymous, 1986; Hartung,
1982; Pozzanl et al., 1968) (Section 6.1.3.).
Pertinent data regarding the absorption of succlnonHrlle and
n1cot1non1tr1le following an Inhalation exposure could not be located 1n the
available literature as cited 1n Appendix A. The only data that Indicate
absorption of succlnonltrlle and nlcotlnonltrlle following oral exposure are
LD5Q studies using rats and mice (Hartung, 1982; NIOSH, 1987) (Section
6.1.3.).
5.2. DISTRIBUTION
The distribution of methacrylonltrlle In the organs of rats following
Intraperltoneal Injection has been studied by Haguenoer et al. (1976). At
high doses of methacrylonltrlle (1440, 600 and 300 mg/kg), rats died within
5-30 minutes following Injection. Methacry1on1tr1le, free hydrogen cyanide
and relatively low levels of bound hydrogen cyanide were found In the heart,
lungs, liver, spleen, kidneys, stomach, Intestines, skin, muscle, brain and
testicles. Haguenoer et al. (1976) concluded that methacrylonltrlle was
UpophlUc and was distributed rapidly to the various organs before death.
At lower doses of methacrylonltrlle (150 and 100 mg/kg), death was delayed
between 2 and 24 hours following Injection. Methacrylonltrlle was found to
be distributed to the same organs as when higher doses were administered,
0033d -12- 09/09/87
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although tissue concentrations of methacrylonltrlle were predictably lower.
Tissue concentrations of bound HCN were higher at the lower
methacrylonltrlle doses, which Indicates that the rats had more time before
death to bind the liberated HGN 1n the form of thlosulfate.
Pertinent data regarding the distribution of sucdnonltrlle or
nlcotlnonltrlle could not be located In the available literature as cited In
Appendix A.
5.3. METABOLISM
In vitro studies have demonstrated that rabbit, rat and mouse liver
slices and mlcrosomes are capable of liberating cyanide when Incubated with
sucdnonltrlle (Wlllhlte and Smith, 1981; Contessa and Santl, 1973; Floreanl
et al., 1980, 1981; Tanll and Hashimoto, 1985). Liver slices or mlcrosomes
taken from mice or rats pretreated with CC1. had a markedly diminished
capacity to liberate cyanide from succlnonltrlle (Tanll and Hashimoto, 1985;
WHlhUe and Smith, 1981; Contessa and Santl, 1973; Contessa et al., 1978).
In contrast to CC1. pretreatment, liver slices taken from rats pretreated
with ethanol showed a markedly elevated capacity for liberating cyanide from
sucdnonltrlle (Contessa et al., 1978).
Cyanide was found In the brain, liver and other organs of experimental
animals (mice and rabbits) Injected Intravenously or Intraperltoneally, or
dosed orally with succlnonltrlle (Wlllhlte and Smith, 1981; Contessa and
Santl, 1973; Tanll and Hashimoto, 1985). In agreement with ^n vitro
studies, pretreatment of these animals with CC1. Inhibited the liberation
of cyanide in vivo.
A series of U> vitro experiments by Tan11 and Hashimoto (1984a,b, 1986)
demonstrated that mouse hepatic mlcrosomes are capable of liberating cyanide
from methacrylonltrlle. As with sucdnonltrlle, mlcrosomes from mice
pretreated with CC1 were unable to liberate cyanide from methacrylonltrlle
0033d -13- 09/09/87
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(Tanll and Hashimoto, 1984a,b) and mlcrosomes prepared from mice pretreated
with ethanol had an enhanced ability to liberate cyanide from
methacrylonltMle (Tan11 and Hashimoto, 1986).
Rats exposed by Inhalation to doses between 3180 and 5700 ppm
(8726-15,641 mg/m3) methacrylonltrlle demonstrated signs that were similar
to cyanide poisoning, Indicating that cyanide had been liberated from the
parent compound (Peter and Bolt, 1985). Further evidence Indicating the in
vivo liberation of cyanide from methacrylonltrlle was the effectiveness of
cyanide antidotes 1n the treatment of acute methacrylonltrlle toxlclty In
rats and rabbits (Pozzanl et a!., 1968).
Haguenoer et al. (1976) found dose-related differences 1n the metabolism
of methacrylonltrlle In rats. Rats were Injected 1ntraper1toneally with
methacrylon1tr1le at doses of 1440, 600, 300, 150 or 100 mg/kg. Death at
each of the dose levels was from cyanide liberated from the parent compound,
but the time until death Increased with decreasing methacrylonltrlle dose.
Cyanide was found to be liberated very rapidly from methacrylonltrlle in
vVvo, and at the three higher doses (1440, 600 and 300 mg/kg), death
occurred ~5, 15 and 30 minutes, respectively, following Injection. At the
lower doses, death was delayed until -2-24 hours following Injection and
more bound HCN In the form of thlocyanate was found 1n the organs of the
rats. Haguenoer et al. (1976) hypothesized that at the lower doses, the
rats had more time to detoxify the cyanide liberated from methacrylonltrlle
by binding the cyanide In the form of thlocyanate.
Pertinent data regarding the metabolism of n1cot1non1tr1le could not be
located 1n the available literature as cited 1n Appendix A.
0033d -14- 09/09/87
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5.4. EXCRETION
SucdnonltMle Injected Intravenously Into dogs at doses of 3 and 10
mg/kg had a half-life 1n the blood of 21 and 19 hours, respectively (Lodl et
al., 1973). The half-life of sucdnonltMle In the blood of humans Injected
with 250 mg Intravenously was -24 hours. In humans, 95% of an Intravenously
administered dose of sucdnonltrlle was eliminated as thlocyanate 1on 1n the
urine, while 2-3% was eliminated unchanged 1n the urine (Lod1 et al., 1973).
Several Investigators (Cavanna and Pocchlarl, 1972; Curry, 1974, 1975;
Contessa et al., 1978; Contessa and Santl, 1973) reported that experimental
animals (mice, rats and rabbits) Injected 1ntraper1toneally or Intravenously
with sucdnonltrlle excreted the unmetabollzed parent compound or thlo-
cyanate In the urine. CC1. pretreatment was found to Inhibit the urinary
excretion of thlocyanate 1n the rat (Contessa et al., 1978). Also, urinary
excretion of cyanoacetlc add was observed In mice Injected with sucdno-
nltrlle (Merkow et al., 1959).
Methacrylonltrlle and free and bound HCN were eliminated 1n the urine of
rats Injected IntraperHoneally with methacrylonltrlle (Haguenoer et al.,
1976). Methacrylonltrlle was eliminated In very small quantities 1n the
urine, and 4-5 days following Injection was not detected 1n the urine. Free
HCN was not present 1n the urine 1n significant amounts after the first day.
The levels of combined HCN 1n the urine were high the first 2 days and then
declined rapidly to normal. Of the Injected dose, 10-16X of methacrylo-
nltrlle was eliminated 1n the form of free and combined HCN In the urine.
Pertinent data regarding the excretion of n1cot1non1tr1le could not be
located 1n the available literature as cited In Appendix A.
0033d -15- 05/26/87
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5.5. SUMMARY
Pertinent data regarding the rate and extent of absorption of the
nltrlles were not located, but the demonstrated tox1c1ty of these chemicals
(Chapter 6) Indicates that methacrylonltrlle Is absorbed after Inhalation
exposure In dogs and rats and after oral exposure 1n rats and mice, and that
succlnonltrlle and nlcotlnonltrlle are absorbed following oral exposure In
rats and mice. Methacrylonltrlle was llpophlllc and distributed rapidly to
various organs of the rat (Haguenoer et a!., 1976). The metabolism of
succ1non1tr1le has been studied In vivo and In vitro using experimental
animals (mice, rats and rabbits), and the primary metabolic pathway appears
to be liberation of free HCN from the parent compound (W1llh1te and Smith,
1981; Contessa and Santl, 1973; Floreanl et al., 1980, 1981; Tanll and
Hashimoto, 1985). Liberation of free cyanide also appears to be the primary
pathway of methacrylonltrlle metabolism Iji vivo and in vitro 1n experimental
animals (Tanll and Hashimoto, 1984a,b, 1986; Peter and Bolt, 1985; Pozzanl
et al., 1968; Haguenoer et al., 1976). Succlnonltrlle administered
Intravenously to humans (Lod1 et al., 1973) or 1ntraper1toneally or
Intravenously to experimental animals (Cavanna and Pocch1ar1, 1972; Curry,
1974, 1975; Contessa et al., 1978; Contessa and Santl, 1973) Is excreted 1n
the urine primarily as the parent compound and thlocyanate Ion.
Methacrylon1tr1le administered 1ntraper1toneally to rats was found to be
excreted 1n the urine as the parent compound, free cyanide and bound cyanide
In the form of thlocyanate Ion (Haguenoer et al., 1976).
0033d -16- 09/09/87
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6. EFFECTS
6.1. SYSTEMIC TOXICITY
6.1.1. Inhalation Exposures.
6.1.1.1. SUBCHRONIC Only one study was found on the systemic
toxldty of methacrylonltrlle following subchronlc Inhalation exposures In
beagle dogs and Harlan-VMstar rats (Pozzanl et al., 1968). Groups of 12
male and 12 female rats were exposed to 0, 19.3, 52.6 or 109.3 ppm (0, 53,
144 or 300 mg/m3), 7 hours/day, 5 days/week for 91 days. Endpolnts of
toxlclty examined were overt signs, body weight changes, liver and kidney
weights and gross and hlstologlcal examination of 19 tissues. The brain was
not examined microscopically. The only treatment-related effects were
deaths during the first or second day of one 52.6 ppm male and seven 109.3
ppm males, and significantly Increased relative liver weights 1n males and
females at 109.3 ppm and In males at 52.6 ppm.
Groups of three male dogs were exposed to methacrylonltrlle at concen-
trations of 0, 3.2, 8.8 or 13.5 ppm (0, 9, 24 or 37 mg/m3), 7 hours/day, 5
days/week for 90 days. Endpolnts examined were body weight changes, overt
signs, hematocrlt, total and differential white cell counts, BUN, SGOT,
SGPT, SAP, liver and kidney weights and gross and hlstologlcal examination
of 27 tissues, Including the brain. At 13.5 ppm, CNS toxlclty, as evidenced
by convulsions and loss of motor control of the hindquarters, was observed
In 2/3 dogs. One of these dogs had hlstopathologlcal brain lesions, Includ-
ing some demy ell nation of the corpus callosum. SGOT and SGPT levels were
markedly elevated 1n 1/3 dogs at 8.8 ppm, but the elevations were transient.
No other treatment-related effects were observed.
Pertinent data regarding subchronlc Inhalation exposure to succlno-
nltrlle or n1cot1non1tr1le could not be located 1n the available literature
as dted In Appendix A.
0033d -17- 05/26/87
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6.1.1.2. CHRONIC -- Pertinent data regarding chronic Inhalation
exposure to succlnonltMle, methacrylonltrlle or n1cot1non1tr1le could not
be located In the available literature as cited In Appendix A.
6.1.2. Oral Exposures.
6.1.2.1. SUBCHRONIC ~ Pertinent data regarding subchronlc oral
exposure to sucdnonltrlle, methacrylonltrlle or nicotlnonltrlle could not
be located 1n the available literature as cited 1n Appendix A.
6.1.2.2. CHRONIC ~ Pertinent data regarding chronic oral exposure to
succlnonHMle, methacrylonltrlle or nicotlnonltrlle could not be located In
the available literature as cited In Appendix A.
6.1.3. Other Relevant Information. The acute systemic toxlclty of
succ1non1tr1le appears to be due to release of cyanide by metabolism of the
parent compound. At autopsy, cyanide was found In the urine and various
viscera of a man who had been receiving Intramuscular Injections of succlno-
nltrlle and died following convulsions. Cyanide derived from succlnonltrlle
was thought to be the toxic agent (Marlgo and Pappalardo, 1966). The blood
of mice Injected 1ntraper1toneally with succlnonltrlle contained cyanide and
thlocyanate (a major cyanide metabolite) (Doherty et al., 1982). Pretreat-
ment with CC1. lowered the blood levels of cyanide and thlocyanate and
prevented all signs of toxlclty. Also, thlosulfate, a cyanide antagonist,
protected mice treated with succlnonltrlle against death.
The toxlclty of methacrylonltrlle also appears to be due to cyanide
liberation. Pozzanl et al. (1968) found that a standard therapy for cyanide
Intoxication reduced the toxic effects of methacrylonltrlle 1n rats and mice
after an Inhalation exposure. Haguenoer et al. (1976) found that the time
to death of rats Injected Intraperltoneally correlated positively with dose
and tissue level of cyanide (see Section 5.3.).
0033d -18- 05/26/87
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Other toxic effects have been observed In animals treated with met-
hacrylonltMle and sucdnonHMle. Szabo and Reynolds (1975) and Szabo et
al. (1982) reported that methacrylon1tr1le and sucdnonltrlle were weakly to
moderately ulcerogenlc and adrenocortlcolytlc 1n Sprague-Oawley rats dosed
either orally or subcutaneously (route not clearly specified), 3 times/day
for 4 days. Total doses were 34 mmol/kg for methacrylonKrUe and 5.3
mmol/kg for sucdnonltrlle.
Information regarding the toxlclty of n1cot1non1tr1le 1s limited. Majka
et al. (1979) found that n1cot1non1tr1le caused Irreversible opacity of the
cornea when Introduced Into the eyes of rats and rabbits. LD,.- and LC,.
values for methacrylonltMle are presented 1n Table 6-1. The oral L05Q
for sucdnonltrlle In rats 1s 450 mg/kg and 129 mg/kg for mice (Hartung,
1982); the IntraperHoneal LD5Q 1s 63.1 mg/kg (NIOSH, 1987). The oral
L05Q for mice 1n rats for nlcotlnonltrlle 1s 1185 mg/kg (NIOSH, 1987).
6.2. CARCINOGENICITY
6.2.1. Inhalation. Pertinent data regarding the cardnogenldty of
sucdnonltrlle, nlcotlnonltrlle or methacrylonltrlle by Inhalation exposure
could not be located In the available literature as dted 1n Appendix A.
6.2.2. Oral. Pertinent data regarding the cardnogenldty of
succ1non1tr1le, nlcotlnonltrlle or methacrylonltrlle by oral exposure could
not be located In the available literature as cited 1n Appendix A.
6.2.3. Other Relevant Information. Bolt et al. (1986) predicted that
methacrylonltrlle would prove more carcinogenic than the known carcinogen,
acrylonltMle. Cardnogenldty studies with methacrylonltrlle were not
located and this chemical 1s not scheduled for testing by NTP (1987).
0033d -19- 09/08/87
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or
TABLE 6-1
Values for Methacrylonltrlle
Species
Rat
Rat
Rat
Rat
Mouse
Mouse
RabbU
Rat
Mouse
Mouse
RabbU
Guinea pig
RabbU
Route of
Administration
oral
oral
oral
oral
oral
oral
oral
Inhalation
Inhalation
Inhalation
Inhalation
Inhalation
dermal
L050 or LC50
250 mg/kg
25-50 mg/kg
240 mg/kg
120 mg/kg
20-25 mg/kg
11.6 mg/kg
16 mg/kg
328 ppm (900 mg/m3)
for 4 hours
36 ppm (99 mg/m3}
for 4 hours
400 ppm (1098 mg/m3)
for 4 hours
37 ppm (102 mg/m3)
for 4 hours
88 ppm (241 mg/m3)
for 4 hours
320 mg/kg
Reference
Anonymous, 1986
Hartung, 1982
Pozzanl et al.,
1968
Kurzallev, 1985
Hartung, 1982
Kurzallev, 1985
Kurzallev, 1985
Anonymous, 1986
Anonymous, 1986
Hartung, 1982
Anonymous, 1986
Anonymous, 1986
Pozzanl et al. ,
1968
0033d
-20-
05/26/87
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6.3. MUTAGENICITY
N1cot1non1tr1le was not mutagenlc In Salmonella typhlmurlum strains
TA98, TA100, TA1535 and TA1537 with or without rat liver S-9 when tested 1n
the spot test at 3 ymol/plate (Florin et al., 1980). Pertinent data
regarding the mutagenlclty of sucdnonltrlle or methacrylonltrlle could not
be located 1n the available literature as cited In Appendix A.
6.4. TERATOGENICITY
SucclnonHrlle appears to be a teratogen In the hamster. Pregnant
Syrian golden hamsters were dosed Intraperltoneally with sucdnonltrlle
dissolved In distilled water (Doherty et al., 1983) on day 8 of gestation.
The single doses of sucdnonltrlle given and the number of dams at each dose
level were 0.78-3.02 mmol/kg (18), 4.56 mmol/kg (9) and 6.24 mmol/kg (10).
Six dams received water Intraperltoneally and served as controls. The
hamsters were sacrificed on day 11 of gestation and the number of resorp-
tlons and malformed fetuses were noted; there were no malformed fetuses 1n
the controls. Doses of sucdnonltrlle ranging from 0.78-3.02 mmol/kg did
not produce significant teratogenlc effects, although 2 fetuses had exen-
cephaly and one fetus had a crooked tall. At 4.56 or 6.24 mmol/kg, a high
Incidence of malformations (60-8054 of the Utters) was noted 1n the off-
spring. The most frequent abnormalities were neural tube defects (exen-
cephaly and encephalocoele). A dose-related significantly decreased crown-
rump length was also observed at 4.56 and 6.24 mmol/kg. Sucdnonltrlle
treatment did not affect the Incidence of resorptlons. Maternal toxldty
(dyspnea, hypothermia and ataxla) was evident In 20% of the animals treated
at the higher doses.
The teratogenlc effects of sucdnonltrlle appear to be due to cyanide
released during metabolism of the parent molecule (Doherty et al., 1983).
0033d -21- 05/26/87
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Treatment of succlnonltrlle-dosed dams with sodium thlosulfate, a cyanide
antagonist, provided significant protection against fetal anomalies.
Pertinent data regarding the teratogenlclty of n1cot1non1tr1le and
methacrylonltrlle could not be located 1n the available literature as cited
In Appendix A.
6.5. OTHER REPRODUCTIVE EFFECTS
Pertinent data regarding other reproductive effects of sucdnonltrlle,
methacrylon1tr1le or n1cot1non1tr1le could not be located In the available
literature as dted In Appendix A.
6.6. SUMMARY
One study was located regarding the toxldty of methacrylonltrlle by
subchronlc Inhalation exposure (Pozzanl et al., 1968). In this study,
exposure of rats to concentrations >52.6 ppm (>144 mg/m3), but not 19.3
ppm (53 mg/m3) for 7 hours/day, 5 days/week for 91 days resulted In
Increased liver weight and death. Exposure of dogs for 7 hours/day, 5
days/week for 90 days resulted In transiently elevated SGOT and SGPT levels
at 8.8 ppm (24 mg/m3) and loss of motor control of hind limbs and hlsto-
pathologlcal brain lesions at 13.5 ppm (37 mg/m3). No effects were
observed In dogs at 3.2 ppm (9 mg/m3).
The acute toxldty of the nltrlles appears to be due to release of
cyanide during metabolism of the parent compound (Marlgo and Pappalardo,
1966; Haguenoer et al., 1976; Pozzanl et al., 1968).
Information regarding the carclnogenlclty of sucdnonltrlle, nlcotlno-
nltrlle and methacrylonltrlle, and the mutagenldty of methacrylon1tr1le and
sucdnonltrlle was not located. One study Indicated that n1cot1non1tr1le
was not mutagenlc 1n S. typh1mur1um (Florin et al., 1980).
0033d -22- 05/26/87
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A study by Doherty et al. (1983) Indicated that succlnonltMle was
teratogenlc In hamsters treated 1ntraper1toneally at >4.56 mmol/kg. No
Information was located regarding the teratogenlclty of either nlcotlno-
nltrlle or methacrylonltrlle.-
0033d -23- 05/26/87
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7. EXISTING GUIDELINES AND STANDARDS
7.1. HUMAN
ACGIH (1986-1987) adopted a TWA-TLV for methacrylonltrlle of 1 ppm or 3
mg/m3. The TLV was based on the subchronlc Inhalation study using beagle
dogs by Pozzanl et al. (1968) and by analogy to acrylonltMle (ACGIH, 1986).
The TWA workplace environmental limit for a 10-hour workshlft for
sucdnonltrlle 1s 6 ppm (20 mg/m3) NIOSH (1978).
Pertinent guidelines and standards for n1cot1non1tr1le, Including EPA
ambient water and air quality criteria drinking water standards, FAO/WHO
ADIs, EPA or FDA tolerances for raw agricultural commodities or foods, and
ACGIH, NIOSH or OSHA occupational exposure limits could not be located In
the available literature as cited 1n Appendix A.
7.2. AQUATIC
Guidelines and standards for the protection of aquatic organisms from
the effects of the selected nltrlles could not be located 1n the available
literature as cited In Appendix A.
0033d -24- 09/09/87
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8. RISK ASSESSMENT
8.1. CARCINOGENICITY
Pertinent data regarding the carclnogenldty of succ1non1tr11e,
nlcotlnonltrlle and methacrylonltrlle following Inhalation, oral or other
routes could not be located In the available literature as dted In
Appendix A. Therefore, an EPA classification of 0 1s assigned to these
compounds.
8.2. SYSTEMIC TOXICITY
8.2.1. Inhalation Exposure.
8.2.1.1. LESS THAN LIFETIME EXPOSURES (SUBCHRONIC) -- The only study
that examined the toxldty of methacrylonltrlle after subchronlc Inhalation
exposure Is that of Pozzanl et al. (1968). Exposure of rats to concentra-
tions >52.6 ppm (>144 mg/m3), but not 19.3 ppm (53 mg/m3), for 7 hours/
day, 5 days/week for 91 days resulted 1n Increased liver weight and death.
Exposure of dogs for 7 hours/day, 5 days/week for 90 days resulted In
transiently elevated SGOT and SGPT levels at 8.8 ppm (24 mg/m3) and loss
of motor control of hind limbs and hlstopathologlcal brain lesions at 13.5
ppm (37 mg/m3). No effects were observed In dogs at 3.2 ppm (9 mg/m3).
Thus, the LOAEL 1s 24 mg/m3. Expanding this exposure concentration over a
24-hour day and 7 day-week gives a calculated LOAEL of 5 mg/m3. The NOEL
1s 9 mg/m3. Expanding this exposure over a 24-hour day and a 7-day week,
and multiplying by the reference dog Inhalation rate of 4.3 mVday and
dividing by the reference dog body weight of 12.7 kg (U.S. EPA, 1985) yields
a NOEL of 0.63 mg/kg/day. Dividing by an uncertainty factor of 100 (10 for
Interspedes extrapolation and 10 to protect sensitive Individuals), the
subchronlc RfD human exposure level 1s estimated as 0.006 mg/kg/day or 0.4
0033d -25- 09/09/87
-------
mg/day for a 70 kg human. Dividing the RfD exposure level by 20 mVday,
the Inhalation rate for a 70 kg human, yields a concentration 1n air of 0.02
mg/m3.
Pertinent data regarding the effects of subchronlc Inhalation exposure
to succlnonltrlle or n1cot1non1tr1le could not be located In the available
literature as cited 1n Appendix A.
8.2.1.2. CHRONIC EXPOSURES -- Pertinent data regarding the effects of
chronic Inhalation exposure of methacrylon1tr1le, succlnonltrlle or
n1cot1non1tr1le could not be located 1n the available literature as cited In
Appendix A. A chronic Inhalation RfD for methacrylonltrlle can be estimated
by dividing the subchronlc Inhalation RfD by an additional uncertainty
factor of 10. Applying the additional uncertainty factor, the chronic
Inhalation RfD for methacrylonltrlle Is 0.002 mg/m3, or 0.04 mg/day for a
70 kg human. The level of confidence In this RfD 1s medium because It 1s
based on a well conducted subchronlc study using two species; both a NOEL
and a LOAEL can be distinguished from the observations and results.
8.2.2. Oral Exposure.
8.2.2.1. LESS THAN LIFETIME EXPOSURES (SUBCHRONIC) -- Pertinent data
regarding the effects of subchronlc oral exposure to methacrylonltrlle,
succlnonltrlle and nicotlnonltrlle could not be located 1n the available
literature as cited In Apppendlx A. A subchronlc oral RfD for methacrylo-
nltrlle can be calculated using Inhalation data from Pozzanl et al. (1968).
The NOEL from the study of Pozzanl et al. (1968) occurred at a concentration
of 9 mg/m3, 7 hours/day, 5 days/week. Expanding for an equivalent human
exposure and multiplying by the reference Inhalation rate of 4.3 ma/day
for a dog and by an absorption factor of 0.5, and then dividing by the
reference dog body weight of 12.7 kg, a transformed animal dose of 0.32
mg/kg/day can be calculated.
0033d -26- 09/10/87
-------
The RfD 1s calculated by dividing the NOEL by an uncertainty factor of 100
(10 for Interspedes extrapolation and 10 for sensitive Individuals). The
calculated subchronlc oral RfD Is 0.003 mg/kg/day, or 0.2 mg/day for a 70 kg
human.
The level of confidence In the subchronlc oral RfD 1s low because H Is
based on only one study (Pozzanl et al., 1968), and because this was an
Inhalation study of the toxldty of methacrylonltrlle.
8.2.2.2. CHRONIC EXPOSURES -- Pertinent data regarding the effects of
chronic oral exposure to methacrylonltrlle, succ1non1tr1le and methacrylo-
nltrlle could not be located In the available literature as dted In
Appendix A. A chronic oral RfD can be derived by dividing the subchronlc
oral RfD by an additional uncertainty factor of 10 to extrapolate from
subchronlc to chronic exposure. Dividing the subchronlc RfD derived from
the study of Pozzanl et al. (1968) by 10, a chronic oral RfD of 0.0003
mg/kg/day, or 0.02 mg/day for a 70 kg human 1s derived. The level of
confidence 1n this RfD Is low for reasons stated previously (see Section
8.2.2.1.) and because the study was subchronlc.
0033d -27- 09/09/87
-------
9. REPORTABLE QUANTITIES
9.1. BASED ON SYSTEMIC TOXICITY
The toxldty of methacrylonHMle was discussed 1n Chapter 6. Table 9-1
summarizes the only studies 1n which toxic effects of subchronlc or chronic
exposure were observed.
Reportable quantities were determined using data from the subchronlc
Inhalation toxlclty study of methacrylonltrlle by Pozzanl et al. (1968).
The most severe effect, death 1n Harlan-Wlstar rats, occurred at an equiva-
lent human dose of 3.27 mg/kg/day. Dividing by an uncertainty factor of 10
to approximate chronic exposure and 70 kg gives an MED of 22.9 mg/day (Table
9-2). This MED corresponds to an RV. of 3.5. The RV corresponding to
death 1s 10, and multiplication of this RVg by the RVd yields a CS of
35. This CS corresponds to an RQ of 100 (see Table 9-2).
The second most severe effects were loss of motor control 1n the hind
limbs of beagle dogs and histopathologlcal brain lesions, which occurred at
a human equivalent dose of 1.48 mg/kg/day. When this Is divided by an
uncertainty factor of 10 (to convert subchronlc exposure to chronic
exposure) and then multiplied by 70 kg, a MED of 10.4 mg/day 1s obtained.
This MED corresponds to an RV. of 4.0. The RV corresponding to loss of
motor control 1s 9 and multiplication of this RV by the RV. yields a CS
of 36 (see Table 9-2). This CS corresponds to an RQ of 100.
The third most severe effect was a marked but transitory elevation of
SGOT and SGPT values 1n beagle dogs. This occurred at a human equivalent
dose of 0.96 mg/kg/day. Division of this dose by 10 (to convert subchronlc
to chronic exposure) and multiplication by 70 kg yields an MED of 6.7
mg/day. This MED corresponds to an RV. of 4.3.
0033d -28- 09/09/87
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The RVg associated with elevation of SCOT and SGPT values Is 6 and
multiplication of this RVg by the RVd yields a CS of 26. The RQ
associated with this CS 1s 100 (see Table 9-2).
The RQs determined from the three effects (death, loss of motor control
1n hind limbs and elevated SGOT and SGPT levels) are the same (100). The
highest CS (36) corresponded to the effect of loss of motor control and
brain lesions In dogs and this was chosen as the basis for the RQ (Table
9-3). Data were Insufficient to derive RQs for sucdnonltrlle and
nlcotlnonltrlle (Tables 9-4 and 9-5).
9.2. BASED ON CARCINOGENICITY
Pertinent data regarding the cardnogenlclty of methacrylonltrlle,
succlnlnonltrlle or nlcotlnonltrlle could not be located 1n the available
literature as cited In Appendix A; therefore an RQ based on cardnogenlclty
cannot be derived.
0033d -31- 05/26/87
-------
TABLE 9-3
MethacrylonltMle
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route: Inhalation
Dose*: 10.4 mg/day
Effect: loss of motor control and brain lesions
Reference: Pozzanl et al., 1968
RVd: 4.0
RVe: 9
Composite Score: 36
RQ: 100
^Equivalent human dose
0033d -32- 05/26/87
-------
TABLE 9-4
SucclnonHMIe
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route:
Dose:
Effect:
Reference:
RVd:
RVe:
Composite Score:
RQ: Data were Insufficient to derive an RQ
0033d -33- 05/26/87
-------
TABLE 9-5
N1cot1non1tr1le
Minimum Effective Dose (MED) and Reportable Quantity (RQ)
Route:
Dose:
Effect:
Reference:
RVd:
RVe:
Composite Score:
RQ: Data were Insufficient to derive an RQ
0033d -34- 05/26/87
-------
10. REFERENCES
ACGIH (American Conference of Governmental Industrial Hyglenlsts). 1986.
Documentation of the Threshold Limit Values and Biological Indices, 5th ed.
Cincinnati, OH. p. 370.
ACGIH (American Conference of Governmental Industrial Hyglenlsts).
1986-1987. TLVs: Threshold Limit Values and Biological Exposure Indices for
1986-1987. Cincinnati, OH. p. 23.
AldMch. 1984-1985. Aldrlch Catalog/Handbook of Fine Chemicals. Aldrlch
Chemical Co., Milwaukee, MI.
Anonymous. 1986. Methyl acrylonltrlle. Dangerous Prop. Ind. Mater. Rep.
6(1): 76-81.
Bolt, H.M., H. Peter and H.J. Wlegand. 1986. Biological reactive metabo-
lites 1n human toxldty. Adv. Exp. Med. B1ol. 197: 1013-1016.
Cavanna, R. and F. Pocchlarl. 1972. Fate of sucdnon1tr11e-l-l4C 1n the
mouse. Blochem. Pharmacol. 21(18): 2529-2531.
CMR (Chemical Marketing Reporter). 1986. 1987 OPD Chemical Buyers
Directory, 74th ed. Schnell Publishing Co., Inc., New York.
Contessa, A.R. and R. Santl. 1973. Liberation of cyanide from sucdno-
nltrlle. Blochem. Pharmacol. 22(7): 827-832.
0033d -35- 05/26/87
-------
Contessa, A.R., M. Floreanl, A.C. Bonettl and R. Santl. 1978. Liberation
of cyanide from succlnonHMle. 2. The effect of ethanol. Blochem.
Pharmacol. 27(8): 1135-1138.
Curry, S.H. 1974. Excretion of succlnonltrlle In mice. IRCS Llbr. Compend.
2(7): 1444. (CA 082/025606H)
Curry, S.H. 1975. Cumulative excretion of succlnonltrlle In mice. Blochem.
Pharmacol. 24(3): 351-354.
Dean, J.A., Ed. 1985. Lanne's Handbook of Chemistry, 13th ed. McGraw-Hill
Book Co., New York. p. 7-245.
DIGeronlmo, M.J. and A.D. Antolne. 1976. Metabolism of acetonltMle and
proplonltMle by Nocardla rhodochrous. Appl. Environ. Mlcroblol. 31:
900-906.
Doherty, P.A., R.P. Smith and V.H. Perm. 1982. Tetramethyl substitution on
succlnonltMle confers pentelenetetrazol-llke activity and blocks cyanide
release 1n mice. J. Phamarcol. Exp. Ther. 223(3): 635-641.
Doherty, P.A., R.P. Smith and V.H. Perm. 1983. Comparison of the terato-
genlc potential of two aliphatic nitrlles In hamsters: Succlnonltrlle and
tetramethylsucdnonltrlle. Fund. Appl. Toxlcol. 3(1): 41-48.
E1senre1ch, S.3., B.B. Looney and J.D. Thornton. 1981. Airborne organic
contaminants of the Great Lakes ecosystem. Environ. Sc1. Technol. 15(1):
30-38.
0033d -36- 09/09/87
-------
Floreanl, M., F. Carpenedo, R. Santl and A.R. Contessa. 1980. Studies on
the systems Involved 1n sucdnonltMle metabolism In Hver. Pharmacol. Res.
Commun. 12(5): 433-439.
Floreanl, M., F. Carpenedo, R. Santl and A.R. Contessa. 1981. Metabolism
of sucdnlnonUrlle In liver: Studies on the systems Involved 1n cyanide
release. Eur. J. Drug Metab. Pharmacol. 6(2): 135-140.
Florin, I., L. Rutberg, M. Curvall and C.R. Enzell. 1980. Screening of
tobacco smoke constituents for mutagenlclty using the Ames1 test.
Toxicology. 15: 219-232.
Haguenoer, 3.M., B. Fromont, J. Dequldt and M.C. Jacquemont. 1976. Experi-
mental poisoning by methacrylonltrlle. Bull. Soc. Pharm. Lille. 32(2-3):
185-196.
Hansch, C. and A.3. Leo. 1984. Medchem Project. Issue No. 26. Pomona
College, Claremont, CA.
Hartung, R. 1982. Cyanides and nltrlles. IJK Patty's Industrial Hygiene
and Toxicology, Vol. IIC, G.D. Clayton and F.E. Clayton, Ed. John Wiley and
Sons Inc., New York. p. 4863-4900.
Hashimoto, S., H. Bandow, H. Aklmoto, J.H. Meng and X.Y. Tang. 1984.
Products and mechanism for the hydroxyl radical Initiated oxidation of
acrylonltrlle, methacrylonltrlle and allylcyanlde 1n the presence of nitric
oxide. Int. J. Chem. Klnet. 16(11): 1385-1400.
0033d -37- 09/09/87
-------
Hawley, G.G. 1981. The Condensed Chemical Dictionary, 10th ed. Van
Nostrand Relnhold Co., New York. p. 430.
H1ne, J. and P.K. Mookerjee.' 1975. The Intrinsic hydrophlllc character of
organic compounds. Correlations 1n terms of structural contributions. J.
Org. Chem. 49(3): 292-298.
Jaffe, H.H. and G.O. Doak. 1955. The basicities of substituted pyMcMnes
and their 1-oxides. J. Am. Chem. Soc. 77: 4441-4444.
Kuney, J.H., Ed. 1985. Chemcyclopedla 1986, Vol. 4. American Chemical
Society, Washington, DC.
Kurzallev, S.A. 1985. Characteristics of the toxic effect of methacrylo-
nltrlle. Gig. Tr. Prof. Zabol. 5: 37-40. (Rus.) (CA 103/033202R)
Lod1, F., E. Marozzl, G. Barbl and C.A. Maggl. 1973. Pharmacoklnetlcs of
succlnc acid dlnUrlle. Farmaco. Ed. Prat. 28(2): 105-114. (In Italian
with English translation)
Lutln, P.A. 1970. Removal of organic nltrlles from wastewater systems. J.
Water Pollut. Control Fed. 42: 1632-1642.
Lyman, W.J., W.F. Reehl and D.H. Rosenblatt. 1982. Handbook of Chemical
Property Estimation Methods. McGraw-Hill Book Co., New York. p. 4-9, 5-5,
7-5, 15-13, 15-21, 15-27.
0033d -38- 09/09/87
-------
Majka, 3., K. Knochbloch and S. Szividzikowski. 1979. Evaluation of acute
toxlclty of 3-cyanopyridinc. Mod. Pr. 30(2): 109-113. (Pol.) (CA
092/016527N)
Malaney, G.W. and R.M. Gerhold. 1969. Structural determinants in the
oxidation of aliphatic compounds by activated sludge. J. Water Pollut.
Control Fed. 4: R18-R33.
Marlgo, M. and G. Pappalardo. 1966. A ratal incident Horn therapeutic
administration of succinonHMle. Med. Leg. Assicur. 14: 155-185. (Hal.)
(Cited in NIOSH, 1978)
Merkow, L.P., S.H. Lipton, J.J. Lalich and P.M. Strong. 1959. Metabolism
of amlno nHrlle and related compounds by the rat. Cxptl. Biol. Med. 102:
728-732. (CA 54:59601)
Neely, W.B. and G.C. Blau. 1985. Environmental Exposure from Chemicals,
Vol. 1. CRC Press Inc., Boca Raton, FL. p. 31.
Nemec, J. and L.S. Kirch. 1981. Methacryllc acid and derivatives, in:
Kirk Othmer encyclopedia of Chemical Technology, Vol. 15, 3rd ed., M.
Grayson and D. Eckroth, Ed. John Wiley and Sons, New York. p. 363.
NIOSH (National Institute for Occupational Safety and Health). 1978.
Criteria for Recommended Standard...Occupational Exposure to NUri>$
NIOSH, Washington, DC.
0033d -39- 09/08/87
-------
NIOSH (National Institute for Occupational Safety and Health). 1987. KILCS
(Registry of Toxic Effects of Chemical Substances). On-line: January, 1987.
NTP (National Toxicology Program). 1987. Management Status Report.
January 13, 1987.
Offermanns, H., A. Kleemann, H. Tanner, H. Beschke and H. freidrich. 1984.
Vitamins (nlcotamide and nicotlnic acid). In: Klrk-Othmer encyclopedia of
Chemical Technology, Vol. 24, 3rd ed., M. Grayson and D. Eckroth, Ed. John
Wiley and Sons, New York. p. 65-67.
Perry, R.H. and 0. Green. 1984. Perry's Chemical Handbook. Physical and
Chemical Data, 6th ed. McGraw-Hill Book Co., New York.
Peter, H. and H.M. Bolt. 1985. Effect of antidotes on the acute toxicity
of methacrylonitrile. FYI Submission to OTS. Doc. ID FYI-OTS-0385-0390.
(Also published in Int. Arch. Occup. Environ. Health. 55: 175-177)
Pozzanl, U.C., C.R. Kinkead and J.M. King. 1968. The mammalian toxicity of
methacrylonitrile. Am. Ind. Hyg. Assoc. J. 29(3): 202-210.
Riddlck, J.A., W.B. Bunger and T.K. Sakano. 1986. Techniques of Chemistry.
Vol. II: Organic Solvents. John Wiley and Sons, New York.
Sadtler. 1961. Sadtler Standard UV Spectra No. 5426. Sadtler Research
Laboratory, Philadelphia, PA.
0033d 40- 09/08/87
-------
SchmoHz, I., A. Wenger, D. Hoffmann and T.C. Tso. 1979. Chemical shid'^s
on tobacco smoke: 63. On the fate of nicotine during pyrolysls and in a
burning cigarette. 3. Agric. Food Chem. 27(3): 602-609.
Smiley, R.A. 1981. Nitriles. In: Kirk-Othmer Encyclopedia of Chemical
Technology, Vol. 15, 3rd ed., M. Grayson, Ed. John Wiley and Sons, New
York. p. 888-909.
SRI (Stanford Research Institute). 1985. 1985 Directory of Chemical
Producers: United States of America. SRI International, Menlo Park, CA.
Swarm, R.L., D.A. Laskowski, P.O. McCall, K. Vander Kuy and H.J. Dishburger.
1983. A rapid method for the estimation of the environmental parameters
octanol/water partition coefficient, soil sorption constant, water to air
ratio and water solubility. Res. Rev. 85: 17-28.
Szabo, S. and E.S. Reynolds. 1975. Structure-activity relations Tor
ulcerogenlc and adrenocortlcolytlc effects of alky! nitriles, amines and
thiols. Environ. Health Perspect. 11: 135 140.
Szabo, S., E.S. Reynolds and S.H. linger. 1982. Structur t> activity
relations between alkyl nucleophlllc chemicals causing duodenal uif^r anrt
adrcnocortical necrosis. J. Pharmacol. Exp. Ther. 223(1): 68-76.
Tanii, H. and K. Hashimoto. 1984a. Structure-toxicity relationship of
aliphatic nitriles. Toxicol. Lett. 22(2): 267-272.
0033d 41 - 09/08/87
-------
Tanll, H. and K. Hashimoto. 1984b. Studies on the mechanism of acute
toxldty of nHrlles In mice. Arch. Toxlcol. 55(1): 47-54.
Tan11, H. and K. Hashimoto. 1985. Structure-acute toxldty relationship of
dlnltrlles In mice. Arch. Toxlcol. 57(2): 88-93.
Tan11, H. and K. Hashimoto. 1986. Influence of ethanol on the \n_ vivo and
1n vitro metabolism of nltrlles 1n mice. Arch. Toxlcol. 58(3): 171-176.
U.S. EPA. 1980. Guidelines and Methodology Used 1n the Preparation of
Health Effect Assessment Chapters of the Consent Decree Water Criteria
Documents. Federal Register. 45(231): 49347-49357.
U.S. EPA. 1984. Methodology and Guidelines for Reportable Quantity
Determinations Based on Chronic Toxldty Data. Prepared by the Office of
Health and Environmental Assessment, Environmental Criteria and Assessment
Office, Cincinnati, OH for the Office of Solid Waste and Emergency Response,
Washington, DC.
U.S. EPA. 1985. Reference Values for Risk Assessment. First Draft,
ECAO-CIN-477. Environmental Criteria and Assessment Office, Cincinnati, OH.
U.S. EPA. 1986. Methodology for Evaluating Potential Cardnogenldty In
Support of Reportable Quantity Adjustments Pursuant to CERCLA Section 102.
Prepared by the Office of Environmental Health Assessment, Carcinogen
Assessment Group, Washington, DC for the Office of Solid Waste and Emergency
Response, Washington, DC.
0033d -42- 09/09/87
-------
U.S. EPA. 1907a. Graphical exposure Modeling System (GEMS). CIDGP
computer program. Office of Toxic Substances, Washington, DC.
U.S. EPA. 1987b. Graphical Exposure Modeling System (GCMS). fate of
Atmospheric Pollutants (FAP). Office of Toxic Substances, Washington, DC.
Willhite, C.C. and R.P. Smith. 1981. The role of cyanide liberation in the
acute toxicity of aliphatic nltriles. Toxicol. Appl. Pharmacol. 59(3):
589-602.
Wlndholz, M., Ed. 1983. The Merck Index, 10th ed. Merck and Co., Inc.,
Rahway, NJ. p. 850.
0033d 43- 09/08/87
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APPENDIX A
LITERATURE SEARCHED
This HCCl) is based on data identified by computerized literature
searches of the following:
TSCATS
CASR online (U.S. EPA Chemical Activities Statu-, Report)
TOXLINE
TOXBACK 76
FOXBACK 65
RTECS
OHM TADS
STORET
SRC environmental Fate Data Bases
SANSS
AQUIRE
TSCAPP
NTIS
federal Register
These searches were conducted in January, 1987. In addition, hand searches
were made of Chemical Abstracts (Collective Indices 5-9), and the following
secondary sources should be reviewed:
ACGIH (American Conference of Governmental Industrial Hygienists).
1986. Documentation of the Threshold Limit Values and Biological
Exposure Indices, 5th ed. Cincinnati, OH.
ACGIH (American Conference of Governmental Industrial Hygienists).
1906 1987. TLVs: Threshold Limit Values for Chemical Substances In
the Work environment adopted by ACGIH with Intended Changes for
1986-1987. Cincinnati, OH. Ill p.
Clayton, G.D. and F.E. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2A. John Wiley and
Sons, NY. 2878 p.
Clayton, G.D. and F.C. Clayton, Ed. 1981. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2B. John Wiley and
Sons, NY. p. 2879-3816.
Clayton, G.D. and F.E. Clayton, Ed. 1982. Patty's Industrial
Hygiene and Toxicology, 3rd rev. ed., Vol. 2C. John Wiley and
Sons, NY. p. 3817-5112.
0033d
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Grayson, M. and D. Eckroth, Ed. 19701984. Kirk -Ottimer Encyclo-
pedia of Chemical Technology, 3rd cd. John Wiley and Sons, NY. 23
Volumes.
Hamilton, A. and H.I. Hardy. 1974. Industrial Toxicology, 3rd ed
Publishing Sciences Group, Inc., Littleton, MA. 57b p,
IARC (International Agency for Research on Cancer). IARC Mono
graphs on the Evaluation of Carcinogenic Risk of Chemicals to
Humans. WHO, IARC, Lyons, France.
Jaber, H.M., W.R. Mabcy, A.T. Lieu, T.W. Chou and H.L. Johnson.
1904. Data acquisition Tor environmental transport and fate
screening Tor compounds of interest to the Office of Solid Waste.
SRI International, Menlo Park, CA. EPA 600/604-010. NTIS
PB84 243906.
NTP (National Toxicology Program). 1906. Toxicology Research and
Testing Program. Chemicals on Standard Protocol. Management
Status.
Ouellette, R.P. and J.A. King. 1977. Chemical Week Pesticide
Register. McGraw-Hill Book Co., NY.
Sax, I.N. 1904. Dangerous Properties of Industrial Materials, 6th
ed. Van Nostrand Reinhold Co., NY.
SRI (Stanford Research Institute). 1986. Directory of Chemical
Producers. Menlo Park, CA.
U.S. EPA. 1906. Report on Status Report in the Special Review
Program, Registration Standards Program and the Data Call in
Programs. Registration Standards and the Data Call in Programs.
Office of Pesticide Programs, Washington, DC.
U.S. EPA. 1905. CSB Existing Chemical Assessment Tracking System.
Name and CAS Number Ordered Indexes. Office of Toxic Substances,
Washington, DC.
USITC (U.S. International Trade Commission). 1985. Synthetic-
Organic Chemicals. U.S. Production and Sales, 1984, USIIC Publ.
1422, Washington, DC.
Verschueren, K. 1983. Handbook of Environmental Data on Organic
Chemicals, 2nd ed. Van Nostrand Reinhold Co., NY.
Windholz, M., Ed. 1983. The Merck Index, 10th ed. Merck and Co.,
Inc., Rahway, NJ.
Worthing, C.R. and S.B. Walker, Ed. 1983. The Pesticide Manual.
British Crop Protection Council. 695 p.
0033d 45- 09/08/87
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In addition, approximately 30 compendia of aquatic toxicity data wore
reviewed, including the following:
Battcllc's Columbus Laboratories. 1971. Water Quality Criteria
Data Book. Volume 3. Effects of Chemicals on Aquatic Life.
Selected Data From the LHrrature through 1968. Prepared for the
U.S. EPA under Contract No. 68-01-0007. Washington, DC.
Johnson, W.W. and M.T. Mnley. 1980. Handbook of Acute Toxicity
of Chemicals to fish and Aquatic Invertebrates. Summaries of
Toxicity Tests Conducted at Columbia National Fisheries Research
Laboratory. 1965 1978. U.S. Dcpt. Interior, Fish and Wildlife
Serv. Res. Pub!. 137, Washington, DC.
McKee, J.E. and H.W. Wolf. 1963. Water Quality Criteria, 2nd ed.
Prepared for the Resources Agency of California, State Water
Quality Control Board. Publ. No. 3-A.
Pimental, D. 1971. Ecological Effects of Pesticides on Non Target
Species. Prepared for the U.S. EPA, Washington, DC. PB -269605.
Schneider, B.A. 1979. Toxicology Handbook. Mammalian and Aquatic
Data. Book 1: Toxicology Data. Office of Pesticide Programs, U.S.
[PA, Washington, DC. EPA 540/9 79-003. NTIS PB 80-196876.
U.S. Environmental Protection A«enqi
Region 5, Library (PL-12J)
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