TECHNICAL REPORT DATA
(fteae read Instruction* on the rtvene before completing
NO.
EPA/600/8-88/050
2.
3. RECIPIENT'S ACCESSION NO
PB88-178967
TITLE AND SUBTITLE
Health Effects Assessment for Nitrophenols
6. REPORT DATE
6. PERFORMING ORGANIZATION CODE
7 AUTHOR(S)
*. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND ADDRESS
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
12. SPONSORING AGENCY NAME AND ADDRESS
13. TYPE OF REPORT AND PERIOD COVERED
Environmental Criteria and Assessment Office
Office of Research and Development
U.S Environmental Protection Agency
Cincinnati. OH 45268
14. SPONSORING AGENCY CODE
EPA/600/22
15. SUPPLEMENTARY NOTES
16. ABSTRACT
This report summarizes and evaluates information relevant to a preliminary interim
assessment of adverse health effects associated with specific chemicals or compounds.
The Office of Emergency and Remedial Response (Superfund) uses these documents in
preparing cost-benefit analyses under Executive Order 12991 for decision-making under
CERCLA. All estimates of acceptable intakes and carcinogenic potency presented in
this document should be considered as preliminary and reflect limited resources
allocated to this project. The intent in these assessments is to suggest acceptable
exposure levels whenever sufficient data are available. The interim values presented
reflect the relative degree of hazard associated with exposure or risk to the
chemical(s) addressed. Whenever possible, two categories of values have been
estimated for systemic toxicants (toxicants for which cancer is not the endpoint of
concern). The first, RfD5 or subchronic reference dose, is an estimate of an exposure
levtl that would not be expected to cause adverse effects when exposure occurs during
a limited time interval. The RfD is an estimate of an exposure level that would not
be expected to cause adverse effects when exposure occurs for a significant portion
of the lifespan. For compounds for which there is sufficient evidence of
carcinogenicity, qj*s have been computed, if appropriate, based on oral and
inhalation data if available.
7.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.IDENTIFIERS/OPEN ENDED TERMS C. COSATI Field/Group
8. DISTRIBUTION STATEMENT
Public
19. SECURITY CLASS (This Report)
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21. NO. OF PAGES
20. SECURITY CLASS (This page!
Unclassified
22. PRICE
It PA Farm 2220.1 (R*v. 4-77) PNCVIOU* EDITION |» OBSOLETE
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EPA/600/8-88/050
July, 1987
HEALTH EFFECTS ASSESSMENT
FOR NITROPHENOLS
ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
OFFICE OF HEALTH AND ENVIRONMENTAL ASSESSMENT
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
CINCINNATI, OH 45268
fl.5. EnvTronaeBtaT Pro-beet Ion Xgency
Region 5, Library (5PL-16)
£30 E, Dearborn St'-eet, Boom 1670
Chicago, IL 60501
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DISCLAIMER
This document has been reviewed In accordance with the U.S.
Environmental Protection Agency's peer and administrative review policies
and approved for publication. Mention of trade names or commercial products
does not constitute endorsement or recommendation for use.
11
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PREFACE
This report summarized and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with nltro-
phenols. All estimates of acceptable Intakes and carcinogenic potency
presented In this document should be considered as preliminary and reflect
limited resources allocated to this project. Pertinent toxlcologlc and
environmental data were located through on-line literature searches of the
Chemical Abstracts, TOXLINE, CANCERLINE and the CHEMFATE/OATALOG data bases.
The basic literature searched supporting this document 1s current up to
June, 1986. Secondary sources of Information -have also ben relied upon In
the preparation of this report and represent large-scale health assessment
efforts that entail extensive peer and Agency review. The following Office
of Health and Environmental Assessment (OHEA) sources have been extensively
utilized:
U.S. EPA. 1980. Ambient Water Quality Criteria Document for
NHrophenols. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincin-
nati, OH for the Office of Water Regulations and Standards, Wash-
ington, DC. EPA 440/5-80-063. NTIS PB81-117749.
U.S. EPA. 1983a. Reportable Quantity Document for 2-N1tropenol.
Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1983b. Reportable Quantity Document for p-NHrophenol.
Prepared by the Office of Health and Environmental Assessment,
• Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Emergency and Remedial Response, Washington, DC.
U.S. EPA. 1983c. Reportable Quantity Document for NHrophenol
(Mixed). Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincin-
nati, OH for the Office of Emergency and Remedial Response, Wash-
ington, DC.
U.S. EPA. 1985. Health and Environmental Effects Profile for
Nltrophenols. Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincin-
nati, OH for the Office of Solid Waste and Emergency Response,
Washington, D.C.
The Intent In these assessments 1s to suggest acceptable exposure levels
for noncarclnogens and risk cancer potency estimates for carcinogens
whenever sufficient data were available. Values were not derived or larger
uncertainty factors were employed when the variable data were limited In
scope tending to generate conservative (I.e., protective) estimates.
Nevertheless, the Interim values presented reflect the relative degree of
hazard or risk associated with exposure to the chemlcal(s) addressed.
Ill
-------
Whenever possible, two categories of values have been estimated for
systemic toxicants (toxicants for which cancer Is not the endpolnt of
concern). The first, RfD$ (formerly AIS) or subchronlc reference dose, Is
an estimate of an exposure level that would not be expected to cause adverse
effects- when exposure occurs during a limited time Interval (I.e., for an
Interval that does not constitute a significant portion of the llfespan).
This type of exposure estimate has not been extensively used, or rigorously
defined, as previous risk assessment efforts have been primarily directed
towards exposures from toxicants In ambient air or water where lifetime
exposure Is assumed. Animal data used for RFD$ estimates generally
Include exposures with durations of 30-90 days. Subchronlc human data are
rarely available. Reported exposures are usually from chronic occupational
exposure situations or from reports of acute accidental exposure. These
values are developed for both Inhalation (RfD$j) and oral (RfD$rj)
exposures.
The RfD (formerly AIC) 1s similar In concept and addresses chronic
exposure. It 1s an estimate of an exposure level that would not be expected
to cause adverse effects when exposure occurs for a significant portion of
the Hfespan [see U.S. EPA (1980) for a discussion of this concept]. The
RfD Is route-specific and estimates acceptable exposure for either oral
(RfDg) or Inhalation (RfDj) with the Implicit assumption that exposure
by other routes Is Insignificant.
Composite scores (CSs) for noncarclnogens have also been calculated
where data permitted. These values are used for Identifying reportable
quantities and the methodology for their development 1s explained 1n U.S.
EPA (1983).
For compounds for which there 1s sufficient evidence of carclnogenlcHy
RfD$ and RfD values are not derived. For a discussion of rlisk assessment
methodology for carcinogens refer to U.S. EPA (1980). Since cancer Is a
process that Is not characterized by a threshold, any exposure contributes
an Increment of risk. For carcinogens, q-|*s have been computed, If appro-
priate, based on oral and Inhalation data 1f available.
1v
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ABSTRACT
Data were Insufficient for quantitative risk analysis of the nltro-
phenols. Recommendations for further testing await the outcome of the NTP
(1986) skin-painting oncogenldty study with 4-nltrophenol 1n mice.
The acute toxlclty data available do not Indicate either a target organ
or system for these isomers. Both the acute toxlclty and the mechanisms of
toxlclty appear to vary with each Isomer. It does not appear that the risk
assessment of an Isomer may prudently be based on analogy to another, or to
closely related compounds such as 2,4-d1n1trophenol, because of marked
differences In mechanisms of toxlclty.
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ACKNOWLEDGEMENTS
The Initial draft of this report was prepared by Syracuse Research
Corporation under Contract No. 68-03-3112 for EPA's Environmental Criteria
and Assessment Office, Cincinnati, OH. Dr. Christopher DeRosa and Karen
Blackburn were the Technical Project Monitors and John Helms (Office of
Toxic Substances) was the Project Officer. The final documents In this
series were prepared for the Office of Emergency and Remedial Response,
Washington, DC.
Scientists from the following U.S. EPA offices provided review comments
for this document series:
Environmental Criteria and Assessment Office, Cincinnati, OH
Carcinogen Assessment Group
Office of A1r Quality Planning and Standards
Office of Solid Waste
Office of Toxic Substances
Office of Drinking Water
Editorial review for the document series was provided by the following:
Judith Olsen and Erma Durden
Environmental Criteria and Assessment Office
Cincinnati, OH
Technical support services for the document series was provided by the
following:
Bette Zwayer, Jacky Bohanon and K1m Davidson
Environmental Criteria and Assessment Office
Cincinnati, OH
v1
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TABLE OF CONTENTS
1.
2.
3.
4.
5.
6.
7.
ENVIRONMENTAL CHEMISTRY AND FATE
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . .
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS ........
3.1. ACUTE, SUBCHRONIC AND CHRONIC TOXICITY
3.2. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS. . . .
3.3. TOXICANT INTERACTIONS
CARCINOGENICITY
4.1. HUMAN DATA
4.2. BIOASSAYS
4.3. OTHER RELEVANT DATA
4.4. WEIGHT OF EVIDENCE
REGULATORY STANDARDS AND CRITERIA
RECOMMENDATIONS .
REFERENCES
Paqe
1
... 4
. . . 5
. . . 5
. . . 7
. . . 7
. . . 8
. . . 8
. . . 8
. . . 8
. . . 9
. . . 10
. . . 11
. . . 13
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LIST OF ABBREVIATIONS
DNA DeoxyMbonuclelc add
ID50 Dose lethal to 50% of recipients
ppm Parts per million
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1. ENVIRONMENTAL CHEMISTRY AND FATE
Selected physical properties and the available data on the environmental
fate of the nltrophenols are summarized In Table 1-1. NHrophenols can be
classified as nltroaromatlc hydrocarbons.
Available data regarding the environmental fate of the nltrophenols
pertain primarily to 4-n1trophenol. It 1s assumed that the environmental
fate 1s similar for 2-, 3- and 4-n1trophenol. Monitoring data Indicate that
4-nltrophenol 1s removed from the atmosphere by wet and dry deposition (U.S.
EPA, 1985). Direct photolysis or reaction with photochemlcally generated
hydroxyl radicals are also potential removal mechanisms. The estimated
atmospheric removal half-life of the nltrophenols that 1s due to rainfall 1s
3 weeks and the estimated hydroxyl reaction half-life of 2-nltrophenol 1s 9
days (U.S. EPA, 1985). The half-lives of 2- and 3-nltrophenols 1n water
could not be located 1n the available literature. U.S. EPA (1985) reported
that 4-nHrophenol reacts quite rapidly with hydroxyl radicals In water 1n
the presence of sunlight and that the nltrophenols are capable of undergoing
significant blodegradatlon 1n various ambient surface waters. The observed
photolysis half-life of 4-n1trophenol 1n aqueous solution Is reported to
vary from 16 hours to 5.7 days at pH 5, 6.7 days at pH 7 and 13.7 days at pH
11.5 (U.S. EPA, 1985). The soil half-life of 4-n1trophenol was estimated
using a decay rate constant of 0.105/day measured In a model soil ecosystem.
Soil microorganisms are capable of degrading the nltrophenols and the nltro-
phenols may be susceptible to leaching 1n certain soil types, although
blodegradatlon may occur rapidly enough to prevent extensive leaching (U.S.
EPA, 1985).
0072h _1_ 08/27/86
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TABLE 1-1
Physical Properties and Environmental Fate of NHrophenols*
Properties
CAS Registry number:
Molecular weight:
Vapor pressure:
Water solubility:
Log octanol/water
partition coefficient:
pKa:
B1oconcentrat1on
factor:
Soil adsorption
coefficient:
Half-life 1n
A1r:
Water:
Soil:
2-NHrophenol
88-75-5
139.11
0.23 at 20°C
0.152 at 20°C
0.11 at 25°C
21,000 mg/j.
at 20°C
1.79
7.23
8-13.5
(estimated)
113.52,
clay loam
<9 days
NR
NR
3-N1trophenol
554-84-7
139.11
0.75 at 20°C
13,500 mg/i
at 20-25°C
2.00
2.00
3-19.5
(estimated)
52.83,
clay loam
NR
NR
NR
4-N1trophenol
100-02-7
139.11
0.75 at 20°C
16,000 mg/l
at 25°C
1.85-1.91
7.156
11-30 green algae
(Chlorella fusca)
57-180, fish
55.25, clay loam
133-400
clay soils
NR
16 hours to
>6.7 days
6.6 days
(estimated)
'Source: U.S. EPA, 1985
NR - Not reported
0072h
-2-
08/27/86
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4-Nitrophenol 1s produced as a metabolite by m1crob1al and hydrolytlc
decomposition .of the pesticides parathlon, methyl parathlon and fluorodlfen
(U.S. EPA, 1985). Occupational exposure that 1s due to dermal contact with
4-n1trophenol may result from handling crops treated with these pesticides.
The general public may be exposed by 1ngest1on of food containing 4-n1tro-
phenol residues as suggested by the Identification of 4-nltrophenol on
spinach that was treated with parathlon (U.S. EPA, 1985). 2-N1trophenol and
4-n1trophenol have been detected In atmospheric partlculates; thus, exposure
from Inhalation potentially exists (U.S. EPA, 1985). The relatively low
vapor pressures for these compounds at ambient temperatures suggest that
volatilization would be minimal and that exposure by the oral route may be
more relevant.
0072h -3- 08/27/86
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
Pertinent quantitative data regarding the absorption of nltrophenols
after oral or Inhalation exposure could not be located In the available
literature.
0072h -4- 08/08/86
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. ACUTE, SUBCHRONIC AND CHRONIC TOXICITY
Pertinent data regarding subchronlc or chronic oral and Inhalation
toxldty of nltrophenols 1n man or experimental animals could not be located
In the available literature.
Table 3-1 lists oral LD-n values for the nltrophenols 1n rats and
mice. From these data It appears that 4-n1trophenol may be more toxic to
rats and mice than the 2- and 3-1somers. Mice appear to be more sensitive
than rats to 2-n1trophenol and rats may be more sensitive than mice to
3-nltrophenol. Methemoglobln formation was reported after acute 4-nltro-
phenol administration to cats (von Oettlngen, 1941) and after 4-n1trophenol
administration to mice (Smith et al., 1967) (route of administration not
reported 1n secondary sources) but not after oral administration of 3- or
4-n1trophenol to rats (Grant, 1959). The U.S. EPA (1980) concluded that
methemoglob1nem1a may be dependent upon the nltroreductase activity of the
organism, which 1s not extensive 1n most species. Oglno and Yasukura (1957)
reported cataract formation In 4-n1trophenol treated vitamin C-def1c1ent
guinea pigs, but H was unclear whether this effect was primarily from the
vitamin deficiency Itself (U.S. EPA, 1980).
Since 2,4-d1n1trophenol 1s ah uncoupler of oxldatlve phosphorylatlon
(U.S. EPA, 1980), several Investigators have explored the possibility that
mononltrophenols act similarly. Cameron (1958) found substantial differ-
ences In the effect of mononltrophenol on the metabolic activity of rats.
Carbon dioxide output was Increased by 4-n1trophenol, oxygen consumption was
depressed by 3-n1trophenol and 2-n1trophenol had no effect on either
parameter. Of the mono- and d1-n1trophenols tested, only 2,4-d1n1trophenol
0072h -5- 08/27/86
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TABLE 3-1
Acute Toxlclty of Orally Administered NHrophenols*
Isomer
2-N1trophenol
3-N1trophenol
4-N1trophenol
Species
rat
mouse
rat
mouse
rat
rat
mouse
L050
(mg/kg)
2830
1300
930
1410
620
350
470
Reference
Vernot et al. ,
Vernot et al. ,
Vernot et al.,
Falrchlld, 1977
Vernot et al.,
1977
1977
.1977
1977
'Source: U.S. EPA, 1985
0072h
-6-
08/08/86
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stimulated both carbon dioxide output and oxygen consumption. Based on
these results, the U.S. EPA (1980) concluded that the mononltrophenols were
not potent uncouplers of oxldatlve phosphorylatlon.
The findings of direct binding of 3-n1trophenol to erythrocyte
membranes, leading to the formation of ghost cells (Mackleldt et a!., 1972)
and 2- and 4-nltrophenol Inhibition of chloride transport In erythrocytes
(Motals et al., 1978) suggest that these agents may act directly on the cell
membrane. Species were unspecified and no further details were given.
An abstract of a Russian study (Makhlnya, 1969) stated that administra-
tion of 2-, 3- or 4-n1trophenol caused gastritis, enteritis, colitis,
hepatitis, neuritis, splenic hyperplasla and Inhibited oxidation processes
1n an unspecified species. Details were limited.
3.2. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
In a preliminary developmental toxldty test 1n groups of 10 mice.
Plasterer et al. (1985) found that oral administration of 400 mg/kg 4-nltro-
phenol, from days 7-14 of gestation, had no adverse effects on Indices of
fetal survival, birth weights or the Incidence of gross malformations.
Maternal survival and weight gain, however, were significantly decreased.
The oral LQ,Q for adult mice when administered da^ly for 8 days was
calculated to be 625.7 mg/kg In this study.
3.3. TOXICANT INTERACTIONS
Relnke and Moyer (1985) found that ethanol pretreatment caused rapid
mlcrosomal metabolism of 4-nHrophenol to 4-nHrocateehol, which In turn
competed with 4-nltrophenol for conjugation with glucuronlc acid or sulfate.
Much slower rates of metabolic Induction were effected by Interactions with
phenobarbHal and B-napthoflavone.
0072h -7- 11/06/86
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4. CARCINOGENICITY
4.1. HUMAN DATA
Data regarding the carcinogenlcHy of the nHrophenols to humans could
not be located 1n the available literature.
4.2. BIOASSAYS
Pertinent data regarding oral or Inhalation oncogenldty 1n experimental
animals could not be located In the available literature.
4.3. OTHER RELEVANT DATA
Boutwell and Bosch (1959) conducted skin-painting assays In female mice
using 25 yl of 2- or 4-n1trophenol In dloxane, twice weekly for 12 weeks.
The Incidence of any tumor type was not Increased as a result of treatment
with either compound. The U.S. EPA (1985) considered this study Inadequate
for assessment of the oncogenlc potency of nltrophenol.
The NTP (1986) Is currently conducting a chronic skin-painting study
with 4-nltrophenol 1n mice.
The results of mutagenlclty testing of the nltrophenol Isomers have been
summarized by U.S. EPA (1985). For the most part, 2-, 3- or 4-n1trophenol
did not Increase the frequency of reverse mutations In either Salmonella
typhlmurlum or Escherlchla coll (Taylor, 1979a,b; Haworth et al., 1983;
Suzuki et al., 1983; Probst et al., 1981). Fahrlg (1974) reported that
4-n.1trophenol also did not Increase the frequency of forward mutations 1n E_.
coll or Serratla marcescens. or recessive lethal mutations 1n Drosophlla
melanogaster; however, Increases In the frequency of mltotlc gene conver-
sion, probably Indicative of DNA single-strand breaks were found In
Saccharomyces cerevlslae with 4-nltrophenol (Fahrlg, 1974). In confluent
human flbroblast cultures, 4-n1trophenol Inhibited both repair and repHca-
tlve DNA synthesis (Polrler et al., 1975).
0072h -8- 08/27/86
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4.4. WEIGHT OF EVIDENCE
The nltrophenols should be classified as IARC Group 3 or EPA Group 0
(U.S. EPA, 1986). These classifications apply to chemicals with Inadequate
relevant carclnogenlcHy data.
0072h -9- 02/04/87
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5. REGULATORY STANDARDS AND CRITERIA
PerMnent guidelines and standards Including EPA ambient water and air
quality criteria, drinking water standards, HAs, AADIs and ACGIH, NIOSH or
OSHA occupational exposure limits could not be located 1n the available
literature. The U.S. EPA (1980) defined organoleptlc detection thresholds
for nltrophenols of 0.24-389 mg/8. based upon the Soviet literature. U.S.
EPA (1980) stated that the absence of chronic toxldty data precluded
derivation of water criteria for the nltrophenols.
The tolerance for the herbicide fluorodlfen and Its metabolites (Includ-
ing 4-n1trophenol) on peanut hulls, peanuts and peanut vine hay Is 0.2 ppm
(CFR, 1982). For soybean forage, soybeans, and seed and pod vegetables and
their forages, the tolerance 1s 0.1 ppm (CFR, 1982).
0072h -10- 08/08/86
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6. RECOMMENDATIONS
Results from a limited number of mutagenldty tests In prokaryotlc
systems Indicate that the nltrophenols are not potent mutagens, although
effects on DNA synthesis In human flbroblasts wHh 4-nKrophenol (Po1r1era et
al., 1975) are cause for concern. Both 2- and 4-nltrophenol were negative
1n skin-painting studies using mice; 4-nltrophenol 1s currently being
retested 1n this system by the NTP (1986). Recommendations for further
cardnogenldty testing of these compounds await the results of the NTP
(1986) study In progress.
If the results of this study do not suggest a carcinogenic role for the
nltrophenols, subchronlc threshold toxldty testing would be In order,
Initially by oral exposure. The oral LD5Q data suggest different
thresholds of toxldty for the different Isomers of nltrophenol In different
species (U.S. EPA, 1985). Other acute toxldty data Indicate that the
different Isomers may have different mechanisms of toxldty. Cameron (1958),
for example, observed marked differences In the Impact of the various
Isomers on the metabolic activity of rats. 4-NHrophenol has been
associated with ca-taract formation In guinea pigs (Oglno and Yasukura, 1957)
and methemoglob1nem1a In cats (von Oettlngen, 1941) and mice (Smith et al.,
1967). An abstract of a Russian study (Makhlnya, 1969) associates gas^
trHls, enteritis, colitis, hepatitis, neuritis, splenic hyperplasla and
Inhibited oxidation processes with each of the nltrophenol Isomers. These
data are Insufficient to suggest a target organ for these compounds and
these data suggest that risk assessment for one Isomer should not be based
by analogy on data obtained with another Isomer. Similarly, risk assessment
0072h -11- 01/23/87
-------
of the nltrophenols should not be based on analogy to 2,4-d1n1tropheno1
since these chemicals appear to differ markedly In their mechanisms of
toxldty (U.S. EPA, 1980).
Although 4-n1trophenol had no apparent effects on reproductive Indices
or gross malformation 1n mice treated during gestation (Plasterer et al.,
1985), the small number of animals/test group and the limited parameters of
developmental toxldty measured render this study Inadequate to serve as the
sole basis for evaluating the reproductive toxlclty of this compound. It Is
recommended that the developmental toxldty of all three Isomers be
evaluated more completely and that animals from subchronlc studies be
evaluated to determine potential effects of these compounds on reproductive
performance.
0072h -12- 01/23/87
-------
7. REFERENCES
Boutwell, R.K. and O.K. Bosch. 1959. The tumor-promoting action of phenol
and related compounds for mouse skin. Cancer Res. 19: 413-424.
Cameron, M.A.M. 1958. The action of nltrophenols on the metabolic rate of
rats. Br. 3. Pharmacol. 13: 25-29.
CFR (Code of Federal Regulations). 1982. Fluorodlfen: Tolerances for
Residues. 40 CFR 180.290.
Fahrlg, R. 1974. Comparative mutagenlclty studies with pesticides. IARC
Scl. Publ. 10: 161-181.
Falrchlld, E.O., Ed. 1977. Agricultural chemicals and pesticides. A
subfile of the NIOSH Registry of Toxic Effects of Chemical Substances.
NIOSH, Cincinnati, OH. (CUed In U.S. EPA, 1980)
Grant, C.M. 1959. The action of nHrophenols on the pulmonary ventilation
of rats. Br. 0. Pharmacol. 14: 401-403. (Cited 1n U.S. EPA, 1985)
Haworth, S., T. Lawlor, K. Mortelmans, W. Speck and E. Zelger. 1983.
Salmonella mutagenlclty test results for 250 chemicals. Environ. Mutagen.
Suppl. 1: 3-142. (CHed 1n U.S..EPA, 1985)
Mackleldt, H., et al. 1972. The hydrophoblc expansion of erythrocyte
membranes by the phenol anesthetics. Blochem. Blophys. Acta. 225: 178.
(Cited In U.S. EPA, 1980)
0072h -13- 08/08/86
-------
Makhlnya, A.P. 1969. [Comparative hygienic and sanitary toxlcologlcal
studies on nltrophenol Isomers 1n relation to their normalization 1n
reservoir waters.] (Rus.) Prom. Zagryazneulya Vodoeuov. 9: 84-85. (CA
72:47231c) (Cited In U.S. EPA. 1983b)
Motals, R., F. Sola and J.L. Cousin. 1978. Uncouplers of oxldatlve
phosphorylatlon, a structure-activity study of their Inhibitory effect on
passive chloride permeability. Blochem. Blophys. Acta. 510: 201-207.
(Cited 1n U.S. EPA, 1980, 1985)
NTP (National Toxicology Program). 1986. Management Status Report.
3/12/86.
Oglno, S. and K. Yasukura. 1957. Biochemical studies of cataracts. VI.
Production of cataracts 1n guinea pigs with dinltrophenol. Am J. Ophthamol.
43: 936-946. (Cited 1n U.S. EPA, 1980, 1985)
Plasterer, M.R., W.S. Bradshaw, G.H. Booth, M.W. Carter, R.L. Schuler and
B.D. Hardln. 1985. Developmental toxldty of nine selected compounds
following prenatal exposure 1n the mouse: Naphthalene, p-n1trophenol, sodium
selenlte, dimethyl phvhalate, ethylenethlourea and four glycol ether
derivatives. J. Toxlcol. Environ. Health. 15(1).: 25-38.
Po1r1er, M.C., B.T. Dedcco and M.W. L1eke1man. 1975. Nonspecific Inhibi-
tion of DNA repair synthesis by tumor promoters 1n human dlplold flbroblasts
damaged with N-acetoxy-2-acetylamlno-fluorene. Cancer Res. 35: 1392-1397.
(Cited In U.S. EPA, 1985)
0072h -14- 08/27/86
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hepatocyte cultures: A comparison with bacterial mutagenlclty using 218
compounds. Environ. Mutagen. 3: 11-32. (CHed In U.S. EPA, 1985)
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somal oxidation which Is highly Induclble by ethanol. Drug Metab. Dlspos.
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Smith, R.P., A.A. Alkaltls and P.R. Schafer. 1967. Chemically Induced
methemoglob1nem1a 1n the mouse. Blochem. Pharm. 16: 317-328. (CHed In
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zene derivatives In the presence of norharman. Mutat.. Res. 120: 105-110.
(Cited In U.S. EPA, 1985)
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communication dated June 12, 1979 to Mutagenlclty Task Force, regarding
mutagenlclty testing of ortho- and para-nltrophenols. {CHed In U.S. EPA,
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Taylor, G. 1979b. Laboratory Investigation Branch, DRDS, NIOSH. Written
communication dated June 12, 1979 to Mutagenlclty Task Force, NIOSH, regard-
Ing mutagenlclty testing of meta-nltrophenol. (CHed In U.S. EPA,1985)
0072h -15- 08/08/86
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U.S. EPA. 1980. Ambient Water Quality Criteria Document for NHrophenols.
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Criteria and Assessment Office, Cincinnati, OH for the Office of Hater Regu-
lations and Standards, Washington, DC. EPA 440/5-80-063. NTIS PB81-117749.
j
U.S. EPA. 1983a. Reportable Quantity Document for 2-N1trophenol. Prepared
by the Office of Health and Environmental Assessment, Environmental Criteria
and Assessment Office, Cincinnati, OH for the Office of Emergency and
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by the Office of Health and Environmental Assessment, Environmental Criteria
and Assessment Office, Cincinnati, OH for the Office of Emergency and
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Prepared by the Office of Health and Environmental Assessment, Environmental
Criteria and Assessment Office, Cincinnati, OH for the Office of 'Emergency
and Remedial Response., Washington, DC.
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Prepared by the Office of Health and Environmental Assessment, Environmental
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and Emergency Response, Washington, DC.
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Register. 5^1(185): 33992-34003.
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toxldty and skin conversion data for some organic and Inorganic compounds
and aqueous solution. Toxlcol. Appl. Pharmacol. 42(2): 417-423. (Cited In
U.S. EPA, 1985)
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toxldty and potential dangers. A review of the literature. U.S. Publ.
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