TECHNICAL REPORT DATA
ffttut read Instruction* on the reverie btfort compltnng)
1. TEPORT -JO.
EPA/600/8-88/033
2.
3. RECIPIENT'S ACCESSION NO
PB88-180211/AS
4. TITLE AND SUBTITLE
Health Effects Assessment for 1,2-Diphenylhydrazine
6. REPORT DATE
6. PERFORMING ORGANIZATION CODE
7 AUTHORtS)
I. 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, RfD$ or subchronic 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. 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, qi*s have been computed, if appropriate, based on oral and
inhalation data if available.
17.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS C. COSAT1 Field/Group
18. DISTRIBUTION STATEMENT
Public
19. SECURITY CLASS (This Report I
Unclassified
21. NO. OF PAGES
20. SECURITY CLASS (This page)
Unclassified
22. PRICE
EPA F*rm 2220-1 (R«». 4-77) PKCVIOUS COITION is OMOUKTC
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EPA/600/8-88/033
May, 1987
HEALTH EFFECTS ASSESSMENT
FOR 1,2-DIPHENYLHYDRAZINE
ENVIRONMENTAL CRITERIA AND ASSESSMENT OFFICE
OFFICE OF HEALTH AND ENVIRONMENTAL ASSESSMENT
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
CINCINNATI, OH 45268
-------
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 summarizes and evaluates Information relevant to a prelimi-
nary Interim assessment of adverse health effects associated with
1,2-d1phenylhydraz1ne. All estimates of acceptable Intakes and carcinogenic
potency presented 1n this document should be considered as preliminary and
reflect limited resources allocated to this project. Pertinent toxlcologlc
and environmental data were located through on-Hne literature searches of
the Chemical Abstracts, TOXLINE, CANCERLINE and the CHEMFATE/OATALOG data
bases. The basic literature searched supporting this document is current up
to May, 1986. Secondary sources of Information have also been relied upon
In the preparation of this report and represent large-scale health assess-
ment 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. 1980a. Ambient Water Quality Criteria Document for
1,2-01phenylhydraz1ne. Prepared by the Office of Health and
Environmental Assessment, Environmental Criteria and Assessment
Office, Cincinnati, OH for the Office of Water Regulations and
Standards, Washington, DC. EPA 440/5-80-062. NTIS PB81-117731.
U.S. EPA. 1980b. Hazard Profile for 1,2-01phenylhydraz1ne.
Prepared by the Office of Health and Environmental Assessment,
Environmental Criteria and Assessment Office, Cincinnati,, OH for
the Office of Solid Waste, Washington, DC.
The Intent 1n these assessments 1s to suggest acceptable exposure levels
whenever sufficient data were available.. Values were not derived or larger
uncertainty factors were employed when the variable data was limited In
scope, which tended to generate conservative (I.e., protective) estimates.
Nevertheless, the Interim values presented reflect the relative degree of
hazard associated with exposure or risk to the chemlcal(s) addressed.
Whenever possible, two categories of values have been estimated for
systemic toxicants (toxicants for which cancer 1s 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 Hfespan).
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 1n ambient air or water where lifetime
exposure 1s 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$i) and oral (RfO$o)
exposures.
111
-------
The RfO (formerly AIC) Is similar 1n concept and addresses chronic
exposure. It 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 Hfespan [see U.S. EPA (1980b) for a discussion of ttils concept]. The
RfO 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 noncardnogens have also been calculated
where data permitted. These values are used for Identifying reportable
quantities and the methodology for their development Is explained 1n U.S.
EPA (1983).
For compounds for which there Is sufficient evidence of carclnogenlcTty
RfD$ and RfD values are not derived. For a discussion of risk assessment
methodology for carcinogens refer to U.S. EPA (1980b). Since cancer 1s a
process that 1s 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
-------
ABSTRACT
In order to place the risk assessment evaluation In proper context,
refer to the preface of this document. The preface outlines limitations
applicable to all documents of this series as well as the appropriate
Interpretation and use of the quantitative estimates presented.
The oral carclnogenldty of 1,2-dlphenylhydrazlne was demonstrated In
2-year feeding studies using rats and mice (NCI, 1978). Based on the
concentration-related Increase In hepatic carcinomas and neoplastlc nodules
In treated male rats, the U.S. EPA (1980a) calculated a human q-|* of 0.768
(mg/kg/day)-1.
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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. Or. 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 Kim Davidson
Environmental Criteria and Assessment Office
Cincinnati, OH
v1
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TABLE OF CONTENTS
1.
2.
3,
4.
5.
6.
7.
kPPE
ENVIRONMENTAL CHEMISTRY AND FATE
ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS . . .
2.1. ORAL
2.2. INHALATION
TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC .......
3.1.1. Oral
3.1.2. Inhalation
3.2. CHRONIC
3.2.1. Oral. .
3.2.2. Inhalation
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS. . . .
3.4. TOXICANT INTERACTIONS
CARCINOGENICITY
4.1. HUMAN DATA
4.2. BIOASSAYS
4.2.1. Oral. .....
4.2.2. Inhalation
4.3. OTHER RELEVANT DATA.
4.4. WEIGHT OF EVIDENCE
REGULATORY STANDARDS AND CRITERIA
RISK ASSESSMENT .......
6.1. SUBCHRONIC REFERENCE DOSE (RfOs)
6.2. REFERENCE DOSE (RfD)
6.3. CARCINOGENIC POTENCY (q-,*)
6.3.1. Oral
6.3.2. Inhalation
REFERENCES
NDIX
Page
. . . 1
. . . 3
. . . 3
. . . 3
. . . 4
. . . 4
. . . 4
, , 4
4
. . . 4
. . . 5
. . . 5
. . . 5
. . . 6
. . . 6
. . . 6
. . . 6
, . , 9
. . . 9
. . . 10
. . . 11
. . . 12
. . . 12
. . . 12
. . . 12
. . . 12
12
14
. . . 18
V11
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LIST OF ABBREVIATIONS
ADI Acceptable dally Intake
CAS Chemical Abstract Service
CS Composite score
DMBA Dimethyl benzanthracene
DNA Deoxyrlbonuclelc add
Koc Soil sorptlon coefficient
Kow Octanol/water partition coefficient
LOEL Lowest-observed-effect level
MED Minimum effective dose
NOEL No-observed-effect level
ppm Parts per million
RfD Reference dose
RfDi Inhalation reference dose
RfDg Oral reference dose
RfD$i Subchronlc Inhalation reference dose
RfDgg Subchronlc oral reference dose
RV,j Dose-rating value
RVe Effect-rating value
TWA Time-weighted average
UV Ultraviolet
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1. ENVIRONMENTAL CHEMISTRY AND FATE
The relevant physical and chemical properties and environmental fate of
1,2-d1phenylhydraz1ne are reported 1n Table 1-1.
In the atmosphere, 1,2-dlphenylhydrazlne has the potential to undergo
direct photolysis, as Indicated by UV absorption >290 nm (Sadtler, n.d.),
autooxldlzatlon (U.S. EPA, 1981) and reaction with photochemlcally generated
HO radical {U.S. EPA, 1986). Based on a hydroxyl reaction rate constant of
3.4xlO-11 cma/molecule-sec and an ambient HO radical concentration of
S.OxlO5 molecules/cm3, the hydroxyl reaction half-life 1s calculated to
be 7.08 hours (U.S. EPA, 1986). The aquatic half-life of 1,2-dlphenylhydra-
zlne Is based on the observation that 1,2-d1phenylhydraz1ne (10 yg/l) 1n
dilute aqueous solution was found to be unstable, with <10X remaining for
longer than 1 day of preservation (1n the dark) under any of the conditions
tested (I.e., room temperature or 4°C at pH 2, 7 or 10 with or without
chlorine). 1,2-01phenylhydraz1ne decomposed primarily to azobenzene at pH
10, to benzldlne at pH 2 and to an unidentified but oxldlzable compound at
pH 7 (U.S. EPA, 1981). The half-life of 1,2-d1phenylhydraz1ne at a concen-
tration of 100 jig/i. Tn a municipal sewage effluent was 15 and 60 minutes
under aerobic and anaerobic conditions, respectively (U.S. EPA, 1981).
1,2-D1phenylhydraz1ne should not significantly bloaccumulate or adsorb to
sediments. The half-life of 1,2-dlphenylhydrazlne 1n soil was not located
1n the available literature. 1,2-D1phenylhydraz1ne can undergo sublimation
(U.S. EPA, 1981), suggesting that volatilization from soil surfaces may
occur. Based on Us reactivity 1n water, It 1s likely to undergo signifi-
cant chemical and blodegradatlon reactions 1n soil. The estimated K
value of 947 Indicates that 1,2-d1pheny1hydraz1ne should have low mobility
In soil.
Q074h -1- 12/05/86
-------
TABLE 1-1
Relevant Physical and Chemical Properties of 1,2-01pheny1hydraz1ne
Property
Value
Reference
CAS number:
Chemical class:
Molecular weight:
Vapor pressure:
Water solubility:
Log octanol/water
partition coefficient:
Bloconcentratlon factor:
Soil adsorption
coefficient:
Half-lives:
Air
Water
Soil
122-66-7
substituted hydrazlne
184.24
NA
314 mg/i at 25°C
(estimated)*
221 mg/i
(temperature NA)
2.94
101 (estimated)
947 (estimated)
-7 hours (estimated)
<1 day
NA
Lyman et al.,
1982
U.S. EPA, 1981
Hansch and Leo,
1985
Lyman et al.,
1982
Lyman et al.,
1982
U.S. EPA, 1986b
U.S. EPA, 1981
"Calculated using log Kow value listed above and the following equation:
log S = -1.37 log Kow +7.26 (Lyman et al., 1982)
NA = Not available
0074h
-2-
12/05/86
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2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1. ORAL
Rats given an oral dose of either 200 or 400 mg/kg 1,2-d1phenylhydraz1ne
excreted hydrazobenzene, benzldlne and two unidentified metabolites In the
urine, but the proportion of the dose eliminated this way was not quantified
and conclusions regarding the rate and amount of gastrointestinal absorption
could not be made from these data (Dutk1ew1cz and Szymanska, 1976).
There are no pertinent human data on the gastrointestinal absorption of
1,2-d1phenylhydraz1ne.
2.2. INHALATION
Outk1ew1cz and Szymanska (1976) Identified one urinary metabolite after
Intratracheal administration of 1,2-d1phenylhydraz1ne In rats, but quantHa-
tlon was not performed. No direct assessment of the respiratory absorption
of 1,2-d1phenylhydraz1ne was found 1n the available animal literature, and
pertinent human data could not be located 1n the available literature.
0074h -3- 08/14/86
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3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS
3.1. SUBCHRONIC
3.1.1. Oral. NCI (1978) exposed rats and mice to dietary 1,2-d1phenyl-
hydrazlne for 4 weeks, followed by a 2-week observation period. Dietary
concentrations for male rats and mice ranged from 0.007-0.423%, for female
rats from 0.00008-5.138% and for female mice from 0.0003-5.138%. Lethality
was first observed at 0.108% 1n rats and 0.301% In mice. Intestinal
hemorrhage was grossly observed In mice at unspecified concentration levels.
Because of the lack of sufficient details of the sublethal effects In
this study, a NOEL or LOEL cannot be assumed.
3.1.2. Inhalation. Pertinent data regarding the subchronlc toxldty of
1,2-dlphenylhydrazlne after Inhalation exposure could not be located In the
available literature.
3.2. CHRONIC
3.2.1. Oral. NCI (1978) conducted 78-week bloassays of dietary
1,2-dlphenylhydrazlne In groups of -50 rats/sex and -50 mice/sex. Rats were
observed for 28-30 weeks following the end of treatment and mice for 17-18
weeks following the end of treatment. TWA dietary concentrations were 0.008
or 0.03% (80 or 300 ppm) for male rats, 0.004 or 0.01% (40 or 100 ppm) for
female rats, 0.008 or 0.04% (80 or 400 ppm) for male mice and 0.004 or 0.04%
(40 or 400 ppm) for female mice. Controls consisted of 49-50 animals/sex of
each species for both the low and high groups. Reduced survival was
observed In female rats and 1n mice of both sexes In the high-dose groups.
High-dose mice also had reduced mean body weights at termination. Although
the authors concluded that no compound-related nonneoplastlc lesions were
observed, an examination of the raw data suggested that Inflammation of the
lung, splenic hyperplasla and hyperkeratosls and acanthosls of the stomach
In both species may have been related to treatment.
0074h -4- 12/05/86
-------
3.2.2. Inhalation. Pertinent data regarding toxlclty after chronic
Inhalation exposure to 1,2-d1phenylhydraz1ne could not be located 1n the
available literature.
3.3. TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
Pertinent data regarding the reproductive toxlclty of 1,2-dlphenylhydra-
zlne, after either oral or Inhalation exposure, could not be located 1n the
available literature.
3.4. TOXICANT INTERACTIONS
Several authors (Marhold et al., 1968; Genln et al., 1975; Kurlyandsk11
et al., 1976) demonstrated synerglsm between 1,2-d1phenylhydraz1ne, or
related compounds, and benzldlne, 1n tumor Induction (U.S. EPA, 1980a).
0074h -5- 08/14/86
-------
4. CARCINOGENICITY
4.1. HUMAN DATA
There were no pertinent ep1dem1olog1cal or occupational data 1n the
available literature regarding oral or Inhalation exposure specifically to
1,2-d1phenylhydraz1ne. The U.S. EPA (1980a) expressed concern over the
oncogenlc potential of 1,2-d1phenylhydraz1ne because of evidence that
workers Involved In dye manufacturing had Increased Incidences of bladder
cancer (Wynder et a!., 1963; Anthony et al., 1970).
4.2. BIOASSAYS
4.2.1. Oral. The most pertinent cancer data from the chronic NCI (1978)
bloassay In rats and mice (see Section 3.2.1.) are presented In Tables 4-1
and 4-2, respectively. Of the several treatment-related tumor types found,
the U.S. EPA (1980a) considered the Increased Incidence of hepatic neo-
plastlc nodules/hepatocellular carcinomas In male rats to be of the greatest
biological significance. Assuming rats consume the dietary equivalent of 5%
of their body weight dally (U.S. EPA, I980c), the TWA concentrations
correspond to 4 and 15 mgAg/day for male rats.
Qualitative evidence of cardnogenldty was provided by PUss (1974),
who studied the cardnogenldty of oral 1,2-d1pheny1hydraz1ne given for 588
days to rats and mice; 30 mg of 1,2-d1phenylhydraz1ne/mouse or rat was added
to the food 5 times/week. Tumors (primarily pulmonary adenomas, leukemlas
and liver tumors) developed 1n 50% of all treated mice. Incidence data for
rats or control mice were not given In the descriptions provided by U.S. EPA
(1980a, 1981). Apparently, Pllss (1974) replaced some animals that had
parasitic Infections during the course of the experiment.
0074h -6- 01/22/87
-------
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4.2.2. Inhalation. Pertinent data regarding the cardnogenldty of
!,2-d1phenylhydraz1ne after Inhalation exposure In experimental animals
could not be located 1n the available literature.
4.3. OTHER RELEVANT DATA
A variety of tumor types was observed by PUss (1974) after repeated
subcutaneous or eplcutaneous administration of 1,2-d1phenylhydraz1ne to
mice, or subcutaneous Injections 1n rats. Increased Incidences of rhabdo-
myosarcoma, pulmonary and hepatic tumors, Zymbal's gland tumors, leukemia,
and neoplasla of the spleen, uterus and mammary glands were observed. U.S.
EPA (1980a) noted that control data were provided only for eplcutaneous
administration.
SpHz et al. (1950) have suggested that 1,2-d1phenyl- hydrazlne 1s not
carcinogenic by the subcutaneous route (further details not provided),
although several Soviet authors (Genln et al., 1975; Shabad and Genln, 1975;
Kurlyandskll et al., 1976) have shown the add1t1v1ty of subcutaneous
1,2-d1phenylhydraz1ne and benzldlne sulfate 1n causing bladder tumors.
Maronpot et. al. (1983) demonstrated the cardnogenlclty of
1,2-d1phenylhydraz1ne 1n a mouse strain A pulmonary test system,
There 1s evidence 1n rats (see Sections 2.1. and 2.2.) that
1,2-d1phenylhydraz1ne 1s metabolized to hydrazobenzene and ben;r1d1ne as well
as other Intermediates. Given that azobenzene and benzldlne have known
human carcinogenic potential, the weight of evidence for probable human
cardnogenlclty 1s further substantiated
Dlphenylhydrazlne was mutagenlc toward Salmonella typh'imurlum strain
TA100, 1n the presence of rat liver S-9 (Haworth et al., 1983). The tech-
nical grade material was not genotoxlc 1n an Escher1ch1a col 1 WP2 uvrA
reversion assay (Ounkel et al., 1985), and practical grade dlphenylhydrazlne
0074h -9- 01/23/87
-------
did not cause sex-linked recessive lethal mutations In Drosophlla (Yoon et
a!., 1985). Seller (1977), however, showed that an 1ntraper1toneal dose of
1,2-d1phenylhydraz1ne had an Inhibitory effect upon testlcular ONA synthesis
In male mice.
4.4. WEIGHT OF EVIDENCE
IARC (1974) did not evaluate 1,2-d1phenylhydraz1ne for carcinogenic
potency. There are sufficient data In both rats and mice to consider
1,2-d1phenylhydraz1ne a potential human carcinogen (NCI, 1978). In the
absence of definitive human data and In the presence of sufficient evidence
In rats and mice (NCI, 1978), 1,2-d1phenylhydraz1ne can be classified an EPA
Group 82 (U.S. EPA, 1986a), or IARC Group 28, carcinogen.
0074h -10- 01/22/87
-------
5. REGULATORY STANDARDS AND CRITERIA
U.S. EPA (1980a) recommended ambient water quality criteria of 4, 42 and
422 yig/4, for dlphenylhydrazlne, corresponding to excess cancer risk
levels of 10~7, 10~6 and 1CT5, respectively. The criteria are based
on the Induction of hepatocellular carcinomas and neoplastlc nodules In male
F344 rats (NCI, 1978).
Other pertinent guidelines and standards, Including drinking water
standards, ADIs, HAs, AADIs and ACGIH, OSHA or NIOSH occupational exposure
limits could not be located 1n the available literature.
0074h -11- 08/14/86
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6. RISK ASSESSMENT
6.1. SUBCHRONIC REFERENCE DOSE (RfD )
O
Because of the demonstrated oncogenldty of 1,2-dlphenylhydrazlne In
experimental animals (NCI, 1978), calculation of an RfOSQ or RfDSI 1s
Inappropriate.
6.2. REFERENCE DOSE (RfD)
Because of the demonstrated oncogenldty of 1,2-d1phenylhydraz1ne 1n
experimental animals (NCI, 1978), calculation of an RfDQ or RfCL 1s
Inappropriate.
6.3. CARCINOGENIC POTENCY (q^)
6.3.1. Oral. U.S. EPA (1980a) calculated a human q^ of 0.768
(mg/kg/day)"1 for 1,2-d1phenylhydraz1ne, using the linearized multistage
model that was adopted by the U.S. EPA (198Qc). This value was based upon
the Incidence of hepatocellular carcinomas and neoplastlc nodules 1n male
F344 rats treated chronically with 0.008% or 0.03% dietary 1,2-dlphenyl-
hydrazlne (NCI, 1978). The data used In this computation are reported In
Table 6-1. Because the Incidence of liver tumors 1n the male rats Is the
most convincing cardnogenldty data available, the q * derived by the
U.S. EPA (1980a), which has undergone both Internal Agency and external
review, 1s adopted for the purposes of this document.
6.3.2. Inhalation. In the absence of pertinent data regarding the
cardnogenldty of 1,2-d1phenylhydraz1ne after Inhalation exposure, a unit
risk for Inhalation exposure 1s not listed 1n this document.
0074h -12- 05/13/87
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TABLE 6-1
Cancer Data Sheet for Derivation of a
for 1,2-01phenylhydraz1ne
Reference: NCI, 1978; U.S. EPA, 1980a
Specles/straln/sex: rats, F344, male
Route/vehicle: diet
Length of exposure (le) = 78 weeks
Length of experiment (LE) = 104 weeks
Llfespan of animal (L) = 104 weeks
Body weight = 0.380 kg (measured)
Tumor site and type: hepatocellular carcinomas and neoplastlc nodules
Transformed Dose Incidence
(mg/kg/day) No. Responding/No. Examined
0 6/95
4 13/49
15 37/49
0074h -13- 08/14/86
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0074h -16- 02/06/87
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Wynder, E.L., et al. 1963. An ep1dem1o1og1cal Investigation of cancer In
the bladder. Cancer. 16: 1388. (Cited 1n U.S. EPA, 1980a)
Yoon, J.S., J.M. Mason, R. Valencia, R.C. Woodruff and S. ZlmmeMng. 1985.
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7(3): 349-367.
0074h -17- 02/06/87
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