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Benzo[g,h,i]perylene
CASRN 191-24-2
Contents
0461
Benzo[g,h,i]perylene; CASRN 191-24-2
Health assessment information on a chemical substance is included in IRIS only
after a comprehensive review of chronic toxicity data by U.S. EPA health
scientists from several Program Offices and the Office of Research and
Development. The summaries presented in Sections I and II represent a
consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are
provided in the Background Documents.
STATUS OF DATA FOR Benzo[g,h,i]perylene
File On-Line 12/01/1990
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) no data
Inhalation RfC Assessment (I.B.) no data
Carcinogenicity Assessment (II.) on-line 12/01/1990
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- Benzo[g,h,i]perylene
CASRN -- 191-24-2
Not available at this time.
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Benzo[g,h,i]perylene
CASRN -- 191-24-2
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Benzo[g,h,i]perylene
CASRN -- 191-24-2
Last Revised -- 12/01/1990
Section II provides information on three aspects of the carcinogenic
assessment for the substance in question; the weight-of-evidence judgment of
the likelihood that the substance is a human carcinogen, and quantitative
estimates of risk from oral exposure and from inhalation exposure. The
quantitative risk estimates are presented in three ways. The slope factor is
the result of application of a low-dose extrapolation procedure and is
presented as the risk per (mg/kg)/day. The unit risk is the quantitative
estimate in terms of either risk per ug/L drinking water or risk per ug/cu.m
air breathed. The third form in which risk is presented is a drinking water
or air concentration providing cancer risks of 1 in 10,000, 1 in 100,000 or 1
in 1,000,000. The rationale and methods used to develop the carcinogenicity
information in IRIS are described in The Risk Assessment Guidelines of 1986
(EPA/600/8-87/045) and in the IRIS Background Document. IRIS summaries
developed since the publication of EPA's more recent Proposed Guidelines for
Carcinogen Risk Assessment also utilize those Guidelines where indicated
(Federal Register 61(79):17960-18011, April 23, 1996). Users are referred to
Section I of this IRIS file for information on long-term toxic effects other
than carcinogenicity.
__II.A. EVIDENCE FOR CLASSIFICATION AS TO HUMAN CARCINOGENICITY
___II.A.1. WEIGHT-OF-EVIDENCE CLASSIFICATION
Classification -- D; not classifiable as to human carcinogenicity
Basis -- Based on no human data and inadequate animal data from lung implant,
skin-painting and subcutaneous injection bioassays.
___II.A.2. HUMAN CARCINOGENICITY DATA
None.
___II.A.3. ANIMAL CARCINOGENICITY DATA
Inadequate. Benzo[g,h,i]perylene appeared to increase lung epidermoid
tumors when administered with trioctanonin in a lung implant study (Deutsch-
Wenzel et al., 1983). Benzo[g,h,i]perylene was tested for complete
carcinogenic activity and initiating activity in mouse skin painting assays
and did not produce positive results in either type of assay (Wynder and
Hoffmann, 1959; Hoffmann and Wynder, 1966; Muller, 1968; Van Duuren et al.,
1973). Benzo[g,h,i]perylene did not induce tumor formation when injected
subcutaneously (Muller, 1968) and was tested as a cocarcinogen with
benzo(a)pyrene (Van Duuren et al., 1973; Van Duuren and Goldschmidt, 1976).
In a lifetime implant study, 3-month-old female Osborne-Mendel rats (34
to 35/group) received a lung implant of benzo[g,h,i]perylene in 0.05 mL of a
1:1 (v:v) mixture of beeswax and trioctanonin (Deutsch-Wenzel et al., 1983).
Rats received either 0.16 mg (0.65 mg/kg), 0.83 mg (3.4 mg/kg) or 4.15 mg (17
mg/kg). Controls consisted of an untreated group and a group receiving an
implant of the vehicle. Median survival times (weeks) were: untreated
controls, 118; vehicle implant controls, 104; 0.16 mg dose, 109; 0.83 mg dose,
114; and 4.15 mg dose, 106. Epidermoid carcinomas in the lung and thorax were
observed at the following incidences: 0/35, 0/35, 0/35, 1/35 (3%), and 4/34
(12%) for the untreated controls, vehicle controls, low-, mid-, and high-dose
groups, respectively. The apparent increased incidence of tumors was not
statistically significant and no distant tumors were seen.
Benzo[g,h,i]perylene was tested as both a complete carcinogen and as a
tumor initiator in female Ha/ICR/mil Swiss albino mice (Hoffmann and Wynder,
1966; Wynder and Hoffman, 1959). Two groups of 20 mice received dermal
applications of 0.1 or 0.05% benzo[g,h,i]perylene 3 times/week for 1 year.
The mice were observed for 3 additional months and then sacrificed. No
tumorswere observed in the low-dose group and a papilloma was observed in the
high-dose group in the tenth month. In a second part of the study,
benzo[g,h,i]perylene was applied as an initiator to 30 mice. Ten separate
applications of 0.1% each were given over a 2-day period; beginning 28 days
later 2.5% croton oil was applied 3 times/week for the remainder of the year.
These mice were observed for 3 additional months; 2/27 surviving mice had
developed papillomas in this group. A control group of 30 mice received
applications of 2.5% croton oil (3 times/week) without an initiator; no tumor
or survival data were reported.
The ability of benzo[g,h,i]perylene to act as a cocarcinogen in female
ICR/HA mice when combined with benzo[a]pyrene was examined in a series of
experiments (Van Duuren et al., 1973; Van Duuren and Goldschmidt, 1976). The
mice (50/group) were treated by dermal application with 21 ug
benzo[g,h,i]perylene and 5 ug benzo[a]pyrene (in combination) 3 times/week for
1 year. At the end of the experiment, 20/37 mice had developed papillomas and
17/37 had developed squamous cell carcinomas. In the control group, which
consisted of three benzo[a]pyrene treatments (5 ug/week), 13/42 mice developed
papillomas and 10/42 developed carcinomas (Van Duuren et al., 1973). In the
second experiment two doses of benzo[g,h,i]perylene (7 and 21 ug) were applied
along with 5 ug benzo[a]pyrene to groups of 50 mice 3 times/week for 368 days.
In the low-dose group 19 mice developed papillomas and 10 carcinomas; in the
high-dose group, 20 mice developed papillomas and 18 carcinomas. No
papillomas or carcinomas developed when 21 ug benzo[g,h,i]perylene was applied
alone. The individual animal data were not given for this experiment.
In a series of experiments, Muller (1968) investigated the carcinogenicity
of benzo[g,h,i]perylene. In the first experiment groups of 50 NMRI mice (sex
unspecified) received dermal applications (2 or 3 times/week) of one of a
variety of concentrations of benzo[g,h,i]perylene in dichloromethane. A
control group receving only 0.2 mL dichloromethane was also utilized. The
study was terminated 675 days after the first application. Survival was
approximately the same in all four groups (33%). No skin papillomas or
carcinomas developed; however, both benign (0/18 low-, 2/14 mid- and 3/17
high-dose groups) and malignant (3/18 low-, 4/14 mid- and 1/17 high-dose
groups) tumors in survivors did occur at other sites (types and sites not
specified). In the control group, 3/17 mice developed benign tumors and 4/17
developed malignant tumors at other sites. Dichloromethane is classified B2,
a probable human carcinogen.
In a second dermal application study, groups of 50 mice initially were
untreated or treated with a single application of either 1 or 2 mg
benzo[g,h,i]perylene. In each group repeated dermal applications of 0.2 mL of
0.5% croton oil (2 times/week) followed for 25 weeks. One mouse in the
promoter control group and another in the high-dose group developed skin
papillomas; 2/28 (0/28), 4/12 (1/12), and 2/21 (1/21) mice developed benign
(malignant) tumors at other sites (unspecified) in the control, low- and high-
dose groups, respectively. In the third part of the experiment three groups
of 50 female NMRI mice received subcutaneous injections of 0 (control), 0.83
or 16.7 mg benzo[g,h,i]perylene suspended in 0.15 mL 10% aqueous gelatin once
every 2 weeks for 6 months [total doses, 0, 10 and 200 mg/animal] and observed
to sacrifice on day 675 after the first injection. At that time the survival
rate was 36% in each group. No tumor was found at the site of injection in
any of the animals. For the control, low- and high-dose groups, respectively,
4/50, 5/50, and 4/50 mice had tumors at other sites. In the final part of the
experiment four groups of 20 NMRI mice (sex unspecified) were given
subcutaneous injections of 0.15 mL 10% aqueous gelatin containing 0 (control),
0.1, 1, or 10 mg suspended benzo[g,h,i]perylene (total doses, 0, 10, or 100
mg/animal) once every 2 weeks for 20 weeks. The animals were observed until
spontaneous death. Survival was not adversely affected by treatment with
benzo[g,h,i]perylene (the last animal died 22 months after the start of the
study). There is no information to indicate if enough animals survived long
enough for tumors to be seen. No skin or subcutaneous tumors were found in
mice treated with benzo[g,h,i]perylene or gelatin. Few tumors were found in
other organs and the incidences in the benzo[g,h,i]perylene-treated groups
were not different from those in the gelatin controls. Earlier skin-painting
studies are summarized in IARC (1983).
___II.A.4. SUPPORTING DATA FOR CARCINOGENICITY
Benzo[g,h,i]perylene produced positive results in tests for reverse
mutation in three strains of Salmonella typhimurium and for forward mutation
in one strain (Andrews et al., 1978; Mossanda et al., 1979; Salamone et al.,
1979; Sakai et al., 1985; Kaden et al., 1979). A test for DNA damage in
Chinese hamster ovary cells also yielded positive results (Garrett and Lewtas,
1983).
__II.B. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM ORAL EXPOSURE
None.
__II.C. QUANTITATIVE ESTIMATE OF CARCINOGENIC RISK FROM INHALATION EXPOSURE
None.
__II.D. EPA DOCUMENTATION, REVIEW, AND CONTACTS (CARCINOGENICITY ASSESSMENT)
___II.D.1. EPA DOCUMENTATION
Source Document -- U.S. EPA, 1990
The 1990 Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons
has received Agency and external review.
___II.D.2. REVIEW (CARCINOGENICITY ASSESSMENT)
Agency Work Group Review -- 02/07/1990
Verification Date -- 02/07/1990
___II.D.3. U.S. EPA CONTACTS (CARCINOGENICITY ASSESSMENT)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
_VI. BIBLIOGRAPHY
Substance Name -- Benzo[g,h,i]perylene
CASRN -- 191-24-2
Last Revised -- 12/01/1990
__VI.A. ORAL RfD REFERENCES
None
__VI.B. INHALATION RfC REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
Andrews, A.W., L.H. Thibault and W. Lijinsky. 1978. The relationship between
carcinogenicity and mutagenicity of some polynuclear hydrocarbons. Mutat.
Res. 51: 311-318.
Deutsch-Wenzel, R., H. Brune, G. Grimmer, G. Dettbarn and J. Misfeld. 1983.
Experimental studies in rat lungs on the carcinogenicity and dose-response
relationships of eight frequently occurring environmental polycyclic aromatic
hydrocarbons. J. Natl. Cancer Inst. 71(3): 539-544.
Garrett, N.E. and J. Lewtas. 1983. Cellular toxicity in Chinese hamster
ovary cell cultures. 1. Analysis of cytotoxicity endpoints for twenty-nine
priority pollutants. Environ. Res. 32(2): 455-465.
Hoffmann, D. and E.L. Wynder, 1966. Beitrag zur carcinogen Wirkung von
Dibenzopyrene. Z. Krebsforsch. 68(2): 137-149. (Ger.) Contribution on the
carcinogenic effect of dibenzopyrenes.
IARC (International Agency for Research on Cancer). 1983. Monographs on the
Evaluation of the Carcinogenic Risk of Chemicals for Humans. Polynuclear
Aromatic Compounds. Part 1. Chemical, Environmental and Experimental Data.
Vol. 32. World Health Organization.
Kaden, D.A., R.A. Hites and W.G. Thilly. 1979. Mutagenicity of soot and
associated polycyclic aromatic hydrocarbons to Salmonella typhimurium. Cancer
Res. 39: 4152-4159.
Mossanda, K., F. Poncelet, A. Fouassin and M. Mercier. 1979. Detection of
mutagenic polycyclic aromatic hydrocarbons in African smoked fish. Food
Cosmet. Toxicol. 17: 141-143.
Muller, E. 1968. Carcinogenic substances in water and soil. XX. Studies on
the carcinogenic properties of 1,12-benzoperylene. Arch. Hyg. Bakteriol.
152: 23-36. (Ger.)
Sakai, M., D. Yoshida and S. Mizusaki. 1985. Mutagenicity of polycyclic
aromatic hydrocarbons and quinones on Salmonella typhimurium TA97. Mutat.
Res. 156: 61-67.
Salamone, M.F., J.A. Heddle and M. Katz. 1979. The mutagenic activity of
thirty polycyclic aromatic hydrocarbons (PAH) and oxides on urban airborne
particulates. Environ. Int. 2: 37-43.
U.S. EPA. 1990. Drinking Water Criteria Document for Polycyclic Aromatic
Hydrocarbons (PAHs). Prepared by the Office of Health and Environmental
Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for
the Office of Drinking Water, Washington, DC. Final Draft. ECAO-CIN-D010,
September, 1990.
Van Duuren, B.L. and B.M. Goldschmidt. 1976. Cocarcinogenic and tumor-
promoting agents in tobacco carcinogenesis. J. Natl. Cancer Inst. 56(6):
1237-1242.
Van Duuren, B.L., C. Katz and B.M. Goldschmidt. 1973. Brief communication:
Cocarcinogenic agents in tobacco carcinogenesis. J. Natl. Cancer Inst.
51(2): 703-705.
Wynder, E.L. and D. Hoffmann. 1959. A study of tobacco carcinogenesis. VII.
The role of higher polycyclic hydrocarbons. Cancer. 12: 1079-1086.
_VII. REVISION HISTORY
Substance Name -- Benzo[g,h,i]perylene
CASRN -- 191-24-2
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Date Section Description
-------- -------- --------------------------------------------------------
12/01/1990 II. Carcinogen assessment on-line
12/01/1990 VI. Bibliography on-line
01/01/1992 IV. Regulatory Action section on-line
VIII. SYNONYMS
Substance Name -- Benzo[g,h,i]perylene
CASRN -- 191-24-2
Last Revised -- 12/01/1990
191-24-2
Benzo(ghi)perylene
benzo(ghi)perylene
HSDB 6177
NSC 89275
1,12-Benzoperylene
1,12-benzperylene
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0461.HTM
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