Toxicity Profiles
Formal Toxicity Summary for BENZO[G,H,I]PERYLENE
NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.
- EXECUTIVE SUMMARY
- 1. INTRODUCTION
- 2. METABOLISM AND DISPOSITION
- 1. INTRODUCTION
- 2.1 ABSORPTION 2.2 DISTRIBUTION 2.3 METABOLISM 2.4 EXCRETION
- 3. NONCARCINOGENIC HEALTH EFFECTS
- 3.1 ORAL EXPOSURES 3.2 INHALATION EXPOSURES 3.3 OTHER ROUTES OF EXPOSURE 3.4 TARGET ORGANS/CRITICAL EFFECTS
- 4. CARCINOGENICITY
- 4.1 ORAL EXPOSURES 4.2 INHALATION EXPOSURES 4.3 OTHER ROUTES OF EXPOSURE 4.4 EPA WEIGHT-OF-EVIDENCE 4.5 CARCINOGENICITY SLOPE FACTORS
- 5. REFERENCES
May 1994
Prepared by: Rosmarie A. Faust, Ph.D., Chemical Hazard Evaluation and Communication Group, Biomedical and Environmental Information Analysis Section, Health and Safety Research Division, *, Oak Ridge, Tennessee.
Prepared for OAK RIDGE RESERVATION ENVIRONMENTAL RESTORATION PROGRAM.
*Managed by Martin Marietta Energy Systems, Inc., for the U.S. Department of Energy under Contract No. DE-AC05-84OR21400.
EXECUTIVE SUMMARY
Benzo[g,h,i]perylene, also known as 1,12-benzoperylene, is a polycyclic aromatic hydrocarbon (PAH) with six aromatic rings. There is no known commercial production or use of benzo[g,h,i]perylene. It occurs naturally in crude oils and is present ubiquitously in products of incomplete combustion and in coal tar (EPA, 1987).
No absorption data were available for benzo[g,h,i]perylene; however, by analogy to other PAHs, primarily benzo[a]pyrene, it would be expected to be absorbed from the gastrointestinal tract, lungs, and skin (EPA, 1991).
No human or animal data were available to evaluate the toxicity of benzo[g,h,i]perylene. Because of the lack of data, EPA has not derived an oral reference dose (RfD) or inhalation reference concentration (RfC) (EPA, 1992).
No oral or inhalation bioassays were available to assess the carcinogenicity of benzo[g,h,i]perylene. Negative results were reported in dermal application studies (Hoffmann and Wynder, 1966; Van Duuren and Goldschmidt, 1976) and in initiation-promotion assays for skin tumorigenesis in mice (Hoffmann and Wynder, 1966; Van Duuren et al., 1970). However, when benzo[g,h,i]perylene was administered simultaneously with benzo[a]pyrene to the skin of mice, an increased incidence of skin tumors was observed compared to the tumor incidence in mice treated with benzo[a]pyrene alone, indicating possible cocarcinogenic activity of benzo[g,h,i]perylene (Van Duuren et al., 1973). Although a few pulmonary tumors were observed in Osborne-Mendel rats when benzo[g,h,i]perylene was administered as single lung implants of >=83 mg (Deutsch-Wenzel et al., 1983), the tumors may have been caused by impurities in the test compound (IARC, 1983). In subcutaneous injection studies, benzo[g,h,i]perylene did not produce injection site tumors in mice (Muller, 1968).
Based on no human data and inadequate data with experimental animals, the United States Environmental Protection Agency (EPA) has classified benzo[g,h,i]perylene in weight-of-evidence Group D, not classifiable as to human carcinogenicity (EPA, 1992).
1. INTRODUCTION
Benzo[g,h,i]perylene (CAS No. 191-24-2), also known as 1,12-benzoperylene, is a polycyclic aromatic hydrocarbon (PAH) with six aromatic rings. It is a crystalline solid with a chemical formula of C22H12 and a molecular weight of 276.3, a melting point of 278.3C (IARC, 1983), a vapor pressure of 1.01x10-10 mm Hg at 25C, and an estimated log octanol/water partition coefficient of 7.04-7.10 (EPA, 1987). Benzo[g,h,i]perylene is practically insoluble in water but is soluble in 1,4-dioxane, dichloromethane, benzene, and acetone (EPA, 1987).
There is no known commercial production or use of benzo[g,h,i]perylene. It occurs naturally in crude oils and is present ubiquitously in products of incomplete combustion and in coal tar (EPA, 1987). It has been identified in cigarette smoke, charcoal-broiled steaks, and edible oils (IARC, 1983) and in soils, groundwater, and surface waters at hazardous waste sites (ATSDR, 1990). Benzo[g,h,i]perylene is one of a number of PAHs on EPA's priority pollutant list (ATSDR, 1990).
2. METABOLISM AND DISPOSITION
2.1 ABSORPTION
Data regarding the gastrointestinal or pulmonary absorption of benzo[g,h,i]perylene in humans or animals were not available. However, data from structurally-related PAHs, primarily benzo[a]pyrene, suggest that benzo[g,h,i]perylene would be absorbed from the gastrointestinal tract, lungs, and skin (EPA, 1991).
2.2 DISTRIBUTION
Information on the distribution of benzo[g,h,i]perylene in humans or animals was not available.
2.3 METABOLISM
Information on the metabolism of benzo[g,h,i]perylene in humans or animals was not available.
2.4 EXCRETION
Information on the excretion of benzo[g,h,i]perylene in humans or animals was not available.
3. NONCARCINOGENIC HEALTH EFFECTS
3.1 ORAL EXPOSURES
Information on the acute, subchronic, chronic, developmental, or reproductive oral toxicity of benzo[g,h,i]perylene in humans or animals was not available. Because of a lack of toxicity data, an oral reference dose (RfD) for benzo[g,h,i]perylene has not been derived (EPA, 1992).
3.2 INHALATION EXPOSURES
Information on the acute, subchronic, or chronic toxicity of benzo[g,h,i]perylene following inhalation exposure in humans or animals was not available.
In a developmental toxicity study, pregnant rats were exposed to unspecified airborne concentrations of oil shale containing various PAHs, including benzo[g,h,i]perylene, on days 6-15 of gestation (Weaver and Gibson, 1979). No treatment-related teratogenic effects were observed when the animals were sacrificed on day 20 of gestation.
Because of the paucity of toxicity data, an inhalation reference concentration (RfC) for benzo[g,h,i]perylene has not been derived (EPA, 1992).
3.3 OTHER ROUTES OF EXPOSURE
Information on the acute, subchronic, chronic, developmental, or reproductive toxicity of benzo[g,h,i]perylene by other routes of exposure in humans or animals was not available.
3.4 TARGET ORGANS/CRITICAL EFFECTS
No target organs or critical effects were identified for oral, inhalation, or other routes of exposure to benzo[g,h,i]perylene.
4. CARCINOGENICITY
4.1 ORAL EXPOSURES
Information on the carcinogenicity of benzo[g,h,i]perylene in humans or animals following oral exposure was not available.
4.2 INHALATION EXPOSURES
Information on the carcinogenicity of benzo[g,h,i]perylene in humans or animals following inhalation exposure was not available.
4.3 OTHER ROUTES OF EXPOSURE
4.3.1 Human
Information on the carcinogenicity of benzo[g,h,i]perylene in humans by other routes of exposure was not available.
4.3.2 Animal
Benzo[g,h,i]perylene was tested for carcinogenicity in skin application, initiation-promotion, lung implant, and subcutaneous (s.c.) injection bioassays.
Hoffmann and Wynder (1966) applied 0.05 or 0.1% benzo[g,h,i]perylene in 1,4-dioxane, 3 times weekly for 12 months, to the skin of 20 female Swiss albino mice/dose group. The mice were observed for an additional 3 months and then sacrificed. One skin papilloma was found in one mouse treated with the low dose in the 10th month; no tumors developed in high-dose and control animals. Application of 21 ug benzo[g,h,i]perylene in acetone to the skin of 50 female ICR/Ha Swiss mice, 3 times weekly for 1 year, produced no skin tumors in treated, vehicle control, or untreated groups (Van Duuren and Goldschmidt, 1976).
In a tumor-initiating experiment, 30 female Swiss albino mice received 10 applications of 0.1% benzo[g,h,i]perylene in 1,4-dioxane every 3 days (Hoffmann and Wynder, 1966). After 28 days, applications of 2.3 mg croton oil were started (duration and frequency not specified). After 6 months, the number of mice with skin papillomas was 2/30, 2/30, and 0/20, respectively, for benzo[g,h,i]perylene-treated, promoter control, and vehicle control groups. In another tumor-initiating study, groups of 20 female ICR/Ha Swiss mice received a single application of 0.8 mg benzo[g,h,i]perylene in benzene, followed 2 weeks later by applications of phorbol myristyl acetate (PMA) in acetone, 3 times weekly for life (Van Duuren et al., 1970). Skin papillomas and carcinomas, respectively, developed in 3/20 and 1/20 of treated mice. In PMA controls, 1/20 mice had skin papillomas. No tumors were seen in vehicle or untreated controls.
Van Duuren et al. (1973) demonstrated cocarcinogenic activity of benzo[g,h,i]perylene when administered in conjunction with benzo[a]pyrene. Groups of 50 female ICR/Ha Swiss mice received dermal applications of 21 ug benzo[g,h,i]perylene in combination with 5 ug benzo[a]pyrene in acetone, 3 times weekly for 1 year. At the end of the study, the incidences of skin papillomas and carcinomas, respectively, were 20/50 and 17/50 in treated animals. In a control group that received benzo[a]pyrene alone, papillomas developed in 13/50 and carcinomas in 10/50 animals. No skin tumors were seen in untreated or vehicle control groups.
In a lifetime study, female Osborne-Mendel rats (34-35/group) received single lung implants of 0.16, 0.83, or 4.15 mg benzo[g,h,i]perylene in a mixture of beeswax and trioctanoin (Deutsch-Wenzel et al., 1983). Additional groups of rats served as untreated and vehicle controls. Epidermoid carcinomas in the lung and thorax were seen in 1/35 and 4/34 rats administered the mid-dose and high dose, respectively, after lifetime observation. No lung tumors occurred in low-dose, untreated, and vehicle control animals. IARC (1983) indicated that the observed tumors in the treated groups may be attributable to impurities in the test compound.
Muller (1968) conducted two s.c. injection studies with mice. In the first study, groups of 50 female NMRI mice received 0, 0.83, or 16.7 benzo[g,h,i]perylene suspended in gelatin once every 2 weeks for 6 months. Survival was 32/50 for each of the groups at day 675 after the first injection. No injection-site tumors were observed in the treated or control groups, and the tumor incidence at other sites was comparable in all groups. In the second study, groups of 20 NMRI mice (sex not given) were administered s.c. injections of 0, 0.1, 1, or 10 mg benzo[g,h,i]perylene suspended in gelatin once every 2 weeks for 20 weeks. Survival was not adversely affected by treatment with benzo[g,h,i]perylene. No skin or subcutaneous tumors were found in mice treated with benzo[g,h,i]perylene or in controls.
Although several noncarcinogenic PAHs have been shown to reduce the ability of benzo[a]pyrene to produce injection site sarcomas, s.c. injections of benzo[g,h,i]perylene in tricaprylin vehicle had no such inhibiting effects (Falk et al., 1964).
4.4 EPA WEIGHT OF EVIDENCE
Classification D--Not classifiable as to human carcinogenicity (EPA, 1992)Basis--Based on no human data and inadequate animal data from lung implant, skin-painting, and subcutaneous injection bioassays.
4.5 CARCINOGENICITY SLOPE FACTORS
No carcinogenicity slope factors were calculated.
5. REFERENCES
ATSDR (Agency for Toxic Substances and Disease Registry). 1990. Toxicological Profile for Polycyclic Aromatic Hydrocarbons. Acenaphthene, Acenaphthylene, Anthracene, Benzo(a)anthracene, Benzo(a)pyrene, Benzo(b)fluoranthene, Benzo(g,i,h)perylene, Benzo(k)fluoranthene, Chrysene, Dibenzo(a,h)anthracene, Fluoranthene, Fluorene, Indeno(1,2,3-c,d)pyrene, Phenanthrene, Pyrene. Prepared by Clement International Corporation, under Contract No. 205-88-0608. ATSDR/TP-90-20.
Deutsch-Wenzel, P., H. Brune, G. Grimmer, et al. 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: 539-544.
Falk, H.L., P. Kotin, and S. Thompson. 1964. "Inhibition of carcinogenesis. The effect of polycyclic hydrocarbons and related compounds." Arch. Environ. Health 9: 169-179.
Hoffmann, D. and E.L. Wynder. 1966. "Contribution to the carcinogenic action of dibenzopyrenes." Z. Krebsforsch. 68: 137-149.
IARC (International Agency for Research on Cancer). 1983. "Benzo[g,h,i}perylene." In: IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals for Humans. Polynuclear Aromatic Compounds. Part 1, Chemical, Environmental and Experimental Data, Vol. 32. IARC, Lyon, France, pp. 195-204.
Muller, E. 1968. "Carcinogenic substances in water and soils. XX. Studies on the carcinogenic properties of 1,12-benzoperylene." Arch. Hyg. 152: 23-26.
United States Environmental Protection Agency (EPA). 1987. Health and Environmental Effects Profile for Benzo(ghi)perylene. Prepared by the Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment for the Office of Solid Waste and Emergency Response, Cincinnati, OH. ECAO-CIN-P276.
United States Environmental Protection Agency (EPA). 1991. Drinking Water Criteria Document for Polycyclic Aromatic Hydrocarbons (PAHs). Prepared by the Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, U.S. Environmental Protection Agency, Cincinnati, OH, for the Office of Drinking Water. ECAO-CIN-D010.
United States Environmental Protection Agency (EPA). 1992. Integrated Risk Information System (IRIS). Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Cincinnati, OH.
Van Duuren, B.L., A. Sivak, B.M. Goldschmidt, et al. 1970. "Initiating activity of aromatic hydrocarbons in two-stage carcinogenesis." J. Natl. Cancer Inst. 44: 1167-1173.
Van Duuren, B.L., C. Katz and B.M. Goldschmidt. 1973. "Brief communication: Cocarcinogenic agents in tobacco carcinogenesis." J. Natl. Cancer Inst. 51: 703-705.
Van Duuren, B.L. and B.M. Goldschmidt. 1976. "Cocarcinogenic and tumor-promoting agents in tobacco carcinogenesis." J. Natl. Cancer Inst. 56: 1237-1242.
Weaver, N.K. and R.L. Gibson. 1979. "The U.S. oil shale industry: A health perspective." Am. Ind.
Hyg. Assoc. J. 40: 460-467.
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