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NMRI male and female mice, which are routinely used in the National Toxicology Program (NTP), in the United States. Animals used in the NTP permit the toxicity of a wide variety of different chemical entities to be compared within the same species and strain. Published studies on PAH toxicity have also been performed on Swiss albino mice and their derivative strains (CD-1, CFW, and ICF mice), since these represent general all-purpose strains used in safety and ef cacy testing. The formation of PAH-induced tumors at speci c organ sites can be dependent upon the rodent species and route of administration. Of most relevance to food intake is the evidence for tumor formation following oral administration. No studies exist regarding cancer in humans following oral administration except those from epidemiological studies. However, data from animal studies exist and these can vary depending on the PAH and whether the exposure is acute, intermediate, or chronic. Each of the 16 priority PAHs will be discussed in turn. The results indicate that benz[a]anthracene, B[a]P, dibenz[a,h]anthracene, and possibly other PAHs as well are carcinogenic to rodents following oral administration at high doses.
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Naphthalene Inhalation of naphthalene will cause lung adenoma in female mice B6C3F1 (148), nasal adenoma in F344 male rats, and neuroblastoma in F344 female rats (149). However, inhalation is not the exposure route for food toxicants, and no data exist for the oral administration of naphthalene. Acenaphthylene No data available. Acenaphthene One study of intermediate duration evaluated the carcinogenic potential of acenaphthene. Male and female mice exposed to 0, 175, 350, or 700 mg/kg/day by gavage for 13 weeks showed no sign of tumorigenesis (148). Fluorene No data available. Anthracene No data available. Phenathrene No data available. Fluoranthene Will cause lung adenoma in several mice strains (e.g., ICR, Swiss, and CD-1 male and female mice) following i.p. administration (148). Pyrene Will cause lung tumors in mice following i.p. injection (148). Chrysene Will cause skin carcinoma following repetitive dermal application in ICR male and female mice (150), and lung carcinoma after intrapulmonary implant to rats (149). No data are available following oral administration. Benz[a]anthracene Mice acutely administered 1.5 mg/kg benz[a]anthracene twice per day for 3 days by oral gavage exhibited an increased incidence of hepatomas and pulmonary adenomas as compared with controls. Mice receiving intermittent gavage doses of 1.5 mg/kg for 5 weeks
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HEALTH RISKS/EFFECTS
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showed a 95% incidence of pulmonary adenomas, 46% incidence of hepatomas, and 5% of forestomach papillomas (1, 111). Benzo[ b] uoranthene No studies on oral administration exist. But dermal application will cause skin cancer in CD-1 mice (151), and lung implants and i.p. exposure will cause lung sarcoma and lung adenoma, in rats and mice, respectively (152, 153). Benzo[ k] uoranthene No studies on oral administration. But dermal application and will cause skin cancer in mice (153) and lung implants will cause lung carcinoma in rats (154), over their life span. Benzo[a]pyrene Oral administration of B[a]P to male and female CFW mice induced gastric papillomas and squamous cell carcinomas. Tumors also arose in distal sites since there was an increase in pulmonary adenomas, thyomas, lymphomas, and leukemias following oral administration. Gastric tumors were seen in 70% of the mice fed 50 250 ppm B[a]P for 4 6 months (155).
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Mice fed B[a]P at a concentration of 33.3 mg/kg/day exhibit forestomach neoplasms following two or more days of consumption (111). Hamsters will also develop papillomas and carcinomas of the alimentary tract following gavage or dietary exposure to B[a]P (111). A 77% incidence of mammary tumors was observed 90 weeks after a single oral dose of 50-mg B[a]P (100 mg/kg) was given to rats. Intragastric doses of 67 100 mg/kg of B[a]P will elicit pulmonary adenomas and forestomach papillomas in mice. The incidence of forestomach tumors (papillomas and carcinomas) was related to the duration of the oral exposure to B[a]P and was dose-dependent. In a similar manner, an association between dietary B[a]P intake and the development of leukemia and tumors of the forestomach and lung has been observed in mice (111).
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Indeno[1,2,3-cd]pyrene No data available. Benzo[g,h,i]perylene No studies on oral administration. In the Osborne Mendel female rat, lung implants with up to 4-mg compound were not tumorigenic (152). Dibenz[a,h]anthracene Forestomach papillomas were found in 10% mice administered with a single oral dose of 0.05 mg/kg dibenz[a, h]anthracene, but this incidence increased to 21% if croton oil (tumor promoter) was subsequently administered for 30 weeks. In another study, mice were fed a total of 9 19 mg dibenz[a,h]anthracene over 5 7 months and tumors in the forestomach were detected (2). After 15 weeks of dosing, 5% of female BALB/c mice had mammary carcinoma but there was no control group. The hydrocarbon will cause skin papillomas in female NMRI/mice following dermal application (156), lung adenomas in NMRI/female mice following subcutaneous administration (156), lung adenoma in A/J mice following i.p. administration (153), and liver adenomas in B6C3F1 mice following i.p. administration (157).
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