Carcinogenic activity of benzo[a]pyrene in a 2 year oral study in Wistar rats

• Published in: Food and chemical toxicology Vol. 50; no. 3-4; pp. 927 - 935
• Main Authors: Wester, P.W., Muller, J.J.A., Slob, W., Mohn, G.R., Dortant, P.M., Kroese, E.D.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.03.2012; Elsevier
• Subjects: Administration, Oral; Animals; appendages; Benzo(a)pyrene - administration & dosage; Benzo(a)pyrene - toxicity; Benzo[a]pyrene; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Carcinogenicity; Carcinogens - administration & dosage; Carcinogens - toxicity; carcinoma; Chemical agents; Female; forestomach; histopathology; humans; inhalation exposure; kidneys; liver neoplasms; Male; Medical sciences; mouth; Neoplasms, Experimental - chemically induced; Neoplasms, Experimental - classification; Neoplasms, Experimental - pathology; Oral; oral exposure; pathogenesis; Polycyclic aromatic hydrocarbons; Rat; Rats; Rats, Wistar; risk assessment; small intestine; Toxicology; Tumors; ALAT; MCV; BMDU; Rat; Oral; BMDL; RBC; Polycyclic aromatic hydrocarbons; BMD; PLT; WBC; Hb; Benzo[a]pyrene; H&E; γ-GT; IARC; Ht; Bw; MCHC; PAH; B[a]P; NOAEL; LD; ASAT; Carcinogenicity; BrdU; Hydrocarbon; Toxicity; Rodentia; Tumorigenicity; Polycyclic aromatic compound; Biological activity; Persistent organic pollutant; Carcinogen; Vertebrata; Mammalia; Animal; Organic compounds
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2011.12.003

► There is high human oral exposure to PAHs. ► Benzo[a]pyrene can be used as a representative of PAHs. ► Benzo[a]pyrene was tested in an oral carcinogenicity study in rats. ► Benzo[a]pyrene is carcinogenic in rats, inducing tumours in liver and forestomach. Because of the relatively high human oral exposure to polycyclic aromatic hydrocarbons (PAHs) compared to the inhalation exposure, the known carcinogenicity of this type of compounds and the limited data from oral studies available with polycyclic aromatic hydrocarbons, an oral carcinogenicity study was performed using benzo[a]pyrene (B[a]P) as a PAH representative. Wistar rats, 52 animals per sex and group were exposed daily (5days a week) to 0, 3, 10 or 30mg B[a]P/kgbw/day by gavage for 104weeks and were subject to gross- and histopathology. The main tumours observed were hepatocellular carcinomas and forestomach tumours. Other tumours induced in this study were tumours of the auditory canal, skin and appendages, oral cavity, small intestine, kidney, and soft tissue sarcomas. For hepatocellular carcinomas and forestomach tumours, the BMDL10 were 3 and 1mg/kg bw/day, respectively. The incidence of altered hepatic foci was increased in the 3mg/kg bw/day group. The increase in liver tumours is considered the most relevant effect for human risk assessment in terms of pathogenesis and sensitivity, and is proposed as the basis for human cancer risk assessment for oral PAH exposure.