Oncogenicity studies conduct

If oncogenicity studies have been conducted by the oral route and another clinical route is to be used in man, the need to repeat such studies should be assessed critically. Oncogenic potential is related to the concentration of the carcinogen at its site of action. Thus, if the oral route results in adequate exposure of the lung, there should be no need to perform additional inhalation oncogenicity studies. Inhalation studies of 1-3 months duration should be performed to assess possible local effects on respiratory tissue and also to gain pharmacokinetic data. 

Following lifetime feeding studies at the prescribed treatment levels, veterinary pathologists examine approximately 50 tissues from each animal for the presence of tumors or other evidence of tissue damage. The results of such oncogenicity studies in mice, conducted with the selected triazine herbicides, are presented in Table 25.6. 

A comprehensive package of toxicology studies has been conducted with PBO. The findings from these indicate a very safe toxicity profile. Until recently there had been no evidence of any oncogenic potential in several rodent chronic and oncogenicity studies. However, a recent re-registration study for EPA employ-... 

Because of their size and duration and the corresponding costs involved, oncogenicity studies are usually conducted towards the end of the development of a pharmaceutical when clinical efficacy has been established and the majority of the toxicity studies have been completed. The requirements in USA, Japan and Europe for clinical trials and marketing are compared in Table 3.4. 

The primary toxic effect elicited by chrysene is oncogenicity. Several studies have been conducted in mice in which chrysene (diluted in a variety of agents) was applied dermally either as a single dose (followed by a tumor promoting agent) or as multiple doses. Increased incidences of dermal tumors (papillomas and carcinomas) were observed in mice administered chrysene and a tumor promoting agent. Several studies were also conducted in which mice or rats received intramuscular or subcutaneous injections of chrysene... 

Slightly irritant to skin and eyes (rabbits), not sensitizing. In sub-chronic, chronic, oncogenicity and reproduction studies, performed in rats, mice, dogs and rabbits, propiconazole proved to be a safe chemical under normal use conditions. Several mutagenicity tests, conducted in different biological systems, demonstrated lack of genetic effects (Valcke, 1989). 

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