A LIFETIME ONCOGENICITY STUDY IN RATS WITH ACRYLAMIDE

Citation
Ma. Friedman et al., A LIFETIME ONCOGENICITY STUDY IN RATS WITH ACRYLAMIDE, Fundamental and applied toxicology, 27(1), 1995, pp. 95-105
Citations number
55
Categorie Soggetti
Toxicology
ISSN journal
02720590
Volume
27
Issue
1
Year of publication
1995
Pages
95 - 105
Database
ISI
SICI code
0272-0590(1995)27:1<95:ALOSIR>2.0.ZU;2-2
Abstract
A lifetime oncogenicity study in Fischer 344 rats was conducted to acc urately characterize the carcinogenic potency of acrylamide. Acrylamid e was administered in drinking water throughout the 106-week study at concentrations required to provide a dose of 0, 0.1, 0.5, or 2.0 mg/kg /day to males or 0, 1.0, or 3.0 mg/kg/day to females. Complete necrops y and gross pathology examinations were performed on all study animals . Histopathology examinations were conducted on selected tissues of al l high-dose and control animals. Selected tissues from intermediate an d low-dose groups were subjected to histopathological examinations as required to clarify high- and control-dose group observations. There w as no visual observation of neurotoxicity in any study animal but scia tic nerve degeneration was observed in the male and female high-dose g roups. Increased mortality related to acrylamide was observed in the h igh-dose male group from Month 17 to the end of the study and in the h igh-dose females during Month 24. Mesotheliomas of the testicular tuni c were significantly increased in the high-dose male group. The combin ed incidence of mammary gland adenocarcinomas and fibroadenomas was si gnificantly increased in both acrylamide-dosed female groups. Males an d females in the high-dose groups as well as females of the low-dose g roup had significantly (p < 0.001) increased thyroid follicular cell a denomas and adenocarcinomas. A variety of other tumor types observed w ith increased incidence in a previous acrylamide oncogenicity study (i .e., combined CNS glial neoplasms, papillomas of the oral cavity, aden omas of the clitoral gland, and uterine adenocarcinomas) were not obse rved to be present at increased incidence in this study. This study co nfirms previously described acrylamide induction of benign tumors of t he thyroid and mammary glands as well as mesotheliomas of the testis. By using a larger number of animals with an unbalanced study design, t his study showed that acrylamide did not induce glial tumors and demon strated that the no-observable-effect level for scrotal mesotheliomas is 0.5 mg/kg. It also demonstrated that the increased incidence of mam mary tumors was again within historical control ranges. (C) 1995 Socie ty of Toxicology.