A Lifetime Oncogenicity Study in Rats with Acrylamide

Abstract

A lifetime oncogenicity study in Fischer 344 rats was conducted to accurately characterize the carcinogenic potency of acrylamide. Acrylamide 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 necropsy and gross pathology examinations were performed on all study animals. Histopathology examinations were conducted on selected tissues of all high-dose and control animals. Selected tissues from intermediate and low-dose groups were subjected to histopathological examinations as required to clarify high- and controldose group observations. There was no visual observation of neurotoxicity in any study animal but sciatic nerve degeneration was observed in the male and female high-dose groups. Increased mortality related to acrylamide was observed in the high- dose male group from Month 17 to the end of the study and in the high-dose females during Month 24. Mesotheliomas of the testicular tunic were significantly increased in the high-dose male group. The combined incidence of mammary gland adenocarcinomas and fibroadenomas was significantly increased in both acrylamide-dosed female groups. Males and females in the high-dose groups as well as females of the low-dose group had significantly ( p <0.001) increased thyroid follicular cell adenomas and adenocarcinomas. A variety of other tumor types observed with increased incidence in a previous acrylamide onco genicity study (i.e., combined CNS glial neoplasms, papillomas of the oral cavity, adenomas of the clitoral gland, and uterine adenocarcinomas) were not observed to be present at increased incidence in this study. This study confirms previously described acrylamide induction of benign tumors of the thyroid and mammary glands as well as mesotheliomas of the testis. By using a larger number of animals with an unbalanced study design, this study showed that acrylamide did not induce glial tumors and demonstrated that the no-observable-effect level for scrotal mesotheliomas is 0.5 mg/kg. It also demonstrated that the in creased incidence of mammary tumors was again within historical control ranges.

Dietary Acrylamide and Cancer Risk in Humans: A Review

“…Two long-term feeding studies examined the carcinogenicity of acrylamide in rats (Johnson et al, 1986;Friedman et al, 1995). In these studies, rats were exposed to high doses (up to 2.0 mg/kg/day) of acrylamide in drinking water for 2 years.…”

Diverse action of acrylamide on cytochrome P450 and glutathione S-transferase isozyme activities, mRNA levels and protein levels in human hepatocarcinoma cells

“…It is well established that the administration of acrylamide via various routes in laboratory animals results in an increased incidence of various tumors in lungs, thyroid glands, oral cavities, mammary glands, the central nervous system, the uterus, and the clitoral gland (Bull et al 1984;Johnson et al 1986;Friedman et al 1995). Epidemiological studies have also been carried out to analyze the affect of acrylamide in humans.…”

Acrylamid und Human-Biomonitoring

“…Bei 18-monatiger Dosierung von 2 mg AA pro kg Körpergewicht wurden bei Ratten Degenerationen des N. tibialis gefunden [32]. In einer Langzeitstudie (18 Monate) wurden bei einer Dosierung von 2 mg AA pro kg Körpergewicht vermehrt mikroskopische Degenerationen des N. ischiadicus beobachtet [33]. Offen ist bisher die Frage, ob diese neurotoxischen Wirkungen vom AA selbst oder seinem Metaboliten, dem Glycidamid, hervorgerufen werden.…”