Subchronic and chronic studies of the effects of oral administration of acrylic acid to rats.

ABSTRACT

In a 3-month study, groups of 10 male and 10 female Wistar rats were dosed by gavage, 5 times per week, with acrylic acid at doses of 150 or 375 mg/kg body weight. Five male and five female rats in the low-dose group died and six males and nine females given 375 mg/kg died. Pathological examination revealed a dose-dependent pronounced irritation in the forestomach and glandular stomach with ulcerations and purulent rhinitides and tubular necroses. Therefore, in comparison with drinking water administration using approximately equivalent doses (2000 or 5000 ppm; see below), administration by gavage was determined not to be suitable for long-term studies using as high as possible doses. In a 12-month study, Wistar rats (20 rats/group/sex) were given drinking water containing 120, 800, 2000 or 5000 ppm acrylic acid (providing doses of about 9, 61, 140 and 331 mg/kg body weight/day, respectively). Satellite groups (10 rats/group/sex) were treated concurrently for 3 months. Acrylic acid at 5000 ppm, and temporarily also at 2000 ppm, led to reduced drinking water consumption in male rats and, to a slight extent, also in female rats. In the males, feed consumption was reduced at 5000 ppm and body weight gain was retarded at 5000 ppm and marginally also at 2000 ppm. These findings indicate palatability problems and their consequences. There were no indications of systemic toxicity and/or any carcinogenic potential. In a carcinogenicity study, Wistar rats (50/group/sex) were given acrylic acid in the drinking water at concentrations of 0, 120, 400 or 1200 ppm (8, 27 or 78 mg/kg body weight/day, respectively) over 26 (males) or 28 (females) months. The concentrations were chosen on the basis of the interim results from the 12-month drinking water study, which had started earlier, and taking into account the longer study duration and geriatric effects to be expected. This carcinogenicity study did not reveal any toxic changes or indications of a carcinogenic potential of acrylic acid with the exception of slightly reduced (statistically not significant) consumption of drinking water.