Acrylic acid: two-generation reproduction toxicity study in Wistar rats with continuous administration in the drinking water

In a two-generation reproduction toxicity study, groups of 25 male and 25 female Wistar rats (for both F0 and F1 generations) received acrylic acid (AA) in the drinking water at concentrations of 0 (control), 500, 2500 and 5000 ppm for at least 70 days prior to mating, through mating, gestation, lactation and to weaning. The study continued through to weaning of the F2 offspring at 21 days of age. Achieved intakes of AA for the F0 and F1 parents during premating ranged from 46 (500 ppm) to 502 (5000 ppm) mg/kg/day. AA had no adverse effects on fertility and reproductive performance of the parent rats at doses up to 5000 ppm. General systemic toxicity was apparent with reduced body weights, food and water consumption in F0 parents at 5000 ppm and in F1 parents at 2500 and 5000 ppm; the only treatment-related pathological finding was a minimal hyperkeratosis of the limiting ridge of the forestomach with a minimal oedema of the submucosa of the glandular stomach in both parental generations at 5000 ppm. Dose-related signs of developmental toxicity were detected in F1 and F2 pups at 2500 and 5000 ppm in the form of retarded growth and some delay in the eye/auditory canal opening in F2 pups, but there was no evidence that AA had an adverse influence on pup morphology. Thus, the no-observed-adverse-effect level (NOAEL) is 5000 ppm for fertility and reproductive performance of the parents, 2500 ppm (F0 parents) or 500 ppm (F1 parents) for general systemic toxicity and 500 ppm for developmental toxicity.