DEVELOPMENTAL TOXICITY STUDY OF INHALED ACRYLIC-ACID IN NEW-ZEALAND WHITE-RABBITS

In range-finding and definitive developmental toxicity studies, timed pregnant New Zealand White rabbits were exposed to acrylic acid (GAS N o. 79-10-7) vapour for 13 consecutive days during pregnancy. In the ra nge-finding study, eight pregnant does/group were exposed to 30, 60, 1 25 or 250 ppm acrylic acid vapour on gestation days (gd) 10-22 of preg nancy. Monitors of toxicity included body weight measurements, daily f ood consumption measurements and clinical observations. Three of the e ight does/group were killed on the day following the last exposure (gd 23), and the remaining does were killed and autopsied on gd 29. At au topsy, special attention was given to gross observation of maternal na sal turbinates, and nasal turbinates from all does were evaluated hist ologically. No evaluation of foetuses was performed in the range-findi ng study. In the definitive study, 16 does/group were exposed to conce ntrations of 25, 75 or 225 ppm acrylic acid vapour from gd 6 to 18, th e major period of organogenesis. Monitors of maternal toxicity include d clinical observations and measurements of body weight and daily food consumption measurements. Does were killed and autopsied on gd 29. Ma ternal liver and kidney weights were measured and external, visceral a nd skeletal evaluations of foetuses were conducted. Maternal nasal tur binates were not evaluated histologically in the definitive study. Eff ects in does from both studies included consistent concentration-relat ed reductions in food consumption and body weight gains throughout the exposure period at concentrations of acrylic acid vapour above 60 ppm . Characteristic clinical signs of sensory irritation, including perin asal and perioral wetness and severe nasal congestion, were noted in d oes from both studies at or above vapour concentrations of 75 ppm. Gro ss observation of nasal turbinates immediately following exposures in the range-finding study indicated colour changes in the nasal turbinat es of does in the 60 and 250 ppm groups. Colour changes in the nasal t urbinates were noted in one doe from the 250 ppm exposure group killed on gd 29. Pertinent autopsy findings in the does from the definitive study included ulceration of the nasal turbinates of a single doe in t he 225 ppm group. Histological evaluation of turbinates from does kill ed the day following exposures in the range-finding study revealed les ions in the nasal epithelium in all acrylic acid-exposed groups. The s everity of the lesions was concentration related. Microscopic evaluati on of turbinates from does killed on gd 29 showed the presence of nasa l lesions in the 60, 125 and 250 ppm groups. However, the nasal tissue s had recovered considerably during the post-exposure interval. Despit e the severe effects on the nasal mucosa of does in both studies, ther e was no evidence of developmental toxicity including teratogenicity a t any exposure concentration used in the definitive study. (C) 1997 El sevier Science Ltd.