Developmental toxicity studies with atrazine and its major metabolites in rats and rabbits.
Bottom Line: ATR administration by gavage to pregnant rats and rabbits from implantation (gestation day [GD] 6 in rat, GD 7 in rabbit) through closure of the palate (GD 15 in rat and GD 19 in rabbit) did not statistically significantly alter the incidence of developmental abnormalities or malformations at dose levels up to 100 (rat) or 75 (rabbit) mg/kg bw/day.There were no effects on developmental toxicity parameters for DEA, DIA, DACT, or OH-ATR at oral dose levels up to 100, 100, 150, or 125 mg/kg bw/day, respectively, with the exception of reductions in fetal body weight by DACT and OH-ATR in the presence of decreased maternal body weight gain.The 500-ppm dose level resulted in significantly reduced maternal body weight gain.
Affiliation: Tetra Tech Sciences, Arlington, Virginia.Show MeSH
Related in: MedlinePlus
Mentions: There were three unexpected deaths of treated does, all in the low-dose ATR group (1 mg/kg bw/day). Two deaths appear to have resulted from dosing accidents, and one doe was found dead and was possibly aborting. Three other does were killed late in the study because they were aborting: one in the middle dose group (5 mg/kg/day) and two in the high-dose group (75 mg/kg/day). All other does were killed as scheduled on GD 29. Maternal food consumption was significantly decreased in does administered the 75 mg/kg bw/day dose level of ATR on GD 7 to 20 (Fig.3); after treatment ended (GD 19), evidence of recovery was observed. A statistically significant reduction of maternal body weight to about 80% of control at its greatest was observed in the 75 mg/kg bw/day dose group from GD 14 through study termination (Fig.3). Body weight change was negative in the 75 mg/kg bw/day dose group during the treatment period but became positive after the treatment period; however, body weight gain over the pregnancy corrected for uterine weight remained depressed by 320 g compared to control (Figs.2 and 4). In the middle dose group (5 mg/kg bw/day), mean body weight gains were also significantly diminished from GD 14 to 19 (Fig.4). In the middle and low-dose groups (1 and 5 mg/kg bw/day), no statistically significant reduction of body weight gain was apparent. All does in the 75 mg/kg bw/day dose group exhibited significant stool changes. Stool changes were also observed to some degree in the other dose groups. There was blood on the vulva or in the cage of 4/19 75 mg/kg bw/day dose group does. No significant treatment-associated gross pathology findings were observed at necropsy.