EVALUATION OF EFFECTS OF ORAL-EXPOSURE TO AMETRYN ON DEVELOPMENT OF MICE

The developmental toxicity potential of ametryn was assessed, involvin g teratogenic and reproductive studies on 180 and 170 presumed pregnan t albino mice respectively, given doses of 0, 292, 438, 584 and 779 mg kg(-1) day(-1) orally on days 6-15 of presumed gestation. During the gestation period, body weight, food consumption, water intake, mortali ty and general behavioural changes were recorded. On day 18, mice for teratogenic studies were killed and some parameters assessed. There we re more deaths for the 584 mg kg(-1) day(-1) (31%) and 779 mg kg(-1) d ay(-1) (49%) groups than for the 438 mg kg(-1) day(-1) (10%) and 292 m g kg(-1) day(-1) (0%) groups. Reductions in mean body weight gain duri ng exposure and post-exposure periods were recorded for the two highes t dose levels; however, the corrected maternal weight (minus the uteru s) remained unchanged for all the groups. Differences in food consumpt ion and water intake were insignificant at all dose levels. Teratogeni c parameters such as litter size decreased at the two highest doses as a result of significant resorptions and abortions. Other parameters s uch as termed fetuses per litter, fetal body weight, placental weight, crown-rump length and tail length, were reduced significantly. No ext ernal, visceral or skeletal changes were observed except delayed ossif ication. These results show that ametryn is embryotoxic to mice at 584 mg kg(-1) and above. The 170 presumed pregnant mice (F-0) allowed to deliver F-1 pups did so after 20(+/-2) days and F-2 pups obtained from matured F-1 (not given any ametryn) were also delivered after 20(+/-1 ) days. There was F-1 pup weight reduction for the two highest doses w hereas F-2 pups showed a non-significant reduction only for 779 mg kg( -1) day(-1) group. F-1 fetal viability was 50-75% before day 4 and 75- 99% after day 4 for the two highest doses compared to 100% survival fo r other dosage groups. No deaths were recorded for F-2 generation pups . Food and water intakes, crown-rump length and tail length increments were insignificant for both generations. The appearance of developmen tal milestones like pinna attachment, hair growth, vaginal opening and testes descension remained unaffected for all the doses, but times of incisor eruptions, eye and ear opening were slightly lengthened for F -1 generation at 779 mg kg(-1). This observation was not noted in F-2 generation pups. A battery of behavioural tests conducted for F-1 and F-2 pups did not reveal changes in movements such as pivoting, negativ e geotaxis reflex nor in post-weaning test such as consummatory activi ty and activity wheel. The growth of the skeletal system was unaffecte d by ametryn after day 10 post-delivery(F-1 generation) and day 0 (F-2 ) generation. Ametryn has little or no effect on reproductive and/or d evelopmental characteristics of mice at doses below maternal toxicity. (C) 1998 SCI.