This study was conducted to assess the potential for a mixture of 5 pesticides (alachlor, atratine, cyanazin, metolachlor, and metribuzin) and one fertilizer component, ammonium nitrate (Iowa Pesticide/Fertilizer mixture) administered in the drinking water at specified levels to cause developmental toxicity.
IOWA was administered in the drinking water to timed-pregnant Sprague-Dawley (CD) rats (26-29 per group) on gestational days 6 to 20 at dose levels of lX, l0X, and l00X in reagent grade water containing 512 ppm propylene glycol, where X was the median concentration of the components observed in groundwater determination in IOWA. A vehicle control formulation containing 512 ppm propylene glycol in reagent grade water and blank reagent grade drinking water were also administered to two ddditional groups. Estimated mean exposure to the components of the mixture was 96-102% of the target dose for each dose level based on the medn result of the analysis of marker compounds metribuzin and ammonium nitrate. Animals were observed daily for clinical signs of toxicity. Food and water consumption and body weights were determined on gd 0, 3, 6, 9, 12, 15, 18, and 20. All animals were killed on gd 20 and examined for maternal body weight, implant status, fetal weight, sex, and morphological development including external, visceral, and skeletal development.
IOWA-exposed females did not exhibit any significant treatment-related clinical signs of toxicity. Maternal food consumption did not differ significantly between the water and vehicle control groups and was not consistently altered by IOWA treatment in a dose-related manner. Maternal water consumption tended to be higher in the vehicle control group than in the water control group, but there was little difference between the vehicle control group and the lOWA-treated groups. Maternal body weights were unaffected by treatment. Maternal liver weight (absolute and relative) was slightly higher in the vehicle control group compared to the water control group, consistent with exposure to the propylene glyco1 in the vehicle control formulation. However, there was no difference in the maternal liver weight between the vehicle control and the IOWA-treated groups. Thus, l00X IOWA was the maternal no-observed-adverse-effect level in this study.
Gravid uterine weight was unaffected by exposure to IOWA. In dddition, there was no effect of treatment on prenatal development or fetal body weight. IOWA exposure did not alter the incidence of fetal malformations or variations. Thus, l00X IOWA was the developmental NOAEL.
In summary, IOWA administered to pregnant CD rats at l00X, i.e., 100 fold greater concentration than the median real-life exposure, on gestational days 6 to 20 was a NOAEL for both maternal and developmental toxicity.