dinitrobenzenes and Fetal-Resorption

The fungicide dinocap is currently used in the control of powdery mildew. We have reported that dinocap is teratogenic in the CD-1 mouse, causing cleft palate, otolith defects, and fetal weight deficits well below maternotoxic dose levels. In this study the maternal and fetal toxicity of dinocap was determined in the Sprague-Dawley rat and Syrian golden hamster, and adult-to-developmental (A/D) toxicity ratios were calculated and compared with the previously established A/D ratio of dinocap in the mouse. Dinocap in corn oil was administered by gavage to pregnant rats on gestation days 7-20 (0, 100, 150, 200 mg/kg/day) and to hamsters on gestation days 7-14 (0, 12.5, 25, 50, 75, 100, 200 mg/kg/day). Dams were killed on day 21 (rat) or day 15 (hamster), and litters were removed, counted, and weighed; half of each litter was necropsied for soft tissue defects, and the remaining half was processed for skeletal examination. In the rat, maternal extrauterine weight gain was significantly affected at 150 and 200 mg/kg/day, relative liver weight was elevated at 100 mg/kg/day and above, and fetal weight was lower at 150 and 200 mg/kg/day. In the hamster, maternal extrauterine weight was lower at 12.5 mg/kg/day and above; fetal weight was reduced, and the incidence of dilated renal pelvis was higher, at 25 mg/kg/day and above. Thus the A/D ratios for dinocap in the rat and hamster are similar, approximately 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cricetinae; Dinitrobenzenes; Female; Fetal Death; Fetal Resorption; Fungicides, Industrial; Liver; Mesocricetus; Nitrobenzenes; Pregnancy; Rats; Rats, Inbred Strains; Species Specificity; Teratogens

Technical-grade dinocap, a complex-mixture fungicide, is teratogenic in the CD-1 mouse, causing cleft palate and otolith defects. In this study we compared the developmental toxicities of 2,4-dinitro-6-(1-methylheptyl)phenyl crotonate and 2,6-dinitro-4-(1-methylheptyl)phenyl crotonate, model isomers of the major active ingredients of technical dinocap, to the known teratogenicity of the technical compound. Individual isomers, both isomers combined, or technical dinocap were administered to pregnant mice on days 7-16 of gestation. Some dams were killed at term and litters were removed, dead fetuses and resorptions were counted, and live fetuses were weighed and preserved in Bodian's fixative for examination for cleft palate. Other treated dams were allowed to give birth: postnatal viability and growth, development of swimming behavior, and otolith formation were evaluated. As in previous studies, technical-grade dinocap caused cleft palate and weight deficits in fetuses at term and increased neonatal mortality and abnormal swimming behavior, torticollis, and deficient otolith formation in surviving pups. Neither of the purified isomers exhibited any developmental toxicity when administered under identical conditions. Thus, it is concluded that these isomers are not the active teratogenic component(s) in technical-grade dinocap.

Topics: Animals; Dinitrobenzenes; Female; Fetal Death; Fetal Resorption; Insecticides; Isomerism; Mice; Motor Activity; Nitrobenzenes; Otolithic Membrane; Pregnancy; Swimming; Teratogens; Torticollis

Adult male Sprague Dawley rats were gavaged with 2,4-dinitrotoluene (2,4-DNT) dissolved in corn oil at 0, 60, 180, or 240 mg/kg/day for five days. A single oral dose (0.5 mg/kg) of triethylenemelamine was used as a positive control. Induction of dominant lethal events was scored on the basis of early fetal deaths. At the two lower doses, no consistent changes were observed in the numbers of pre-implantation losses, implantation sites, or living or non-living fetuses. The highest dose of 2,4-DNT tested resulted in a marked decrease in the numbers of sperm-positive females (determined by microscopic examination of vaginal smears for sperm) and pregnant females. These two effects diminished in the latter weeks of mating. The low number of pregnant females at the highest dose made meaningful statistical evaluations difficult. The results indicate that 2,4-DNT does not cause dominant lethal mutations but does adversely affect reproductive performance.

Topics: Animals; Body Weight; Corpus Luteum; Dinitrobenzenes; Embryo Implantation; Female; Fertility; Fetal Resorption; Fetus; Genes, Dominant; Genes, Lethal; Male; Mutagenicity Tests; Mutagens; Nitrobenzenes; Pregnancy; Rats; Rats, Inbred Strains; Sexual Behavior, Animal