Maternal toxicity

Developmental toxicity is shown by the disubstituted methyl-, butyl-, and octyltins, but not by the corresponding monosubstituted compounds. The major reported effect is teratogenicity, with effects on fetuses shown at doses close to maternally toxic ones in most cases. NOAELs for dimethyltin, dibutyltin, and dioctyltin are 10 (10), 2.5 (1.0), and 45 (30) mg/kg body weight per day for teratogenicity (maternal toxicity NOAELs in parentheses). 

A study on Wistar rats by Farr et al. (2001) showed no maternal toxicity at doses up to 5 mg/kg body weight for dibutyltin dichloride signs of maternal toxicity — reduced body weight gain, decreased food consumption, and thymus weight — were observed at 10 mg/kg body weight. No teratogenic effects were seen at 10 mg/kg... 

Monomethyltin Rat MMTC 8 weeks at 0, 30, 150, and 750 mg/kg diet = 0, 1.5, 7.5, and 37.5 mg/kg body weight Fertility, developmental toxicity, and maternal toxicity (screening) NOAEL = 7.5 Appel Waalkens-Berendsen (2004a)... 

Dimethyltin Rat DMTC Gestation days 7-17 at 0,5, 10, 15, and 20 mg/kg body weight Maternal toxicity reduction in fetal body weight reduced thymus weight in dams LOAEL=15 NOAEL=10 Noda (2001)... 

Monobutyltin Rat MBTC Gestation days 7-17at0, 50, 100, 200, and 400 mg/kg body weight Maternal toxicity thymic atrophy dose-dependent developmental toxicity fetuses with visceral or skeletal abnormalities NOAEL >400 Noda etal. (1992)... 

Dibutyltin Rat DBTC Gestation days 7-15at0, 2.5, 5, 7.5, and 10 mg/kg body weight Maternal toxicity body weight gain Teratogenicity LOAEL = 7.5 NOAEL = 5 LOAEL = 5 NOAEL = 2.5 Ema et al. (1991)... 

Monooctyltin/ dioctyltin (contd) Rat DOT stabilizer mix (DOT(IOMA) MOT(IOMA) 80 20) Gestation days 6-15 at 0, 1,5, and 25 mg/kg body weight Marginal maternal toxicity marginal but significant embryo-fetal lethal effect LOAEL = 25 NOAEL = 5 Sobering AG (1991)... 

Dibutyltin No significant neurotoxicity reported Yes. NOAEL = 2.5 (teratogenicity) and 1.0/5.0 (maternal toxicity) mg/kg body weight per day (as DBTC) Aromatase inhibition present (at least 10 times less potent than tributyltin) no imposex in vivo in invertebrates Yes. NOAEL could not be determined lowest dose reported to cause immunological effects = 2.5 mg/kg body weight per day (as DBTC)... 

EI Dupont deNemours Co. 1973. Maternal toxicity, embryotoxicity and teratogenic potential of neoprene accelerators applied to skin of rats during organogenesis. OTS0556789. Sect 8D. 

HCDD. Administration of 0.1-100 / g HCDD/kg/day was associated with a dose-related decrease in maternal weight-gain during gestation. Gross necropsy examination at the time of cesarean section revealed evidence of maternal toxicity only among dams receiving 100 /xg/kg/day (pale, friable liver 3/20 dams serous atrophy of fat, 1/20 dams). 

OCDD. Signs of maternal toxicity were not observed in rats given 100 or 500 mg/kg/day OCDD. Examination of the fetuses did not reveal changes in fetal body measurements, incidence of fetal resorptions, or incidence of any fetal anomaly among litters or the fetal population. At 500 mg/kg/day, the incidence of subcutaneous edema was significantly increased among the fetal population (23/100 compared with 8/156 in controls) but not among litters (9/18 compared with 6/28 in controls). 

D are summarized in Table I. Doses of 4 jug/kg/day or more produced maternal toxicity and 100% embryonic lethality. Two and 1 / g/kg/day treatments were also toxic for the mothers and resulted in reduced number of viable fetuses per litter and reduced fetal weights. Lower doses... 

Studies in animals indicate that trichloroethylene can act as a developmental toxicant, especially at doses also resulting in maternal toxicity. Significant decreases in litter size have been reported in rats treated by gavage... 

II. 7%, and 30% of pups from dams treated at 0, 475, 633, 844, and 1,125 mg/kg/day, respectively (Narotsky et al. 1995). In a study in mice that did not use maternally toxic doses, no developmental effects were observed in the offspring of B6C3Fj mice treated by gavage with 240 mg/kg/day trichloroethylene in com oil on gestation days 1-5, 6-10, or 1-15 (Cosby and Dukelow 1992). 

---