Developmental toxicity of an octyltin stabilizer in NMRI mice

The octyltin stabilizer ZK 30.434 is a mixture of 80% dioctyltin diisooctyl thioglycolate (DOTTG) and 20% of monooctyltin triisooctylthioglycolate (MOT TG) and is used as stabilizer for rigid polyvinylchloride (PVC) materials. One of the applications of such stabilized films is the packaging of foodst uffs. Exposure to humans occurs via migration of DOTTG/MOTTG from PVC mater ials. In the present study the developmental toxicity of DOTTG/MOTTG in NMR I mice was investigated. Dams were treated orally with doses of 20, 30, 45, 67, or 100 mg/kg/day DOTTG/MOTTG from gestation day 6 through 17 (plug = d ay 1). Resorption rates were significantly increased and fetal weights sign ificantly reduced in the study group at the 2 highest doses. External anoma lies, such as bent forelimbs, cleft palate, and exencephaly were reported i n the group treated with 100 mg/kg/day DOTTG/MOTTG, with the 67-mg/kd dose also exhibiting a significant increase in cleft palate. Moreover, an increa se in skeletal anomalies was reported in fetuses exposed to 100 mg/kg/day. The doses of 20, 30, and 45 mg/kg/day elicited a significant increase in su pernumerary lumbar ribs. It can be concluded that DOTTG/MOTTG is embryo-fet otoxic and induces developmental effects. The study revealed the need for t he establishment of different No-Observed Adverse Effect Levels (NOAEL) for the endpoints investigated. (C) 2001 Elsevier Science Inc. All rights rese rved.