Developmental toxicity of an octyltin stabilizer in NMRI mice.
The octyltin stabilizer ZK 30.434 is a mixture of 80% dioctyltin diisooctylthioglycolate (DOTTG) and 20% of monooctyltin triisooctylthioglycolate (MOTTG) and is used as stabilizer for rigid polyvinylchloride (PVC) materials. One of the applications of such stabilized films is the packaging of foodstuffs. Exposure to humans occurs via migration of DOTTG/MOTTG from PVC materials. In the present study the developmental toxicity of DOTTG/MOTTG in NMRI 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 = day 1). Resorption rates were significantly increased and fetal weights significantly reduced in the study group at the 2 highest doses. External anomalies, such as bent forelimbs, cleft palate, and exencephaly were reported in 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 increase 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 supernumerary lumbar ribs. It can be concluded that DOTTG/MOTTG is embryo-fetotoxic and induces developmental effects. The study revealed the need for the establishment of different No-Observed Adverse Effect Levels (NOAEL) for the endpoints investigated.
Faqi
A S
AS
Institute of Clinical Pharmacology and Toxicology, Department of Toxicology, Freie Universität Berlin, Berlin, Germany.
Schweinfurth
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Chahoud
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D000014:Abnormalities, Drug-Induced; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000002:abnormalities / Q000187:drug effects; D002972:Cleft Palate / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D020567:Fetal Weight / Q000187:drug effects; D005552:Forelimb / Q000002:abnormalities / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D009436:Neural Tube Defects / Q000139:chemically induced; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity*; D013864:Thioglycolates / Q000008:administration & dosage / Q000633:toxicity*; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology
D009942:Organometallic Compounds; D013723:Teratogens; D013864:Thioglycolates; C432204:ZK 30434