Potential teratogenicity of di-n-butyltin dichloride and other dibutyltin compounds

Citation
Ch. Farr et al., Potential teratogenicity of di-n-butyltin dichloride and other dibutyltin compounds, TER CAR MUT, 21(6), 2001, pp. 405-415
Citations number
13
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TERATOGENESIS CARCINOGENESIS AND MUTAGENESIS
ISSN journal
02703211 → ACNP
Volume
21
Issue
6
Year of publication
2001
Pages
405 - 415
Database
ISI
SICI code
0270-3211(2001)21:6<405:PTODDA>2.0.ZU;2-E
Abstract
The developmental toxicity of di-n-butyltin dichloride (DBT-dC) was evaluat ed in Wistar rats following oral administration. No maternal toxicity, embr yotoxicity, or malformations were observed at 1, 2.5, or 5 mg DBT-dC/kg bod y weight. Signs of maternal toxicity, including decreased food consumption, body weight gain, and thymus weight, were observed at 10 mg/kg body weight DBT-dC. At this dose, no evidence of embryotoxicity, including such measur es as total resorptions, viable fetuses, or fetal weights, was noted in any litter data. There was a slightly increased frequency of total malformatio ns at the 10 mg/kg dose level of 4/262 treated vs. 1/269 control fetuses. A ll defects occurred singly with no clustering nor organ system pattern of o ccurrence, which would be indicative of a teratogenic effect. The no-observ ed-adverse-effect-level (NOAEL) for prenatal as well as maternal toxicity w as considered to be 5 mg DBT-dC/kg body weight. The interpretation and util ity of previously published studies on the developmental toxicity of dibuty ltin compounds are confounded by dose regimen and data reporting deficienci es. These studies suggest that, after oral administration during days 6-17 of pregnancy, the NOAEL for malformations in rats of different strains rang es from 1.7 to 5 mg/kg body weight. In these studies, the maternal LD50 was reported to be about 8 mg/kg body weight in one study but at greater than 15 mg/kg in others. Thus, the NOAEL for teratogenicity may be roughly estim ated to be from one-tenth to one-third of the maternal LD50. When evaluated , thymus involution, a typical but reversible effect of di- and tributyltin compounds, was also observed at 5-10 mg/kg body weight. The most susceptib le time for inducing teratogenic effects is reported to be days 7-9 of preg nancy, but malformations have also been found with dosing over longer durat ion at lower doses. It is doubtful that the findings of malformations at hi ghly toxic doses in animals has any health hazard significance, especially when human exposure to dibutyltins typically occurs at several orders of ma gnitude lower than the doses used in these studies. Further comparative pha rmacokinetic studies would be necessary in order to refine the hazard chara cterization. Teratogenesis Carcinog. Mutagen. 21:405-415,2001. (C) 2001 Wil ey-Liss, Inc.