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.