Registration Dossier

Administrative data

Description of key information

The treatment related histopathological change of decreased cellularity in the thymic cortex was reported for 15/25 females of the high dose group. The observed decreased cell population in the cortex was described as multifocal to diffuse and severity varied from minimal to marked. The histopathological evaluation of the thymus was extended to the lower dose groups and there was no treatment related changes observed in these animals.

Based on the Thymus effect, the NOAEL is > 8.5 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
8.5 mg/kg bw/day
Study duration:
subacute
Species:
rat
Organ:
thymus

Additional information

A robust review of data for organotin compounds (including dibutyltin) by the EU’s Scientific Panel on Contaminants in the Food Chain (SPCFC, 2004) appears to include the other studies reported above, with the exception of an OECD 421 study. The available data for repeat-dose (subchronic) studies are restricted to rats, exposed to dibutyltin chloride. Determination of NOAELs is variable, but thymus weight is considered a critical endpoint. In a first study (Gaunt et al., 1968), the NOAEL was set at 40 ppm (equivalent to 2 mg/kg bw/day) but thymus was not included among the organs weighed at termination. Another study (Pennincks et al., 1982) concludes reduction of relative thymus weight of approximately 45% at a dose level as low as 50 ppm in diet (equivalent to 2.5 mg/kg bw/day) administered for 14 days. The modern fully compliant OECD 421 study (Waalkens-Berendsen, 2003) identifies an effect level at approximately 2 mg/kg bw/day and NOAEL at 0.3 m/kg bw/day. Since an in vitro study demonstrated that DBTC can be used as an anchor compound following oral exposure, and 2-2.5 mg/kg bw/day appears a borderline effect level, a NOAEL of 0.3 mg/kg bw/day is considered amply protective and appropriate for setting DNELs.

A read-across approach was considered appropriate from dibutyltin chloride to other dibutyltins. Under gastric conditions dibutyltins are hydrolysed to form dibutyltin chloride. This is demonstrated in various dibutyltin compounds presented in the TNO report V5047, (presented as individual reports as under Toxicokinetics).

Justification for classification or non-classification

The substance is classified with R48/R25 according to Directive 67/548/EEC. According to Regulation (EC) no 1272/2008 the test substance would be classified as a STOT Rep. Exp. 1 with Hazard statement: H372: Causes damage to thymus through prolonged or repeated exposure and should be accompanied with the signal word 'Danger'.