Registration Dossier

Administrative data

Description of key information

The following studies have been submitted to address the repeated dose toxicity: oral endpoint:
Waalkens-Berendsen DH (2003) Dibutyldichlorostannane (CAS # 683-18-1): Reproduction/developmental toxicity screening test in rats, TNO, Project Organisation, Ecotoxicology, Utrechtseweg 48, P.O. Box 370, 3700 AJ Zeist, The Netherlands, Report No.: V 4906, Organotin Environmental Programme (ORTEP) Association, Stabilizer Task Force. Report Date.: 2003-12-04.
Barnes, J. M. and Stoner, H. B. (1958). Toxic properties of some dialkyl and trialkyl tin salts. Brit. J. Industr. Med., 1958, 15, 15.
Gaunt et al (1968). Acute and Short-term Toxicity Studies on Di-n-butyltin Dichloride in Rats. Fd Cosmet. Toxicol. Vol. 6, pp. 599-608.
Penninks A. H. & Seinen W. (1982). COMPARATIVE TOXICITY OF ALKYLTIN AND ESTERTIN STABILIZERS. Fd Chem. Toxic. Vol. 20. pp. 909 to 916.
The Gaunt et al (1968) study has been allocated a Klimisch core of 2 on the basis that the study predates GLP; however, method was comparable to OECD Guideline 408. The effect of DBT exposure on the thymus of was not assessed in this study. No information on the stability or homogeneity of the test material in the DBTC-prepared diets. The study was performed with dibutyltin dichloride.
The Penninks and Seinen (1982) study has also been allocated a Klimisch score of 2 on the basis that the study is a short-term feeding study with no information on the stability of the test substance in the diet or homogeneity of the test diets provided. The purity of the test substance (dibutyltin dichloride) is not reported. The Barnes and Stoner (1958) study has been allocated a Klimisch score of 4.
Dibutyltin chloride was the test substance employed in all the studies presented under repeated dose toxicity. Under gastric conditions, the substance in question is anticipated to hydrolyse to dibutyltin chloride. A read-across approach from dibutyltin chloride was considered acceptable when dosing repeatedly via the oral route.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
0.3 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Additional information

A robust review of data for organotin compounds (including dibutyltin) by the European Food Safety Authority´s Scientific Panel on Contaminants in the Food Chain (EFSA, 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 (Specific Target Organ Toxicant) - repeated Exposure Category 1 with Hazard statement: H372: Causes damage to thymus through prolonged or repeated exposure and should be accompanied with the signal word 'Danger'.