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Administrative data

Description of key information

The following studies have been submitted to address the repeated dose toxicity: oral endpoint:
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, dibutyltin dimethoxystannane 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
2 mg/kg bw/day
Study duration:
subchronic
Species:
rat

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 above studies. 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. One study concludes effects at a dose level as low as 50 ppm in diet/2.5 mg/kg bw/day (Pennincks et al, 1982). Another study of equivalent reliability identifies 2 mg/kg bw/day as a NOAEL (Gaunt et al, 1968). As the only reliable sub-chronic study available Gaunt et al, (1968) was selected as the key study for this data requirement.

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'.