Dibutyltin dichloride

Endpoint summary

Description of key information

A number of studies have been submitted to address the acute oral toxicity and acute inhalation toxicity endpoints.  The following studies have both been allocated a Klimisch score of 2 and are the key studies for acute oral toxicity and acute inhalation toxicity respectively:
Günzel P (1969). Dibutyltin dichloride: Systemic Test of Rat Tolerance to a Single Oral Dose. (DL50). Testing laboratory: Schering AG, Hauptlaboratorium Exp. Med. Forschung. Report no.: 925. Owner company: CK Witco GmbH, Postfach 1620, D-59180, Bergkamen. Report date: 1969-07-17.
Stevens J (1980). Acute aerosol inhalation toxicity in the rat of TK 10777 dibutylzinndichlorid. Testing laboratory: Ciba-Geigy Limited, Basle, Switzerland. Report no.: 801469. Owner company: Plastics and Additives Division. Report date: 1980-10-24.
Both study reports have been considered to be sufficiently reliable and applicable to provide key information for the regulatory endpoint.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

219 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LC50

Value:

59 mg/m³ air

Additional information

ORAL:

 

Günzel P (1969) was submitted as the key study for this endpoint. Although the study predates GLP, the methodology employed is to a good scientific standard and is sufficiently documented for assessment and is therefore considered adequate for use as the key study for this endpoint and was accordingly assigned a reliability score of 2 (reliable with restrictions) in accordance with the criteria outlined in Klimisch (1997). In the Systemic Test of Rat Tolerance to a Single Oral Dose (DL50) (Schering AG Prot No.: 925), the test material was found to have an DL50 of 219 mg/kg with confidence limits of 157 - 277 mg/kg. From dosages of 200 mg and up, apathy, dyspnoea and diarrhoea were observed. Deaths occurred 2 - 13 days after application.

 

Six further studies were included as supporting information of this endpoint and are briefly summarised below:

 

Reference: Barnes JM & Stoner HB (1958)

Reliability and rationale for score: 4 (not assignable), Limited details of the toxic effects reported. Acute lethal doses not reported.

Result: The dialkyl tin compounds cause a generalized illness with damage to the biliary tract as the main pathological feature. The authors did not report the acute lethal dose (LD50), but for males, the acute lethal dose would be expected to be between 200 and 400 mg/kg.

 

 

Reference: Gaunt et al (1958)

Reliability and rationale for score: 2 (reliable with restrictions) Study meets generally accepted scientific standards, is sufficiently documented, and acceptable for assessment. Source and purity of test material not reported.

Result: Di-n-butyltin dichloride given to rats in acute oral doses of 50 mg/kg produced oedema and inflammation of the bile duct. When di-n-butyltin dichloride was fed to rats for 90 days at dietary levels of 0 (control), 10, 20, 40 or 80 ppm, there was a slight reduction of growth and food intake at the highest dietary level. The only other finding was a mild anaemia at the 80 ppm level. The no-effect level established in the diet of rats for 90 days was 40 ppm, a level approximately equivalent to an intake of 2 mg/kg/day.

 

 

Reference: Mazayev V. et al (1971). Four summaries were submitted from this publication as the investigation was performed on multiple species.

Reliability and rationale for score: 4 (not assignable) Details of the toxic effects were not reported other than the lethal dose value. No method reported. This was applicable to all of the studies presented.

Result:

- Rat: LD50 values were reported as 112 and 182 mg/kg bw for dichlordibutyltin (administered in vegetable oil) exposure in rats.

- Mouse: The LD50 value was reported as 35 mg/kg bw for dichlordibutyltin (administered in vegetable oil) exposure in mice.

- Guinea pig: The LD50 value was reported as 190 mg/kg bw for dichlordibutyltin (administered in vegetable oil) exposure in guinea pigs.

- Rabbit: The LD50 value was reported as 125 mg/kg bw for dichlordibutyltin (administered in vegetable oil) exposure in rabbits.

 

Reference: Mesch K A and Kugele T G (1992)

Reliability and rationale for score: 4 (not assignable) Details of the toxic effects were not reported other than the lethal dose value.

Result: The LD50 stated in this paper for acute toxicity to rats for dibutyltin dichloride is 126 mg/kg bw. No test method is reported, as this paper simply provides a review of study results for risk assessment puposes only.

 

 

Reference: Schafer EW and Bowles WA (1985)

Reliability and rationale for score: 4 (not assignable) Provided for information purposes only; documentation insufficient for assessment.

Result: In an acute toxicity study in deer mice the test material was found to have an Approximate Lethal Dose (ALD) of 470 mg/kg. No details on toxic effects were provided in the report.

 

 

Reference: KEMI report, Nordenhäll et al (1994). Cited study, Hill Top Research (1978)

Reliability and rationale for score: 4 (not assignable) secondary source

Result: The study was performed in male and female Sprague Dawley rats. The results are based on the assumption that DBTC was dosed at 100% pure liquid and that the relative density is 1.37 g/cm³. The LD50 for males was found to be 0.926 ml/kg with a 95% confidence interval of 0.570-1.50 ml/kg. The LD50 for females was found to be 1.71 ml/kg with a 95% confidence interval of 1.26-2.33 ml/kg. By using the relative density it can be calculated that DBTC will be classed as harmful.

 

INHALATION:

 

Stevens J (1980) was provided as the key study to address acute toxicity via the inhalation route. The study predates GLP, but was performed to a good scientific standard with a good level of reporting and is therefore considered adequate for use as the key study for this endpoint and was accordingly assigned a reliability score of 2 (reliable with restrictions) in accordance with the criteria outlined in Klimisch (1997).Rats were exposed to the test substance in 1:2.5 (v/v) Acetone:Ethanol diluted 1:1 (w/w) with distilled water as an aerosol for 4 hours (nose only exposure). The LC50 was reported to be 59 mg/m³. No deaths occurred in the control or vehicle groups. Although no rats died during exposure to concentrations of 50 and 73 mg/m³, 8 and 18 rats, respectively, died during the observation period. Exposure to 212 and 365 mg/m³resulted in the deaths of 5 and 11 rats respectively, during exposure; 19 and 20 rats, respectively, had succumbed prior to Day 4 of the observation period.

 

A further four studies were included for supporting information and are summarised below.

 

Reference: Coate WB (1976)

Reliability and rationale for score: 2 (reliable with restrictions) Study predates GLP. Purity and source of test material not provided. Sufficient information for assessment.

Result: Dibutyltin dichloride when administered to rats as a respirable aerosol is a highly toxic compound with a one-hour LC50 of approximately 0.53 mg/litre of air.

 

 

Reference: Ciba-Geigy Ltd. (1963)

Reliability and rationale for score: 2 (reliable with restrictions) Study predates GLP. Composition and source of test material not provided.

Result: In an LC50 of dibutyltin dichloride study in rats (Ciba-Geigy project number: Siss 2841) the test material was found to have an LC50 of 100 mg/m³, air. This value indicates the test material is highly toxic to the rat. No animals died at the low concentration of 28 ± 3 mg/m³. All animals had died within 48 hrs for all other concentrations.

 

 

Reference: Frances S (1975)

Reliability and rationale for score: 2 (reliable with restrictions) Study predates GLP. Particle size diameter not reported. Purity of test material not provided. Sufficient information for assessment.

Result: Dibutyltin dichloride when administered to rats as a respirable aerosol for one-hour gave an LC50 of 26.5 mg/L/hr in this study.

 

 

Reference: KEMI report, Nordenhäll et al (1994). Cited study, International Bio-Research, Inc. (1976)

Reliability and rationale for score: 4 (not assignable). Secondary source

Result: The KEMI report states the results conducted by IBR, the LD50 was given as >31.1 mg/l in male albino rats.

 

DERMAL:

As the substance was previously determined to be corrosive to the skin, further assessment would be unethical and would produce no meaningful results. Therefore, further testing was omitted.

Justification for classification or non-classification

Although results obtained in the acute oral key studys suggest a less severe classification, the substance is included in Annex I of Directive 67/548/EEC and already classified with T, R25 – Toxic if swallowed; T+, R26 – Very toxic by inhalation and Xn, R21 – Harmful in contact with skin. The results from the available data does not contest the classification for acute oral toxicity (the substance does not require a more severe classification) and supports the level of classification for acute inhalation toxicity.

For acute inhalation toxicity, according to the directive 67/458/EEC, the substance should be classified as T+ (very toxic) R26 (Very toxic by inhalation) and accordingly under the regulation EC No. 1272/2008, the substance should be classified as Category 2 H330 (Fatal if inhaled) with the signal word "Danger".

For acute toxicity via the oral route, according to the directive 67/458/EEC, the substance should be classified as T (toxic) R25 (Toxic if swallowed) and accordingly under the regulation EC No. 1272/2008, the substance should be classified as Category 3 H301 (Toxic if swallowed) and the signal word "Danger".

For acute toxicity through dermal exposure, according to the directive 67/458/EEC, the substance should be classified as Xn (Harmful) R21 (Harmful in contact with skin) and accordingly under the regulation EC No. 1272/2008, the substance should be classified as Category 4 H312 (Harmful in contact with skin) with the signal word "Warning".