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Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Information describing the potential behaviour of the test substance within the body during the early phase of biotransformation was presented in Schilt & Zondervan-van den Beuken (2004) in an in vitro, non pre-validated, simulated gastric hydrolysis test. The study was performed and reported to a high standard and as such was assigned a reliability score of 2 in accordance with the criteria as outlined in Klimisch (1997) for assessing the quality of data. Under the conditions of the test, it was not possible to measure the hydrolysis of the test substance due to the difficulties presented with the analytical procedures and the physico-chemical properties of the test substance. It was concluded that DOTO would not fully hydrolyse in the test system.

 

In accordance with point 8.8.1 of column 1 (Standard Information Required), Annex VIII of REACH (Regulation EC No. 1907/2006), assessment of the toxicokinetic behaviour of the substance is performed to the extent that can be derived from the relevant available information. A toxicokinetic assessment was performed based on the available physical-chemical data and toxicological information available. Further testing for the assessment of toxicokinetic behaviour is omitted on this basis.

Toxicokinetic Assessment of the Substance dioctyltin oxide (DOTO)

1.0             Introduction

Physico-chemical properties and the results of in vitro studies and in vivo acute and repeat dose toxicity studies for dioctyltin oxide (DOTO – CAS No. 870-08-6) have been used to determine a toxicokinetic profile. 

 

2.0             Physico-chemical properties

DOTO is a colourless to off-white/white odourless solid and has the molecular formula C16H34OSn with a molecular weight of 361.1506 g/mol. It is very sparingly water soluble (0.0000152 g/L at 20 °C) with an estimated log Pow value of 9.26.  Due to technical difficulties with the analytical methods appropriate for this substance, including sensitivity and the poor solubility of the registered substance, not only in water, but also in organic solvents, it was not possible to determine its hydrolytic stability.

 

3.0             Absorption

3.1             Oral absorption

In an in vitro study simulating gastric conditions to determine the extent of hydrolysis to dioctyltin chloride, no meaningful results were obtained, because DOTO was extremely insoluble in the test system and only partially hydrolysed. It was noted that the particle size of the test substance influenced the level ofdioctyltin chlorideformed and was considered to be the cause of the high variability between replicates. Increased temperatures higher than 37 °C (up to 60 °C) increased the speed of hydrolysis. The percentage of hydrolysis never exceeded 55 % and in most cases was considerably lower (2-5 %); it was concluded that DOTO would not hydrolyse to an appreciable extent under gastric conditions. DOTO appeared to be relatively resistant to the simulated gastric hydrolysis.

The available information on acute oral toxicity supports a limited oral absorption, as the reported LD50values are generally higher than a limit dose of 2000 mg/kg bw (up to greater than 6000 mg/kg bw). Some oral absorption is also demonstrated by results of a fully compliant OECD 422 study, using the dietary route of exposure, because treatment at a dietary level equivalent to 1.5-2.4 mg/kg/day resulted in adverse effects on thymus; at a higher dietary concentration (equivalent to 11-17 mg/kg/day) treatment also affected reproductive parameters and some signs of liver involvement were also noted.

As a worst-case estimate, for risk assessment purposes DOTO is considered to be absorbed at 50 % or less following oral administration. For risk assessment purposes 50 % is assumed.

3.2             Dermal absorption

No information is available on dermal absorption. DOTO is a solid particulate (i.e. with an effective MW of many times the molar mass of 361.1506 g), is poorly soluble in water (0.0000152 g/L at 20 °C), and has an estimated log Pow value of 9.26. All these factors indicate the rate of transfer between the stratum corneum and the epidermis will be slow, and will limit absorption across the skin. In accordance with criteria in Chapter R.7c: Endpoint specific guidance (Guidance on information requirements and chemical safety assessment) a default dermal absorption value of 10 % may be assigned for soluble substances with a MW >500 and log Pow >>4. In this case the material is an insoluble particulate solid (insoluble material is considered in the guidance to have practically no absorption) so absorption would be considerably lower than 10 %, and a value of 1 % is considered appropriate for risk assessment purposes.

In the dermal toxicity study on Dioctyltin dilaurate from Blackburn et al., there was no absorption of tin into the blood of the study animals found. The stubstance Dioctyltin dilaurate hydrolyses at once in contact with water into Dioctyltin oxide and Lauric acid.

Thus can be concluded, that there is no dermal absorption of DOTO.

3.3             Inhalation absorption

No information is available on inhalation toxicity of the substance, or on inhalation absorption.The particle size distribution of the substance was investigated using a method based on a procedure designed to be compatible with that given in `Particle Size Distribution, Fibre Length and Diameter Distribution', June 1996 European Commission technical guidance document. Sieving apparatus was used in a screening test to investigate particle size of 100 µm. A cascade impactor was then employed to investigate particles in the size range of 0.3 to 10 µm. The study showed that most part of DOTO would not reach the lower tract of the respiratory system, as the proportion of the test material having an inhalable particle size of <100 µm was 15.2 %; that having a thoracic particle size of <10.0 µm was 1.21 % and that having a respirable particle size of <5.5 µm was 0.40 %.

As a worst case and really conservative approach, the inhalation absorption in humans is considered to be complete (100 %) for risk assessment purposes.

 

4.0             Distribution

Results of the OECD 422 study suggest that once absorbed DOTO is widely distributed within the body, as the target organ was the thymus and, at higher doses, the reproductive system and the liver. Given the high estimated log Pow and the extremely low water solubility, micellular solubilisation may play a major role for absorption, and preferential partition to tissues with high lipid content. 

 

5.0             Metabolism

No information is available. Given the length of the chain (octyl), DOTO is not anticipated to undergo significant biotransformation.

 

6.0             Elimination

Unchanged DOTO is expected to be excreted mainly via the faeces.

A bioaccumulation study in fish with a structurally related substance determined a BCF of >100. No upper limit appears to have been verified hence it is not possible to estimate the extent of elimination of the material from fatty tissues.

7.0              Conclusion

For risk assessment purposes, moderate absorption following oral administration is assumed (50 %) for DOTO, but it is estimated to be less absorbed following dermal exposure (1 %), and completely absorbed following inhalation (100 %).

The substance is considered to be widely distributed within the body, hardly metabolised, and excreted mainly unchanged in the faeces.

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