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Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
1
Absorption rate - inhalation (%):
100

Additional information

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.

Introduction

Physico-chemical properties and the results ofin vitrostudies andin vivoacute and repeat dose toxicity studies for Oc2Sn(Mal-Et)2(CAS 68109-88-6, 2-butenedioic acid, 1,1'-(dioctylstannylene) 4,4'-diethyl ester) are used to infer as far as practicable, a toxicokinetic profile for Oc2Sn(Mal-Et)2,or where no information is available, by readacross to, dioctyltin oxide (DOTO – CAS No. 870-08-6) 

 

The rationale for the read across to dioctyltin oxide (DOTO) is that Oc2Sn(Mal-Et)2will hydrolyse to DOTO in the presence of gastric juice. This is based on direct evidence with Oc2Sn(Mal-Et)2(rapid hydrolysis was observed aquaeous hydrolysis studies as a at low pH, see dossier) and also , from hydrolysis studies with simulated gastric juice and dibutyltin dilaureate (IPCS, 2006). In this study the hydrolysis half life of the dibutyltin dilaureate was <0.5 hour. Further evidence may also derived from studies performed with dioctyltin diluareate (CAS 3648-18-8), and also dioctylbis(2,4-pentanedionato-O,O')-tin (CAS 54068-28-9)(please see the hydrolysis data included in the iuclid dossier).

 

The resulting 2-butenedioic acid ethyl ester (maleic ethyl ester) will be consumed by gut flora, or if absorbed, will be excreted rapidly in the urine. Therefore the fate only of the remaining DOTO portion is considered here.

 

 

Physicochemical properties

Oc2Sn(Mal-Et)2is an extremely pale yellow liquid and has the molecular formula C28-H48-O8-Sn with a molecular weight of 631.38592 g/mol. It is very slightly water soluble (1.193 mg/L at 20 °C) with a log Pow value of >6.5. The melting point is 16 to 18 ºC, with a boiling point of 248ºC.

Oc2Sn(Mal-Et)2will hydrolyse to DOTO in the presence of gastric juice. The remaining 2-butenedioic acid ethyl ester will be consumed by gut flora, or if absorbed, will be excreted rapidly in the urine.Therefore the following assessment was made for DOTO.

Oral absorption

In anin vitrostudy 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.

 

Dermal absorption

Oc2Sn(Mal-Et)2is larger than DOTO and hence the following assessment for DOTO is considered to represent the worst case scenario forOc2Sn(Mal-Et)2. Oc2Sn(Mal-Et)2is unlikely to hydrolyse rapidly on the skin.

 

No information is available on dermal absorption.Oc2Sn(Mal-Et)2hasa molecular weight of 631.38592 g/mol with a log Pow value of >6.5.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 forsolublesubstances with a MW >500 and log Pow >4. In this case the material is onlyvery slightly water soluble(insoluble material is considered in the guidance to have practically no absorption) so absorption would be considerably lower than 10%.

As a conservative estimate, Avalue of 1% is used for risk assessment purposes forOc2Sn(Mal-Et)2.

 

 

Inhalation absorption

No information is available on inhalation toxicity of the substance, or on inhalation absorption. As a worst case and really conservative approach, the inhalation absorption of material reaching the alveoli in humans is considered to be complete (100%) for risk assessment purposes.

 

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 POWof DOTO and the extremely low water solubility, micellular solubilisation may play a major role for absorption, and preferential partition to tissues with high lipid content. 

 

Metabolism

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

 

Elimination

Unchanged DOTO is expected to be excreted mainlyviathe faeces.

A bioaccumulation study in fish with a structurally related substance determined aBCF 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.

 

Conclusion

Based on the properties of DOTO the oral absorption ofOc2Sn(Mal-Et)2is estimated at 50%, inhalation absorption is estimated at 100% and dermal absorption is estimated at 1%. No information is available to describe to fate of the material.