Dioctyltin dilaurate

Endpoint summary

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 of in vitro studies and in vivo acute and repeat dose toxicity studies for dioctyltin dilaurate (DOTL – CAS No. 3648-18-8) have been used to determine a toxicokinetic profile.

 

Physicochemical properties

DOTL is a colourless liquid and has the molecular formula C₄₀H₈₀O₄Sn with a molecular weight of 743.8 g/mol. It is very sparingly water soluble (0.0000152 g/L at 20°C). DOTL was determined to be hydrolytically unstable at pH 4, 7 and 9, with a half life of less than 4.5 hours. The test material was observed to immediately hydrolyse to dioctyltin oxide (DOTO) and lauric acid in the presence of water. Based on these findings, testing for a partition coefficient was alsonot technically possible. 

 

Absorption

Oral absorption

In an in vitro study simulating gastric conditions to determine the extent of hydrolysis to DOTL, no meaningful results were obtained, because DOTL isimmediately hydrolysed to DOTO (insoluble) and lauric acid in the presence of water. Therefore no reaction rate constants or half life values could be calculated. Based on the results obtained it could be concluded that the half life of the test material is below 4.5 hours.It was noted that the transformation rate was slightly elevated in acidic conditions but not to any significant levels. DOTL appears to rapidly hydrolyse under simulated gastricconditions.

As DOTL is anticipated tobe immediately hydrolysed to DOTO and lauric acid in the gut, it can be considered that the absorption of DOTL would be equivalent to that of its hydrolysed components. In a similar study conducted with DOTO 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.

Lauric acid is a 12-carbon medium chain fatty acids. As a component of triglycerides lauric acid is naturally occurring in the body and in the diet. It is also available for use in food and feed supplements and used as a therapeutic agent for a range of conditions, there is a vast amount of published medical papers. Lauric acid, comprises about half of the fatty acid content in coconut oil, laurel oil, and in palm kernel oil; it is also found in human breast milk, cow's milk, and goat's milk. As a result lauric acid is considered to be readily absorbed following the fatty acid metabolic pathway and non-toxic.

With respect to DOTO the available information on acute oral toxicity supports a limited oral absorption, as the reported LD₅₀ values 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 DOTL is considered to be absorbed at 50 % or less following oral administration. For risk assessment purposes 50 % is assumed.

Dermal absorption

No information is available on dermal absorption. DOTL is a liquid with a large MW of 743.8 g/mol and is poorly soluble in water (0.0000152 g/L at 20 °C).  Given its poor solubility,it will associate with itself and will not easily diffuse across lipid bilayers, or penertrate the stratum corneum (its large size will limit it transmission through the lipid filled channels between dead cells in the stratum corneum). These factors indicate the rate of transfer from the stratum corneum and the epidermis will be slow, and will limit absorption across the skin. As such a value of 1% for dermal absorption is considered a very conservative estimate.

Inhalation absorption

No information is available on inhalation toxicity of the substance, or on inhalation absorption. The vapour pressure of the test material was determined in accordance with standardised guidelines at temperatures of 20, 25 and 50 °C and calculated to be 0.0015, 0.0022 and 0.011 Pa, respectively. Based on the results of this study DOTL is considered to have a low vapour pressure.

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

 

Distribution

Results of the OECD 422 study suggest that, once hydrolysed and absorbed as DOTO, the material 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 of DOTO, 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 results of submitted hydrolysis study (Lange, 2012a) and the resultant formation of DOTO no significant biotransformation anticipated to occur.

Lauric acid would be expected to follow the fatty acid metabolism pathway following dissociations from DOTL.

 

Elimination

Once hydrolysed and absorbed as DOTO,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.

 

Conclusion

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

The substance is considered to be immediately hydrolysed to DOTO and lauric acid in the gut,widely distributed within the body, hardly metabolised, and excreted mainly as unchanged DOTO in the faeces.