Dihydro-2,2-dioctyl-6H-1,3,2-oxathiastannin-6-one

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

No experimental studies of the absorption, distribution, metabolism or elimination of Dihydro-2,2-dioctyl-6H-1,3,2-oxathiastannin-6-one (synonym:Dioctyltin mercaptopropionate; CAS No.3033-29-2; EC No. 221-218-4) in mammals are available. However, the physical chemical properties and the existing toxicity studies on the substance, as well as data and toxicity studies on the read-across structurally similar substance Dioctyloxostannane (synonyms: dioctyltin oxide, DOTO; CAS No. 870-08-6; EC No. 212-791-1) have been used to infer as far as possible, its potential toxicokinetics.

 

The substance Dioctyltin mercaptopropionate is a white powder, with a d(0.5) value determined to be 201 µm and d(0.9) 648 µm. Its molecular weight (MW) is 449.2788g/mol. The substance is very poorly water-soluble (< 0.4 mg/L at pH 7.7), and its partition coefficient (Log Kow/Log Pow) was calculated to be 4.1185.The vapour pressure was calculated to be 1.05x 10^-6Pa at 25 °C (Modified Grain method).By read-across from DOTO, Dioctyltin mercaptopropionate is categorised as not readily biodegradable.

 

Absorption

In an in vitro study simulating gastric conditions to determine the extent of hydrolysis of DOTO 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 of dioctyltin chloride formed and was considered to be the cause of the high variability between replicates. Increased temperatures to 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. This behaviour is expected to be applicable also to Dioctyltin mercaptopropionate, because its particle size is even greater than that of DOTO, and the toxophore, the organotin moiety, is the same.

 

The available information on acute oral toxicity supports a limited oral absorption, as the LD50 of Dioctyltin mercaptopropionate is higher than 2000 mg/kg bw. Some oral absorption was demonstrated in a fully compliant OECD 422 study performed with the read-across substance DOTO, using the dietary route of exposure. Treatment at a dietary level of 25 ppm of DOTO resulted in adverse effects on thymus; at a higher dietary concentration of 250 ppm some signs of liver involvement were also noted. As a worst-case estimate, for risk assessment purposes Dioctyltin mercaptopropionateis considered to be absorbed at 50% or less following oral administration. For the purposes of human health risk assessment 50% absorption is assumed.

 

Dioctyltin mercaptopropionate is a heavy molecule (MW 449.2788g/mol) and d(0.5) and d(0.9) values indicate it is too large to reach the respiratory system. In addition, the extremely low vapour pressure indicates that Dioctyltin mercaptopropionate would not be available for inhalation as a vapour, and the extremely low water-solubility suggest that any particles reaching the upper respiratory tract could be coughed or sneezed out of the body or swallowed. In the absence of any quantitative data, and using a really conservative approach, for human health risk assessment purposes absorption by inhalation o fDioctyltin mercaptopropionate is assumed to be 100%.

 

All physical-chemical properties of Dioctyltin mercaptopropionate suggest that the substance is unlikely to be absorbed through the skin. This is further supported by the lack of any skin irritating or corrosive properties in in vitro studies with Dioctyltin mercaptopropionate, a lack of any sensitisation potential in a fully compliant Local lymph Node Assay performed with the read-across substance DOTO, and the acute dermal LD₅₀ greater than 2000 mg/kg bw, also determined with the read-across substance DOTO. Therefore, for human health risk assessment and using a really conservative approach, dermal absorption is estimated to be 1%.

 

Distribution

Results of the OECD 422 study suggest that once absorbed the read-across substance DOTO is widely distributed within the body, as the target organ was the thymus and, at higher doses, the liver. This is considered also applicable to Dioctyltin mercaptopropionate. Given the relatively high log Pow and the extremely low water solubility of Dioctyltin mercaptopropionate, micellular solubilisation may play a major role for absorption, and preferential partition to tissues with high lipid content.

 

Metabolism and Excretion

As mentioned above, no appreciable hydrolysis is expected to occur for Dioctyltin mercaptopropionate under gastric conditions and metabolism of the entire molecule is considered unlikely. For metabolism of the aliphatic chain to occur, detachment from the tin would be needed, which is considered highly unlikely. Excretion of unchanged Dioctyltin mercaptopropionate is expected to occur mainly via the faeces.

Read-across to DOTO (Dioctyltin oxide)

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.

Justification for Read-Across

The target substance Dihydro-2,2-dioctyl-6H-1,3,2-oxathiastannin-6-one (Public name: Dioctyltin mercaptopropionate, CAS: 3033-29-2, EC: 221-218-4) is a mono-constituent organotin substance that consists of a tin as central metal element with two octyl-ligands and one 3-mercaptopropionate-ligand. The source substance dioctyltin oxide (Public name: DOTO, CAS: 870-08-6, EC: 212-791-1) is also an organotin compound and has the identical structure elements as the target substance in respect of the tin-alkyl moiety.

According to WHO IPCS CIRCAD (2006) organotin compounds are characterized by a tin–carbon bond and have the general formula RxSn(L)(4−x), where R is an organic alkyl or aryl group and L is an organic (or sometimes inorganic) ligand. The organotin moiety is significant toxicologically. The anionic ligand influences physicochemical properties but generally has little or no effect on the toxicology. Applying this WHO characterization to target and source, they can be described (C8H32)2SnL, with L source = O2- and L target = (SCH2CH2COO)2-.

Since the target substance and the source substances share the identical organotin moiety, and the organotin moiety is generally recognized as the relevant toxophore of organotins and the toxicity estimates (AE) respectively toxicity limits for organotins are expressed as tin, the overall ecotoxicity/systemic toxicity of the target can be interpolated by assessing the (eco-)toxicity of the source (WHO IPCS CIRCAD, 2006, BAUA AGS TRGS 900, 2014, Summer KH, Klein D and Greim H, 2003). As the source has a higher relative amount of tin based on molecular weight (source 32.87%, target 26.42%) the read-across approach to DOTO can be assessed as conservative (worst case).

The purity of the source and target substance are expected to be high, based on the manufacturing method. The impurity profile is not expected to have strong effects on substance properties and any impurity of (eco-)toxicological relevance of the source substances is expected to be present in the target substance. Consequently, the hazard profiles of the source substances, including those of their impurities, are intrinsically covered. Differences in impurities are not expected and thus do not have an impact on the (eco-)toxic properties. The dominating intrinsic property of mercaptopropionic acid - which is as mercaptopropionate the moiety of the target substance, which is not covered by the source substance and thus may pose a source specific impurity - is its corrosivity. However this is a local effect covered by studies on the target substance itself and thus excluded from the read- across approach. In addition, mercaptopropionic acid and derivatives thereof are natural constituents of the environment and human nutrition.

The bioavailability of both substances varies in a predictable manner and is assumed to be dependent on the water solubility. The prediction of the effects of the target substance based on the relationship between solubility and (eco-)toxicity or on a worst-case basis. The respective ligands of source and target are expected to be of no (eco-)toxic importance based on intrinsic properties but may have an effect on solubility respectively bioavailability.

 

References

BAUA (Bundesanstalt für Arbeitsschutz und Arbeitsmedizin (Federal Institute for Occupational Safety and Health)) AGS (Ausschuss für Gefahrstoffe (Committee on Hazardous Substances)) TRGS (Technical Rules for Hazardous Substances) 900 (2014). Begründung zu n-Octylzinnverbindungen, April 2014.

Summer KH, Klein D, Griem H (2003). Ecological and toxicological aspects of mono- and disubstituted methyl-, butyl-, octyl-, and dodecyltin compounds - Update 2002. GSF National Research Center for Environment and Health, Neuherberg, for the Organotin Environmental Programme (ORTEP) Association.

World Health Organization (WHO) International Programme on Chemical Safety (IPCS) Concise International Chemical Assessment Document (CICAD) 73 Mono- and disubstituted methyltin, butyltin, and octyltin compounds (2006). Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organization, and the World Health Organization, and produced within the framework of the Inter-Organization Programme for the Sound Management of Chemicals. World Health Organization ISBN 978 92 4 153073.