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Administrative data

Link to relevant study record(s)

Description of key information

he following study was included to address dermal absorption:
Ward, R.J. (2003) Dibutyltin bis(2-ethylhexyl mercaptoacetate): in vitro absorption through human and rat epidermis. Testing Laboratory: Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, SK10 4TJ, UK. Owner Company: Tin Stabilizer Association, 1900 Arch Street, Philadelphia, PA 19103-1498, USA. Project No.: JV1699. Company study number: CO1374. Report date: 2003-01-08
The study was assigned a reliability score of 2 as the study was read-across from dibutyltin bis(2-ethylhexylmercaptoacetate).

Key value for chemical safety assessment

Absorption rate - dermal (%):
1

Additional information

Ward, R.J. (2003) was presented as the key study for this endpoint. The study was performed to the guideline OECD 428 and in compliance with GLP. The study was assigned a reliability score of 2 as the study was performed on dibutyltin 2-bis (2-ethylhexyl mercaptoacetate) and read-across to the substance in question, but is still considered reliable and adequate for assessment. From the study, the following points were noted:

1. Following 24 hours dermal contact, the amount of dibutyltin bis(2-ethylhexlymercaptoacetate) required to alter the barrier function of rat epidermis was approximately 100 µL/cm2(= 21120 µg tin/cm2).

2. The results indicate that at a dose level of 100 µL/cm2, approximately up to 18-45 % of the tin dose was unaccounted for, possibly due to adherence of the test material to the glass apparatus used during the study, especially during the decontamination process.

3. At 100 µL/cm2, the absorption of tin through human epiderims was very slow, when compared with the absorption rates of other penetrants measured using the same in vitro technique. (Dugard et al 1984; Dugard and Scott, 1984).

4. The proportions of dibutyltin bis(2-ethylhexylmercaptoacetate) absorbed through human epidermis were 0.0004% and 0.0010% (occluded and unoccluded respectively) of dose after 24 hours exposure, compared to 0.261% and 0.189% through rat epidermis.

5. The absorption of tin from dibutyltin bis(2-ethylhexylmercaptoacetate) through rat epidermis significantly overestimated absorption through human epidermis.

6. The vast majority of the applied tin dose was washed from the surface of the epidermis during the decontamination process, with only relatively small proportions of the dose (human up to 1%; rat up to 10%) remaining associated with the epidermis and therefore not regarded as systemically available.

The results obtained from an in vitro gastric hydrolysis study (Yoder 2000) support the use of Dibutyltin Dichloride (DBTC) as an appropriate surrogate for mammalian toxicology studies of the corresponding DBT moiety. A study conducted via the oral route on the thioester DBT (2-EHMA) demonstrated this substance readily hydrolized to DBTC under physiological conditions (100% hydrolysis within 1hour).  Thus, it is considered that DBTC is an appropriate anchor compound and surrogate for the repeat dose toxicity, genotoxicity, reproduction and developmental toxicity and other long term toxicology endpoints, for all dibutyltin compounds when they are assessed following oral administration of the test material. Acute toxicity and irritation endpoints are not covered under the category approach and were evaluated individually for each dibutyltin compound. Sensitization, although not related to the hydrolysis discussion above, is considered acceptable to read across for Dibutyltin substances and as a group they are considered to be sensitisers.

In addition actual available data for the substance is limited to anin vitrostudy demontrating that DBTL may be quickly hydrolised at a pH compatible with stomach acid to form other butyl tin derivatives and therefore data from other dibutyl tin compounds can be used in case of oral exposure. Further data reviewed by the EU’s Scientific Panel on Contaminants in the Food Chain (EFSA/SPCFC) indicated that tributyl tin may be dubutylated to dibutyl- and monobutyl tin, and dibutyl tin acetate is further metabolised to monobutyl tin. These data would suggest that the toxicity of all the butylated tin compounds can be read across.

The EFSA/SPCFC review suggets that oral absorption of tributyl and dibutyl tin is incomplete, based on 41% unmetabolised dibutyl tin acetate recovered from the faeces of treated mice. A figure of 50% is considered and appropriate estimate of oral absorption.

In the 2003 Dermal Absorption study by Ward, 100 µL/cm2(= 21120 µg tin/cm2) was found to alter the barrier function of the rat epidermis. At 100 µL/cm2, approximately up to 18-45 % of the tin dose was unaccounted for, possibly due to adherence of the test material to the glass apparatus. The absorption of tin through human epiderims was very slow, when compared with the absorption rates of other penetrants. The proportions of dibutyltin bis(2-ethylhexylmercaptoacetate) absorbed through human epidermis were 0.0004% and 0.0010% (occluded and unoccluded respectively) after 24 hours exposure, compared to 0.261% and 0.189% through rat epidermis. The majority of the applied tin dose was washed from the surface of the epidermis during decontamination, only a relatively small proportion of the dose (human up to 1%; rat up to 10%) remained associated with the epidermis and therefore was not regarded as systemically available.