2-ethylhexyl 10-ethyl-4-[[2-[(2-ethylhexyl)oxy]-2-oxoethyl]thio]-4-octyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylhexyl 10-ethyl-4,4-dioctyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate

EC Number:

239-622-4

EC Name:

2-ethylhexyl 10-ethyl-4,4-dioctyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate

Cas Number:

15571-58-1

Molecular formula:

C36H72O4S2Sn

IUPAC Name:

2-ethylhexyl 10-ethyl-4,4-dioctyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecan-1-oate

Constituent 2

Reference substance name:

Dioctyltin bis(2-EHMA)

IUPAC Name:

Dioctyltin bis(2-EHMA)

Details on test material:

Dioctyltin bis(2-EHMA) [CAS No. 15571-58-1]; colorless liquid, 99.73% (w/w) DOT(2-EHMA), 15.7% w/w tin, source: Crompton GmbH.

Radiolabelling:

no

Test animals

Species:

other: rat and human epidermis

Administration / exposure

Type of coverage:

other: occluded and unoccluded

Vehicle:

ethanol

Duration of exposure:

24 hour(s)

Doses:

Absorption was determined via both occluded and unoccluded applications to human and rat epidermis (100 µl/cm²; equivalent to a dose of 17,007 µg tin/cm²).

Details on study design:

Absorption of tin compouds was measured (not DOTE only).

Results and discussion

Any other information on results incl. tables

HUMAN EPIDERMIS: A dose of 17,007 ug tin/cm² was determined to alter the barrier function of the epidermis.  From the occluded and unoccluded applications, the rates of tin absorption over the 0-24 h exposure period were below the limit of quantification (0.001 ug/cm²/h).  In terms of  percent applied tin, 0.0001% was absorbed from the occluded dose,  and  0.0001% was absorbed from the unoccluded dose after  24 hours of exposure.

RAT EPIDERMIS: Absorption of tin through rat epidermis was much faster than through human epidermis.  From the occluded application, the  maximum rate of tin absorption (0.035 ug/cm²/h) occurred during 16-24 hours of exposure, and the mean rate of tin absorption over the whole  24-h exposure period was 0.021 ug/cm²/h.  From the unoccluded application, the maximum rate of tin absorption occurred during 12-24 hours of  exposure and was 0.033 ug/cm²/h.  The mean rate of tin absorption over the whole  24-h exposure period was 0.025 ug/cm²/h.  In terms of percent applied tin, 0.003% was absorbed from the occluded dose, and 0.004% was  absorbed from the unoccluded dose after 24 hours of exposure.  The overall recovery of tin from the test system after 24-h exposure was low and may be due to adsorption of the test substance to the glass  equipment used.  The recovery was 45.5% (human) and 25.2% (rat) of theapplied occluded doses, and 29.6% (human) and 30.5% (rat) were  recovered from the unoccluded test systems.  Of the recovered tin, 2.1% (human) and 5.5% (rat) were obtained from the surface of the epidermis and donor chamber.  The mean amounts of tin  absorbed by 24 hours were 0.010 ug/cm² (unoccluded) and 0.011 ug/cm² (occluded) through human epidermis and 0.641 ug/cm² (unoccluded)  and 0.547ug/cm² (occluded) through rat epidermis.  These results show that the absorption of tin from dioctyltin bis(2-ethylhexylmercaptoacetate) through rat epidermis significantly  overestimated absorption from human epidermis.  By 24 hours only a small amount of the applied tin (3% in human and 1% in the rat) is  associated with the epidermis and is not regarded as systemically available.

The recovery was 45.5% (human) and 25.2% (rat) of the applied occluded doses, and 29.6% (human) and 30.5% (rat) were recovered from the unoccluded test systems.

Applicant's summary and conclusion

Conclusions:

Bioaccumulation potential cannot be judged based on study results.
Absorption of tin from DOT(EHMA) through rat epidermis significantly overestimates absorption through human epidermis.

Executive summary:

A dermal absorption study was carried out with DOT(2 -EHMA). Absorption of tin compounds was determined via both occluded and unoccluded applications to human and rat epidermis.

Of the recovered tin, 2.1% (human) and 5.5% (rat) were obtained from the surface of the epidermis and donor chamber.  The mean amounts of tin absorbed by 24 hours were 0.010 ug/cm² (unoccluded) and 0.011 ug/cm² (occluded) through human epidermis and 0.641 ug/cm² (unoccluded) and 0.547ug/cm² (occluded) through rat epidermis.

The results show that the absorption of tin from dioctyltin bis(2-ethylhexylmercaptoacetate) through rat epidermis significantly over-estimated absorption from human epidermis.  By 24 hours only a smallamount of the applied tin (3% in human and 1% in the rat)  is associated with the epidermis and is not regarded as systemically available.