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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study without detailed documentations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Objective of study:
absorption
Test guideline
Qualifier:
according to
Guideline:
other: OECD Draft Guideline for Dermal Delivery and Percutaneous Absorption: In Vitro Method [OECD TG 428]
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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

Route of administration:
dermal
Vehicle:
other: ethanol
Details on exposure:
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).
Duration and frequency of treatment / exposure:
24 hour(s)
Doses / concentrations
Remarks:
Doses / Concentrations:
17,007 ug tin/cm2
Positive control:
no
Details on study design:
Absorption of tin compouds was measured (not DOTE only).

Results and discussion

Main ADME results
Type:
absorption
Results:
Absorption of tin from DOT(EHMA) through rat epidermis significantly overestimates absorption through human epidermis.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
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:
Interpretation of results (migrated information): 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 tins 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 

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.