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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted on read-across material
Justification for type of information:
Read-across to structurally similar substance.
Read-across performed on structurally similar substance data for the substance (DOTI) and the read-across substance (DOTE) can be used for the registration as they are isomers differing only slightly in the structure of the C-8 alcohol of the mercaptoester ligand.
Cross-reference
Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Reason / purpose for cross-reference:
other: read-across target
Qualifier:
according to guideline
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Version / remarks:
OECD Draft Guideline for Dermal Delivery and Percutaneous Absorption: In Vitro Method [OECD TG 428]
Deviations:
no
GLP compliance:
yes
Radiolabelling:
no
Species:
other: rat and human epidermis
Type of coverage:
other: occluded and unoccluded applications
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).
Control animals:
no
Details on study design:
Absorption of tin compouds was measured (not DOTE only).
Key result
Time point:
24 h
Dose:
17007 µg tin/cm²
Parameter:
rate
Absorption:
0.025 other: µg/cm²/h
Remarks on result:
other: Absorption of tin from DOT(EHMA) through rat epidermis significantly overestimates absorption through human epidermis.

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 µg/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 µg/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 µg/cm²/h.  From the unoccluded application, the maximum rate of tin absorption occurred during 12-24 hours of  exposure and was 0.033 µg/cm²/h.  The mean rate of tin absorption over the whole  24-h exposure period was 0.025 µg/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 material 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 µg/cm² (unoccluded) and 0.011 µg/cm² (occluded) through human epidermis and 0.641 µg/cm² (unoccluded)  and 0.547 µg/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.

Conclusions:
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 µg/cm² (unoccluded) and 0.011 µg/cm² (occluded) through human epidermis and 0.641 µg/cm² (unoccluded) 

and 0.547 µg/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.

Data source

Materials and methods

Test material

Constituent 1
Chemical structure
Reference substance name:
Triisooctyl 2,2',2''-[(octylstannylidyne)tris(thio)]triacetate
EC Number:
247-665-5
EC Name:
Triisooctyl 2,2',2''-[(octylstannylidyne)tris(thio)]triacetate
Cas Number:
26401-86-5
Molecular formula:
C38H74O6S3Sn
IUPAC Name:
Triisooctyl 2,2',2''-[(octylstannylidyne)tris(thio)]triacetate

Results and discussion

Percutaneous absorption
Key result
Time point:
24 h
Dose:
17007 µg tin/cm²
Parameter:
rate
Absorption:
0.025 other: µg/cm²/h
Remarks on result:
other: Absorption of tin from DOT(EHMA) through rat epidermis significantly overestimates absorption through human epidermis.

Applicant's summary and conclusion