Triisooctyl 2,2',2''-[(octylstannylidyne)tris(thio)]triacetate

Dermal absorption

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.

Materials and methods

Test material

Test material information

Constituent 1

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.