N-(1,1-dimethylethyl)bis(2-benzothiazolesulfen)amide

Dermal absorption

Administrative data

Endpoint:

dermal absorption, other

Remarks:

Estimated by calculation

Type of information:

calculation (if not (Q)SAR)

Remarks:

Estimated by calculation

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Calculation was based on 2 methods, and resulted in similar results.

Data source

Reference

Reference Type:

other: internal document

Title:

No information

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

N-(1,1-dimethylethyl)bis(2-benzothiazolesulfen)amide

EC Number:

407-430-1

EC Name:

N-(1,1-dimethylethyl)bis(2-benzothiazolesulfen)amide

Cas Number:

3741-80-8

Molecular formula:

C18H17N3S4

IUPAC Name:

bis(1,3-benzothiazol-2-ylsulfanyl)(tert-butyl)amine

Applicant's summary and conclusion

Executive summary:

In the CSR of 2011, a basic toxicokinetics assessment, including dermal absorption, was performed for N-(1,1-dimethylethyl)bis(2 -benzothiazolesulfen)amide (TBSI ) according to REACH guidance on basic toxicokinetics requirements. Meanwhile the REACH guidance was updated (REACH, 2012). The qualitative assessment on toxicokinetics was repeated based on latest guidance.

In addition, upon request from the Belgian Competent Authorities, a theoretical quantitative assessment of dermal absorption was performed based on available state-of-the art tools and literature basis for calculation.

 

Initial assessment of dermal absorption

The initial assessment of dermal uptake of TBSI was mainly determined by the molecular weight, log Pow and water solubility of the substance:

-       The molecular weight of TBSI (404 g/mol) enables dermal uptake. Dermal uptake is less favourable at higher molecular weights (> 500 g/mol).

-       The Log Pow of TBSI is ca. 6.7. According to the above noted source, the dermal uptake is optimal when the Log Pow is 2 -3. At Log Pow > 4, the substance will be taken up into the stratum corneum, but further migration into the epidermis is slow. At Log Pow > 6, both the uptake in the stratum corneum and the migration into the epidermis are considered to be slow.

-       The water solubility of TBSI is ca. 0,002 mg/L. Such a low water solubility results in a slow partitioning from the stratum corneum into the epidermis. The uptake of TBSI via the dermal exposure route will therefore be slow, and systemic exposure will be limited.

 

The qualitative assessment can be confirmed according to most recent ECHA Guidance on information requirements and chemical safety assessment (Chapter R.7c: Endpoint specific guidance, November 2012 Version 1.1), which confirms that most arguments are not in favour of dermal absorption. The substance is a solid, and its low water solubility prevents the substance to partition from the stratum corneum into the epidermis. In addition the high log Pow >4 limits the transfer rate between stratum corneum and epidermis. The substance does not have surfactant properties, and no irritation, sensitisation or acute dermal toxicity were detected.

A further quantitative assessment was performed by means of Dermwin application, based on US EPA risk assessment for dermal absorption, resulting in following results for TBSI:

-       Dermal permeability coefficient (Kp) of 0.241 cm/hr.

-       Dermally Absorbed Dose (DAD) of 0. 416 µg/kg/day for a life time exposure.

-       However, the latter takes into account full dermal exposure (>17500 cm2 in adults), whereas for chemicals mostly only default surface areas are used, e.g. hands (857,5 cm2, or ca. 5% of total body surface; see Table 1). This leads to a realistic worst case exposure of 0.021 µg/kg bw/day systemic exposure to TBSI by dermal route.

However as the correlation of the DermWin method was limited (r2 = 0.66) , a second method was applied, starting from a similar equation for but applying a correction factor for high lipophilicity (Kroes et al., 2007). By applying this correction, the method is considered to be more specific and reliable. Results were as follows:

-       Corrected Permeability coefficient (Kp) = 0.097 cm/hr for TBSI.

-       From this value, Maximum flux (Jmax) was calculated to be 0. 00017 µg/cm2/h for TBSI.

-       Maximum potential absorption (Qabs) for hands (857,5 cm2 for 8h) was calculated to be 1.17 µg/adult/day or 0.019 µg/kg bw/day (assuming 60 kg body weight).

Reference: Kroes, R. et al. Food and Chemical Toxicology 45 (2007) 2533-2562, Application of the threshold of toxicological concern (TTC) to the safety evaluation of cosmetic ingredients.