Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
According to REACH Annex VIII column 1 (8.6.1), the following study for repeated dose toxicity is required: Short-term repeated dose toxicity study (28 days), one species, male and female, most appropriate route of administration, having regard to the likely route of human exposure.
Further, according to column 2, the short-term toxicity study (28 days) does not need to be conducted if i.a. a reliable sub-chronic (90 days) or chronic toxicity study is available, provided that an appropriate species, dosage, solvent and route of administration were used.
There is a suitable Klimisch 2 oral toxicity study available, conducted in a scientifically reasonable manner similar to OECD 408 and assessing the toxicological properties of 3-methyl-1,3-thiazolidine-2-thione after oral gavage over 90 days.
In general, the oral route is the most suitable one to assess systemic effects in humans, which is the main aim of this endpoint. The dermal or inhalative route is only scientifically relevant in case of considerable exposure, any route-specific toxicological mode of action or local effects, whereas sufficient information on the latter can be gained via irritation tests (REACH No. 8.1. or 8.2).
According to REACH Annex VIII column 2 (8.6.1), the appropriate route shall be chosen on the following basis: Testing by the dermal route is appropriate if: (1) inhalation of the substance is unlikely; and (2) skin contact in production and/or use is likely; and (3) the physicochemical and toxicological properties suggest potential for a significant rate of absorption through the skin.
Although inhalation of 3-methyl-1,3-thiazolidine-2-thione is unlikely, the latter conditions do not apply. Skin contact in production and/or use is unlikely as all identified process categories indicate no likelihood of exposure, i.e. use in closed process, no likelihood of exposure, all transfer is done in dedicated vessels or filling lines.
The physicochemical and toxicological properties do not suggest potential for a significant rate of absorption through the skin. Skin absorption is influenced by several factors, i.a.:
- Molecular weight: Less than 100 favors dermal uptake. Above 500 the molecule may be too large. With a molecular weight of 133.2351 g/mole, absorption is possible, possibly even favoured.
- LogPow: For substances with Log P values <0, poor lipophilicity will limit penetration into the stratum corneum and hence dermal absorption. Values <–1 suggest that a substance is not likely to be sufficiently lipophilic to cross the stratum corneum, therefore dermal absorption is likely to be low. Values between 1 and 4 are favourable for absorption. Since 3-methyl-1,3-thiazolidine-2-thione has a logPow of 0.59 at 20.3°C, dermal absorption may be possible, but less likely to occur.
- Water solubility: If water solubility is above 10,000 mg/l and the Log P value below 0 the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Dermal uptake for these substances will be low. As stated above, log Pow is 0.59, and additionally, the substance was found to be rather soluble in water, i.e. 3.65 g/L (at 30°C and pH 4.7). Also here, dermal absorption may occur to a minor extent due to the moderate to high hydrophilicity of the compound.
- Skin irritation / corrosion: If the substance is a skin irritant or corrosive, damage to the skin surface may enhance penetration. 3-methyl-1,3-thiazolidine-2-thione was not classified as irritant to the skin. Further, the substance does not need to be classified as irritating to the eye, which is in general considered to be more sensitive than the skin. Last but not least, in the available LLNA, no evidence of systemic toxicity or irritation was found. Therefore, no additional penetration enhancement must be considered.
In consequence, the available 90 day oral toxicity study similar to OECD 408 is sufficient to cover this endpoint, no repeated dose testing via dermal route needs to be performed and can consequently be waived due to animal welfare.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion