bis(O,O-2-ethylhexyl-thiophosphoryl)polysulfide

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

exposure considerations

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

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.
There is a suitable Klimisch 1 GLP OECD 422 guideline study available, assessing the toxicological properties of the registered substance after oral gavage over 6-7 weeks. 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 the registered substance to any toxicologically relevant amount is unlikely, the latter conditions do not apply. Due to the inherent low toxicity of the substance (NOAEL = 1000 mg/kg (OECD 422, oral)), a very high exposure to the substance would be required, which is excluded due to the taken workplace safety precautions. Even if exposure arises, exposition of workers would be magnitudes below any possible dose levels which could reveal any effects in animal models. Based on the current knowledge, the substance is not classified as acute toxic, STOR RE, or as irritant, and any theoretical exposure which could lead to any effects in humans, even with applying appropriate uncertainty factors, would be magnitudes below the actual one. Further, 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 e.g. 739.14 g/mol of the component containing 3 sulphur atoms in a row, absorption is unlikely.
- LogPow: for substances having a logPow above 6, the rate of transfer between the stratum corneum and the epidermis will be slow and will limit absorption across the skin. Uptake into the stratum corneum itself may be slow. Since the substance has a logPow of > 7.2, dermal absorption may practically not occur.
- Water solubility: The substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Therefore, if the water solubility is below 1 mg/L, dermal uptake is likely to be low. As stated above, log Pow is >7.2, and additionally, the substance was found to be insoluble in water, i.e. < 4.5 µg/l. Also here, dermal absorption may practically not occur due to the fact that the substance is insoluble in water.
- Skin irritation / corrosion: If the substance is a skin irritant or corrosive, damage to the skin surface may enhance penetration. The substance is 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. Therefore, no additional penetration enhancement must be considered. In consequence, the available OECD 422 study (oral exposure route) 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.