Reaction products of pentaerythritol, propoxylated and 1-chloro-2,3-epoxypropane with hydrogen sulfide

Endpoint summary

Description of key information

Based on the available data, a theoretical assessment of the toxicokinetic behaviour of the test substance was performed.

The substance has a low bioaccumulation potential and for risk assessment purposes, 100% is used for oral, dermal and inhalation absorption.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

A substance can enter the body via the gastrointestinal tract, the lungs, or the skin, depending on the exposure route. After oral administration, in general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract. GPM-800 dissolves in water (62 g/L (at 20°C), therefore it is expected to readily dissolve into the gastrointestinal fluids. In principle, this would allow passive diffusion (passage of small water-soluble molecules through aqueous pores or carriage of such molecules across membranes with the bulk passage of water). GPM-800 is a polymeric mercaptan with a considerable size range (appr. 490 -1474 g/mol). As absorption is estimated to be still possible via this route for molecules with a molecular weight below 1000, some uptake via passive diffusion is expected for GPM-800. Furthermore, the substance dissolves in n-octanol, which results in a moderate to high partition coefficient (log Pow > 1.2 (at 20°C)). This lipophilic characteristic favors absorption by passive diffusion. The hydrolysis rate is slow (t1/2 > 1 year at 25°C at pH 4, 7 and 9) and is not further expected to influence the uptake. In conclusion, its solubility in water, its moderate to high partition coefficient and its molecular size will allow oral absorption. For risk assessment purposes oral absorption of GPM-800 is therefore set at 100% . The oral toxicity data do not provide reason to deviate from the proposed oral absorption factor. Once absorbed, wide distribution of GPM-800 throughout the body is expected based on its water solubility and its molecular weight range. As GPM-800 dissolves both in water and in n-octanol, it is expected not to have a special preference for fatty tissues. GPM-800 is expected to be excreted via urine. Based on these considerations, GPM-800 is not expected to bio-accumulate significantly in the body upon exposure. GPM-800 is a liquid with low volatility, as reflected in a low vapour pressure (0.16 Pa at 20°C) and absence of a boiling point (substance decomposes at ≥320°C). This implies that exposure via inhalation of vapour of GPM-800 is not likely to occur. However, liquid aerosols can be formed, which can be inhaled. Once GPM-800 reaches the lung tissue, it will readily dissolve in the mucus lining of the respiratory tract. The moderate to high lipohilicity allows the substance to cross the alveolar and capillary membranes by passive diffusion and be absorbed. Based on the above data, for risk assessment purposes the inhalation absorption of GPM-800 is set at 100%. In general, liquids such as GPM-800 are taken up more readily than dry particulates. In order to cross the skin, a compound must first penetrate into the stratum corneum (non-viable layer of corneocytes forming a complex lipid membrane) and subsequently reaches the viable epidermis, the dermis and the vascular network. The stratum corneum provides its greatest barrier function against hydrophilic compounds, whereas the viable epidermis is most resistant to penetration by highly lipophilic compounds. The combined characteristics of moderate water solubility and moderate to high lipophilicity of GPM-800 enables the substance to cross both barriers. Therefore dermal absorption is likely to be high. GPM-800 is surface active, with a surface tension of 29.9 mN/m (at 20°C, at 250 mg/L). However at this value, this characteristic is not expected to be of major influence on the uptake (only surfactants which reduce the surface tension of an aqueous solution < 10 mN/m are expected to enhance dermal uptake). On the other hand, the molecular size of GPM-800 (appr. 490 -1474 g/mol; representative size 800 g/mole) is expected to hamper dermal absorption as it may be too large for uptake across biomembranes. According to the criteria given in the REACH Guidance, 10% dermal absorption will be considered in case MW >500 and log Pow <-1 or >4, otherwise 100% dermal absorption should be used. Both the molecular weight of GPM-800 (approx. 490 -1474 g/mol) and the moderate partition coefficient do not meet the criteria for limited dermal absorption. Therefore, for risk assessment purposes dermal absorption is set at 100%.