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The following remarks on the toxicokinetics of the multi-constituent substance HPP 12879-1 (Reaction mass of 2,6-Bis[(dimethylamino)methyl]-4-(1-{3-[(dimethylamino)methyl]-4- hydroxyphenyl}-1-methylethyl)phenol and 4-(1-{3,5-Bis[(dimethylamino)methyl]-4-hydroxyphenyl}-1-methylethyl)-2,6 -bis[(dimethylamino)methyl]phenol) are based on physico-chemical properties of the compound and on available toxicological data. Experimental toxicokinetic studies were not performed.

The substance is a white organic solid with a very low vapour pressure under normal ambient conditions (2.1 x 10-4 Pa at 20°C), therefore inhalation exposure to the vapour is expected to be negligible.

The physico-chemical characteristics of the substance (good water solubility of 4.1 g/L at 20°C, moderate log Pow of 3.2 - 4.0 at 25°C and a molecular mass of 342 - 456 g/mol) are favourable for intestinal absorption after oral intake. Due to the lack of acute or subacute toxicity studies in animals there is no proof of systemic availability of the substance after oral administration.

Because of the moderate lipophilicity of HPP 12879-1 accumulation of the unchanged compound in fatty tissues would be conceivable in individuals that are frequently exposed to that substance.

Due to the good water solubility, a log Pow of 3.2 - 4.0 at 25°C and a molecular mass of 342 - 456 g/mol dermal absorption of the substance seems conceivable. However, no signs of systemic toxicity were observed in an acute dermal toxicity study in rats (LD50 > 2000 mg/kg bw; Haferkorn, 2016) and in a local lymph node assay (LLNA) in mice (Leidenfrost, 2016). As the skin sensitisation study revealed a moderate skin sensitising potential after dermal contact of the substance formulated in acetone/olive oil (4:1 v/v), at least for a solution of the substance in acetone/olive oil (4:1 v/v) some dermal absorption has to be assumed.

Based on the results of three in vitro genotoxicity tests (negative with and without metabolic activation in an Ames test (Sokolowski, 2015a), in a HPRT test (Wollny, 2016) as well as in a mammalian cell micronucleus test (Sokolowski, 2015b)) it is concluded that DNA-reactive metabolites of the substance will most probably not be generated in mammals in the course of hepatic biotransformation.

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