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Key value for chemical safety assessment

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There are no studies available for the determination of toxicokinetics or dermal absorption.

Diphenyl(2,4,6 -trimethylbenzoyl)phosphine oxide is a powder with a molecular weight of 348 g/mol and a very low vapour pressure of 3x10e6Pa at 20 °C. In agreement with its logPow of 3.1, only 12mg can be dissolved in one liter of water. Due to its low vapour pressure, exposure to vapor is unlikely. The combination of a molecular weight below 500g/mol and moderate lipophilicity (logPoW between 1 and 4) favor oral as well as dermal uptake. Though acute dermal and oral toxicity tests did not show signs of systemic toxicity, sensitization was observed, hinting to dermal uptake of at least small amounts. In several repeated dose oral toxicity studies damage of testes, liver and kidneys was observed. From the logPoW below 4 it is expected, that the substance does not bioaccumulate. This is confirmed by the repeated dose studies. For the 28day and 90day study almost the same doses were used, which showed well-comparable effects, independent of exposure time. For example, the mid dose of 250mg/kg (28day) or 300mg/kg (90day) showed increased liver and kidney weights, that worsened to partly histopathologically confirmed organ damage in the high dose group in both studies. Testes atrophy was detected in the high dose of both groups and in the mid dose in rats treated for 90days. Reduced testes size was palpable after 7 weeks in this dose group, which is after the 4 week time frame in the sub-acute study. Since testes damage was observed app. 2 -3 weeks after signs of liver and kidney damage were detected, this effect might require functional impairment of metabolism and excretion. In any case, the strong effects on liver and kidney suggest good oral uptake, metabolism in the liver and excretion via urine.

No mutagenicity or chromosomal aberration was observed (Ames, HPRT, CA), so no reactivity with macromolecules is expected prior to excretion.