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Description of key information

According to the results of the key study (OECD method 427, GLP compliant, Klimisch 1), the absorbed dose (receptor fluid and receptor rinse) and dermal delivery (sum of amounts measured in living epidermis/dermis and receptor fluid) were 1.21% (0.66 µg equiv/cm2) and 2.92% (1.60 µg equiv/cm2) of the applied dose of registered item, respectively. In a second key study (OCED method 408, GLP compliant, Klimisch 1),the toxicokinetics behaviour of the substance was studied in a repeated dose toxicity study. The maximal systemic abosrption after oral administration were 6% for female rats at 20mg/kg/day dose level (lower dose). The maximum plasmatic concentration (Cmax) was reached at 30 minutes after administration (Tmax = 0.5)

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - dermal (%):
2.92

Additional information

In the first key study on dermal absorption (OECD method 427, GLP compliant, Klimisch 1) human breast and abdominal skin samples were used. Skin samples were dermatomed (390-400 μm in thickness) and mounted in flow-through diffusion cells, using bovine serum albumin (5%, w/v) in calcium and magnesium free phosphate-buffered saline as the receptor fluid and skin was maintained at approximately 32°C.

The phenyl methyl pyrazolone had been tested in two different condition, in a typical oxydative conditions (with para-phenylenediamine, PPD, 3%) and in a non-oxydative conditions (mixed with water).

-       In oxydative conditions, about twenty mg/cm² of this mixture (corresponding to exactly 50.5 μg/cm² of phenyl methyl pyrazolone) was applied to the skin surface and left for 30 minutes. After this time period, the remaining formulation on the skin surface was removed simulating use conditions. Twenty-four hours after application, the percutaneous absorption of [14C]- phenyl methyl pyrazolone was estimated by measuring its concentration by liquid scintillation counting in the following compartments/samples: skin washes (dislodgeable dose), stratum corneum (isolated by tape strippings), living epidermis/dermis, unexposed skin and receptor fluid.

-       In non-oxidative conditions, using a formulation without primary intermediate and mixed with water (1:1, w/w) to yield a final concentration of 0.25% phenyl methyl pyrazolone (about 20 mg/cm2 were applied, corresponding exactly to 50.5 μg/cm2).Most of the phenyl methyl pyrazolone applied on the skin surface was removed with the skin washes (about 92% and 93% of the applied dose in oxidative and non-oxidative conditions, respectively), and the total recovery rate was about 95% and 96% in oxidative and non-oxidative conditions, respectively. The mean amounts of phenyl methyl pyrazolone considered as absorbed (dermal delivery) were estimated as follows (sum of amounts measured in living epidermis/dermis and receptor fluid): 0.31 ± 0.24 μg equiv/cm2 (0.56 ± 0.44% of the applied dose) and 1.60 ± 0.30 μg equiv/cm2 (2.92 ± 0.53% of the applied dose) in oxidative and non-oxidative conditions, respectively.

In a second key study (OCED method 408, GLP compliant, Klimisch 1),the toxicokinetics behaviour of the substance was studied in a repeated dose toxicity study.

A satelite group of rats in a subchronic repeated toxicity study (OECD method 408) was used. After daily oral administration of the test substance at 20, 100, 500 mg/kg bw/day, bloods were collected at different time point (week 1 and week 13). The test item was quantified in blood samples using HPLC/UV method. Cmax, Tmax and AUC were calculated and rate of systemic exposure after administration was calculated in each dose group.