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Description of key information

Specific test data are not available on the toxicokinetics of the test item. However, some evidence for the absorption/distribution of the test item is available in rats.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
10
Absorption rate - inhalation (%):
100

Additional information

Specific data are not available on the toxicokinetics, metabolism and distribution of the test substance. The pure peroxide is not commercially available. The test substance as tested, was a 50% peroxide, paste, in silicone oil.

 

Oral Absorptionl

The peroxide has a low molecular weight, poor water solubility, and relatively high log Pow value (6). Any lipophilic compound may be taken up by micellar solubilization but this mechanism may be of particular importance for highly lipophilic compounds (log P>4), particularly those that are poorly soluble in water (< 1mg/L) that would otherwise be poorly absorbed. While the physico-chemical properties may provide a general clue to the absorption potential of the test substance, the biological evidence for the absorption and distribution of the test item can be inferred from the availablein vivo studies in rats (repeated oral gavage, and skin sensitization study).

 

In a 28-day repeated oral gavage study in rats, treatment-related microscopic findings in liver, thyroid, testes, and epididymis were noted at the high dose, 1000 mg/kg/day, resulting in a No-Observed-Adverse-Effect-Level (NOAEL) of 300 mg/kg body weight/day. The microscopic changes in hepatocytes in the centrilobular region of the liver was considered to be an adaptive metabolic response. Clinical chemistry changes in blood, related to the liver function, were noted at 1000 mg/kg/day in alanine aminotransferase, and alkaline phosphatase levels for both sexes. The follicular cell hypertrophy seen in the thyroid was considered a secondary effect of the adaptive hepatocellular cytoplasmic changes in liver. For some males at 1000 mg/kg bw/day, microscopic changes in testes (increased Sertoli-cell vacuolation with focal, segmental tubular degeneration accompanied, in some cases, by spermatid retention in stage X tubule), and epididymis (interstitial edema, oligospermia and/or increased intraductal cellular debris of the males showing testicular change) were noted.

In another oral gavage study in rats for 90-days at dose levels of 100, 300 or 1000 mg/kg bw/day, treatment-related effects in body weight development, hematology parameters, adverse effects on sperms (concentration, motility and morphology), reduced testes, epididymides and cauda epididymis weights and microscopic changes in the bone marrow, testes/epididymides and thymic atrophy were noted at 1000 mg/kg bw/day and some microscopic changes in males treated with 300 mg/kg bw/day. These were considered treatment-related adverse effects. Some, but not all of these parameters recovered after a 4-week recovery period without the substance exposure. The lowest NOAEL from this study was 100 mg/kg bw/day in males.

These results were considered as the evidence of absorption of the test substance from the gastrointestinal tract of the rat, and distribution into several internal organs at sufficient concentrations, of either the test substance or its metabolite(s), causing biological effects at tissue / cellular levels in a generally dose-dependent manner. However, this information does not provide quantitative data as to how much of the substance was absorbed.The presence of arachis oil as the vehicle in the oral gavage formulation could have favored the test substance’s absorption from the digestive tract due greater chances of emulsification and digestion.   

 

Dermal Absorption

The test item is not an irritant to the rat skin, but since the substance has been identified as a skin sensitizer in rats, some local uptake must have occurred to cause a positive immune system effect, which is a systemic response. Based on the physical properties (molecular weight; poor water solubility; log P=6; low vapor pressure, -0.009 Pa at 25 degrees C; and the physical nature of the test item i.e., paste), the test substance is expected to have a relatively low dermal absorption rate. It was assumed to be 10% for long term systemic DNEL calculations.

Absorption through Inhalation

The vapor pressure (-0.009 Pa at 25oC) of the test item is low. Therefore, inhalation is not expected to be a major route of exposure. No animal data are available on absorption through inhalation.

The test substance is biodegradable. No other information is available on the metabolism or elimination of the test substance.