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Administrative data

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Description of key information

Short description of key information on bioaccumulation potential result: 
The physicochemical properties of the test substance, and extensive toxicity studies in animals provide strong support in determining the ADME profile for this substance, and therefore may substitute for the experimentation of in vivo effects.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

With respect to molecular weight (381.2 g MW; <500 Mn Dalton), water solubility (0.13 ppm), and Log Kow (6.84), it is concluded that the test material is absorbed in the gastro-intestinal tract after oral administration.

While the Mn is less than 500 Daltons, absorption via skin is expected to be limited because of its low water solubility and high low Kow [OECD Guidance Notes on Dermal Absorption, Draft 22 October 200]. This is supported by the absence of systemic toxicity in the acute dermal study.

 

Inhalative exposure is of no relevance due to the low vapor pressure.

 

Extensive distribution can be assumed from the target tissues identified in a subacute toxicological study. After oral exposure to high doses of this substance, bone marrow and thymus have been identified as target organs.

The test material is expected to undergo glucuronidation, hydroxylation, oxidation and/or reduction mediated by various enzymes in the liver, skin, or intestinal microflora. The metabolites have function groups suitable for conjugation reaction with phase II enzymes.

 

The primary route of elimination is expected to be the urine and bile with the more soluble metabolites being readily eliminated. Based on its physicochemical properties, bioaccumulation in exposed organisms is not expected.

 

Discussion on bioaccumulation potential result:

This substance has a molecular weight of 381. Because it has a low water solubility and a high log Kow it is expected to have limited dermal absorption. Intestinal absorption was expected to be low as well, because no significant adverse effects were observed following oral dosing at 2000 mg/kg in an acute toxicity study with rats and at 350 mg/kg/d (NOAEL) for combined repeat dose toxicity study with a reproductive/developmental screen.. The lack of adverse effects is expected to be at least partially due to limited gastrointestinal/dermal absorption of the test substance after treatment, and/or a very low index of inherent toxicity for this substance, and/or its metabolite(s).