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Description of key information

Short description of key information on bioaccumulation potential result: 
CAS 297730-93-9 is absorbed through the intestinal tract and is not expected to be absorbed dermally. It is not expected to accumulate in the body after prolonged exposure.

Key value for chemical safety assessment

Additional information

The acute oral and dermal toxicity tests with T-7145 showed the LD50 being higher than 2000 mg/kg body weight in both cases. The subacute toxicity is also low with a NOAEL of 1000 mg/kg. Below, a summary of the toxicokinetic behaviour of T-7145 is given.

Dissolution of a compound is required for absorption from the gastro-intestinal tract into the blood. Based on the physico-chemical properties of T-7145, the initial dissolution is expected to be low. In the presence of gastric acid and/or bile salts, the solubility of T -7145 may be increased in the gastro-intestinal fluids. Therefore, the compound may be absorbed to a high extent from the gastro-intestinal tract (1). In the intestine, T-7145 will probably be partly hydrolysed at the ether bond.

In general, fluorides are absorbed from the intestines, the lung and the skin. The intestine is the major site of absorption. The degree of absorption of a fluoride compound is best correlated with its solubility. Relative soluble fluoro compounds are almost completely absorbed (2). T-7145 has a low water solubility « 0.004 mgll) at pH 6. However, at lower pH, like in the stomach, the solubility will probably strongly increase.

After absorption of T-7145, probably oxidative dehalogenation will take place (3). From literature (see 2 for review) it is known that fluoride has been detected in all organs and tissues, and it is concentrated in bone, thyroid, aorta, and perhaps kidney. Fluoride is primarily deposited in bone and teeth, and the skeletal burden is related to intake and age. Storage in bone reflects skeletal turnover, growing bone showing greater deposition than bone in mature animals.

The major amount of fluorine excretion is via the kidneys; however, small amounts of fluoride appear in sweat, milk, and intestinal secretions. When sweating is excessive, the fraction of total fluoride excretion in sweat can reach nearly one-half. About 90% of the fluoride filtered by the glomerulus is reabsorbed by the renal tubules.

After dehalogenation, the compound may undergo hydroxylation, followed by rapid sulphation or glucuronidation. The resulting metabolites will be extensively excreted via urine or bile.

Since it is generally accepted that substances with log po/w ranging from 0.1 to 6 penetrate the skin easily (4), it is to be expected T-7145 will be absorbed to some extent through the skin. However, the submitted studies do not show evidence for extensive dermal absorption.

Based on the expected kinetic behaviour in the body, as described above, T-7145 will not accumulate in the body after prolonged exposure.

The anticipated toxicokinetic behaviour is supported by the acute and subacute oral and dermal toxicity data.