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Description of key information

Key value for chemical safety assessment

Additional information

Assessment of the toxicokinetic behavior

The test substance (molecular weight of 314 g/mol) is a clear, slightly yellow liquid (BASF, 2012) with a vapor pressure of 0.065 Pa at 20°C (BASF, 2013). The substance is characterized with a water solubility of 16.7 mg/l (BASF, 2013) and good solubility in organic solvents (> 100 g/l in ethanol, aceton and toluol, Ciba-Geigy, 1989). The log Pow was determined to be 4.0 at a temperature of 23°C (BASF, 2013). No studies are available investigating the toxicokinetic properties of the test substance. The toxicokinetic behavior is therefore assessed based on physic-chemical properties and on available toxicity studies.

Absorption

Absorption through the gastrointestinal tract is favored for a molecular weight below 500 g/mol (ECHA GD 7c, 2008). In addition, moderate log Pow values are favorable for absorption by passive diffusion. Therefore, based on the physico-chemical parameters, absorption of the test article after oral exposure is expected. This is in line with the data obtained by a subacute oral repeated dose toxicity study (Harlan, 2012). Here, hepatocellular hypertrophy was observed histologically in males of the high dose group (500 mg/kg bw/day), which was considered to be an adaptive change due to increased metabolic load. Increased incidence and severity of tubular basophilia in the kidneys were observed in females at 500 mg/kg bw/day. These findings demonstrate that absorption of the test article has occurred.

Dermal uptake is favored for chemicals with a molecular weight < 100 g/mol, while for chemicals with a molecular weight > 500 g/mol, dermal uptake is not favored (ECHA GD 7c,2008). In addition, Log P values between 1 and 4 favor dermal absorption. With a molecular weight of 314 g/mol and a log P of 4.0, the test article is possibly absorbed through skin. The available toxicity data does not give any indications for dermal penetration. In a guinea pig maximization test the substance was negative (RCC, 2001). However, this result does not rule out dermal absorption and based on the physico-chemical data, dermal penetration is expected.

No information from acute or repeated dose toxicity studies is available, which could provide information about the systemic distribution of the test substance after inhalation. Upon exposure to aerosol or vapors absorption through the respiratory tract is expected.

Metabolism

Considering the hepatocellular hypertrophy observed in the subacute toxicity study, the substance or one of the major components is likely to be subject to hepatic metabolism.

Excretion

Smaller molecules (< 300 g/mol) tend to be excreted in the urine, especially when they are soluble in water. Larger molecules are expected to be eliminated via biliary excretion. The test substance is predicted to be metabolized and broken down to smaller molecules in the liver. Upon phase II metabolism in the liver the water solubility of these smaller breakdown products is increased and excretion is expected to occur predominantly via urine. Some excretion might also occur through feces.