Calcium diethyl bis[[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]phosphonate]

Endpoint summary

Description of key information

The orally given test material and its possible metabolites are retained for only a limited time in male rats and are preferentially excreted in the feces, but also via the kidneys and by respiration.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Assessment of the toxicokinetik behaviour of test substance

 

The test substance (molecular weight of 694.8 g/mol; NATEC, 1983) is a white solid powder (RCC, 1998) with a log P_ow of 0.8 (Ciba-Geigy Ltd, 1989) and a water solubility of 2.4 g/L (Ciba-Geigy Ltd., 1992). The melting point is above 300°C, therefore a study to assess the vapor pressure was not conducted in accordance to column 2 of Annex VII of REACH Regulation (EC) No 1907/2006.

The toxicokinetic properties of the test article were examined in an ADE study performed with rats, investigating the absorption, distribution and excretion characteristics (NATEC, 1983).

Absorption/Distribution

Oral application

The results of the available toxicokinetics study showed, that ¹⁴C-labeled test material given orally is absorbed only in small portions from the gastrointestinal tracts into the blood, reaching a maximum within the first and second hour after administration. Absorbed radioactivity was concentrated significantly but only temporarily in the livers. The radioactivity in the liver and the clearly lower concentrations in the remaining organs and tissues of the test animals were almost completely eliminated during the progress of experiment.

Dermal application

No toxicokinetic data is available for the dermal route. In a guinea pig maximization test, the test article did not cause sensitization after dermal challenge application (Ciba-Geigy, 1985). This result does not suggest systemic availability of the test substance after dermal exposure. In general, absorption is favored for chemicals with a molecular weight < 100 and with a log P_ow of 1-4. In conclusion, a dermal absorption of the test substance seems not very likely, based on the sensitization data and the molecular weight.

Exposure by inhalation

No toxicokinetic data is available for the inhalative route. In an acute inhalation toxicity study the test article was applied as aerosol for 4 hours at a measured concentration of 2350 mg/m³ air to ten male and ten female rats (Ciba-Geigy, 1980). No mortality was observed during the observation period. Clinical signs of toxicity included slight exophthalmos and curved body positions, and slight to moderate ruffled fur. No pathological abnormalities of the organs were observed in all animals at termination of the study. The results of this study do not indicate systemic availability of the test article, however absorption cannot be excluded. Particle size distribution (BASF, 2010) revealed a mass median diameter of 1.85 µm, demonstrating that the test substance can be inspired and may reach the alveolar region.

Metabolism

Using the OECD toolbox 2.0, the liver metabolism simulator provided 15 metabolites (OECD toolbox vs. 2.0, 2010). In general, the simulators predicted hydroxylation of the alkyl side chain and the aromatic ring, after which also further oxidation to aldehydes was proposed. Furthermore, metabolites were proposed where dealkylation of the phosphate group took place, leading to the cleavage products ethanol and acetaldehyde. Studies on genotoxicity (Ames-Test, Nucleus Anomaly Test) gave no indications of a reactivity of test substance or its metabolites under the test conditions (i.e. no increased mutagenicity and cytotoxicity in treatments with metabolic activation).

Excretion

The available toxicokinetic study could show that within 168 hours after oral administration an average of 87.6% and 86.3% (high dose and low dose, respectively) of the dose was excreted, mainly via the feces (85.4% and 84.9%). Further amounts of radioactivity were exhaled.