Tar bases, coal, lutidine fraction

Endpoint summary

Description of key information

Studies on the toxicokinetics, metabolism and distribution of the UVCB substance are lacking. The constituents of the UVCB substance appear to be readily absorbed from the gastrointestinal tract and the lungs, as evident from the available repeated oral and inhalation dose toxicity studies. The substance is moderately absorbed through the skin. Two major metabolism pathways can be expected for the methylpyridines: hydroxylation of the alkyl groups, with additional oxidation to the corresponding carboxyl compounds, or oxidation of the nitrogen atom. Taking into consideration the low octanol-water partition coefficients of the constituents of the UVCB substance, no bioaccumulation is expected. The carboxyl metabolites of methylpyridines are anticipated to be excreted in the urine as such or conjugated with glycine. The metabolites with oxidation on the nitrogen atom are expected to be excreted in urine without conjugation.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Toxicokinetics

Physical-chemical properties

The test substance is a UVCB composed of dimethylpyridines (lutidines), methylpyridines (picolines), trimethylpyridines (collidines), and other pyridine derivatives. The substance is a liquid at room temperature. The molecular weight of the main constituents is 107.15 g/mol, the molecular weight of the further constituents is 93.1 g/mol (picolines) and 121.18 g/mol (collidines). The vapour pressure of the substance is 607 Pa at 25 °C. The log Pow values of the constituents are in the range from 1.09 to 2.08 and the water solubility is >501 g/L at 20 °C. The substance is stable in water at pH 4, 7 and 9.

Absorption

GI absorption

Based on the molecular weight, the log Pow and the water solubility, the substance is likely to be absorbed in the gastrointestinal tract. The absorption is likely to be triggered by passage via passive diffusion, which is favoured for small molecules (molecular weight <200 g/mol) with moderate log P value and high water solubility. Evidence of oral absorption is seen in acute and repeated dose toxicological studies via the oral route of exposure leading to adverse effects in the test animals. However, the extent of adsorption of an orally administered dose cannot be concluded from the reported data.

Dermal absorption

The UVCB substance is a liquid with a high water solubility, a molecular weight of 107.15 g/mol (and a range from 93.1 to 121.18 g/mol) and a vapour pressure of 607 Pa at room temperature. Dermal absorption is favourable for uptake at a molecular weight of <100 g/mol, and the molecular weight of the constituents of the UVCB is only slightly above this value. Based on the water solubility, dermal absorption through the stratum corneum is expected to be limited. Furthermore, the vapour pressure of the substance is 607 Pa, which may result in significant evaporation from the skin prior to absorption. Data on the dermal absorption of the substance are lacking, but the available acute dermal toxicity study demonstrated that the substance was systemically available after a single application, as adverse effects were observed at higher doses. However, the extent of adsorption of a dermally administered dose cannot be concluded from the reported data.

Respiratory absorption

The substance is a liquid that is added as a co-formulant to plant protection products, which are applied by spraying. Furthermore, the substance has a vapour pressure of 607 Pa. It is therefore available for inhalation as an aerosol or vapour. The log P in the range from 1.09 to 2.08 favours absorption across the respiratory tract epithelium by passive diffusion. Furthermore, substances absorbed via the gastrointestinal tract are likely to be absorbed also in the respiratory tract.

Distribution

Data on the distribution of the UVCB substance are lacking. Methyl derivatives of pyridine are anticipated to be distributed to various tissues and organs, such as kidneys, liver, plasma and lungs. They are not likely to be distributed to fat or breast milk, and are unlikely to accumulate in tissues and organs.

Metabolism

Data on the metabolism of the UVCB substance are lacking. Methyl derivatives of pyridine appear to undergo metabolism by cytochrome P450 enzymes. Two major metabolism pathways can be expected for the methyl substituted pyridines: hydroxylation of the alkyl groups, with additional oxidation to the corresponding carboxyl compounds, or oxidation of the nitrogen atom.

Accumulation and excretion

The UVCB substance is water soluble and the log P of the constituents is in the range from 1.09 to 2.08. It is very unlikely that the substance will accumulate in tissues. Methyl derivatives of pyridine are excreted in the urine, and to a lesser extend in exhaled air and faeces. The carboxyl metabolites of methylpyridines are anticipated to be excreted in the urine as such or conjugated with glycine. The metabolites with oxidation on the nitrogen atom are expected to be excreted in urine without conjugation.