Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

The registration substance is expected to be readily bioavailable for oral routes. Dermal adsorption is expected to be less efficient. Due to the anticipated deleterious effect on respiratory tract, the inhalation route is not relevant for the systemic bioavailbility. 
The availabiel data are indicative of extensive metabolism in the liver. No bioaccumulating potential can be derived.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Assessment on the toxicokinetic profile of the registration substance

No experimental data investigating the subchronic/chronic toxicity of the registration substance is available. However, the subchronic/chronic toxicity can be reasonably derived based on:

-       the provided 28-day toxicity study

-      chemical structure and relevant phys-chem data

-      Cytotoxicity data obtained in the preliminary studies in in-vitro genotoxicity studies.

Considering that the given molecular mass of the registration substance (392 g/mol for Na-salt, 512 g/mol for TEA salt, 370 g/mol for acid) is in the range of absorbable molecular size and that the calculated LogKow of the acid (4.92 according to EPIWIN) is indicative of high liphophilicity under acidic condition, it can be reasonably derived that the substance will be readily adsorbed for oral routes and distributed via lymphatic tissues. The dermal absorption is likely to be lower due to the given pKa of 4.6 (at pH > 4 exclusively deprotonated salt exists with a calculated Log Kow of 1.7).

The given LogPow (1.7 for salt and 4.9 for acid) is indicative that the elimination as unchanged is not likely to occur. Two cases can be imagined: the degradation is not efficient and the internal burden increases with increasing exposure duration vs. the degradation is efficient and the internal burden is less dependent on the exposure duration. The second case would correspond to “no bioaccumulating” potential.

The available experimental toxicity data are indicative of extensive metabolism. The structural feature of highly branched alkenyl moiety imply a certain degree of reluctance to be degraded and based hereupon a metabolic overload can be predicted. In the 28 –day toxicity study, liver was identified as the target organ and the alteration patterns of the findings (liver weight increase and hepatocellular hypertrophy were indicative of metabolic overload. The effects in liver disappeared completely within the recovery period of 14 days, indicating that the chemical burden decreased rapidly.

Further evidence is given in the preliminary cytotoxicity study in in-vitro genotoxicity studies. When the metabolic activation added the cytotoxicity decreased, indicating that detoxification occurs with metabolic activation. The fact that the metabolic activation by action of liver enzymes is associated with detoxification implies that the liver is likely to serve as the detoxification organ under in-vivo condition.

 

In conclusion, no bioaccumulating potential can be derived.