Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

No experimental data investigating the toxicokinetic profile is available. 
Based on the evidences from the toxicity studies no bioaccumulation 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 toxicokinetic property of the registration substance is available.

The assessment will be performed based on the following data:

- combined repeated dose toxicity with reproductive/developmental toxicity screening study on the read-across substance (Pentapropenylsuccinimido)-hexanoate, sodium and triethanolamine salts

- 28-day study on the registration substance

- chemical structure and liphophilicity

- cytotoxicity data obtained in the preliminary studies in in-vitro genotoxicity on the registration substance

- BCF study in fish on the registration substance (endpoint study record provided under IUCLID Chapter 5.3.1

The justification for the read-across is provided and is not further mentioned here. The discussion will be focused on the indications relevant for the bioaccumulating potential assessment of the registration substance.

Considering that the registration substance is soluble in octanol and is of molecular mass of 378 g/mol (calculated), it can be reasonably derived that the substance will be readily adsorbed and distributed via lymphatic tissues. The given LogPow of 3.74 is indicative that the elimination as unchanged molecule 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 corresponds to “no bioaccumulating property”.

The structural feature of N-alkylated imide in the center of molecule and highly branched alkenyl moiety imply a certain degree of reluctance to undergo degradation process. A metabolic overload can be predicted in case of an extensive metabolism. In the available two mid-term studies, the liver was identified as the target organ and the observed alteration pattern of the findings (liver weight increase, hepatocellular hypertrophy, follicular cell hypotrophy in thyroid gland, prolonged bleeding time, altered values of glucose and cholesterols) are indicative of adaptation/metabolic overload/functional impairment. In addition, the effects in liver disappeared completely within the recovery period of 14 days, indicating that the chemical burden must have decreased rapidly with the cessation of treatment. An extensive metabolism can be derived.  

Further support is given in the preliminary cytotoxicity study in in-vitro genotoxicity studies. The cytotoxicity with S9-mix was significantly reduced when compared to that of without S9-mix. 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.

Besides of toxicity studies, the no bioaccumulating potential/extensive metabolism can also be derived from the result obtained in the bioconcentration study in fish. The BCF in fish bioaccumulation study was< 158 at concentration of 0,06 mg/l. Assuming that the substance is readily bioavailable, and the LogPow is indicative of no elimination as unchanged molecule, the obtained low BCF value is demonstrative of an efficient elimination in fish.  

Combining all the available evidences, it can be concluded that an extensive metabolism occurs in the liver.   Based on the general rule of the biotransformation, the most likely degradation pathway is the ß-oxidation of N-alkyl chain, followed by the hydrolysis at the imine/imide moiety. The resulting metabolite, highly branched alkenyl-succinic acid, could undergo urinary excretion either as it is, or conjugated.

In conclusion, no bioaccumulating property can be derived.