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Description of key information

Short description of key information on bioaccumulation potential result: 
The metabolism of quinoline has been extensively studied. Some evidences show that the pathway that lead to the mutagenic/carcinogenic properties of quinoline involves an epoxide in 2-3 position. 2 other detoxication ways are known.
Quinoline is absorbed through the gastro-intestinal tract and metabolites are found in urine.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

No standard toxicokinetics study has been identified for quinoline. The main purpose of the studies was to identify the active (mutagen) metabolite and /or metabolic pathway. To achieve this, the in vitro metabolism has been studied with liver fractions (S9 or microsomes) from different species and in different induction conditions. Some studies were also based on the identification of the metabolite by mutagenicity tests.

Quinoline is metabolized through different pathways: one leading to the 5,6 -dihydrodiol derivatives which is a desactivation way, another one produces quinoline -N oxide and the third one, which is the activation pathway, involves an epoxidation in position 2 -3. This epoxide is able to interact with nucleic acids. The next step of this way is the production of 3 -OH quinoline. 2 -OH quinoline has also been found.

The critical position for the mutagenic / carcinogenic property was confirmed to be in position 2 -3, by a screening carcinogenicity test, mutagenicity test and also by preventing the epoxide formation by substitution (fluoro-, chloro-) of quinoline.

The other epoxide formed on the position 5,6 of the benzene moiety, is not mutagenic and substitution with fluorine for instance, showed that this epoxide is not involved in the mutagenic/carcinogenic properties of quinoline.

CYP2A6 has been shown to be implicated in the formation of quinoline N-oxide by human microsomes. The same isoenzyme is responsible for the formation of 5,6 -dihydrodiol (in rat and human microsomes).

The formation of 3 -OH quinoline is caused by CYP2E1, and the production of this metabolite is higher in rat than in human microsomes. Some differences may exist in the metabolism profile of the rat and of the humans.

The transformation of epoxide to the diol metabolite is catalized by epoxide hydrolase in human microsomes. The role of this enzyme in rat is not clear, controversial results have been obtained.

The metabolite profile of quinoline is strongly dependent on the inducers. This fact is also confirmed by mutagenicity tests (see the part 7.6).

The absorption/excretion of quinoline has been studied in rabbit. Quinoline is absorbed through the gastro-intestinal tract and metabolites are found in urine within 24 after the administration. Nothing is known about the distribution and the full excretion pattern has not been examinated.

As quinoline is a weak base with a pKa around 5, the absorption is likely to take place in the small intestine rather than in the stomach.

According to effect acute toxic effects of quinoline, dermal absorption is possible but the extent is about 5-fold less important than by the oral route on the basis of the LD50 values.