N-(n-octyl)-2-pyrrolidinone

Endpoint summary

Description of key information

NOP is considered to be able to penetrate through the skin and to be systemically available after oral and dermal administration. But there are no indications for a potential of NOP for accumulation. 

Additional information

N-(n-Octyl)pyrrolidin-2-one (NOP, CAS No. 2687-94-7) is a liquid substance with a molecular weight of 197.3 g/mol and a water solubility of 1 g/l. The log pO/W is 4.15 at pH 7.

Evidence for systemic availability of NOP comes both from acute oral and dermal toxicity studies and from repeated dose toxicity studies in rats: In the acute oral toxicity study in rats, clinical symptoms were observed at 2200 mg/kg bw (1992). In the acute dermal toxicity study in rabbits, clinical signs of toxicity were noted in the high dose group of 4000 mg/kg bw (1992). In the subacute toxicity study with gavage doses of 0, 50, 200, and 1000 mg/kg bw/d, clinico-chemical and pathological effects were observed at 200 and 1000 mg/kg bw/day (1992). In a 28-day oral (gavage) study, rats were dosed with 0, 5, 55, or 320 mg/kg bw/d (once daily) (1989). Changes in general health, bodyweight gain, hematological and biochemical parameters were apparent in rats receiving 320 mg/kg/day. In a 90-day dietary feeding study in rats (1991) in which rats were dosed with 0, 60, 600, and 10000 ppm/kg/day, systemic toxicity in males and females was noted in high dose group, as changes in body weight gain and food consumption as well as changes in liver weights and some mild hepatocyte hypertrophy was observed. These effects are clear indicators of the systemic availability of NOP.

A study of the penetration of NOP through pig-skin in vitro showed a moderate penetration (30% absorption) when applied undiluted and a fast and virtually complete penetration, if applied as a saturated aqueous solution (2005).

Considering the chemical structure of NOP, Cytochrome P450 linked oxidations of the octyl-group and of the heterocyclic ring system as weil as the oxidative desalkylation are possible steps in the phase l-metabolism of NOP. In the phase ll-metabolism, consequent conjugation reactions can be assumed.

Studies on genotoxicity - Ames-Test (1992 and 2001), in vitro CA (1992), MLA (1991) and in vivo MNT (1989) - were negative, i.e. there is no indication of a reactivity of NOP or its metabolites under the test conditions chosen.

Despite the high log pO/W-value, the results of the 28 day study in rats with a recovery period of 14 days and the considerations on the metabolism do not indicate a potential of NOP for accumulation.