Pyrrolidine

Endpoint summary

Additional information

The following reliable studies are available:

The effect of pyrrolidine was tested on the diploid strain D61.M of Saccharamyces cerevisiae. Cytotoxicity was found at concentrations of 11.9 mM (which corresponds with 846.3 mg/L) and above. Pyrrolidine was shown not to induce aneuploidy or other genetic effects without metabolic activation.

A mouse lymphoma assay was conducted according to OECD 476 guideline and GLP principles with pyrrolidine. The spontaneous mutation frequencies in the solvent-treated control cultures were between the minimum and maximum value of the historical control data range. Positive control chemicals, methyl methane sulfonate and cyclophosphamide induced appropriate responses. In the absence of S9-mix, pyrrolidine did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in an independent repeat experiment with modifications in the duration of treatment time. In the second experiment, cytotoxicity was observed at the highest test concentrations. In the presence of S9-mix, pyrrolidine did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in an independent repeat experiment with modifications in the concentration of the S9 for metabolic activation. In the presence of S9-mix, no toxicity was observed and all dose levels were evaluated. Based on these data, it is concluded that pyrrolidine is not mutagenic in the mouse lymphoma L5178Y test system with or without metabolic activation under the experimental conditions described in this report.

An NMRI mouse bone marrow micronucleus assay, performed according to GLP and OECD 474, was performed with piperidine. The data obtained with piperidine can be read across to pyrrolidine, the rationale can be found in Section 13. Five animals per sex and per dose were treated orally at a single time point with the test item (99.3 % a.i.) at doses of 0, 40, 120, and 400 mg/kg bw (CCR/BG Chemie, 1989). Bone marrow cells were harvested at 24, 48 and 72 h post-treatment. The vehicle was aqua dest. In the highest dose of 400 mg/kg bw all treated animals expressed toxic reactions such as eyelid closure and apathy. None of the treated animals died. The mean number of normochromatic erythrocytes was enhanced after the treatment with highest dose of the test item as compared to the corresponding negative control, indicating that the test article had cytotoxic properties. There was no significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after any treatment time or dose level. The positive control induced the appropriate response.

Several publications on the genotoxicity of pyrrolidine are available, but based on the limited information given, they were assigned reliability 4 and not further considered.

Justification for selection of genetic toxicity endpoint
No single study was selected, since the endpoint conclusion was derived based on a weight-of-evidence approach.

Short description of key information:
An in vitro study with Saccharamyces cerevisiae (Klimisch score = 2) and a mouse lymphoma assay with and without metabolic activation were negative (Klimisch score = 1). In addition, an in vivo cytogenetic mutagenicity test with Klimisch reliability 1 on the Read Across substance piperidine was negative. The rationale for Read Across is provided in Section 13.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data, pyrrolidine is not classified for mutagenicity.