N‐Vinyl‐2‐pyrrolidone

MAK Value Documentation, addendum – Translation of the German version from 2014

  Andrea Hartwig¹ (Chair of the Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Deutsche Forschungsgemeinschaft)
  MAK Commission<sup>2

1</sup> Institute of Applied Biosciences, Department of Food Chemistry and Toxicology, Karlsruhe Institute of Technology (KIT), Adenauerring 20a, Building 50.41, 76131 Karlsruhe, Germany
² Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area, Deutsche Forschungsgemeinschaft, Kennedyallee 40, 53175 Bonn, Germany

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated N‐vinyl‐2‐pyrrolidone [88‐12‐0], considering all toxicological endpoints. Available publications and unpublished study reports are described in detail.

The main critical effects are the carcinogenic effects in the liver, nose and larynx after inhalation, with cell proliferation in the liver and degeneration and hyperplasia in the nasal epithelium starting at 0.5 ml/m³ being the most sensitive endpoints. The no observed adverse effect concentration (NOAEC) for both organs is 0.2 ml/m³. As a NOAEC was obtained and the substance is not genotoxic, N‐vinyl‐2‐pyrrolidone is classified in Carcinogen Category 4.

As the NOAEC of 0.2 ml/m³ for cell proliferation in the liver after 28 days was lower than that after 7 days, a MAK value for N‐vinyl‐2‐pyrrolidone of 0.02 ml/m³ has been established, taking into account the short study duration. As the MAK value is derived from a systemic effect, the substance is classified in Peak Limitation Category II with the default excursion factor of 2, because the half‐life in humans is not known.

In a developmental toxicity study in rats, N‐vinyl‐2‐pyrrolidone at 20 ml/m³ markedly reduced body weights in dams and foetuses and increased the incidence of variations in foetuses. As developmental toxicity occurred at a maternally toxic concentration, and the 250‐fold difference between the NOAEC for developmental toxicity of 5 ml/m³ and the MAK value of 0.02 ml/m³ is sufficiently large, N‐vinyl‐2‐pyrrolidone is classified in Pregnancy Risk Group C.

N‐Vinyl‐2‐pyrrolidone is neither mutagenic nor clastogenic and therefore not classified in one of the categories for germ cell mutagens.

As the amount calculated to be absorbed through the skin is far above the amount absorbed daily by exposure at the level of the MAK value, N‐vinyl‐2‐pyrrolidone is designated with an “H” (for substances that can be absorbed through the skin in systemically toxic amounts).

The substance is not regarded as a sensitizer, because there are no corresponding clinical findings in humans and a Buehler test in guinea pigs was negative.

---