Polyvinylpyrrolidone

Summary

Abstract

The Food Safety Commission of Japan (FSCJ) conducted a risk assessment of ‘polyvinylpyrrolidone’ (CAS number: 9003-39-8), a food additive used for producing foods in capsules and/or tablet form, based on data from various studies. The food additive ‘polyvinylpyrrolidone’ (hereinafter referred to as ‘this additive’) contains polyvinylpyrrolidone (hereinafter referred to as ‘PVP’) as well as the residual monomer, 1-vinyl-2-pyrrolidone (hereinafter referred to as ‘NVP’) and hydrazine as impurities. FSCJ considered that PVP taken orally is barely absorbed from the digestive tract and is directly excreted into feces, based on toxicokinetic studies done on experimental animals. According to case reports available, oral intake of pharmaceutical products containing PVP seldom but evidently cause allergic reactions in humans. Allergenicity of PVP thus cannot be ruled out, but these reports on allergenicity lacked any information on doses; FSCJ therefore does not neglect the possibility that PVP potentially acts as a sensitizer in a limited population through unidentified mechanisms. Therefore, FSCJ deemed that most of the allergic reactions observed after oral intake of PVP might be attributable to sensitization caused by topical or other application of povidone-iodine. It deemed that the probability of sensitizing through oral intake of PVP alone is extremely low. FSCJ concluded that NVP is of no concern for genotoxicity, acute toxicity and repeated dose toxicity on human health. Therefore FSCJ considered that the carcinogenicity of NVP manifested due to a mechanism other than a genotoxic one. FSCJ concluded that it is difficult to assess the carcinogenicity based on the amount of intake of NVP included in this additive. Regarding the safety of hydrazine, carcinogenicity and genotoxicity have been reported. FSCJ thus concluded that the no-observed-adverse-effect level (NOAEL) cannot be established. Based on the quantitative carcinogenic risk assessments of hydrazine performed in the United States and Europe, and based on the amount of hydrazine contained (500 ppb at the highest estimate), FSCJ estimated the carcinogenic risk level of humans exposed to this additive at an estimated daily intake (480 mg/person/day) in Japan. Consequently the risk level was estimated to be 9.0×10⁻⁷ (about 1.1 millionths). This estimated risk level is smaller than one-in-a-million, which is generally considered negligible as a genotoxic carcinogenic risk level. The risk is thus considered extremely low. FSCJ concluded that consumption of hydrazine contained in this additive does not pose safety concerns for the consumers. Based on the above findings, this additive is considered to be of no concern for food safety as long as used appropriately as a food additive, and FSCJ concluded that it is unnecessary to specify the acceptable daily intake (ADI). The risk management agency thus must take appropriate measures to prevent development of allergy upon use of this additive. Regarding hydrazine, the risk management agency must continue to commit itself to reduce the risk to a technically feasible level.