NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Propylene Glycol (PG).

Abstract

The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for propylene glycol (PG) to cause adverse effects on reproduction and development in humans. PG was selected for evaluation because of the potential for widespread human exposure through its use in food, tobacco, pharmaceutical products, cosmetics, various paints and coatings and as an antifreeze and de-icing solution. PG is a small, hydroxy-substituted hydrocarbon used as a chemical intermediate in the production of unsaturated polyester resins and in the production of plasticizers. The results of this evaluation on PG are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Propylene Glycol, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to PG on human development and reproduction. There is negligible concern for adverse developmental and reproductive effects in humans at current, proposed, or estimated exposure levels. There is no direct evidence that exposure of people to PG adversely affects reproduction or development. Studies in pregnant laboratory animals at oral doses of PG greater than 1,200 mg/kg body weight/ day and up to 10,400 mg/kg body weight/day in mice, did not produce developmental toxicity in offspring. In a continuous breeding study, no effects on fertility were observed in male or female mice at doses up to 10,100 mg/kg body weight/day in drinking water. The pharmacokinetics of PG indicates that the lack of adverse effects observed in laboratory animals is relevant to humans. The rate-limiting step in PG metabolism is conversion to the more toxic lactaldehyde product by alcohol dehydrogenase. Studies indicate that this enzyme saturates in humans at doses 8-10- fold lower than in rats and rabbits, thus affording less toxicity in humans. It is estimated that the average daily intake of PG from food products in the US is 34 mg/kg body weight/day for a 70 kg person, which is over 300 -fold lower than the highest dose tested in laboratory animals. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available in electronic PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511).