NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di-n-Octyl Phthalate (DnOP).

The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for di-n-octyl phthalate (DnOP) to cause adverse effects on reproduction and development in humans. DnOP is one of 7 phthalate chemicals evaluated by the NTP CERHR Phthalates Expert Panel. These phthalates were selected for evaluation because of high production volume, extent of human exposures, use in children's products, and/or published evidence of repro- ductive or developmental toxicity. Available information indicates that there are no commercial uses of pure DnOP. However, DnOP comprises approximately 20% of the commercially important C6-10 phthalate mixture, which is used in flooring and carpet tiles, tarps, pool liners, and garden hoses. DnOP is approved by the FDA as an indirect food additive and is used in seam cements, bottle cap liners, and conveyor belts. The results of this evaluation on DnOP 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 DnOP, 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 DnOP on human development and reproduction. Limited studies in mice and rats show that high exposures to DnOP may cause adverse developmental effects, but no evidence of reproductive effects was observed. In a continuous breeding study, no adverse effects were observed in the treated parents or their offspring after dosed feed exposure of mice (approx. 1,800, 3,600, or 7,500 mg/kg body weight/day). Human exposure information for DnOP was not available but it was assumed that the general US population would be exposed to 3-30 mug/kg body weight/day, based upon the range of estimated exposures for DEHP. Based on this assumption, NTP concluded that there is negligible concern for effects on adult reproductive systems. Two developmental studies were evaluated by the panel. In the first study, pregnant rats were treated with 5,000 and 10,000 mg/kg body weight/day DnOP by intraperitoneal injection on gestational days 5, 10, and 15. Increased fetal malformations and reduced body weights were observed at both doses. In the second study, pregnant mice were treated by gavage with approx. 10,000 mg/kg bodyweight/day on gestational days 6-13 and were allowed to deliver the pups. The treated group had reduced litter size, but birth weights and pup survival to postnatal day 3 were not affected. These studies did not determine an exposure level at which no adverse effects occur. The NTP concluded that there is insufficient information on developmental toxicity to reach a conclusion regarding the potential for DnOP to adversely affect human development. 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).