NTP Center Reports on Phthalate Concerns.

An expert panel convened by the National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) has announced that after intensive evaluation of seven phthalates, only one presents a serious concern to human reproduction or development. Di(2-ethylhexyl) phthalate, or DEHP, is considered of serious concern for the possibility of adverse effects on the developing reproductive tract of male infants exposed to high concentrations of the phthalate through medical procedures using phthalate-containing equipment such as intravenous bags and tubing.

The center is currently preparing the NTP Center Report on Phthalates, due for release late this summer. Michael Shelby, director of the CERHR, says, "The report will provide an independent, scientifically rigorous document for use by all stakeholders in any further discussions that might ensue on the reproductive effects of these seven phthalates."

Created in 1998 by the NTP and the NIEHS to assess the human reproductive health risks associated with exposures to environmental chemicals, the CERHR announced in April 1999 that it was turning its attention to the risks posed by seven phthalates, which are used as plasticizers in a spectrum of polyvinyl chloride-based products ranging from flexible tubing to plastic toys. The phthalates selected for evaluation included DEHP, butyl benzyl phthalate (BBP), di-n-butyl phthalate (DBP), di-isononyl phthalate (DINP), di-isodecyl phthalate (DIDP), di-n-hexyl phthalate (DnHP), and di-n-octyl phthalate (DnOP). The chemicals were selected based on their high production volume, the number of people potentially exposed to them, their use in products especially intended for children (such as toys), and evidence of reproductive or developmental toxicity. To evaluate the seven phthalates, the center brought together a panel of 16 experts in toxicology, epidemiology, and other relevant fields from government, research, and academic institutions from across the United States.

Over a period of 15 months, the panel evaluated the published data for each phthalate to determine whether or not it is likely to present a risk to human reproduction or development. The panel considered the amount and quality of data available in two primary areas: human exposures to the phthalate in question and experimental evidence for its reproductive and developmental toxicity.

The panel assigned minimal concern to DINP for adverse developmental outcomes in children exposed in utero and for adverse effects on the reproductive system of exposed adults. There was, however, low concern for potential developmental and reproductive health effects in children who might be exposed through mouthing toys or other DINP-containing objects. For BBP, DnOP, DBP, and DIDP, there was minimal or negligible concern for adverse effects on the reproductive system of exposed adults or for potential developmental and reproductive health effects of exposed children. For one chemical, DnHP, there were insufficient data for the panel to reach any conclusions. The panel had only minimal concern that current estimated exposures to DEHP would adversely affect the reproductive system of adults.

Following initial publication of the panel's findings in October 2000, the NTP and the CERHR have gathered public comments that will be incorporated into the NTP Center Report on Phthalates, along with newly available data published since the panel's last meeting. The final report will also include critical data needs and a list of planned or ongoing studies that address those needs.

Two studies released since the panel Completed its reports have provided interesting postscripts to their findings. First is a report by scientists from the NTP and the Centers for Disease Control and Prevention, published in the October 2000 issue of EHP, which found that the highest DBP metabolite concentrations in a large study sampling were found in women of reproductive age. (This study also provides the first measure of phthalate metabolites in the body; other studies, including those reviewed by the panel, were calculations of doses based on exposure data.) Second is an article published in the December 2000 issue of the Journal of Pediatric Surgery by scientists at the University of Heidelberg medical complex in Mannheim, Germany, which firmly bolsters the panel's concern that premature infants are exposed to high doses of DEHP through the use of medical equipment made of phthalate-containing polyvinyl chloride plastic. The German authors are now investigating whether the high DEHP doses they observed are related to the hepatobiliary dysfunction common with tube-feeding.

Seven Phthalate Esters Tested and Their Uses

Chemical                              Uses

* di(2-ethylhexyl) phthalate (DEHP)   Building products, food
                                      packaging, children's products,
                                      medical equipment

* butyl benzyl phthalate (BBP)        Vinyl tile, food conveyor belts,
                                      artificial leather, traffic cones

* di-n-butyl phthalate (DBP)          Latex adhesives, cellulose
                                      plastics, dyes

* di-isononyl phthalate (DINP)        Garden hoses, shoes/shoe soles,
                                      toys, construction materials

* di-isodecyl phthalate (DIDP)        Automobile undercoating, wires
                                      and cables, shoes, carpet
                                      backing, pool liners

* di-n-hexyl phthalate (DnHP)         Automobile parts, tool handles,
                                      dishwasher baskets, flooring,
                                      tarps, flea collars

* di-n-octyl phthalate (DnOP)         Flooring and carpet tile, canvas
                                      tarps, notebook covers

The final report will be available to federal and state regulatory and health agencies, nongovernmental organizations, industry groups, and the public, and will be posted on the CERHR Web site at http:// cerhr.niehs.nih.gov/.