Butylparaben Studies Recommended By National Toxicology Program

The National Toxicology Program Board of Scientific Counselors recommended that toxicity testing be conducted on the preservative butylparaben due to the ingredient's widespread exposure to humans through OTCs, personal care products and foods.

NTP presented data on the substance and 14 other ingredients to the Board of Scientific Counselors during an Aug. 18 meeting in Research Triangle Park, N.C. Butylparaben was one of 11 chemicals the board recommended for toxicology testing (See ¹ (Also see "NTP Board Shows Support For More Dietary Supplement Evaluations" - Pink Sheet, 29 Aug, 2005.) ).

The National Institutes of Environmental Health Sciences nominated the substance for study.

NTP advised toxicological characterization studies for butylparaben, including tests for genotoxicity, subchronic toxicity, chronic toxicity/carcinogencity and reproductive toxicity as determined appropriate during the study design phase.

"The rationale for a study of this agent is to presume widespread exposure through personal care products," board member Scott Masten, PhD, Office of Chemical Nomination and Selection NIEHS/NTP, said.

He noted that while two Japanese studies conducted in 2001 and 2002 by Oishi et al., found negative effects on sperm count and adverse effects on testosterone in rats and mice, neither study assessed reproductive function.

"There appears to be a lack of data on reproductive function," Masten said, adding, "There may be some other data gaps that can also be addressed by further study."

A preservative in cosmetics, food and pharmaceuticals including Children's Tylenol liquid products, parabens are suspected to have adverse effects on male rodent reproductive systems, as well as estrogenic activity in experimental cell systems and animal models.

Barbara Pence, PhD, Texas Tech University Health Sciences, suggested that toxicity in children should be considered based on the high potential for exposure to butylparaben in children.

"One of the things that surprised me is all the exposure that babies will undergo with these compounds in baby lotions, in Tylenol, in children's medications and all this," she said.

Butylparaben was nominated by NIEHS for testing last year, but the Board of Scientific Counselors deferred it, citing a lack of background information.

The Cosmetic, Toiletry & Fragrance Association submitted comments to the board supporting the safety of butylparaben in cosmetics as shown in two unpublished studies.

In one in vitro study conducted by CTFA, the association measured dermal penetration of butyl and methyl paraben in a cosmetic vehicle on viable human and rat skin.

The study showed that "while penetration is significant, the skin has substantial capability to metabolize parabens, therefore limiting systemic exposure."

In a "full thickness" pilot study, metabolism of butylparaben on human donor skin was seen to be "essentially complete," according to CTFA.

The trade group also presented a study on male reproduction in rats, challenging the findings of the Japanese study by using the same experimental design but with more animals and additional endpoints.

The CTFA results showed no effects on daily sperm production at orally administered doses up to 1,000 mg/kg/day, unlike the Japanese study, which found significantly decreased sperm production at all doses.

The board expressed concern over discrepancies in the literature. "No compelling hypothesis has been set forth which... would explain the inconsistent outcomes in the literature and the additional studies provided to the NTP in conjunction with its consideration of this compound," Cheryl Walker, PhD, University of Texas, said in prepared comments presented to the board.

The CTFA results raise critical issues to be considered when designing additional studies, Masten pointed out.

"Absorption was greater for both butyl and methyl paraben in human skin preparations than in rat skin preparations, and on the flip side, the metabolism... was lower in human skin preparations than rat skin," he said.

Following the Board of Scientific Counselor's review, butyl paraben and other nominated ingredients will be presented to the NTP Executive Committee, which will make a final recommendation to the NTP director on whether to test, defer, or not test each of the substances.