Concentrations of the Sunscreen Agent Benzophenone-3 in Residents of the United States: National Health and Nutrition Examination Survey 2003-2004

Antonia M. Calafat; Lee-Yang Wong; Xiaoyun Ye; John A. Reidy; Larry L. Needham


Environ Health Perspect. 2008;116(7):893-897. 

In This Article

Abstract and Introduction

Background: The capability of benzophenone-3 (BP-3) to absorb and dissipate ultraviolet radiation facilitates its use as a sunscreen agent. BP-3 has other uses in many consumer products (e.g., as fragrance and flavor enhancer, photoinitiator, ultraviolet curing agent, polymerization inhibitor).
Objectives: Our goal was to assess exposure to BP-3 in a representative sample of the U.S. general population ≥ 6 years of age.
Methods: Using automated solid-phase extraction coupled to high-performance liquid chromatography-tandem mass spectrometry, we analyzed 2,517 urine samples collected as part of the 2003-2004 National Health and Nutrition Examination Survey.
Results: We detected BP-3 in 96.8% of the samples. The geometric mean and 95th percentile concentrations were 22.9 μg/L (22.2 μg/g creatinine) and 1,040 μg/L (1,070 μg/g creatinine), respectively. Least-square geometric mean (LSGM) concentrations were significantly higher (p ≤ 0.04) for females than for males, regardless of age. LSGM concentrations were significantly higher for non-Hispanic whites than for non-Hispanic blacks (p ≤ 0.01), regardless of age. Females were more likely than males [adjusted odds ratio (OR) = 3.5 ; 95% confidence interval (95% CI), 1.9-6.5], and non-Hispanic whites were more likely than non-Hispanic blacks (adjusted OR = 6.8 ; 95% CI, 2.9-16.2) to have concentrations above the 95th percentile.
Conclusions: Exposure to BP-3 was prevalent in the general U.S. population during 2003-2004. Differences by sex and race/ethnicity probably reflect differences in use of personal care products containing BP-3.

Benzophenone-3 [2-hydroxy-4-methoxybenzophenone, oxybenzophenone (BP-3)], a commonly used sunscreen agent that absorbs and dissipates ultraviolet radiation, is used in a variety of cosmetic products (Gonzalez et al. 2006; National Library of Medicine 2007; Rastogi 2002). BP-3 also has been used as ultraviolet stabilizer in plastic surface coatings for food packaging to prevent polymer or food photodegradation (Suzuki et al. 2005) and is approved by the U.S. Food and Drug Administration as an indirect food additive.

Human exposure to BP-3 has not been associated with adverse health effects, and acute toxicity from BP-3 is low. However, results from animal studies—primarily dietary studies that affected body weight gain—showed alterations in liver, kidney, and reproductive organs in rats and mice administered BP-3 dermally and orally (National Toxicology Program 1992). Although the maximum dose that could be administered dermally was similar to the lowest orally administered dose, which produced little systemic toxicity, these results suggested that oral and dermal exposure routes might affect the animals similarly (National Toxicology Program 1992). BP-3 also shows estrogen-like activity in vitro and in vivo (Schlumpf et al. 2001, 2003, 2004a, 2004b; Suzuki et al. 2005), although in one study BP-3's estrogenic activity was observed only in the presence of a rat liver preparation, suggesting metabolic activation of BP-3 (Morohoshi et al. 2005). BP-3 can also display antiandrogenic activity in vitro (Ma et al. 2003; Schreurs et al. 2005). Thus, BP-3 might exhibit endocrine-disrupting action via both mechanisms in animals. Therefore, in vivo effects due to these combined activities should be further investigated.

The focus of pharmaceuticals and ingredients in personal care products, including organic sunscreen agents, as environmental pollutants is increasing because these compounds may enter the aquatic environment not primarily as a result of manufacturing practices but from their steady and widespread use in human and veterinary daily activities. Furthermore, little is known about the potential hazards associated with recurring human or ecologic exposures to these synthetic substances, many of which are bioactive (Daughton 2002; Daughton and Ternes 1999). BP-3, one of these substances, has been detected in surface waters (Balmer et al. 2005; Cuderman and Heath 2007), drinking water (Loraine and Pettigrove 2006; Stackelberg et al. 2004), and wastewater [Balmer et al. 2005; Centers for Disease Control and Prevention (CDC) 2003; Loraine and Pettigrove 2006] in North America and in Europe.

The widespread inclusion of sunscreen agents in personal care and consumer products (Gonzalez et al. 2006; National Library of Medicine 2007; Rastogi 2002) increases the potential for human exposure to BP-3. Data support the absorption of BP-3 through human skin (Gonzalez et al. 2006; Hayden et al. 2005; Janjua et al. 2004; Jiang et al. 1999; Sarveiya et al. 2004). Application of some of these products to large areas of the body and frequent reapplication increase the daily systemic absorption of BP-3. In some cases, as much as 10% of the applied dose can be absorbed (Jiang et al. 1999).

Like many xenobiotics, BP-3 undergoes phase I and phase II biotransformations. In rats, after oral and dermal administrations of 100 mg BP-3/kg body weight (Kadry et al. 1995; Okereke et al. 1993, 1994, 1995), the parent compound and three oxidative metabolites (2,4-dihydroxylbenzophenone, 2,2′-dihydroxy-4-methoxybenzophenone, and 2,3,4-trihydroxybenzophenone) were detected in plasma, tissues, and urine. Urine was the major route of excretion; BP-3 and its metabolites were excreted mainly as glucuronide conjugates (Kadry et al. 1995; Okereke et al. 1993). Similarly, BP-3 and 2,4-dihydroxylbenzophenone were detected in human urine collected after a volunteer applied a commercially available sunscreen (Felix et al. 1998). These data suggest that the conjugated species of BP-3 and its metabolites in urine can be used as biomarkers of exposure. Oxidative metabolites of BP-3 can themselves be used as sunscreen agents. Although BP-3 can be biotransformed to several metabolites, exposure to BP-3 can be assessed by measuring the total (free plus conjugated) concentrations of BP-3 in urine.

The detection of BP-3 in the aquatic environment and the widespread use of products containing BP-3 have raised interest about assessing human exposure to this compound for risk assessment. We report here the first nationally representative data on the urinary concentrations of BP-3 in the U.S. general population ≥ 6 years of age, stratified by age group, sex, and race/ethnicity.


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