Phthalates in our food

Abstract

Phthalates are a group of chemicals used to make plastics softer and more flexible. They are used in hundreds of products, such as vinyl flooring, adhesives, detergents, lubricating oils, automotive plastics, plastic clothes (raincoats) and personal-care products (soaps, shampoos, hair sprays and nail polishes). People are exposed to phthalates by eating and drinking foods that have been in contact with containers and products containing phthalates. To a lesser extent, exposure can occur from breathing in air that contains vapors or dust contaminated with phthalate particles. Once phthalates enter a person's body, they are converted into breakdown products that pass out quickly in urine. However, biomonitoring studies that measure urine metabolites in humans show widespread exposure to phthalates. Phthalates have been labeled as potential endocrine disrupting chemicals (EDCs) because studies have demonstrated that they interfere with hormones of the reproductive system. Recently, we reported for the first time concentrations of phthalates in United States food and used these finding to estimate dietary phthalate intake.¹ The estimated intakes for individual phthalates in our study were more than an order of magnitude lower than EPA Reference Doses (RfDs), but more studies are needed to evaluate cumulative exposure to phthalates as byproducts of food consumption.

Keywords: :

• phthalates
• endocrine disruption
• chemical exposure
• food contamination
• biomonitoring
• reproductive toxicology

This article refers to:

Introduction

Phthalate esters are added to plastics to provide cheaper, lighter, stronger and safer products and consumer goods. Plastics can be designed to keep our foods fresh, provide therapeutic benefits through timed-release pharmaceuticals and prevent electronics and other household items from starting or spreading fires.^2,3 Phthalates are not chemically bound to their parent polymers and therefore readily leach, migrate or off-gas from plastics, particularly when products are exposed to high temperatures. Following absorption into the body, phthalates are rapidly hydrolyzed to the corresponding monoesters with metabolites excreted in urine and feces. In humans, phthalates are eliminated mostly within hours, with excretion complete by a day or two.⁴

In animal studies, phthalates have been identified as EDCs primarily because of their effects on the male reproductive system.⁵ Studies have shown a wide-range of effects in males termed the phthalate syndrome, which includes infertility, decreased sperm count, cryptorchidism (undescended testes), hypospadias (malformation of the penis in which the urethra does not open at the tip of the organ) and other reproductive tract malformations. These findings led the National Toxicology Program (NTP) to convene an expert panel in 2000 to examine the experimental evidence surrounding phthalate reproductive and developmental toxicity and to investigate the extent of human exposure. The panel concluded that there was “concern” about possible exposures to the most common phthalate, di-2-ethylhexyl phthalate (DEPH), in healthy infants, and “serious concern” for exposures in very sick infants, due to potential leaching from medical equipment.⁶ These concerns prompted the European Union to ban certain phthalates from cosmetics and children’s products.

Shortly after, a study in young girls showed possible associations between premature breast development and early phthalate exposure.⁷ Then a study in women linked shortened pregnancy with phthalate exposure.⁸ Average gestational age at birth was significantly shorter in 65 newborns with detectable mono-(2-ethylhexyl) phthalate (MEHP) in cord serum compared with 19 newborns with MEHP-negative cord serum.⁸ In 2005 the NTP re-evaluated the scientific literature on DEHP and considered these new studies. However, this panel found “insufficient evidence” that phthalate exposure during pregnancy, childhood or adulthood causes adverse health effects.⁹ In May 2005 Swan et al. reported an association between phthalates and decreased anogenital distance (AGD)—the space between the anus and the genitalia—among male infants.¹⁰ Reduced AGD is a developmental end point reflective of alterations in anti-androgenic exposure and has been tied to reduced sperm quality in young men.¹¹ Phthalate exposure was assessed by measuring metabolites in the mothers' urine during pregnancy. Swan reported that those babies whose mothers were exposed to higher levels of four phthalate metabolites—[mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monoethyl phthalate (MEP) and mono-isobutyl phthalate (MiBP)]—had shorter anogenital indexes and were more likely to have small genitalia and partially undescended testicles. The associations between three metabolites of DEHP measured in the study and the anogenital index were not statistically significant. The panel concluded that the Swan study was useful for the evaluation process, but the data were insufficient to show that prenatal exposure to DEHP was harmful to male infants.⁹

Phthalate metabolism

Upon ingestion, phthalates normally follow a two-phase metabolic process. During the first phase, the diester phthalate is hydrolyzed into a monoester phthalate in the intestine, liver and kidney. Normally, this step would lead to detoxification, but in vivo studies have shown that diester phthalates become more bioactive when they are hydrolyzed to monoester phthalates.¹² Short-chain phthalates are mainly excreted in urine as monoester phthalates, while the more long-chain phthalates undergo several biotransformations, including further hydroxylation, oxidation and phase II conjugation before they are excreted in urine and feces.¹³

Endocrine disrupting properties of phthalates

Phthalates have been implicated as EDCs primarily due to their effects on the reproductive system. Studies have reported that exposure to phthalates can cause damage to sperm,¹⁴ early puberty in females,¹⁵ anomalies of reproductive tract,¹⁶ adverse outcomes of pregnancy^17,18 and liver tumors in rodents.¹⁹ Various phthalates and their metabolites have documented biochemical activity as PPAR activators, thyroid hormone axis antagonists or as antiandrogens.²⁰ Stahlhut et al. found positive associations for waist circumference, BMI and measures of insulin resistance with several urinary phthalate levels in an analysis of data from the National Health and Nutrition Examination Survey (NHANES).²¹ Generally, short chain phthalates (those with ester chains of four to six carbon atoms) have been shown to have more potent effects on the male reproductive system than longer chain phthalates. However, recent human studies show exposure to multiple phthalates. Thus, risk assessment strategies need to consider combined effects of phthalates as mixtures.^22,23

Phthalate exposure levels in humans

The ubiquitous use of phthalate in plastics, personal care products and food packaging results in widespread exposure to the general population. Ingestion, inhalation, intravenous injection and skin absorption are potential pathways of exposure. Human exposure to phthalates can occur as a result of direct contact or through the leaching of phthalates from one product into another, as may occur with food packaging or intravenous fluids, or by general contamination of the ambient environment. In the fourth NHANES report, CDC showed that the majority of people in the USA have detectable concentrations of several phthalate monoesters in urine [(monoethyl phthalate (MEP), monoethyl-hexyl phthalate (MEHP), monobutyl phthalate (MBP) and monobenzyl phthalate (MBzP)], reflecting widespread exposure to the parent compounds among the general population.²⁴ The study also reported that adult women have higher levels of urinary metabolites than men for phthalates that are used in soaps, body washes, shampoos, cosmetics and similar personal care products. Fatty foods such as milk, butter, oils and meats are thought to be the main exposure source for certain phthalates such as DEHP, dibutyl phthalate (DBP) and diisobutyl phthalate (DIBP) because they are lipophilic.²⁵

Phthalates can migrate into food during production, packaging and preparation. Food exposures have been estimated primarily based on duplicate diet composite studies in which phthalates were measured in samples of all food and drink consumed by participants.²⁶ Duplicate diet studies provide the best analysis of overall dietary exposure assessment because they capture exposures from food as prepared and eaten. However, these studies are costly and usually test only a small number of individuals and, thus, may not be representative of the larger population in that country. Broader studies analyzing individual food items for phthalates, total diet studies, as well as market basket studies are needed. Some surveys have been conducted in Europe, Canada and China.^25,27-29

Phthalates are difficult to measure in food because of their ubiquitous occurrence in many products including many lab-based materials. To our knowledge, our study is the first to measure phthalate concentrations in foods from the US. In this study, we sampled 72 commonly consumed foods from supermarkets in New York for nine specific phthalate esters shown in Figure 1.¹ We detected phthalates in various food types in ranges from zero to 100%. Despite this wide variance, every food group in our study had at least some detectable level of phthalates. For example, DEHP was detected in 74% of food samples, including all seven infant food samples, whereas dicyclohexyl phthalate (DCHP) was detected in only 6% of food samples. Other phthalate esters were detected at the following frequencies: DEP (57%), DiBP (55%), benzyl butyl phthalate (BBzP) (54%), dimethyl Phthalate (DMP) (37%), DBP (31%) (Table 1).¹ Estimated intakes of all phthalates were fairly comparable between adults and infants on a body weight basis, with the exception of DEHP, which was more than 2-fold higher in babies than adults.¹

Figure 1. Structural formulas of nine phthalate esters sampled in food.¹

Table 1. Detection frequencies of phthalates in sampled food

Phthalate	Abbreviation	Percent detection frequency
Di-2-ethylhexyl phthalate	DEHP	74
Diethyl phthalate	DEP	57
Di-iso-butyl phthalate	DiBP	55
Butyl benzyl phthalate	BBzP	54
Dimethyl phthalate	DMP	37
Di-n-butyl phthalate	DBP	31
Di-n-hexyl phthalate	DnHP	15
Di-n-octyl phthalate	DnOP	12
Dicyclohexyl phthalate	DCHP	6

Several studies have estimated phthalate intakes based on measured concentrations in media and consumption rates. Most of these studies have reported higher levels of phthalates because they included non-dietary intakes, and because concentrations measured in food surveys were often higher than measured in our food samples. For example, in a study conducted in Europe, Wormuth et al. (2006) estimated total phthalate intakes that accounted for food and non-food pathways of exposure.²⁵ They reported that total intakes from all sources reported by for DEHP, DBP, BBzP and DiBP were approximately 3.0, 4.0, 0.4 and 0.6 µg/kg-day, respectively, which is considerably higher than our US estimates of 0.7, 0.2, 0.1 and 0.02 µg/kg-day based only on our food survey (Tables 2 and 3).¹

Table 2. Food group consumption rate and sample content

Food Group	Consumption (g/kg-day)	Source	Container type
Beverages	13	tea, juice, sports drinks	plastic
Dairy	3.5	milk, pudding, cheese, butter, yogurt	plastic
Fish	0.23	salmon, tuna, shrimp, clams, sardines	plastic and paper wrap
Beef	0.73	ground beef, beef	foam tray with plastic wrap
Pork	0.36	sausage, pork, bacon, ham	plastic and paper wrap
Poultry	0.71	ground turkey and chicken, breast, bacon, drumsticks	plastic and paper wrap
Fruits/ vegetables	3.4	soups, canned fruits, canned tomato sauce	plastic and metal cans
Grain	2.2	bread, cake mix, cereals, rice, cookies	plastic and paper wrap

Table 3. Phthalate concentrations in food groups (ng/g wet weight)

	DEHP	DBP	BBzP	DiBP
Beverages	3.9	0.7	0.1	0.3
Dairy	126.5	85	3.6	1.6
Fish	31.7	11	1.6	1
Beef	1.9	0.7	0.6	0.1
Pork	44.5	1.5	ND	2
Poultry	18.6	0.7	0.7	0.1

Conclusions

Our data suggest that dietary intakes of individual phthalates are much less than currently published RfD benchmarks. The current published oral RfD for DEHP set by EPA in 1986, based primarily on studies in guinea pigs and rats conducted in 1953,³⁰ is 20 µg/kg-day,^31,32 whereas our estimate of total dietary intake is only 0.7 µg/kg-day.¹ However, if individual phthalates operate along similar modes of actions, then cumulative exposure estimates, from all food sources, may exceed the RfD. To date, EPA has not published RfDs for the other individual phthalates measured in our study or possible mixtures of phthalates, but they are undertaking a comprehensive Phthalate Action Plan.³³ The FDA regulates phthalates in food contact substances (such as plastic wrap), cosmetics, pharmaceuticals and medical devices. FDA announced in June 2008 that, in tandem with its review of the safety of bisphenol A (BPA) in such products, it is conducting a comprehensive inventory of regulated products that contain phthalates.³⁴

Our study suggests that previous phthalate exposure assessments may be comparatively higher due to consideration of total exposure patterns, and/or differences in the food samples measured to determine average concentrations. While our study focused only on food exposures, the use of phthalates in many consumer products has been recognized as important sources for human exposure. Our study measured a limited sample of foods purchased from grocery stores in only one geographic location, and did not evaluate foods as packaged, processed or served in homes or restaurants. Further representative surveys of phthalates in US food are needed, as is research on the toxicity of phthalate mixtures in food and from other sources. Future studies should also focus on the influence of packaging as well as the preparation of foods.