Phthalates

Phthalates:(pronounced) tha-layts or phthalate esters , are phthalic acid and are mainly used as plasticizers substances added to plastics to increase their flexibility, transparency, durability, and longevity. They are used primarily to soften polyvinyl chloride (PVC). Phthalates are being phased out of many products in the United States, Canada, European Union over health concerns.
 
Phthalates are easily released into the environment because there is no covalent bond between the phthalates and plastics in which they are mixed. As plastics age and break down, the release of phthalates accelerates. People are commonly exposed to phthalates, and most Americans tested by the Centers for Disease Control and Prevention metabolites of multiple phthalates in their urine. Because phthalate plasticizers are not chemically bound to PVC, they can easily leach and evaporate into food or the atmosphere. Phthalate exposure can be through direct use or by indirect means through leaching and general environmental contamination.
Diet is believed to be the main source of di(2-ethylhexyl) phthalate (DEHP) and other phthalates in the general population. Fatty foods such as milk, butter, and meats are a major source. Phthalates are used in a large variety of products, from enteric coatings of pharmaceutical pills and nutritional supplements to viscosity control agents, gelling agents, film formers, stabilizers, dispersants, lubricants, binders, and suspending agents.
 
End-applications include adhesives and glues, agricultural adjuvants, building materials, personal-care products, medical devices, detergents, surfactants,, packaging, children's toys, modelling clay, waxes, paints, printing inks and coatings, pharmaceuticals, food products, and textiles. Phthalates are also frequently used in soft plastic fishing lures, sex toys made of so-called "jelly rubber". Phthalates are used in a variety of household applications such as shower curtains, vinyl upholstery, adhesives, floor tiles, food containers and wrappers, and cleaning materials. Personal-care items containing phthalates include perfume, eye shadow, moisturizer, nail polish, liquid soap, and hair spray.They are also found in modern electronics and medical applications such as catheters and blood transfusion devices.
 
The most widely used phthalates are the diisodecyl phthalate and the diisononyl phthalate. DEHP is the dominant plasticizer used in due to its low cost. Benzylbutylphthalate (BBP) is used in the manufacture of foamed PVC, which is mostly used as a flooring material. A 2012 Swedish study of children found that phthalates from PVC flooring was taken up into their bodies, showing that children can ingest phthalates not only from food but also by breathing and through the skin.

In general, children's exposure to phthalates is greater than that of adults. In a 1990s Canadian study that modeled ambient exposures, it was estimated that daily exposure to DEHP was 9 μg / kg bodyweight / day in infants, 19 μg / kg bodyweight / day in toddlers, 14 μg / kg bodyweight / day in children, and 6 μg / kg bodyweight/day in adults. 
Infants and toddlers are at the greatest risk of exposure, because of their mouthing behavior. Body-care products containing phthalates are a source of exposure for infants. The authors of a 2008 study "observed that reported use of infant lotion, infant powder, and infant shampoo were associated with increased infant urine concentrations of [phthalate metabolites], and this association is strongest in younger infants. These findings suggest that dermal exposures may contribute significantly to phthalate body burden in this population." Though they did not examine health outcomes, they noted that "Young infants are more vulnerable to the potential adverse effects of phthalates given their increased dosage per unit body surface area, metabolic capabilities, and developing endocrine and reproductive systems."

 

In 2008, the United States National Research Council recommended that the cumulative effects of phthalates and other antiandrogens be investigated. It criticized US EPA guidances, which stipulate that, when examining cumulative effects, the chemicals examined should have similar mechanisms of action or similar structures, as too restrictive. It recommended instead that the effects of chemicals that cause similar adverse outcomes should be examined cumulatively.[12]:9 Thus, the effect of phthalates should be examined together with other antiandrogens, which otherwise may have been excluded because their mechanisms or structure are different.

Breast cancer[edit source | editbeta]

Much of the current research on effects of phthalate exposure has been focused towards children and men's health,[13] however, women may be at higher risk for potential adverse health effects of phthalates due to increased cosmetic use. Diethyl phthalate and dibutyl phthalate are especially ubiquitous in cosmetics and personal care products.[13] According to in vivo and observational studies by Davis et al. (1994) and Lopez-Carillo et al. (2010), there is an association between phthalate exposure and endocrine disruption leading to development of breast cancer. Furthermore, it has been well documented that endocrine disruptors such as phthalates can be additive, so even very small amounts can interact with other chemicals to have cumulative, adverse "cocktail effects" [14]

Phthalate parent compounds and/or their metabolites have recently been implicated as a cause of breast cancer (BC). A 2010 study published in Environmental Health Perspectives for the first time implicated that the exposure to diethyl phthalates (DEP), a parent compound of the monoethyl phthalate (MEP) metabolite, may be associated with increased risk of BC (Odds Ratio of 2.20, p value for trend, p<0.003). The case-control study was age matched to 233 BC cases residing in northern Mexico. The phthalate level was determined in urine samples collected pretreatment from the cases. This is only a preliminary finding therefore additional research is required. Interestingly, exposure to the parent phthalate, butylbenzyl phthalate (BBzP) of the monobenzyl phthalate (MBzP) metabolite showed a negative association with breast cancer (Odds ratio=0.46, p value for trend, p<.008). This finding may be associated with the demethylation of the estrogen receptor complex in breast cancer cells of this particular phthalate resulting in a negative effect.[13] This explanation will require further confirmatory research since confounders may be playing an unknown role. It is also known that DEP is found in a high proportion of personal care products, deodorants and perfumes whereas in contrast, BBzP is not detected in most deodorants and hair products and in less than one-third of all products tested,[13] so degree of exposure may also be influencing results. A higher phthalate tertile (microgram/g creatinine) of DEP/MEP was compared to a lower phthalate tertile of BBzP/MBzP in this study. In most cases of breast cancer the cause is unknown and less than 25% of patients have a history of commonly associated risk factors.[13] such as: early menarche, later age at first childbirth, nulliparity, family history of BC, or history of benign breast biopsy [15]

Endocrine disruption[edit source | editbeta]

Main article: Endocrine disruptor

In studies of rodents exposed to certain phthalates, high doses have been shown to change hormone levels and cause birth defects.[2] A recent British study showed that the phthalate di(n-butyl) phthalate (DBP) or its metabolite monobutyl phthalate (MBP) suppresses steroidogenesis by fetal-type Leydig cells in primates as in rodents.[16]

In a study published in 2005, lead investigator Dr. Shanna Swan reported in the "Swan Study" that human phthalate exposure during pregnancy results in decreased anogenital distance among baby boys. In this study, phthalate metabolites were measured in urine samples collected from the pregnant women who gave birth to the infants. After birth, the genital features and anogenital distance of these women's babies were measured and correlated with the residue levels in the mother's urine. Boys born to mothers with the highest levels of phthalates were 7 times more likely to have a shortened anogenital distance.[17] An editorial concerning this paper in the same volume stated that the study population was small, and "needs to be investigated more thoroughly in a larger, more diverse population".[18] While anogenital distance is routinely used as a measure of fetal exposure to endocrine disruptors in animals,[19] this parameter is rarely assessed in humans, and its significance is unknown.[20] One paper states that "Whether anogenital distance measurements in humans relate to clinically important outcomes remains to be determined,"[21] and a National Toxicology Program expert panel concluded that anogenital distance is a "'novel index' whose relevance in humans 'has not been established,'" and that there is "insufficient evidence in humans" that DEHP causes harm.[22] The Swan study is thought by some to "suggest that male reproductive development in humans could be affected by prenatal exposure to environmentally relevant levels of phthalates".[23] Authors of a 2006 study of boys with undescended testis hypothesized that exposure to a combination of phthalates and anti-androgenic pesticides may have contributed to that condition.[24]

In contrast to the Swan study, an earlier study found that "adolescents exposed to significant quantities of DEHP as neonates showed no significant adverse effects on their physical growth and pubertal maturity."[25] This study, however, examined children exposed intravenously to phthalate diesters, and intravenous exposure results in little metabolic conversion of the relatively nontoxic phthalate diester to its more toxic monoester metabolite.[26]

In November 2009, Swan et al., in the International Journal of Andrology, in a paper titled "Prenatal phthalate exposure and reduced masculine play in boys",

"... suggest that prenatal exposure to antiandrogenic phthalates may be associated with less male-typical play behaviour in boys. ... [and] ... suggest that these ubiquitous environmental chemicals have the potential to alter androgen-responsive brain development in humans."[27][28]

Other effects[edit source | editbeta]

There may be a link between the obesity epidemic and endocrine disruption and metabolic interference. Studies conducted on mice exposed to phthalates in utero did not result in metabolic disorder in adults.[29] However, "in a national cross-section of U.S. men, concentrations of several prevalent phthalate metabolites showed statistically significant correlations with abnormal obesity and insulin resistance."[29] Mono-ethylhexyl-phthalate (MEHP), a metabolite of DEHP, has been found to interact with all three peroxisome proliferator-activated receptors (PPARs).[29] PPARs are members of the nuclear receptor superfamily. The author of the study stated "The roles of PPARs in lipid and carbohydrate metabolism raise the question of their activation by a sub-class of pollutants, tentatively named metabolic disrupters."[29] Phthalates belong to this class of metabolic disruptors. It is a possibility that, over many years of exposure to these metabolic disruptors, they are able to deregulate complex metabolic pathways in a subtle manner.[29] A 2011 study of New York City children found an association between phthalate metabolite urinary concentrations and larger body size measurements.[30] A 2012 study suggested that high levels of phthalates may be connected to the current obesity epidemic in children. It was found that obese children show greater exposure to phthalates than nonobese children. It was reported that the obesity risk increases according to the level of the chemical found in the children's bloodstream.[31]

Large amounts of specific phthalates fed to rodents have been shown to damage their liver and testes,[2] and initial rodent studies also indicated hepatocarcinogenicity. Following this result, di(2-ethylhexyl) phthalate was listed as a possible carcinogen by IARC, EC, and WHO. Later studies on primates showed that the mechanism is specific to rodents - humans are resistant to the effect.[32] The carcinogen classification was subsequently withdrawn.

In 2004, a joint Swedish-Danish epidemiologic team found a link between allergies in children and the phthalates DEHP and BBzP. Their review article and meta-analysis of published data relating to phthalates and asthma found an association between phthalates in the home and asthma, especially in children, but this evidence was limited by imprecise data on levels of exposure.[33]

In 2007, a cross-sectional study of U.S. males concluded that urine concentrations of four phthalate metabolites correlate with waist size and three phthalate metabolites correlate with the cellular resistance to insulin, a precursor to Type II diabetes. The authors note the need for follow-up longitudinal studies, as waist size is known to correlate with insulin resistance.[34] A 2012 study found that people with elevated phthalate levels had roughly twice the risk of developing diabetes compared with those with lower levels. They also found that phthalates were associated with disrupted insulin production.[35]

A 2009 study published in the Journal of Pediatrics found that prenatal phthalate exposure was related to low birth weight in infants. Low birth weight is the leading cause of death in children under 5 years of age and increases the risk of cardiovascular and metabolic disease in adulthood.[36] Researchers at the University of Michigan School of Public Health found that women who deliver prematurely have, on average, up to three times the phthalate level in their urine compared to women who carry to term.[37]

In 2009, South Korean scientists reported findings of a statistically significant correlation between urine phthalate concentrations in children and symptoms of ADHD. Although more research is needed in order to conclusively determine the relationship between phthalate and ADHD, the article suggests that consumers should be aware of its potential effects on behavior and neurological disorders.[38] The findings were replicated in The Mount Sinai Children's Environmental Health Study, which enrolled a multiethnic prenatal population in New York City between 1998 and 2002 (n= 404), published in Jan 2010. There was an association of prenatal phthalate exposure with offspring behavior and executive functioning at ages 4 to 9 years.[39] A study published in 2011 followed the children of 319 women who gave birth between 1999 and 2006 to evaluate possible associations between prenatal exposures to phthalates and possible adverse effects in development at age 3 years. The results suggested that prenatal exposure to phthalates had affected the children's mental, motor and behavioral development during the preschool years. The senior epidemiologist on the study stated, "The results are concerning since increasing exposures from the lowest 25% to the highest 25% among the women in our study was associated with a doubling or tripling in the odds of motor and/or behavioral problems in the children".[40]

 

Source: Wikipedia