More education is necessary to make better decisions about the role of plastics in our lives. Even basic research discovers disturbing links between familiar plastics and our bodies. Endocrine mimicking compounds in plastics need to be understood and in some cases avoided. Pthalates are used to "make plastics softer" but Pthalates have a low fidelity to their co-parent molecule and many may be soluble in fats or water.

Phthalates, called “plasticizers,” are a group of industrial chemicals used to make plastics like polyvinyl chloride (PVC) more flexible or resilient and also as solvents. Phthalates are nearly ubiquitous in modern society, found in, among other things, toys, food packaging, hoses, raincoats, shower curtains, vinyl flooring, wall coverings, lubricants, adhesives, detergents, nail polish, hair spray and shampoo.

Phthalates have been found to disrupt the endocrine system. Several phthalate compounds have caused reduced sperm counts, testicular atrophy and structural abnormalities in the reproductive systems of male test animals, and some studies also link phthalates to liver cancer, according to the U.S. Center for Disease Control’s 2005 National Report on Human Exposure to Environmental Chemicals. Though the CDC contends the health hazards of phthalates to humans have not been definitively established, for some years, the U.S. Environmental Protection Agency has regulated phthalates as water and air pollutants.

The Environmental Working Group has focused on phthalates since 1998, when EWG reported that dibutyl phthalate found in 37 nail polishes was also present in the bodies of every single American tested. A 2000 EWG analysis of CDC data, called Beauty Secrets, found that dibutyl phthalate was present in the bodies of every single person tested for industrial pollutants.

In 2003, EWG published its seminal Body Burden study, finding 210 industrial and consumer product chemical, among them, a half-dozen phthalates, in nine adult Americans who had agreed to submit their blood and urine to laboratory analysis. In 2007 EWG published a Parents Buying Guide, a safety guide to help parents find children’s personal care products that are free of phthalates and other potentially dangerous chemicals.

In July 2008, as a result of pressure from EWG and other health groups, the U.S. Congress passed legislation banning six phthalates from children’s toys and cosmetics. Legislators in Washington, Vermont and California have restricted phthalate use in children’s goods, and several major retailers, including Wal-Mart, Toys-R-Us, Lego, Evenflo and Gerber say they will phase out phthalate-laden toys.

EWG advocates a cumulative assessment of the human health risks, especially to infants, of phthalates. As well, EWG is working for passage of a new federal Kid-Safe Chemicals Act to reform the nation’s toxic chemical law to assure that chemicals are safe for babies, children and other vulnerable groups before they are allowed on the market.

(http://www.ewg.org/chemindex/term/480)

Phthalates: Toxicogenomics and inferred human diseases

Sher Singh, Steven Shoei-Lung Li

Phthalates are widely used as plasticizers to soften and increase the flexibility in polyvinyl chloride plastics, but they can leach into the surrounding environment. There is sufficient evidence in rodents that phthalate exposure causes developmental and reproductive toxicity.

The curated interactions between 16 phthalates and genes/proteins were obtained from Comparative Toxicogenomics Database (CTD), and a total of 445 interactions between the five most frequently curated phthalates (DEHP/MEHP and DBP/BBP/MBP) and 249 unique genes/proteins were found. The GeneOntology, pathways and networks of these 249 unique genes/proteins were fully analyzed. The pathways and networks of top 34 genes/proteins were found to be very similar to those of the 249 unique genes/proteins. Thus, the top 34 genes/proteins may serve as molecular biomarkers of phthalate toxicity.

The top three phthalate toxicity categories were found to be cardiotoxicity, hepatotoxicity and nephrotoxicity, and the top 20 diseases included cardiovascular, liver, urologic, endocrine and genital diseases.

Phthalates are a group of similar diesters of phthalic acid used as plasticizers to soften and increase the flexibility in polyvinyl chloride (PVC) plastics. Since phthalates are not covalently bound to plastics, they can leach into the surrounding environment [1] and [2]. Human exposure to phthalates mainly occurs through foods, because of the use of PVC in wrapping materials and food processing [3]. Phthalates are also found in meat, fish, milk products, and other foods with a high fat content. Diethylhexyl phthalate (DEHP) is produced by reacting 2-ethylhexanol with phthalic anhydride, and it is the highest production volume chemical. When ingested through food contamination, DEHP is converted by intestinal lipases to mono-(2-ethylhexyl) phthalate (MEHP), which is then preferentially absorbed. DEHP is currently the only phthalate plasticizer used in PVC medical devices such as intravenous tubing and blood transfusion bags [4]. Other sources of DEHP are indoor air and work exposure in manufacturing factories. Dibutyl phthalate (DBP) is produced by reacting n-butanol with phthalic anhydride. Unlike many phthalates, DBP is not currently used as a plasticizer in PVC plastics. Typically, DBP is used as a component of latex adhesives. It is also used in cosmetics and other personal care products, as a plasticizer in cellulose plastics, and as a solvent for dyes[5]. Monobutyl phthalate (MBP) is the embryotoxic metabolite of butylbenzyl phthalate (BBP) and DBP.

Environmental chemicals have been shown to play a critical role in the etiology of many human diseases. The impact of phthalate exposure on human health has been extensively reviewed and reported by the National Toxicology Program—Center for the Evaluation of Risks to Human Reproduction [6]. There is sufficient evidence in rodents, but not yet in humans, that phthalate exposure causes developmental and reproductive toxicity. The Comparative Toxicogenomics Database (CTD; http://ctd.mdibl.org) has been established to analyze the impact of environmental chemicals on human health [7]. Biocurators at CTD manually curate toxicogenomic data, including over 116,000 interactions between 3900 chemicals and 13,300 genes/proteins from 270 species, 5900 gene/protein–disease direct relationships, and 2500 chemical–disease direct relationships. In order to understand the potential adverse health effects of the most abundantly used DEHP/MEHP and DBP/BBP/MBP, the curated interactions between these five phthalates and genes/proteins were downloaded from CTD, and 249 phthalate-interacting genes/proteins were fully analyzed for their GeneOntology (GO), pathways, networks, and human diseases inferred by the phthalate–gene/protein–disease relationships in this investigation.

Sher Singh, Steven Shoei-Lung Li, Phthalates: Toxicogenomics and inferred human diseases, Genomics, Volume 97, Issue 3, March 2011, Pages 148-157, ISSN 0888-7543, 10.1016/j.ygeno.2010.11.008. (http://www.sciencedirect.com/science/article/pii/S0888754310002454) Keywords: Phthalates; DEHP; MEHP; DBP; BBP; MBP; Genes; Proteins; Toxicity; Diseases

Bisphenol A and phthalates exhibit similar toxicogenomics and health effects

Sher Singh, Steven Shoei-Lung Li

Plastics are widely used in modern life, and their unbound chemicals bisphenol A and phthalates can leach out into the surrounding environment. BPA and PAEs have recently attracted the special attention of the scientific community, regulatory agencies and the general public because of their high production volume, widespread use of plastics, and endocrine-disrupting effects. In The Comparative Toxicogenomics Database, BPA and five most frequently curated PAEs (DEHP/MEHP and DBP/BBP/MBP) were found to have 1932 and 484 interactions with genes/proteins, respectively. Five of their top ten toxicity networks were found to be involved in inflammation, and their top ten diseases included genital, prostatic, endomentrial, ovarian and breast diseases. BPA and PAEs were found to exhibit similar toxicogenomics and adverse effects on human health owning to their 89 common interacting genes/proteins. These 89 genes/proteins may serve as biomarkers to assay the toxicities of different chemicals leached out from the widely used plastics.

Plastics are widely used in modern life. Bisphenol A (BPA, 2,2-bis(4-hydroxyphenyl)propane) is used in the production of polycarbonate plastic containers such as baby bottles and resins that line metal cans for food and beverages. BPA is also used as a plasticizer to soften and increase the flexibility in polyvinyl chloride (PVC) plastic products, printer ink and the “carbonless paper” used for receipts. BPA has another medical use in dental sealants and composites used for filling. The unbound monomeric BPA can leach out into the surrounding environment (Talsness et al., 2009). Phthalates are a group of similar phthalic acid esters (PAEs) used as plasticizers in PVC plastics. Since PAEs are not covalently bound to the plastic matrix, they can easily leach out of products into the external environment ( [Heudorf et al., 2007], [Meeker et al., 2009] and [Silva et al., 2004]). BPA and PAEs have recently attracted the special attention of the scientific community, regulatory agencies and the general public because of their high production volume, widespread use of plastics, and endocrine-disrupting effects (Halden, 2010).

BPA was originally discovered as an artificial estrogen, and its estrogenic effect was used to enhance the rapid growth of cattle and poultry. BPA was also used for a few years as estrogen replacement for women. Since BPA can bind weakly to both estrogen receptors ESR1 and ESR2, it is likely to be an endocrine disruptor. There is extensive literature showing the adverse effects of acute exposure of low doses of BPA in experimental animals (Talsness et al., 2009). In rodents, BPA is associated with early sexual maturation, altered behavior, and effects on prostate and mammary glands (Talsness et al., 2009). In human, BPA is associated with cardiovascular diseases, diabetes, and male sexual dysfunction in exposed workers (Melzer et al., 2010). Epidemiological studies had found associations between blood levels of BPA in women and impaired health, including obesity and endometrial hyperplasia (Lang et al., 2008). Elevated exposure of pregnant women and children are of particular concern because of known windows of vulnerability to BPA that put the developing fetus and children at higher risk, compared with adults exposed to the same levels of BPA (Talsness et al., 2009). It should be further noted that BPA pharmacokinetics in women, female monkeys, and mice was recently found to be very similar (Taylor et al., 2010).

Regarding PAEs, di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used plasticizer for PVC. When ingested through food contamination, DEHP is converted by intestinal lipases to mono-(2-ethylhexyl) phthalate (MEHP), which is preferentially absorbed. Dibutyl phthalate (DBP) is typically used as a component of latex adhesives. It is also used in cosmetics and other personal care products, as a plasticizer in cellulose plastics, and as a solvent for dyes (Thomas et al., 1984). Monobutyl phthalate (MBP) is the metabolite of DBP and butylbenzyl phthalate (BBP). The impact of PAE exposure on human health had been extensively reviewed and reported by the National Toxicology Program — Center for the Evaluation of Risks to Human Reproduction (Program, 2006). There is sufficient evidence in rodents that PAE exposure causes developmental and reproductive toxicity (Meeker et al., 2009).

We have recently reported analyses of the toxicogenomics and possible adverse effects on human health of PAE exposure (Singh and Li, 2011). The top three toxicity categories of PAEs were found to be cardiotoxicity, hepatotoxicity and nephrotoxicity, and the top 20 inferred diseases included cardiovascular, liver, urologic, endocrine and genital diseases. In this investigation, the toxicogenomics and adverse effects on human health of BPA exposure were first analyzed, and then compared with those of PAEs using the same set of The Comparative Toxicogenomics Database (Davis et al., 2009).

Fig. 2. Venn diagram of bisphenol A and phthalate-interacting genes/proteins. BPA and PAEs (DEHP/MEHP and DBP/BBP/MBP) were found to interact with 1232 and 265 unique genes/proteins, respectively. There were 89 common genes/proteins interacting with both BPA and PAEs. Thus, 1143 and 176 genes/proteins were specifically interacted with either BPA or PAEs, respectively.

Sher Singh, Steven Shoei-Lung Li, Bisphenol A and phthalates exhibit similar toxicogenomics and health effects, Gene, Volume 494, Issue 1, 15 February 2012, Pages 85-91, ISSN 0378-1119, 10.1016/j.gene.2011.11.035. (http://www.sciencedirect.com/science/article/pii/S0378111911007050) Keywords: Bisphenol A; Phthalates; Genes; Proteins; Toxicogenomics; Diseases

Are Current Exposures to DEHP High Enough to Cause Concern?

Yes. Potentially high exposures of fetuses and infants to DEHP may lead to adverse effects on the developing male reproductive tract. High DEHP exposures of fetuses and infants can occur when pregnant and breast-feeding women undergo certain medical procedures involving DEHP-containing polyvinyl chloride medical devices. Infants may also be exposed to high levels of DEHP through medical procedures, diet, and/or mouthing of DEHP-containing objects. Based the estimated high levels of exposure that can occur during intensive medical treatments of ill infants and on the apparent sensitivity of the developing male reproductive tract to DEHP, there is particular concern for this subpopulation. The general adult population presently appears to be exposed to DEHP at levels that are not expected to cause adverse effects to the reproductive system. However, more data are needed to better understand human DEHP exposure levels and how these exposures vary across the population. The NTP offers the following conclusions regarding the potential for DEHP to adversely affect human reproduction and development of children. (See pg. 3 for helpful table).

http://ntp.niehs.nih.gov/ntp/ohat/phthalates/dehp/DEHP_BriefDraft1.pdf

Prenatal Phthalate Exposure Is Associated with Childhood Behavior and Executive Functioning

Stephanie M. Engel et al. April 1, 2010 in Children’s Health

Background: Experimental and observational studies have reported biological consequences of phthalate exposure relevant to neurodevelopment.

Objective: Our goal was to examine the association of prenatal phthalate exposure with behavior and executive functioning at 4–9 years of age.

Methods: The Mount Sinai Children’s Environmental Health Study enrolled a multiethnic prenatal population in New York City between 1998 and 2002 (n = 404). Third-trimester maternal urines were collected and analyzed for phthalate metabolites. Children (n = 188, n = 365 visits) were assessed for cognitive and behavioral development between the ages of 4 and 9 years.

Results: In multivariate adjusted models, increased loge concentrations of low molecular weight (LMW) phthalate metabolites were associated with poorer scores on the aggression [? = 1.24; 95% confidence interval (CI), 0.15– 2.34], conduct problems (? = 2.40; 95% CI, 1.34–3.46), attention problems (? = 1.29; 95% CI, 0.16– 2.41), and depression (? = 1.18; 95% CI, 0.11–2.24) clinical scales; and externalizing problems (? = 1.75; 95% CI, 0.61–2.88) and behavioral symptom index (? = 1.55; 95% CI, 0.39–2.71) composite scales. Increased loge concentrations of LMW phthalates were also associated with poorer scores on the global executive composite index (? = 1.23; 95% CI, 0.09–2.36) and the emotional control scale (? = Conclusion: Behavioral domains adversely associated with prenatal exposure to LMW phthalates in our study are commonly found to be affected in children clinically diagnosed with conduct or attention deficit hyperactivity disorders.

Keywords: attention deficit hyperactivity disorder, BASC, BRIEF, environmental exposure, phthalate. Environ Health Perspect 118:565–571 (2010). doi:10.1289/ehp.0901470 [Online 28 January 2010]

We report an association between prenatal exposure to low molecular weight phthalate (LMWP) and poorer parentrated behavioral and executive functioning profiles for children between the ages of 4 and 9 years. Specifically, higher LMWP metabolite concentrations were associated with poorer scores on the aggression, attention problems, conduct problems, depression, and externalizing problems scales, and for the overall BSI on the BASC. Similarly, poorer executive functioning was indicated by elevated scores on the emotional control scale and on the GECindex of the BRIEF. These effects remained statistically significant among boys, even after restricting the eligible surveys to those with Fscores of 0 or 1. All of these effects were consistent with a dose–response gradient.

Taken as a whole, the profile of parentreported behaviors we find associated with prenatal LMWP metabolite concentrations is suggestive of the behavior profiles of children clinically diagnosed with disruptive behavior disorders, for example, oppositional defiant disorder, conduct disorder, or ADHD (Loeber et al. 2009; Reynolds and Kamphaus 1998, Table 13.25)

Fragrances:

Urinary and air phthalate concentrations and self-reported use of personal

care products among minority pregnant women in New York City

Allan C. Just et al.

Two phthalates, diethyl phthalate (DEP) and di-n-butyl phthalate (DnBP), are added as a solvent for fragrances or to prevent products from becoming brittle, and have been found at higher concentrations than other phthalates in testing of personal care products in the United States, South Korea, and China (Houlihan et al., 2002; Koo and Lee, 2004; Hubinger and Havery, 2006; Shen et al., 2007). Among personal care products, DEP and DnBP have been found at the highest concentrations in fragrance products, including perfume (DEP), and in nail polishes (DnBP). Figure 1 shows an adaptation of results from the analysis of DEP in 48 personal care products in the United States (Hubinger and Havery, 2006). The ?ve fragrance products tested had concentrations of DEP ranging from 5486 to 38,663 p.p.m., and the next highest DEP concentration of any other product tested was in a deodorant with 2933 p.p.m. (Hubinger and Havery, 2006). In these data, fragrances have consistently higher concentrations of DEP compared with all other products tested, supporting the separate analysis of perfume from other personal care product categories as potential sources of DEP. According to a review of patent records, nail polishes might contain 50,000 p.p.m (5%) DnBP (Houlihan et al., 2002), a ?nding that was supported by a study that tested six nail enamel products and found concentrations that ranged from below the limit of detection to 59,815 p.p.m., or roughly 6% (Hubinger and Havery, 2006). Thus, nail polishes should be analyzed separately from other categories of personal care products as potential sources of exposure to DnBP because nail polishes seem to be more likely to contain DnBP and at higher concentrations than other product categories. Under current regulations in which ingredients used in fragrances are exempted from disclosure, phthalates are not generally listed as ingredients on consumer products in the United States (Steinemann, 2009).

Phthalates can enter the body through ingestion, dermal absorption, parenteral intake from medical devices, and inhalation. They undergo rapid hydrolysis to monoesters; short-alkyl chain phthalates such as DEP and DnBP are principally excreted in the urine as hydrolytic monoesters or as their corresponding glucuronidated conjugates (Silva et al., 2003).

Journal of Exposure Science and Environmental Epidemiology (2010) 20, 625–633

www.nature.com/jes

Phthalate-free cosmetics (http://www.ewg.org/node/21288):

Deodorant:	Certain Dri Anti-Perspirant Roll-OnDove Powder Anti-Perspirant DeodorantLady Speed Stick Soft Solid Anti-PerspirantSecret Anti-Perspirant & Deodorant Platinum Protection Ambition ScentSoft & Dri Anti-Perspirant Deodorant Clear Gel
Hair gel:	Physique Extra Control Structuring Gel
Hair mousse:	Finesse Touchables Silk Protein Enriched MousseHelene Curtis Thermasilk Heat Activated Mousse for Fine/Thin HairL'Oreal Paris Studio Line: Springing Curls Mousse
Hair spray:	Aussie Mega Styling SprayHelene Curtis Finesse Touchables Silk Protein EnrichedHelene Curtis Thermasilk Heat Activated Firm HairspraySuave Naturals Aloe Vera Extra Hold Hairspray
Hand and body lotions:	Curel Soothing Hands Moisturizing Hand LotionEucerin Dry Skin Therapy Original Moisturizing LotionLubriderm Skin Therapy Moisturizing LotionNeutrogena Hand CreamSuave Naturals Sun Ripened Moisturizing Body Lotion Vaseline Intensive Care Advanced Healing Vaseline Intensive Care Dry Skin Lotion
Nail Polish:	Kiss Colors Nail PolishL'Oreal Jet Set Nail EnamelL'Oreal Jet-Set Quick Dry Nail EnamelMaybelline Shades of Your Nail ColorNaturistics 90 Second Dry! Super Fast Nail Color Revlon Nail Enamel Revlon Super Top Speed Urban Decay

Articles on phthalates in cosmetics (http://www.ewg.org/node/21289):

6/1/2004	The Scotsman Too many products carry chemical danger to children
5/30/2004	The Independent Children at risk from cosmetics
5/25/2004	Los Angeles Times Common chemicals in cosmetics worry some
5/3/2004	Los Angeles Times Questions about some cosmetics
4/30/2004	Women’s enews Activists Push for Safer Ingredients in Makeup
5/7/2003	ChemWeek Europe Considers Phthalates Ban; FDA Rejects Labeling Petition
3/5/2003	New York Newsday New Questions About Common Chemicals
12/15/2002	Sunday Business Post Beauty's Ugly Face
12/2/2002	Chemical Regulation Reporter EU Reaches Agreement to Impose Ban On Use of Toxics in Cosmetic Products
11/26/2002	The Washington Post Beauty Coverup?
11/22/2002	PR Newswire New Web Site Gives Consumers Tips on Toxic Chemicals in Beauty Aids
11/20/2002	Reuters U.S. cosmetics panel allows use of disputed chemical
11/20/2002	Environmental News Network Cosmetics Industry Approves Controversial Chemicals
11/19/2002	PR Newswire US Panel Fails to Protect Americans from Reproductive Toxin in Cosmetics

Ocean Researcher Eliza Ives

Related online resources found here: http://www.ewg.org/node/21290 and here: http://safemama.com/2008/02/10/cheat-sheet-paraben-phthalate-free-baby-care/