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The diesters of 1,2-benzenedicarboxylic acid (phthalic acid), commonly known as phthalates, are a group of man-made chemicals with a wide spectrum of industrial applications. High molecular weight phthalates (for example, di(2-ethylhexyl) phthalate [DEHP], di-isononyl phthalate [DiNP], di-n-octyl phthalate [DnOP]), are primarily used as plasticizers in the manufacture of flexible vinyl which, in turn, is used in consumer products, flooring and wall coverings, food contact applications, and medical devices. Manufacturers use low molecular weight phthalates (for example, diethyl phthalate [DEP] and dibutyl phthalate [DBP]) in personal-care products (for example, perfumes, lotions, cosmetics), as solvents and plasticizers for cellulose acetate, and in making lacquers, varnishes, and coatings, including those used to provide timed releases in some pharmaceuticals. As plasticizers, phthalates make plastics more flexible and harder to break.
Phthalates are everywhere and used in hundreds of products. Phthalates are readily absorbed through the skin, and can also enter the body through ingestion, inhalation, or medical injection procedures such as IV tubing. Generally, 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 inhaling air that contains phthalate vapors or dust contaminated with phthalate particles. Young children may have a greater risk of dust-particle phthalate exposure than adults because of their hand-to-mouth behaviors.
Much of the research on phthalates has focused on endocrine-disrupting effects in males. However, more recent studies link phthalate exposure to early puberty in girls and suggest that females are affected in other ways that may increase the risk of breast cancer. Some phthalates, including butyl benzyl phthalate (BBP), and di-n-butyl phthalate (DBP), act as weak estrogens in cell culture systems. They can bind to estrogen receptors, induce estrogen-appropriate cellular responses and act additively with estradiol in altering these systems. This research implies that, phthalates like BBP target mammary tissue and can potentially accumulate in the fatty tissue of the breast leading to abnormal cellular changes.
Phthalates adversely affect the male reproductive system in animals, inducing hypospadias, cryptorchidism, reduced testosterone production and decreased sperm counts. Phthalate exposure in pregnant women, as measured by urine samples, has been associated with a shortened distance between the anus and genitals in male babies, indicating a feminization had occurred during genital development. Other research in humans has shown that baby boys exposed to phthalates in breast milk had alterations in their hormone levels.
In in-vitro cell systems, BBP, DBP and another common phthalate, di-(2-ethylhexyl) phthalate (DEHP), significantly increase cell proliferation in MCF-7 breast cancer cells. In addition, these three phthalates inhibited the anti-tumor action of tamoxifen in MCF-7 breast cancer cells. In another study exposure of young rats to BBP resulted in increased cellular proliferation in the terminal end buds of mammary tissue. BBP-induced changes in mammary cell gene expression profile were consistent with abnormalities in cellular differentiation and cell-cell communication.
Phthalates have short biological half-lives, metabolize quickly, do not accumulate, and are primarily excreted in the urine. Therefore, the urinary concentrations of phthalate metabolites provide an excellent biomarker of exposure. The metabolism and excretion of phthalates varies based on their chemical structure. Oxidative metabolism is prevalent for high molecular weight phthalates (e.g., DEHP, di-isononyl phthalate). Therefore, biomonitoring strategies should be designed with this consideration in mind. Exposure to high doses of some phthalates causes reproductive and developmental toxicities in both male and female animals. Epidemiological studies, despite their limitations, suggest that phthalates may affect reproductive outcome and children health. Clearly, phthalates pose a serious health risk to human health.
Because phthalates are used in plastic products and such products are ubiquitous, limiting exposure can be challenging. Contaminated food, scented cosmetics, personal care products, and household aerosol sprays contribute to most of the phthalate exposure in the general population. Foods prepackaged in plastics (sliced cheese, plastic milk cartons etc.) likely have higher phthalate concentrations than products not individually wrapped or packaged in non-plastic containers. Fresh vegetables, as opposed to frozen vegetables or highly processed products, tend to contain less phthalates. It is important to be aware that many paper products on today’s market are coated with plastic films, which contain phthalates. Use of non-plastic containers for long-term food storage, preventing direct contact of hot food or beverage with phthalate-containing-plastic surface, avoid heating food in plastic containers, and minimize consumption of highly processed food could decrease significant amounts of exposure. Limiting the use of old teething rings, pacifiers, bottles, railings, crib/playpen bumpers, and plastic books manufactured in the 1980s and before could decrease the exposure in infants and young children. Another major source of exposure comes from vapors of cosmetics, personal care products, and household aerosol spray, such as perfume, nail polish, hair spray, aftershave, and air fresheners. Increasing air exchange and ventilation is another measure one may take to decrease exposure to vapors from household products.
The following selected articles reveal more of the toxic and detrimental effect of phthalates on the body.
Chen, Xueping, Shisan Xu, Tianfeng Tan, Sin Ting Lee, Shuk Han Cheng, Fred Wang Fat Lee, Steven Jing Liang Xu, and Kin Chung Ho. "Toxicity and estrogenic endocrine disrupting activity of phthalates and their mixtures." International journal of environmental research and public health 11, no. 3 (2014): 3156-3168.
Chou, Karen, and Robert O. Wright. "Phthalates in food and medical devices." Journal of Medical Toxicology 2, no. 3 (2006): 126-135.
Hauser, Russ, and A. M. Calafat. "Phthalates and human health." Occupational and environmental medicine 62, no. 11 (2005): 806-818. the body.
Jurewicz, Joanna, and Wojciech Hanke. "Exposure to phthalates: reproductive outcome and children health. A review of epidemiological studies." International journal of occupational medicine and environmental health 24, no. 2 (2011): 115-141.
Hlisníková, Henrieta, Ida Petrovičová, Branislav Kolena, Miroslava Šidlovská, and Alexander Sirotkin. "Effects and mechanisms of phthalates’ action on neurological processes and neural health: a literature review." Pharmacological Reports (2021): 1-19.
Krauskopf, L. G. "Studies on the toxicity of phthalates via ingestion." Environmental health perspectives 3 (1973): 61-72.
Kohn, Michael C., Frederick Parham, Scott A. Masten, Christopher J. Portier, Michael D. Shelby, John W. Brock, and Larry L. Needham. "Human exposure estimates for phthalates." Environmental Health Perspectives 108, no. 10 (2000): A440-A442.
Koo, Hyun Jung, and Byung Mu Lee. "Estimated exposure to phthalates in cosmetics and risk assessment." Journal of Toxicology and Environmental Health, Part A 67, no. 23-24 (2004): 1901-1914.
Lottrup, G., A‐M. Andersson, H. Leffers, G. K. Mortensen, J. Toppari, N. E. Skakkebaek, and K. M. Main. "Possible impact of phthalates on infant reproductive health." International journal of andrology 29, no. 1 (2006): 172-180.
Lyche, Jan L., Arno C. Gutleb, Åke Bergman, Gunnar S. Eriksen, AlberTinka J. Murk, Erik Ropstad, Margaret Saunders, and Janneche U. Skaare. "Reproductive and developmental toxicity of phthalates." Journal of Toxicology and Environmental Health, Part B 12, no. 4 (2009): 225-249.
Mankidy, Rishikesh, Steve Wiseman, Hong Ma, and John P. Giesy. "Biological impact of phthalates." Toxicology letters 217, no. 1 (2013): 50-58.
Meeker, John D., Sheela Sathyanarayana, and Shanna H. Swan. "Phthalates and other additives in plastics: human exposure and associated health outcomes." Philosophical Transactions of the Royal Society B: Biological Sciences 364, no. 1526 (2009): 2097-2113.
Singh, Sher, and Steven Shoei-Lung Li. "Bisphenol A and phthalates exhibit similar toxicogenomics and health effects." Gene 494, no. 1 (2012): 85-91.