Page 5: Sixth Report on Human Biomonitoring of Environmental Chemicals in Canada

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14 Summaries and results for plasticizers

14.1 Phthalates

Diesters of phthalic acid, commonly called phthalates, are a class of high-production volume industrial chemicals that are used in the manufacture of a variety of products available to consumers and industrial products. Table 14.1.1 lists phthalates commonly found in commerce and their major metabolites measured in the Canadian Health Measures Survey (CHMS).

Phthalates are primarily used as plasticizers to impart flexibility and resilience to plastics (Frederiksen et al., 2007; Graham, 1973; HC, 2020). They are also used as solvents in household products, including self-care products, construction and renovation products, and textiles (HC, 2020). In particular, BBP, DnBP, DMP and DEP are found in self-care products such as cosmetics (e.g., hair-care products and fragrance) and non-prescription drugs (Cosmetic Ingredient Review Expert Panel, 2005; ECCC and HC, 2020; EC and HC, 2000; 2015e). DINP, DiBP, DCHP, DnBP, BBP and DEHP are used in construction and renovation products, such as lubricants and greases, adhesives and sealants, paints and coatings, and building materials (ECCC and HC, 2020; EC and HC, 2000; 2015b; 2015d; HC, 2020). DOP, BBP, DMP, DnBP, DIDP, DiBP and DINP are used in electrical items and electronics (ECCC and HC, 2020; EC and HC, 2015b; 2015c; 2015d; 2015e; HC, 2020). Phthalates are also used in the automotive sector (e.g., BBP, DEHP, DiBP and DCHP), in printing ink (e.g., DINP and BBP), and in the formulation of pesticides (e.g., BBP) (ECCC and HC, 2020; EC and HC, 2015d; HC, 2020). Finally, certain phthalates, including BBP, DEHP, DIDP and DMP, can be found in food-packaging materials (ECCC and HC, 2020; EC and HC, 2015c; 2015e; HC, 2020). Prior to restrictions enacted in 2010 (see below), phthalates, namely BBP, DnBP, DINP and DEHP, were used in Canada as plasticizers in soft vinyl toys and childcare articles.

There are no known natural sources of phthalates. Releases to the environment are associated with anthropogenic activities (ECCC and HC, 2020). Releases may occur during the manufacture, processing, transportation and storage of phthalates as well as during the production, use and disposal of products that contain phthalates (ECCC and HC, 2020). Although release into air may occur, water is expected to be the primary receiving medium for phthalates through wastewater effluents from industrial sources and disperse releases from products available to consumers (ECCC and HC, 2020; EC and HC, 2015d).

Phthalates have been detected in food, water, air, soil and dust (Clark, 2003; ECCC and HC, 2020). The general population can be exposed through the inhalation of indoor air; through the ingestion of water, food, beverages, soil and dust; and through the use of products available to consumers (HC, 2020). Other potential sources of exposure are breast milk and the mouthing of children's toys and articles (ECCC and HC, 2020).

In laboratory animals, phthalates have been observed to undergo rapid absorption following oral exposure and generally slow absorption following dermal exposure (ATSDR, 1995; 1997; 2001). Phthalate diesters are converted to their corresponding monoesters in the gastrointestinal tract or saliva prior to absorption (ATSDR, 1995; 1997; 2001; NRC, 2008). Phthalates are rapidly metabolized in the body to form hydrolytic and oxidative monoesters, which can either be excreted in the urine and feces unchanged or can undergo phase II biotransformation to produce glucuronide conjugates with increased water solubility and, as a result, increased urinary excretion (Hauser and Calafat, 2005; Samandar et al., 2009). Although the metabolism and excretion of monoester phthalates varies based on a number of factors, they are generally characterized by rapid metabolism and short biological half-lives (ATSDR, 1995; 1997; 2001; Hauser and Calafat, 2005). Phthalates do not bioaccumulate in humans (CDC, 2009). Measurement of phthalate metabolites in urine has become the most common approach to assessing phthalate exposure in humans, and reflects relatively recent exposure (Blount et al., 2000; Calafat and McKee, 2006).

In laboratory animals, exposure to some phthalates adversely affects the male reproductive system. In particular, prenatal exposure to phthalates, such as DnBP, BBP, DEHP, DCHP and DINP, has been shown to disrupt the androgen-mediated development of the male reproductive tract (David, 2006; EC and HC, 2015b; 2015d; Foster, 2005; Gray et al., 2000; Howdeshell et al., 2007; Main et al., 2006; Mariana et al., 2016; Wine et al., 1997). This response, termed "rat phthalate syndrome," is characterized by malformations of the epididymis, vas deferens, seminal vesicles, prostate and external genitalia, among other effects (Lioy et al., 2015). Adverse effects on the testes have also been observed in mature laboratory animals, although these effects occurred at higher doses (David, 2006; Foster, 2005). There is also evidence from animal studies that phthalates exert adverse effects on the ovaries (EC and HC, 2015b; Hannon and Flaws, 2015; Mariana et al., 2016). Other target organs identified in animal studies include the liver and kidneys, where phthalate exposure may lead to increased organ weights and peroxisome proliferation in the liver (David and Gans, 2003; EC and HC, 2015b; 2015c; 2015d; 2015e; Howdeshell et al., 2007; Main et al., 2006; Wine et al., 1997).

Numerous studies demonstrate exposure to phthalates in the human population, including prenatal exposure (Becker et al., 2009; Blount et al., 2000; HC, 2018a; 2018b; Lioy et al., 2015; Marsee et al., 2006; NTP-CERHR, 2003a; 2003b; 2003c; 2003d; 2003e; 2003f; 2006; Praveena et al., 2018; Silva et al., 2003; Wittassek et al., 2011). An evaluation by Health Canada of 134 epidemiologic studies of phthalates and health outcomes in categories including hormonal effects, growth and development, and reproductive parameters (HC, 2018a) — as well as a Health Canada evaluation of 125 epidemiologic studies of phthalates and health outcomes in categories including behaviour and neurodevelopment, cardiovascular function, oxidative stress, breast cancer, obesity, allergy (inflammation of the airways and skin) and metabolic disorders (HC, 2018b) — determined that no health outcome had sufficient evidence of an association with any assessed phthalate or its metabolite (HC, 2018a; 2018b). The International Agency for Research on Cancer has classified DEHP as possibly carcinogenic to humans (Group 2B) and has determined that BBP's carcinogenicity to humans is not classifiable (Group 3) (IARC, 1999; 2013).

Environment Canada and Health Canada assessed 4 phthalates (DBP, BBP, DEHP and DOP) on an individual basis as part of the First and Second Priority Substances Lists (PSL1 and PSL2) (EC and HC, 1993; 1994a; 1994b; 2000). DBP and BBP were determined not to present a risk to the environment or to human health. DOP was found not to present a risk to the environment; however, at the time of the assessment, the available information was not sufficient to allow a conclusion in terms of human health. A subsequent report concluded that DOP did not pose a risk to human health (EC and HC, 2003). DEHP was determined to present a risk to human health in Canada; however, there was insufficient information to conclude on the potential for risk to the environment at the time of the assessment. State of the Science reports were published in 2015 for the short-chain phthalate DMP, medium-chain phthalates (including DCHP and DiBP), long-chain phthalates (including DIDP) and DINP (EC and HC, 2015b; 2015c; 2015d; 2015e). A screening assessment concluded that the 14 substances in the Phthalate Substance Grouping (including DMP, DiBP, DINP and DIDP) are not harmful to the environment or to human health as set out in section 64 of the Canadian Environmental Protection Act, 1999 (CEPA 1999), but that DEHP, previously assessed under the Priority Substances Assessment Program, is harmful to the environment as set out in section 64(a) of CEPA 1999 (Canada, 1999; ECCC and HC, 2020). In addition, a cumulative risk assessment using a conservative, lower-tiered hazard index approach indicated no concern for potential cumulative risk of medium-chain phthalates for the general Canadian population, specifically the more sensitive subpopulations (pregnant women, women of child-bearing age, infants and children) at current exposure levels (EC and HC, 2015a; ECCC and HC, 2020).

Health Canada has developed and implemented the Phthalates Regulations under the Canada Consumer Product Safety Act concerning the use of 6 phthalates (DEHP, DnBP, BBP, DINP, DIDP and DOP) in soft vinyl children's toys and childcare articles (Canada, 2010). Phthalates used in children's toys and childcare articles are also regulated in the United States and the European Union. DEHP is on the List of Ingredients that are Prohibited for Use in Cosmetic Products (HC, 2019).

Phthalate metabolite concentrations in urine have been measured in a number of biomonitoring studies conducted in Canada, including the Maternal–Infant Research on Environmental Chemicals study (Arbuckle et al., 2014), the First Nations Biomonitoring Initiative (AFN, 2013), and the Canadian Healthy Infant Longitudinal Development (CHILD) study (Navaranjan et al., 2020).

Eleven phthalate metabolites (MnBP, MEP, MBzP, MCHP, MEHP, MOP, MiNP, MMP, MCPP, MEHHP and MEOHP) were measured in the urine of CHMS participants aged 6–49 in cycle 1 (2007–2009) and aged 3–79 in cycle 2 (2009–2011), cycle 5 (2016–2017) and cycle 6 (2018–2019). MiBP was measured in the urine of CHMS participants aged 3–79 in cycles 2, 5 and 6. MCMHP, MECPP, MCiNP, MHiDP, MiDP, MOiDP, MCiOP, MHiNP, MOiNP, 3OH-MBP and MCHpP were measured in the urine of CHMS participants aged 3–79 in cycles 5 and 6. Data from these cycles are presented as both µg/L and µg/g creatinine (Tables 14.1.2 to 14.1.47). Finding a measurable amount of phthalate metabolites in urine is an indicator of exposure to parent phthalates and does not necessarily mean that an adverse health effect will occur.