Reproductive and Developmental Toxicity of Phthalates

Department of Production Animal Clinical Science, Norwegian School of Veterinary Science, Oslo, Norway.
Journal of Toxicology and Environmental Health Part B (Impact Factor: 4.97). 04/2009; 12(4):225-49. DOI: 10.1080/10937400903094091
Source: PubMed


The purposes of this review are to (1) evaluate human and experimental evidence for adverse effects on reproduction and development in humans, produced by exposure to phthalates, and (2) identify knowledge gaps as for future studies. The widespread use of phthalates in consumer products leads to ubiquitous and constant exposure of humans to these chemicals. Phthalates were postulated to produce endocrine-disrupting effects in rodents, where fetal exposure to these compounds was found to induce developmental and reproductive toxicity. The adverse effects observed in rodent models raised concerns as to whether exposure to phthalates represents a potential health risk to humans. At present, di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DBP), and butyl benzyl phthalate (BBP) have been demonstrated to produce reproductive and developmental toxicity; thus, this review focuses on these chemicals. For the general population, DEHP exposure is predominantly via food. The average concentrations of phthalates are highest in children and decrease with age. At present, DEHP exposures in the general population appear to be close to the tolerable daily intake (TDI), suggesting that at least some individuals exceed the TDI. In addition, specific high-risk groups exist with internal levels that are several orders of magnitude above average. Urinary metabolites used as biomarkers for the internal levels provide additional means to determine more specifically phthalate exposure levels in both general and high-risk populations. However, exposure data are not consistent and there are indications that secondary metabolites may be more accurate indicators of the internal exposure compared to primary metabolites. The present human toxicity data are not sufficient for evaluating the occurrence of reproductive effects following phthalate exposure in humans, based on existing relevant animal data. This is especially the case for data on female reproductive toxicity, which are scarce. Therefore, future research needs to focus on developmental and reproductive endpoints in humans. It should be noted that phthalates occur in mixtures but most toxicological information is based on single compounds. Thus, it is concluded that it is important to improve the knowledge of toxic interactions among the different chemicals and to develop measures for combined exposure to various groups of phthalates.

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    • "Due to their high global occurrence in different environmental matrixes, phthalate metabolites were detected in human urine, blood, and breast milk, indicating widespread human exposure (Guo et al., 2012; Hines et al., 2011). The endocrine-disrupting properties of PE were reported, and shown to mimic or antagonize the action of endogenous hormones, which consequently results in adverse effects on reproduction, growth, and development (Crocker et al., 1983; Crisp et al., 1998; Fisher, 2004; Lyche et al., 2009; Yoon et al., 2014; Kim et al., 2010). The PE mode of action is not well understood and may likely be dependent on developmental timing and dosing regimes (Yoon et al., 2014; Akingbemi et al., 2001). "
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    ABSTRACT: The occurrence of phthalate esters (PE) was examined in biota, ambient water, and sediments of two man-made lakes (Asejire and Eleyele) in southwestern Nigeria. Five fish species (Tilapia zillii, Hepsetus odoe, Parachanna obscura, Chrysichthys nigrodigitatus, and Mormyrus rume) were analyzed for PE levels and used for calculating bioconcentration factors (BCF) and biota– sediment accumulation factors (BSAF). In addition, measured PE levels were thereafter used to calculate the phthalate pollution index (PPI) in biota and the environment. At both lakes, all sampled species had k-factor > 1, showing apparently normal growth and health condition. Higher PE levels were found in sediments compared with water at both lakes, with a pattern showing that di(2-ethylhexyl) phthalate (DEHP) was predominant PE. While there were no unique patterns of PE concentrations in both lakes, differences were observed in organ concentration patterns that were evident at both lakes. For T. zillii, the BSAF was higher for dibutyl phthalate (DBP) compared to diethyl phthalate (DEP) and lowest for DEHP. The concentration pattern demonstrated that DBP concentrated more in gills (BCF: 6.7), while DEHP concentrated more in liver (BCF: 15.2) of T. zillii at Asejire. At Eleyele, T. zillii liver and gills concentrated less DEP and DEHP. The PPI value was significantly higher in sediment with respective values of 0.27 and 0.44 at Asejire and Eleyele lakes compared with water with respective values of 0.1 and 0.18 at Asejire and Eleyele lakes. Overall, our findings suggest a broader environmental and human health implication of high PE levels in these lakes, since they provide vast water volumes that are used for municipal domestic water supply. Further, these lakes support intense artisanal fisheries, representing significant sources of aquatic food resources for neighboring communities.
    Journal of Toxicology and Environmental Health Part A 06/2015; 78(12):761-777. DOI:10.1080/15287394.2015.1030487 · 2.35 Impact Factor
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    • "In recent years, reproductive and developmental toxicities of phthalates have been a cause of concern (Howdeshell et al. 2008; Lovekamp-Swan and Davis 2003), and these chemicals have been suspected of endocrine-disrupting effects on humans (Latini 2005; Lyche et al. 2009; Matsumoto et al. 2008). In addition, bis(2-ethylhexyl) phthalate (DEHP) has also been identified as a potential carcinogenic compound (IARC 2012). "
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    ABSTRACT: The first nationwide survey of six phthalates (diethyl phthalate (DEP); dimethyl phthalate (DMP); di-n-butyl phthalate (DBP); butyl benzyl phthalate (BBP); bis(2-ethylhexyl) phthalate (DEHP); din-octyl phthalate (DnOP)) in drinking waters from waterworks was conducted across seven geographical zones in China. Of the six target phthalates, DBP and DEHP were the highest abundant phthalates with median (± interquartile range) values of 0.18 ± 0.47 and 0.18 ± 0.97 μg/L, respectively, but did not exceed the limit values in China's Standards for Drinking Water Quality. These phthalates in drinking water were generally higher in the northern regions of China than those in the southern and eastern regions. Based on the investigated concentrations, lifetime exposure risk assessment indicated that phthalates in drinking water did not pose carcinogenic and noncarcinogenic risks to Chinese residents, even under the conservative scenario (with 95th percentile risk). In addition, we found that DEHP contributed the greatest risk to the total exposure risk of all the selected phthalates and oral ingestion was the main exposure route for phthalates in drinking water.
    Environmental Science and Pollution Research 03/2015; 22(14). DOI:10.1007/s11356-015-4253-9 · 2.83 Impact Factor
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    • "Fetal exposure is of particular concern because phthalate metabolites cross the placenta and have been found in amniotic fluid, placental tissue, cord blood and neonatal meconium [1,4–7]. Experimental animal studies have indicated their adverse reproductive and developmental effects and suggest that phthalates may have endocrine-disrupting properties [8]. "
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    ABSTRACT: Background Widespread phthalate exposure has prompted investigations concerning their potential adverse health effects. The objective of this study was to evaluate the impact of pre and early postnatal phthalate exposure on child psychomotor development basing on the data from the prospective Polish Mother and Child Cohort Study (REPRO PL). Methods Phthalate exposure was determined by measuring 11 phthalate metabolites (MEP, MiBP, MnBP, 3OH-MnBP, MBzP, MEHP, 5OH-MEHP, 5oxo-MEHP, 7OH-MiNP, 7oxo-MiNP, MnOP) in the urine collected from mothers during the third trimester of pregnancy (prenatal exposure) and from their children at 24 th month of age (postnatal exposure). The analysis was performed by HPLC-MS/MS method. Child psychomotor development was assessed at the 2 nd year of age by Bayley Scales of Infant and Toddler Development. Results Child motor development was inversely associated with natural log concentrations (µg/g creatinine) of 3OH-MnBP (β=-2.3; 95% CI -4.0 to -0.6), 5OH-MEHP (β=-1.2; 95% CI -2.2 to -0.3), 5oxo-MEHP (β=-1.8; 95% CI -330 to -0.2) and DEHP metabolites (β=-2.2; 95% CI -3.60 to -0.8) and sum of high molecular weight phthalates (β=-2.5; 95% CI -4.1 to -0.9) in the urine collected from mothers during pregnancy after adjustment for variety of potential confounders. Additional adjustment for postnatal phthalate exposure did not change the results. Postnatal child exposure to phthalates was not associated with any of the measured scores of child psychomotor development. Conclusions The study findings add further support to the possibility that prenatal phthalate exposure may be detrimental to child neurodevelopment and underscore the importance of policies and public health interventions to reduce such exposure.
    Early Human Development 09/2014; 90(9):477–485. DOI:10.1016/j.earlhumdev.2014.06.006 · 1.79 Impact Factor
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