CoChat
Sign Up
Cited by 755Effects and risks of endocrine disrupting chemicalsToxic Organic Pollutants ImpactPesticide Exposure and Toxicity

A Review of Biomonitoring of Phthalate Exposures

Open access
Wang, Yu, Zhu, Hongkai, Kannan, Kurunthachalam·2019·Toxics
DOI 10.3390/toxics7020021PMC PMC6630674
Open this paper in CoChat — free account

Abstract

Phthalates (diesters of phthalic acid) are widely used as plasticizers and additives in many consumer products. Laboratory animal studies have reported the endocrine-disrupting and reproductive effects of phthalates, and human exposure to this class of chemicals is a concern. Several phthalates have been recognized as substances of high concern. Human exposure to phthalates occurs mainly via dietary sources, dermal absorption, and air inhalation. Phthalates are excreted as conjugated monoesters in urine, and some phthalates, such as di-2-ethylhexyl phthalate (DEHP), undergo secondary metabolism, including oxidative transformation, prior to urinary excretion. The occurrence of phthalates and their metabolites in urine, serum, breast milk, and semen has been widely reported. Urine has been the preferred matrix in human biomonitoring studies, and concentrations on the order of several tens to hundreds of nanograms per milliliter have been reported for several phthalate metabolites. Metabolites of diethyl phthalate (DEP), dibutyl- (DBP) and diisobutyl- (DiBP) phthalates, and DEHP were the most abundant compounds measured in urine. Temporal trends in phthalate exposures varied among countries. In the United States (US), DEHP exposure has declined since 2005, whereas DiNP exposure has increased. In China, DEHP exposure has increased since 2000. For many phthalates, exposures in children are higher than those in adults. Human epidemiological studies have shown a significant association between phthalate exposures and adverse reproductive outcomes in women and men, type II diabetes and insulin resistance, overweight/obesity, allergy, and asthma. This review compiles biomonitoring studies of phthalates and exposure doses to assess health risks from phthalate exposures in populations across the globe.

AI snapshot

Written from the paper’s full text.

TL;DR

This review compiles global human biomonitoring and selected epidemiological studies of phthalate exposures, focusing on urinary metabolites and other biological matrices. It reports ubiquitous exposure, higher levels in children, country-specific temporal trends, and associations with reproductive, metabolic, and allergic outcomes, while noting major data gaps.

Key findings

  • Phthalates are widely used plasticizers/additives; annual global production was 4.7 million metric tons in 2006 and ~8 million metric tons in 2015. DEHP, DiNP, and BzBP are common additives that migrate from products.
  • Urine is the preferred biomonitoring matrix; metabolites of DEP, DBP/DiBP, and DEHP are most abundant. Sum of 22 phthalate metabolites in urine was on the order of several to hundreds of µg/L. Kuwait samples from 2006–2007 had the highest median total phthalate metabolite concentration at 1,050 µg/L (maximum 19,300 µg/L), with MEP 411 µg/L, MBP 113 µg/L, and DEHP metabolites 180 µg/L.
  • Temporal trends varied by country: US DEHP exposure declined since 2005 while DiNP exposure increased; a 67% decline in US DEHP exposure was reported between 2005/6 and 2011/12. In China, DEHP exposure increased since 2000/2001. Children often had higher exposures than adults; in DEMOCOPHES, children vs mothers had geometric means of MBP 34.8 vs 23.9 µg/L, MiBP 45.4 vs 30.1 µg/L, and ΣDEHP 47.6 vs 29.2 µg/L, though MEP was higher in mothers (48.2 vs 34.4 µg/L).
  • Epidemiological studies reported associations between phthalate exposures and adverse reproductive outcomes, type II diabetes and insulin resistance, overweight/obesity, allergy, and asthma. For example, higher urinary MBP, MiBP, MBzP, MCPP, and DEHP metabolites were associated with increased diabetes diagnosis in US women, and DEHP metabolites were associated with obesity in adult females and older males.

Methods

  • Narrative review based on a literature search in Web of Science Core Collection, BIOSIS Previews, Derwent Innovations Index, MEDLINE, and SciELO Citation Index, using terms for phthalic acid/phthalates OR phthalate metabolites AND biomonitoring OR epidemiological studies, restricted to publications between 2000 and 2018.
  • The review summarizes biomonitoring of phthalate diesters and their monoester and oxidative metabolites in urine, serum, breast milk, semen, saliva, amniotic fluid, and nails, plus selected epidemiological studies linking exposure to health outcomes. Main analysis is narrative synthesis; no meta-analysis is reported.

Limitations

  • Paper-stated: there is a lack of biomonitoring data on phthalate exposures in developing countries in Africa and South America; lack of analytical standards hinders identification of intermediate biological transformation products; the relevance of matrices such as blood, breast milk, semen, and nails remains largely unknown; and observed associations between phthalate exposure and disease outcomes are exploratory and preliminary.
  • Paper-stated: studies reporting partitioning of phthalates among tissues and organs at steady-state exposure conditions are not available, and interactions of phthalate metabolites with other contaminants should be considered in future investigations.
  • Evident from the text: as a narrative review, it does not report a formal systematic-review protocol, risk-of-bias assessment, or quantitative pooled effect estimates, so causal inference from the cited exposure–health associations is limited.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/toxics7020021

Cites

207 of 207 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

45 of 86 cited sources checked · 14 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    A significant association between urinary concentrations of MBzP, MEHP, and MEP and increased risk of endometriosis was found in women.

    “A significant association between urinary concentrations of MBzP, MEHP, and MEP and increased risk of endometriosis was found in women [206].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [206] Upson, 2013, Phthalates and risk of endometriosis, Environ. Res. source

      The Results report a statistically significant inverse association between urinary MEHP and endometriosis risk, not an increased risk. They suggest increased risk with MBzP and MEP, but explicitly state that those associations were not statistically significant. The supplied passages do not give page numbers. (LLM, conf=0.90)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    A 67% decline in DEHP exposure in the US population between 2005/6 and 2011/12 has been reported.

    “A 67% decline in DEHP exposure in the US population between 2005/6 and 2011/12 has been reported [141].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [141] Zota, 2014, Temporal trends in phthalate exposures: Findings from the National Health and Nutrition Examination Survey, 2001–2010, Environ. Health Perspect. source

      The Results report a decline in DEHP metabolites in the U.S. population, from 45.4 ng/mL in 2005–2006 to 24.8 ng/mL in 2009–2010 (about 45%). The paper’s data end in 2009–2010, so they do not support the claimed 67% decline through 2011–2012. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
  • Premisecitation

    Mean concentrations of MEP, MBP, and DEHP metabolites were one to two orders of magnitude lower in serum and seminal plasma than in urine in young Danish men.

    “The mean concentrations of MEP, MBP, and DEHP metabolites were one to two orders of magnitude lower in serum (MEP: 4.2, MBP: 0.4, and DEHP: 7.6 µg/L) and seminal plasma (1.0, 0.8, and 0.6 µg/L) than in urine (326, 42.5, and 115 µg/L).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [77] Frederiksen, 2010, Correlations between phthalate metabolites in urine, serum, and seminal plasma from young Danish men determined by isotope dilution liquid chromatography tandem mass spectrometry, J. Anal. Toxicol. source
  • Premisecitation

    MEP at 222 μg/g CR was the predominant phthalate metabolite found in urine samples of pregnant women from the Netherlands Generation R study.

    “MEP (222 µg/g CR) was the predominant phthalate metabolite found in urine samples of pregnant women from the Netherlands (Generation R study) [110].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [110] Ye, 2008, Urinary metabolite concentrations of organophosphorous pesticides, bisphenol A, and phthalates among pregnant women in Rotterdam, the Netherlands: The Generation R study, Environ. Res. source
  • Premisecitation

    When only serum is available, MEP and MiBP representing low molecular weight phthalates, and MECPP and MCiOP representing high molecular weight phthalates, have been used as indicators of phthalate exposure.

    “However, when only serum was available for analysis, MEP and MiBP representing low molecular weight phthalates, and MECPP and MCiOP representing high molecular weight phthalates, have been used as indicators of phthalate exposure [77].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [77] Frederiksen, 2010, Correlations between phthalate metabolites in urine, serum, and seminal plasma from young Danish men determined by isotope dilution liquid chromatography tandem mass spectrometry, J. Anal. Toxicol. source

      The “Serum and seminal plasma” section identifies MEP and MiBP as low-molecular-weight indicators and MECPP and MCiOP as high-molecular-weight indicators when only serum is available. It says they “could be used” for this purpose, however, rather than documenting that they have been used. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • Rests on an assumption: Biomonitoring studies of human phthalate exposure have been based on urinary concentrations of phthalate metabolites.
  • May combine two claims. 26
  • Classified as probably not a substantial claim. 18
  • The quote only partly states this claim. 2

  • May combine two claims.

    Premisecitation

    Median concentrations of MBP, MBzP, and MEHP in breast milk were 0.54, 0.50, and 0.49 μg/L, respectively.

    “Median concentrations of MBP, MBzP, and MEHP in breast milk were 0.54, 0.50, and 0.49 µg/L, respectively [24].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [24] Hanberg, 2008, Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vulnerable populations, Environ. Health Perspect. source

      The Results (page unavailable) report that phthalate metabolites in 42 breast-milk samples were generally close to or below the detection limit, and refer to Table 2 for concentrations. The passages available from our copy do not give the claimed medians of 0.54, 0.50, and 0.49 µg/L, so those exact figures cannot be verified. (LLM, conf=0.74)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    MEHHP and MEOHP occurred in the placenta at concentrations of 0.09 and <LOD ng/g.

    “MEHHP and MEOHP also were reported to occur in the placenta at concentrations of 0.09 and <LOD ng/g [144].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [144] Kim, 2016, Association of diethylhexyl phthalate with obesity-related markers and body mass change from birth to 3 months of age, J. Epidemiol. Community Health source

  • May combine two claims.

    Premisecitation

    Median concentrations of MEHHP and MEOHP were 0.31 and <LOD μg/L in maternal blood and 0.32 and <LOD μg/L in cord blood, respectively.

    “Median concentrations of MEHHP and MEOHP were 0.31 and <LOD µg/L in maternal blood and 0.32 and <LOD µg/L in cord blood, respectively.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [144] Kim, 2016, Association of diethylhexyl phthalate with obesity-related markers and body mass change from birth to 3 months of age, J. Epidemiol. Community Health source

  • May combine two claims.

    Premisecitation

    MCPP (0.2 μg/L), MEOHP (0.3 μg/L), MECPP (0.1-0.4 μg/L), and MEHHP (0.2-0.3 μg/L) were detected in some breast milk samples from 33 lactating mothers in North Carolina.

    “MCPP (0.2 µg/L) and MEOHP (0.3 µg/L), MECPP (0.1–0.4 µg/L), and MEHHP (0.2–0.3 µg/L) were detected in some samples [131].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [131] Hines, 2009, Concentrations of phthalate metabolites in milk, urine, saliva, and Serum of lactating North Carolina women, Environ. Health Perspect. source

  • May combine two claims.

    Premisecitation

    MBP, MEHP, MEP, and MiBP were detected in blood serum at median concentrations of 0.54, 0.49, 0.50, and 0.5 μg/L, respectively.

    “MBP, MEHP, MEP, and MiBP were detected in blood serum at median concentrations of 0.54 0.49, 0.50, and 0.5 µg/L, respectively [24]”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [24] Hanberg, 2008, Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vulnerable populations, Environ. Health Perspect. source

      The Results report detectable serum mEHP in a small percentage of samples and seven serum mEP values above the detection limit, but say most blood or serum samples were below that limit. The passages in our copy do not give the four claimed median concentrations or establish detection of serum mBP and miBP at those medians. (LLM, conf=0.78)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    DEHP and BzBP and their monoesters are regarded as allergens, and exposure to them has been associated with asthma and wheezing in adults.

    “DEHP and BzBP and their monoesters are regarded as allergens, and exposure to them has been associated with asthma and wheezing in adults [200,201].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [200] Braun, 2013, Phthalate exposure and children’s health, Curr. Opin. Pediatr. source

      The “Asthma and Allergy” section reports associations between DEHP and BBzP exposure and asthma or wheezing in children, not adults. It describes phthalates as potential adjuvants affecting allergen response, but does not classify DEHP, BBzP, or their monoesters as allergens. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [201] Hoppin, 2013, Phthalate exposure and allergy in the U.S. population: Results from NHANES 2005-2006, Environ. Health Perspect. source

      The Results (Table 3) associate MBzP, a metabolite of BBzP, with current asthma and wheeze in adults. They do not show a significant association between DEHP metabolites and either symptom. The Introduction and Discussion describe DEHP and BBzP as chemicals that may alter responses to allergens, not as allergens themselves. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Two phthalate metabolites (2.2 μg/L MCPP and 2.3 μg/L MECPP) were detected in a saliva sample from a US woman.

    “Two phthalate metabolites (2.2 µg/L MCPP and 2.3 µg/L MECPP) were detected in a saliva sample from a US woman [131].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [131] Hines, 2009, Concentrations of phthalate metabolites in milk, urine, saliva, and Serum of lactating North Carolina women, Environ. Health Perspect. source

  • May combine two claims.

    Premisecitation

    Phthalate metabolites were measured in nail samples from Belgium, and the total concentrations ranged between <12 and 7980 ng/g.

    “Phthalate metabolites were measured in nail samples from Belgium, and the total concentrations ranged between <12 and 7980 ng/g.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [135] Alves, 2016, Ultrasound assisted extraction combined with dispersive liquid-liquid microextraction (US-DLLME)—A fast new approach to measure phthalate metabolites in nails, Anal. Bioanal. Chem. source

      Section 3.4 (p. 14) confirms that phthalate metabolites were measured in nails from ten Belgian individuals. It reports average analyte levels of 3.6–918 ng/g, not a total-concentration range of <12–7980 ng/g; the latter figures are not supported by the passages in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Phthalate exposure was associated with increased body mass and waist circumference.

    “Phthalate exposure was associated with increased body mass and waist circumference [195].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [195] Wang, 2013, Urinary phthalate metabolites are associated with body mass index and waist circumference in Chinese school children, PLoS ONE source

  • May combine two claims.

    Premisecitation

    Some phthalate metabolites (MEP, MBP, and MiBP) were associated with obesity in children, whereas MEHP, MECPP, MEHHP, MEOHP, MBzP, and MCNP were associated with obesity in adults.

    “Some phthalate metabolites (MEP, MBP, and MiBP) were associated with obesity in children, whereas MEHP, MECPP, MEHHP, MEOHP, MBzP, and MCNP were associated with obesity in adults.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [196] Buser, 2014, Age and sex differences in childhood and adulthood obesity association with phthalates: Analyses of NHANES 2007–2010, Int. J. Hyg. Environ. Health source

      The Results sections for children and adolescents and for adults report obesity associations for several listed metabolites, but with important qualifications: MiBP was associated only in males, and the adult results identify individual associations for MECPP, MEHHP, MEOHP, and MCNP. The paper lists MnBP (apparently the claim’s MBP) and MEHP within associated metabolite groups, but does not report individual associations for either; it likewise does not report an individual adult association for MBzP. No page numbers are available in our copy. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The majority of laboratory animal exposure/toxicity studies have focused on DEHP and DBP/DiBP, with limited studies examining the toxicities of other phthalates.

    “Thus far, the majority of the laboratory animal exposure/toxicity studies have focused on DEHP and DBP/DiBP, with limited studies examining the toxicities of other phthalates [164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191].”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [164] Fabjan, 2006, A category approach for reproductive effects of phthalates, Crit. Rev. Toxicol. source

      The “Reproductive Toxicity of Selected Phthalates” section says DEHP and DBP are among the most frequently investigated phthalates and that study availability varies across phthalates. But it names BBP—not DiBP—as the third frequently investigated compound, and its comparison concerns reproductive endpoints rather than laboratory-animal toxicity studies generally. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [165] Lyche, 2009, Reproductive and developmental toxicity of phthalates, J. Toxicol. Environ. Health B Crit. Rev. source

      The indexed passages labeled Abstract contain bibliographic information and keywords naming DEHP and n-butyl phthalate, but no discussion of how many laboratory-animal studies examined each phthalate. Searches for the claimed concentration of studies on DEHP and DBP/DiBP, and the scarcity of studies on other phthalates, found no passage that addresses that comparison. (LLM, conf=0.69)

      Experimental — accuracy not yet measured
    • cites [166] Desvergne, 2011, Endocrine disruptors: From endocrine to metabolic disruption, Annu. Rev. Physiol. source

  • May combine two claims.

    Premisecitation

    MEHP, MBP, and MEP were the major metabolites detected in every nail sample, with a median concentration of 138, 74, and 64 ng/g, respectively.

    “MEHP, MBP, and MEP were the major metabolites detected in every nail sample, with a median concentration of 138, 74, and 64 ng/g, respectively [135].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [135] Alves, 2016, Ultrasound assisted extraction combined with dispersive liquid-liquid microextraction (US-DLLME)—A fast new approach to measure phthalate metabolites in nails, Anal. Bioanal. Chem. source

      Section 3.4 (p. 14) identifies MEHP, MBP isomers, and MEP as the major metabolites and reports detection in 100% of the ten individuals studied. It does not give the claimed median concentrations of 138, 74, and 64 ng/g; it reports only an overall range of average levels and refers to Table 4. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Findingnone given

    Urine has been the preferred matrix in human biomonitoring studies, and concentrations on the order of several tens to hundreds of nanograms per milliliter have been reported for several phthalate metabolites.

    “Urine has been the preferred matrix in human biomonitoring studies, and concentrations on the order of several tens to hundreds of nanograms per milliliter have been reported for several phthalate metabolites.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    For many phthalates, exposures in children are higher than those in adults.

    “For many phthalates, exposures in children are higher than those in adults.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    In the United States, DEHP exposure has declined since 2005.

    “In the United States (US), DEHP exposure has declined since 2005”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    In China, DEHP exposure has increased since 2000.

    “In China, DEHP exposure has increased since 2000.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    In a majority of biomonitoring studies, metabolites of DEHP, DEP, and DBP were the major compounds identified in urine, and the profile varied depending on the country.

    “In a majority of the biomonitoring studies, metabolites of DEHP, DEP, and DBP were the major compounds identified in urine, and the profile varied depending on the country.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    The 95th percentile for DEHP exposure doses calculated for the German general population (n = 85) and children (n = 254) were 21 and 25 μg/kg bw/day, respectively, exceeding the RfD of 20 μg/kg bw/day and the TDI of 20-48 μg/kg bw/day.

    “The 95th percentile for DEHP exposure doses calculated for the general population (n = 85) and children (n = 254) from Germany were 21 and 25 µg/kg bw/day, respectively, which exceeded the RfD (20 µg/kg bw/day) and the TDI (20–48 µg/kg bw/day) [149].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [149] Koch, 2006, Di(2-ethylhexyl)phthalate (DEHP): Human metabolism and internal exposure—An update and latest results, Int. J. Androl. source

  • May combine two claims.

    Findingcitation

    Dust ingestion is a major source of exposure to phthalates in infants and toddlers, whereas diet is the major source for children and adults.

    “Dust ingestion is a major source of exposure to phthalates in infants and toddlers, whereas diet is the major source for children and adults.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Tran, 2015, Occurrence of phthalate diesters in particulate and vapor phases in indoor air and implications for human exposure in Albany, New York, USA, Arch. Environ. Contam. Toxicol. source

  • May combine two claims.

    Findingcitation

    Elevated exposure to phthalates, especially DEHP, in neonates admitted to intensive care units was reported, with median 42 μg/kg bw/day and 95th percentile 1780 μg/kg bw/day, higher than the RfD.

    “elevated exposure to phthalates, especially DEHP, in neonates admitted to intensive care units was reported (median: 42 µg/kg bw/day; 95th percentile: 1780 µg/kg bw/day) [149], and the exposure dose was higher than the RfD.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [149] Koch, 2006, Di(2-ethylhexyl)phthalate (DEHP): Human metabolism and internal exposure—An update and latest results, Int. J. Androl. source

  • The quote only partly states this claim.

    Premisenone given

    Human epidemiological studies have shown a significant association between phthalate exposures and allergy and asthma.

    “allergy, and asthma”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Human exposure to phthalates arises mainly from ingestion, inhalation, and dermal absorption.

    “Human exposure to phthalates arises mainly from ingestion, inhalation, and dermal absorption [17,18].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [17] Guo, 2013, A survey of phthalates and parabens in personal care products from the United States and its implications for human exposure, Environ. Sci. Technol. source
    • cites [18] Guo, 2014, Phthalates and parabens in personal care products from China: Concentrations and human exposure, Arch. Environ. Contam. Toxicol. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Phthalates are synthetic organic chemicals used in industries as solvents, plasticizers, and additives in polyvinyl chloride plastics or personal care products.

    “Phthalates are diesters of phthalic acid (1,2-benzenedicarboxylic acid) and are synthetic organic chemicals used in industries as solvents, plasticizers, and additives in polyvinyl chloride (PVC) plastics or personal care products (PCPs) [1].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Latini, 2005, Monitoring phthalate exposure in humans, Clin. Chim. Acta source

  • The quote only partly states this claim.

    Premisenone given

    Human epidemiological studies have shown a significant association between phthalate exposures and overweight/obesity.

    “overweight/obesity”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Some phthalates, such as DEHP, undergo secondary metabolism, including oxidative transformation, prior to urinary excretion.

    “some phthalates, such as di-2-ethylhexyl phthalate (DEHP), undergo secondary metabolism, including oxidative transformation, prior to urinary excretion.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    The occurrence of phthalates and their metabolites in urine, serum, breast milk, and semen has been widely reported.

    “The occurrence of phthalates and their metabolites in urine, serum, breast milk, and semen has been widely reported.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Although current exposure doses in the general population are below the tolerance limits reported by environmental agencies, certain population groups, especially children, are exposed to high levels of phthalates.

    “Although current exposure doses in the general population are below the tolerance limits reported by environmental agencies, certainly population groups, especially children, are exposed to high levels of phthalates.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    MBP was found in >93% of amniotic fluid samples collected from the US at concentrations two- to threefold lower than those of serum and four- to sevenfold lower than those of urine.

    “MBP was found in >93% of amniotic fluid samples collected from the US [59] at concentrations two- to threefold lower than those of serum and four- to sevenfold lower than those of urine [59].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [59] Silva, 2004, Detection of phthalate metabolites in human amniotic fluid, Bull. Environ. Contam. Toxicol. source

  • May combine two claims.

    Interpretationreasoning

    Because phthalates have a short half-life in human bodies and are excreted quickly in urine as monoester metabolites, the metabolites are suitable biomarkers for human exposure to parent compounds.

    “Because phthalates have a short half-life in human bodies and are excreted quickly in urine as monoester metabolites, the metabolites are suitable biomarkers for human exposure to parent compounds.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Salivary concentrations of phthalate metabolites in 39 adult volunteers were in the ranges of <1 to 10.6 μg/L for PA, 91.4 μg/L for MEP, 65.8 μg/L for MBP, and 354 μg/L for MBzP.

    “Salivary concentrations of phthalate metabolites in 39 adult volunteers were in the ranges of <1 to 10.6 µg/L for PA, 91.4 µg/L for MEP, 65.8 µg/L for MBP, and 354 µg/L for MBzP.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] Silva, 2005, Detection of phthalate metabolites in human saliva, Arch. Toxicol. source

  • May combine two claims.

    Premisecitation

    The oxidative metabolites MEOHP, MEHHP, MECPP, and MCMHP are the major metabolites of DEHP and are appropriate biomarkers of exposure to DEHP.

    “The oxidative metabolites, MEOHP, MEHHP, MECPP, and MCMHP, however, are the major metabolites of DEHP and are appropriate biomarkers of exposure to this compound [21].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Silva, 2007, Quantification of 22 phthalate metabolites in human urine, J. Chromatogr. B Anal. Technol. Biomed. Life Sci. source

  • May combine two claims.

    Premisecitation

    Reported concentrations of phthalates in breast milk were much lower than those in urine but similar to those in amniotic fluid.

    “Studies have reported the occurrence of phthalates in breast milk [158]; the reported concentrations in breast milk were much lower than those in urine but similar to those in amniotic fluid.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [158] Kim, 2015, Concentrations of phthalate metabolites in breast milk in Korea: Estimating exposure to phthalates and potential risks among breast-fed infants, Sci. Total Environ. source

  • May combine two claims.

    Premisecitation

    Children are prone to exposure to DEHP, BzBP, DBP, and DEP and that exposure was associated with allergic rhinitis, atopic dermatitis, and conjunctivitis.

    “Studies indicated that children are prone to exposure to DEHP, BzBP, DBP, and DEP and that exposure was associated with allergic rhinitis, atopic dermatitis, and conjunctivitis [202].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [202] Shibata, 2014, Exposure to house dust phthalates in relation to asthma and allergies in both children and adults, Sci. Total Environ.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Exposure to phthalates has been linked to sex anomalies, endometriosis, altered reproductive development, early puberty and fertility, breast and skin cancer, allergy and asthma, overweight and obesity, insulin resistance, and type II diabetes.

    “As a class of well-studied endocrine disrupting chemicals, exposure to phthalates has been linked to sex anomalies, endometriosis, altered reproductive development, early puberty and fertility, breast and skin cancer, allergy and asthma, overweight and obesity, insulin resistance, and type II diabetes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Exposure to MEP, MiBP, and MBP pose an increased risk of pregnancy loss in Chinese women.

    “Exposure to MEP, MiBP, and MBP pose an increased risk of pregnancy loss in Chinese women.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based). May combine two claims.

    Interpretationnone given

    Although studies have reported the occurrence of phthalate metabolites in other human specimens, including serum, seminal plasma, and amniotic fluid, the relevance of these matrices in understanding toxic effects needs further investigation.

    “Although studies have reported the occurrence of phthalate metabolites in other human specimens, including serum, seminal plasma, and amniotic fluid, the relevance of these matrices in understanding toxic effects needs further investigation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    Biomonitoring studies clearly demonstrate that human exposures are almost ubiquitous, and, in most cases, children have higher exposures than do adults.

    “Biomonitoring studies clearly demonstrate that human exposures are almost ubiquitous, and, in most cases, children have higher exposures than do adults.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    There is a lack of biomonitoring data on phthalate exposures in developing countries in Africa and South America.

    “There is a lack of biomonitoring data on phthalate exposures in developing countries in Africa and South America.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Several other intermediate and transformation products of phthalates appear to exist in human specimens.

    “Although biomonitoring studies select major biomarkers/metabolites of phthalates, several other intermediate and transformation products of phthalates appear to exist in human specimens.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationnone given

    These intermediates may have more pronounced effects on health.

    “These intermediates may have more pronounced effects on health.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Establishing the link between exposure to a single substance class and adverse health outcomes is fraught with uncertainties because humans are exposed to thousands of harmful chemicals.

    “Because humans are exposed to thousands of harmful chemicals, establishing the link between exposure to a single substance class and adverse health outcomes is fraught with uncertainties.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Humans are exposed to thousands of harmful chemicals.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Robust analytical methods exist to measure more than 20 phthalate metabolites in urine, a preferred matrix of choice for biomonitoring studies.

    “Robust analytical methods exist to measure more than 20 phthalate metabolites in urine, a preferred matrix of choice for biomonitoring studies.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Urine is a preferred matrix of choice for biomonitoring studies.
42 of 42

  • The paper relies on this without support.

    Food intake is the main source of phthalate exposure for high molecular weight phthalates.

    “Food intake is the main source of phthalate exposure (for high molecular weight phthalates).”

  • The paper relies on this without support.

    Humans are exposed to thousands of harmful chemicals.

    “Because humans are exposed to thousands of harmful chemicals”

  • The paper relies on this without support.

    Biomonitoring studies of human phthalate exposure have been based on urinary concentrations of phthalate metabolites.

    “The biomonitoring studies of human phthalate exposure have been based on urinary concentrations of phthalate metabolites.”

  • The paper relies on this without support.

    Urine is a preferred matrix of choice for biomonitoring studies.

    “a preferred matrix of choice for biomonitoring studies”
4 of 4

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Maternal-to-newborn MEOHP ratio is outside the stated range

    Minor

    The maternal MEOHP concentration of 14.7 μg/L is about 4.50 times the newborn concentration of 3.27 μg/L, not two- to threefold higher.

    Reported 3 · recomputed 4.495413

  • Gynecomastia measurements are called urinary despite a plasma-study citation

    Minor

    The text attributes DEHP and MEHP concentrations in boys with gynecomastia to urine, while the cited study is titled as a measurement of plasma phthalate levels.

  • Serum metabolites are described as both undetectable and detected

    Minor

    The paper says metabolites in the study's serum samples were below detection limits, but later reports detected serum metabolites with median concentrations from the same cited study.

  • Two different medians are given for the same Bavarian metabolites

    Minor

    The adjoining statements cite the same study but give different median concentrations for both MEHHP and MEOHP, without identifying a different population or measurement basis.

4 of 4

Cites

Flagged first, then by citations

5 of the 212 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Sapozhnikova, 2019, Suspect screening of chemicals in food packaging film by comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry, LCGC N. Am., 37, 52

Cited by

Sorted by citations

Related

Authors
Wang, Y., Zhu, H., & Kannan, K.
Affiliations
New York State Department of Health (US)
Corresponding author
Kannan, Kurunthachalam
ORCID
Venue
Toxics
Publisher
MDPI AG
Published
2019-04-05
Volume
7
Issue
2
Pages
21
ISSN
2305-6304 (ISSN-L)
DOI
10.3390/toxics7020021
PMC
PMC6630674
OpenAlex
W2929721361
Semantic Scholar
cf9640de1512facd0df673c4f5e85b1fad74f893
Cited by
755
References
212
Citations by year
2026: 74 · 2025: 101 · 2024: 156 · 2023: 120 · 2022: 122 · 2021: 115 · 2020: 62 · 2019: 3 · 2018: 1
FWCI
29.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Toxics (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
Keywords
phthalates, human biomonitoring, urinary phthalate metabolites, DEHP, dibutyl phthalate, diisobutyl phthalate, endocrine disruption, reproductive toxicity, exposure trends, children's exposure, type 2 diabetes, insulin resistance, obesity, asthma, allergy, plasticizers

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-12.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-12.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review