Variability and predictors of urinary concentrations of phthalate metabolites during early childhood

Deborah J Watkins, Melissa Eliot, Sheela Sathyanarayana, Antonia M Calafat, Kimberly Yolton, Bruce P Lanphear, Joseph M Braun, Deborah J Watkins, Melissa Eliot, Sheela Sathyanarayana, Antonia M Calafat, Kimberly Yolton, Bruce P Lanphear, Joseph M Braun

Abstract

The variability and predictors of urinary concentrations of phthalate metabolites in preschool-aged children have not been thoroughly examined. Additionally, the impact of temporal changes in the use and restriction of phthalates in children's products has not been assessed. Our objective was to identify demographic, behavioral, and temporal predictors of urinary phthalate metabolite concentrations in young children. Between 2004 and 2011, we collected up to five urine samples from each of 296 children participating in a prospective birth cohort during annual study visits at ages 1-5 years. We used linear mixed models to calculate intraclass correlation coefficients (ICCs), a measure of within-individual reproducibility, and identify demographic predictors of urinary phthalate metabolites. We used multivariable linear regression to examine cross-sectional relationships between food packaging or personal care product use and phthalate metabolites measured at age 5 years. Across annual measurements, monoethyl phthalate exhibited the least variation (ICC = 0.38), while di-2-ethylhexyl phthalate (ΣDEHP) metabolites exhibited the most variation (ICC = 0.09). Concentrations changed with age, suggesting age-related changes in phthalate exposure and perhaps metabolism. Our findings suggest that fast food consumption may be a source of butylbenzyl phthalate and di-isononyl phthalate (DiNP) exposure, and some personal care products may be sources of diethyl phthalate exposure. Concentrations of ΣDEHP metabolites decreased over the study period; however, concentrations of DiNP metabolites increased. This finding suggests that manufacturer practices and regulations, like the Consumer Product Safety Improvement Act of 2008, may decrease DEHP exposure, but additional work characterizing the nature and toxicity of replacements is critically needed.

Figures

Figure 1
Figure 1
Unadjusted urinary phthalate metabolite concentrations in HOME Study children (μg/L). Diamond indicates arithmetic mean, whiskers indicate minimum and maximum, edges of box indicate 25th and 75th percentile, and middle line indicates median. One year n = 277, 2 year n = 232, 3 year n = 234, 4 year n = 170, 5 year n = 201 (All subjects with at least 1 phthalate measurement).
Figure 2
Figure 2
Geometric mean concentrations and smoothed regression of urinary ∑DEHP metabolites and MCOP between 1 and 5 years of age among those born between 2003 and 2004 or 2005–2006. ∑DEHP = sum of MEHP, MEHHP, MEOHP, and MECPP. Children born in 2003–2004 provided urine samples before the CPSIA went into effect, while children born in 2005–2006 provided their 3, 4, and 5 year urine samples after the CPSIA went into effect.

References

    1. Silva M. J.; Barr D. B.; Reidy J. A.; Malek N. A.; Hodge C. C.; Caudill S. P.; Brock J. W.; Needham L. L.; Calafat A. M. Urinary levels of seven phthalate metabolites in the US population from the National Health and Nutrition Examination Survey (NHANES) 1999–2000. Environ. Health Perspect. 2004, 1123331–338.
    1. Teitelbaum S. L.; Britton J. A.; Calafat A. M.; Ye X.; Silva M. J.; Reidy J. A.; Galvez M. P.; Brenner B. L.; Wolff M. S. Temporal variability in urinary concentrations of phthalate metabolites, phytoestrogens and phenols among minority children in the United States. Environ. Res. 2008, 1062257–269.
    1. Koniecki D.; Wang R.; Moody R. P.; Zhu J. P. Phthalates in cosmetic and personal care products: Concentrations and possible dermal exposure. Environ. Res. 2011, 1113329–336.
    1. Koo H. J.; Lee B. M. Estimated exposure to phthalates in cosmetics and risk assessment. J. Toxicol. Environ. Health, Part A 2004, 6723–241901–1914.
    1. Kelley K. E.; Hernandez-Diaz S.; Chaplin E. L.; Hauser R.; Mitchell A. A. Identification of phthalates in medications and dietary supplement formulations in the United States and Canada. Environ. Health Perspect 2012, 1203379–84.
    1. Hauser R.; Calafat A. M. Phthalates and human health. J. Occup. Environ. Med. 2005, 6211806–18.
    1. Braun J. M.; Sathyanarayana S.; Hauser R. Phthalate exposure and children’s health. Curr. Opin. Pediatr. 2013, 252247–54.
    1. Buckley J. P.; Palmieri R. T.; Matuszewski J. M.; Herring A. H.; Baird D. D.; Hartmann K. E.; Hoppin J. A. Consumer product exposures associated with urinary phthalate levels in pregnant women. J. Exposure Sci. Environ. Epidemiol. 2012, 225468–475.
    1. Sathyanarayana S.; Karr C. J.; Lozano P.; Brown E.; Calafat A. M.; Liu F.; Swan S. H. Baby care products: Possible sources of infant phthalate exposure. Pediatrics 2008, 1212E260–E268.
    1. Rudel R. A.; Gray J. M.; Engel C. L.; Rawsthorne T. W.; Dodson R. E.; Ackerman J. M.; Rizzo J.; Nudelman J. L.; Brody J. G. Food packaging and bisphenol A and bis(2-Ethyhexyl) phthalate exposure: Findings from a dietary intervention. Environ. Health Perspect. 2011, 1197914–920.
    1. Carlstedt F.; Jonsson B. A. G.; Bornehag C. G. PVC flooring is related to human uptake of phthalates in infants. Indoor Air 2013, 23132–39.
    1. Lewis R. C.; Meeker J. D.; Peterson K. E.; Lee J. M.; Pace G. G.; Cantoral A.; Tellez-Rojo M. M. Predictors of urinary bisphenol A and phthalate metabolite concentrations in Mexican children. Chemosphere 2013, 93, 2390–2398.
    1. Teitelbaum S. L.; Mervish N.; Moshier E. L.; Vangeepuram N.; Galvez M. P.; Calafat A. M.; Silva M. J.; Brenner B. L.; Wolff M. S. Associations between phthalate metabolite urinary concentrations and body size measures in New York City children. Environ. Res. 2012, 112, 186–193.
    1. Whyatt R. M.; Liu X. H.; Rauh V. A.; Calafat A. M.; Just A. C.; Hoepner L.; Diaz D.; Quinn J.; Adibi J.; Perera F. P.; Factor-Litvak P. Maternal prenatal urinary phthalate metabolite concentrations and child mental, psychomotor, and behavioral development at 3 years of age. Environ. Health Perspect. 2012, 1202290–295.
    1. Kim Y.; Ha E. H.; Kim E. J.; Park H.; Ha M.; Kim J. H.; Hong Y. C.; Chang N.; Kim B. N. Prenatal exposure to phthalates and infant development at 6 months: Prospective mothers and children’s environmental health (MOCEH) study. Environ. Health Perspect. 2011, 119101495–1500.
    1. Engel S. M.; Miodovnik A.; Canfield R. L.; Zhu C. B.; Silva M. J.; Calafat A. M.; Wolff M. S. Prenatal phthalate exposure is associated with childhood behavior and executive functioning. Environ. Health Perspect. 2010, 1184565–571.
    1. Bornehag C. G.; Sundell J.; Weschler C. J.; Sigsgaard T.; Lundgren B.; Hasselgren M.; Hagerhed-Engman L. The association between asthma and allergic symptoms in children and phthalates in house dust: A nested case-control study. Environ. Health Perspect 2004, 112141393–7.
    1. Braun J. M.; Smith K. W.; Williams P. L.; Calafat A. M.; Berry K.; Ehrlich S.; Hauser R. Variability of urinary phthalate metabolite and bisphenol A Concentrations before and during Pregnancy. Environ. Health Perspect. 2012, 1205739–745.
    1. Meeker J. D.; Calafat A. M.; Hauser R. Urinary phthalate metabolites and their biotransformation products: Predictors and temporal variability among men and women. J. Exposure Sci. Environ. Epidemiol. 2012, 224376–385.
    1. Cantonwine D. E.; Cordero J. F.; Rivera-Gonzalez L. O.; Anzalota Del Toro L. V.; Ferguson K. K.; Mukherjee B.; Calafat A. M.; Crespo N.; Jimenez-Velez B.; Padilla I. Y.; Alshawabkeh A. N.; Meeker J. D. Urinary phthalate metabolite concentrations among pregnant women in Northern Puerto Rico: Distribution, temporal variability, and predictors. Environ. Int. 2013, 62C, 1–11.
    1. Kubwabo C.; Rasmussen P. E.; Fan X.; Kosarac I.; Wu F.; Zidek A.; Kuchta S. L. Analysis of selected phthalates in Canadian indoor dust collected using household vacuum and standardized sampling techniques. Indoor Air 2013, 23, 506–514.
    1. CPSIA The Consumer Product Safety Improvement Act of 2008–Phthalates. (accessed June 14).
    1. Zota A. R.; Calafat A. M.; Woodruff T. J. Temporal trends in phthalate exposures: Findings from the national health and nutrition examination survey, 2001–2010. Environ. Health Perspect 2014, 1223235–41.
    1. Koch H. M.; Wittassek M.; Bruning T.; Angerer J.; Heudorf U. Exposure to phthalates in 5–6 years old primary school starters in Germany–A human biomonitoring study and a cumulative risk assessment. Int. J. Hyg. Environ. Health 2011, 2143188–95.
    1. Geraghty S. R.; Khoury J. C.; Morrow A. L.; Lanphear B. P. Reporting individual test results of environmental chemicals in breastmilk: Potential for premature weaning. Breastfeed Med. 2008, 34207–U12.
    1. Silva M. J.; Samandar E.; Preau J. L.; Reidy J. A.; Needham L. L.; Calafat A. M. Quantification of 22 phthalate metabolites in human urine. J. Chromatogr. B: Anal. Technol. Biomed. Life Sci. 2007, 8601106–112.
    1. Mage D. T.; Allen R. H.; Kodali A. Creatinine corrections for estimating children’s and adult’s pesticide intake doses in equilibrium with urinary pesticide and creatinine concentrations. J. Exposure Sci. Environ. Epidemiol. 2008, 184360–8.
    1. Bradley E. L.; Burden R. A.; Leon I.; Mortimer D. N.; Speck D. R.; Castle L. Determination of phthalate diesters in foods. Food Addit. Contam., Part A 2013, 304722–34.
    1. Koch H. M.; Lorber M.; Christensen K. L.; Palmke C.; Koslitz S.; Bruning T. Identifying sources of phthalate exposure with human biomonitoring: Results of a 48h fasting study with urine collection and personal activity patterns. Int. J. Hyg Environ. Health 2013, 2166672–81.
    1. Koniecki D.; Wang R.; Moody R. P.; Zhu J. Phthalates in cosmetic and personal care products: Concentrations and possible dermal exposure. Environ. Res. 2011, 1113329–36.
    1. Koch H. M.; Angerer J. Di-iso-nonylphthalate (DINP) metabolites in human urine after a single oral dose of deuterium-labelled DINP. Int. J. Hyg. Environ. Health 2007, 21019–19.
    1. Koch H. M.; Preuss R.; Angerer J. Di(2-ethylhexyl)phthalate (DEHP): Human metabolism and internal exposure–An update and latest results. Int. J. Androl. 2006, 291155–65discussion 181–5.
    1. Frederiksen H.; Kranich S. K.; Jorgensen N.; Taboureau O.; Petersen J. H.; Andersson A. M. Temporal variability in urinary phthalate metabolite excretion based on spot, morning, and 24-h urine samples: Considerations for epidemiological studies. Environ. Sci. Technol. 2013, 472958–967.
    1. Evaluation of New Scientific Evidence Concerning DiNP and DiDP in Relation to Entry 52 of Annex XVII to Regulation (EC) No 1907/2006 (REACH); European Chemicals Agency, 2012
    1. Langer S.; Beko G.; Weschler C. J.; Brive L. M.; Toftum J.; Callesen M.; Clausen G. Phthalate metabolites in urine samples from Danish children and correlations with phthalates in dust samples from their homes and daycare centers. Int. J. Hyg. Environ. Health 2013, 217, 78–87.
    1. Trasande L.; Attina T. M.; Sathyanarayana S.; Spanier A. J.; Blustein J. Race/ethnicity-specific associations of urinary phthalates with childhood body mass in a nationally representative sample. Environ. Health Perspect. 2013, 1214501–6.
    1. Cirillo T.; Fasano E.; Esposito F.; Del Prete E.; Cocchieri R. A. Study on the influence of temperature, storage time and packaging type on di-n-butylphthalate and di(2-ethylhexyl)phthalate release into packed meals. Food Addit. Contam., Part A 2013, 302403–11.
    1. Beko G.; Weschler C. J.; Langer S.; Callesen M.; Toftum J.; Clausen G. Children’s phthalate intakes and resultant cumulative exposures estimated from urine compared with estimates from dust ingestion, inhalation and dermal absorption in their homes and daycare centers. PloS one 2013, 84e62442.

Source: PubMed

3
Abonnieren