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Estimating pesticide dose from urinary pesticide concentration data by creatinine correction in the Third National Health and Nutrition Examination Survey (NHANES-III)

Abstract

The Third National Health and Nutrition Examination Survey (NHANES-III) of the Centers for Disease Control and Prevention (CDC) recorded data on the urinary concentrations of 12 chemicals (analytes), which were either pesticides or their metabolites, that represent exposure to certain pesticides, in urine samples collected from 1988 to 1994 from a cohort of 978 volunteer subjects, aged 20–59 years. We have used each subject's urinary creatinine concentration and their individual daily creatinine excretion rate (g/day) computed from their age, gender, height and weight, to estimate their daily excretion rate in μg analyte/kg/day. We discuss the mechanisms of excretion of the analytes and certain assumptions needed to compute the equivalent daily dietary intake (μg/kg/day) of the most likely parent pesticide compounds for each excreted analyte. We used literature data on the average amount of parent compound ingested per unit amount of the analyte excreted in the urine, and compared these estimated daily intakes to the US EPA's reference dose (RfD) values for each of those parent pesticides. A Johnson SB distribution (four-parameter lognormal) was fit to these data to estimate the national distribution of exclusive exposures to these 12 parent compounds. Only three such pesticides had a few predicted values above their RfD (lindane 1.6%; 2,4-dichlorophenol 1.3%; chlorpyrifos 0.02%). Given the possibility of a subject's dietary intake of a pesticide's metabolites incorporated into treated food, our results show that few, if any, individuals in the general US population aged 20–59 years and not employed in pesticide application were likely to have exceeded the USEPA RfD for these parent compounds during the years studied.

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Notes

  1. where 1.93=(1440 min/day)(1000 μg/mg)/(72 year-kg/[mg/dl-ml/min-1.73 m2])(3600 cm-kg/m4)0.5 (1.73 m2)(100 ml/dl)

Abbreviations

1NAP:

1-naphthol

2NAP:

2-naphthol

24D:

2,4-dichlorophenoxyacetic acid

24DB:

2,4-dichlorophenoxybutyric acid

24DCP:

2,4-dichlorophenol

245TCP:

2,4,5-trichlorophenol

246TCP:

2,4,6-trichlorophenol

25DCP:

2,5-dichlorophenol

4NP:

4-nitrophenol

BSA:

body surface area

CDC:

Centers for disease control and prevention

CFP:

carbofuranphenol

Cn:

creatinine

CnCl:

creatinine clearance

EPN:

O-ethyl O-p-nitrophenyl phenylphosphonothioate

IPP:

2-isopropoxyphenol

MDL:

minimum detectable level

MLE:

method of maximum likelihood estimation

NCEH:

National Center for Environmental Health

NCHS:

National Center for Health Statistics

NHANES-III:

The Third National Health and Nutrition Examination Survey

PCP:

pentachlorophenol

RfD:

reference dose

TCPY:

3,5,6-trichloro-2-pyridinol

Tm:

transport maximum

USDHHS:

US Department of Health and Human Services

US EPA:

US Environmental Protection Agency

References

  • Adgate J.L., Barr D.B., Clayton C.A., Eberly L.E., Freeman N.C., Lioy P.J., Needham L.L., Pellissari E.D., Quackenboss J.J., Roy A., and Sexton K. Measurement of children's exposure to pesticides: analysis of urinary metabolite levels in a probability-based sample. Environ Health Perspect 2001: 109: 583–590.

    Article  CAS  Google Scholar 

  • Alessio L., Berlin A., Dell'Orto A., Toffoletto F., and Ghezzi I. Reliability of urinary creatinine as a parameter to adjust values of urinary biological indicators. Int Arch Occup Environ Health 1985: 55: 99–106.

    Article  CAS  Google Scholar 

  • Araki S. Effects of urinary volume on urinary concentration of lead, aminolaevulinic acid, coproporphyrin, creatinine, and total solutes. Br J Ind Med 1980: 62: 471–477.

    Google Scholar 

  • Bennett S., and Wilkins H.A. Within-person variation in urinary sodium, potassium and creatinine concentrations, and their relationship to changes in the blood pressure. J Trop Med Hyg 1993: 96: 267–273.

    CAS  PubMed  Google Scholar 

  • Berkhin E.B., and Humphreys M.H. Regulation of renal tubular secretion of organic compounds. Kidney Int 2001: 59: 17–30.

    Article  CAS  Google Scholar 

  • Bingham S.A., and Cummings J.H. The use of creatinine output as a check on the completeness of 24-hour urine collections. Hum Nutr Clin Nutr 1985: 39: 343–353.

    CAS  PubMed  Google Scholar 

  • Buck R.J., Özkaynak H., Xue J., Zartarian V.G., and Hammerstrom K. Modeled estimates of chlorpyrifos exposure and dose for the Minnesota and Arizona NHEXAS populations. J Expos Anal Environ Epidemiol 2001: 11: 253–268.

    Article  CAS  Google Scholar 

  • Cho M.M., and Yi M.M. Variability of daily creatinine excretion in healthy adults. Hum Nutr Clin Nutr 1986: 40: 469–472.

    CAS  PubMed  Google Scholar 

  • Cockcroft D.W., and Gault M.H. Prediction of creatinine clearance from serum creatinine. Nephron 1976: 16: 31–41.

    Article  CAS  Google Scholar 

  • Dell'Orto A., Berlin A., Toffoletto F., Losito B., and Alessio L. Creatinine and specific gravity adjustment of ALA in urinary spot samples: is there any need? Am Ind Hyg Assoc J 1987: 48: A331–A332.

    CAS  PubMed  Google Scholar 

  • Greenblatt D.J., Ransil B.J., Harmatz J.S., Smith T.W., Duhme D.W., and Koch-Weser J. Variability of 24-hour urinary creatinine excretion by normal subjects. J Clin Pharmacol 1976: 16: 321–328.

    Article  CAS  Google Scholar 

  • Hill Jr R.H., Shealy D.B., Head S.L., Williams C.C., Bailey S.L., Gregg M., and Needham. L.L. Pesticide residues in urine of adults living in the United States: reference range concentrations. Environ Res 1995: 71: 99–108.

    Article  CAS  Google Scholar 

  • Johnson N.L. Systems of frequency curves generated by methods of translation. Biometrika 1949: 36: 149–172.

    Article  CAS  Google Scholar 

  • Mage D.T. An explicit solution for SB parameters using four percentile points. Technometrics 1980: 22: 247–251.

    Google Scholar 

  • Mosteller R.D. Simplified calculation of body surface area. New Engl J Med 1987: 317: 1098 (letter).

    CAS  PubMed  Google Scholar 

  • Neithardt A.B., Dooley S.L., and Borensztajn J. Prediction of 24-hour protein excretion in pregnancy with a single voided urine protein-to-creatinine ratio. Am J Obst Gyn 2002: 186: 883–886.

    Article  CAS  Google Scholar 

  • Nolan R.J., Rick D.L., Freshour N.L., and Saunders J.H. Chlorpyrifos: pharmacokinetics in human volunteers. Toxicol Appl Pharm. 1984: 73: 8–15.

    Article  CAS  Google Scholar 

  • Radha E., and Bessman S.P. Effect of exercise on protein degradation: 3-methylhistidine and creatinine excretion. Biochem Med 1983: 29: 96–100.

    Article  CAS  Google Scholar 

  • Sata F., Araki S., Yokoyama K., and Murata K. Adjustment of creatinine-adjusted values in urine to urinary flow rate: a study of eleven heavy metals and organic substances. Int Arch Occup Environ Health 1995: 68: 64–68.

    Article  CAS  Google Scholar 

  • Schwartz G.J., Brion L.P., and Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children and adolescents. Pediatr Clin North Am 1987: 34: 571–590.

    Article  CAS  Google Scholar 

  • Shull B.C., Haughey D., Koup J.R., Baliah T., and Li P.K. A useful method for predicting creatinine clearance in children. Clin Chem 1978: 24: 1167–1169.

    CAS  PubMed  Google Scholar 

  • Trevisan A. Concentration adjustment of spot samples in analysis of urinary xenobiotic metabolites. Am J Ind Med 1990: 17: 637–642.

    Article  CAS  Google Scholar 

  • US Department of Health and Human Services (DHHS). National Center for Health Statistics. Third National Health and Nutrition Examination Survey, 1988–1994, NHANES III Priority Toxicant Reference Range Study Data File (3.5 Diskette, Series 11, No. 4A), Centers for Disease Control and Prevention, Hyattsville, MD, 1999.

  • USEPA. Ambient Water Quality Criteria Document: Chlorinated Phenols p. A-7 EPA 440/5-80-032, Washington, DC, 1980.

  • Vij H.S., and Howell S. Improving the specific gravity adjustment method for assessing urinary concentrations of toxic substances. Am Ind Hyg Assoc J 1998: 59: 375–380.

    Article  CAS  Google Scholar 

  • Waterlow J.C. Observations on the variability of creatinine excretion. Hum Nutr Clin Nutr 1986: 40: 125–129.

    CAS  PubMed  Google Scholar 

  • Wilson N.K., Chuang J.C., Lyu C., Menton R., and Morgan M.K. Aggregate exposures of nine preschool children to persistent organic pollutants at day care and at home. J Expos Anal Environ Epidemiol 2003: 13: 187–202.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported under USEPA Contract 401893671 - DAI to Temple University. Jennifer Weil, MD, of Temple University and David J. Miller, Carol Christensen and Peter Egeghy of US EPA provided technical review. The views expressed are those of the authors, and they do not represent US EPA policy.

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Correspondence to David T Mage.

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Mage, D., Allen, R., Gondy, G. et al. Estimating pesticide dose from urinary pesticide concentration data by creatinine correction in the Third National Health and Nutrition Examination Survey (NHANES-III). J Expo Sci Environ Epidemiol 14, 457–465 (2004). https://doi.org/10.1038/sj.jea.7500343

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