Skip to main content
NCBI home page
EFSA Journal logoLink to EFSA Journal
. 2014 Oct 17;12(10):3869. doi: 10.2903/j.efsa.2014.3869

Scientific Opinion on the risks to public health related to the presence of perchlorate in food, in particular fruits and vegetables

EFSA Panel on Contaminants in the Food Chain (CONTAM)
PMCID: PMC13136994  PMID: 42087945

Abstract

The European Food Safety Authority (EFSA) received a request from the European Commission for a scientific opinion on perchlorate in food, in particular fruits and vegetables. Perchlorate is a contaminant released into the environment from both natural and anthropogenic sources. The use of natural fertilisers and perchlorate contaminated irrigation water may lead to substantial concentrations in leafy vegetables. Water disinfection with chlorinated substances that potentially degrade to perchlorate could be another potential source of contamination. EFSA received analytical results for 11 675 samples submitted by eight Member States, mainly for fruits, vegetables, and fruit and vegetable products. The EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) performed estimates of both chronic and ‘short‐term’ exposure considering the available dataset, and data from the literature on the levels of perchlorate in fruit juices, alcoholic beverages, milk, infant formulae and breast milk. The CONTAM Panel established a tolerable daily intake of 0.3 µg/kg body weight per day, based on the inhibition of thyroid iodine uptake in healthy adults. Amongst the vulnerable subpopulations, potential acute effects of perchlorate have been suggested for fetuses and infants. The CONTAM Panel noted that a single acute exposure to perchlorate at levels found in food and water is unlikely to cause adverse effects on human health, including the more vulnerable groups of the population, and concluded that the establishment of an acute reference dose for perchlorate is not warranted. Overall, the CONTAM Panel concluded that the chronic dietary exposure to perchlorate is of potential concern, in particular for the high consumers in the younger age groups of the population with mild to moderate iodine deficiency. Furthermore, it is possible that exposure to perchlorate is of concern for infants breast‐fed by iodine‐deficient mothers.

Keywords: perchlorate, human dietary exposure, toxicity, risk assessment, benchmark dose (BMD), tolerable daily intake (TDI)

EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain) , 2014. Scientific Opinion on the risks to public health related to the presence of perchlorate in food, in particular fruits and vegetables. EFSA Journal 2014;12(10):3869, 117 pp. doi: 10.2903/j.efsa.2014.3869

Panel members: Diane Benford, Sandra Ceccatelli, Bruce Cottrill, Michael DiNovi, Eugenia Dogliotti, Lutz Edler, Peter Farmer, Peter Fürst, Laurentius (Ron) Hoogenboom, Helle Katrine Knutsen, Anne‐Katrine Lundebye, Manfred Metzler, Antonio Mutti (as of 6 October 2014), Carlo Stefano Nebbia, Michael O'Keeffe, Annette Petersen (as of 6 October 2014), Ivonne Rietjens (until 2 May 2014), Dieter Schrenk, Vittorio Silano (until 21 July 2014), Hendrik van Loveren, Christiane Vleminckx, and Pieter Wester.

Correspondence: contam@efsa.europa.eu

Acknowledgement: The Panel wishes to thank the members of the Working Group on perchlorate in food: Diane Benford, Michael DiNovi, Andrew Hart, Helle Knutsen, Peter Laurberg, Ivonne Rietjens (until 2 May 2014) and Christiane Vleminckx for the preparatory work on this scientific opinion and EFSA staff: Davide Arcella, Katleen Baert, Bistra Benkova, Marco Binaglia, Mari Eskola and Karen Mackay for the support provided to this scientific opinion. The Panel also wishes to thank the members of the Working Group on perchlorate in food_correcting opinion: Michael DiNovi, Peter Fürst, Helle Knutsen, and Christiane Vleminckx for preparation of the corrected version of this scientific opinion. The CONTAM Panel acknowledges all European competent institutions that provided occurrence data on perchlorate in food, and supported the data collection for the Comprehensive European Food Consumption Database. The Panel also acknowledges all other organisations that provided additional occurrence data on perchlorate in food.

Adoption date: 30 September 2014

Published date: 17 October 2014

Correction/Erratum: In the version published on 4 December 2014, corrections were made to the summary, main body of the text and conclusions on the occurrence levels for ‘leafy vegetables’, and the median chronic exposure levels in Table 6. In the version published on 26 May 2015, amendments were made to the abstract, summary, introduction, exposure assessment, risk characterisation, uncertainty analysis, conclusions, recommendations and appendices in order to correct an error in the original occurrence data and to include more recent occurrence data. Further details are available on page 11. The previous versions of the scientific opinion have been removed from the website, but are available on request as are versions showing all the changes made.

Question number: EFSA‐Q‐2015‐00107

On request from: European Commission

References

  1. Aghini‐Lombardi F, Antonangeli L, Martino E, Vitti P, Maccherini D, Leoli F, Rago T, Grasso L, Valeriano R, Balestrieri A and Pinchera A, 1999. The spectrum of thyroid disorders in an iodine‐deficient community: the Pescopagano survey. Journal of Clinical Endocrinology and Metabolism, 84, 561–566. [DOI] [PubMed] [Google Scholar]
  2. Alexander EK, Marqusee E, Lawrence J, Jarolim P, Fischer GA and Larsen PR, 2004. Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism. New England Journal of Medicine, 351, 241–249. [DOI] [PubMed] [Google Scholar]
  3. Amitai Y, Winston G, Sack J, Wasser J, Lewis M, Blount BC, Valentin‐Blasini L, Fisher N, Israeli A and Leventhal A, 2007. Gestational exposure to high perchlorate concentrations in drinking water and neonatal thyroxine levels. Thyroid, 17, 843–850. [DOI] [PubMed] [Google Scholar]
  4. Anastassiades M, Kolberg DI, Mack D, Wildgrube C, Sigalova I, Roux D and Fugel D, 2012. Quick method for the analysis of residues of numerous high polar pesticides in foods of plant origin involving simultaneous extraction with methanol and LC‐MS/MS determination. EU reference laboratory for pesticides requiring single residue methods (EURL‐SRM), 1–43.
  5. Anbar M, Guttmann S and Lewitus Z, 1959. The mode of action of perchlorate ions on the iodine uptake of the thyroid gland. International Journal of Applied Radiation and Isotopes, 7, 87–96. [DOI] [PubMed] [Google Scholar]
  6. Andersen SL, Nøhr SB, Wu CS, Olsen J, Pedersen KM and Laurberg P, 2013. Thyroglobulin in smoking mothers and their newborns at delivery suggests autoregulation of placental iodine transport overcoming thiocyanate inhibition. European Journal of Endocrinology, 168, 723–731. [DOI] [PubMed] [Google Scholar]
  7. Andersson M, de Benoist B, Delange F and Zupan J, 2007. Prevention and control of iodide deficiency in pregnant and lactating women and in children less than 2‐years‐old: conclusions and recommendations of the Technical Consultation. Public Health Nutrition, 10, 1606–1611. [DOI] [PubMed] [Google Scholar]
  8. Andersson M, Karumbunathan V and Zimmermann MB, 2012. Global iodine status in 2011 and trends over the past decade. The Journal of Nutrition, 142, 744–750. [DOI] [PubMed] [Google Scholar]
  9. ANSES (l'Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail) , 2011. AVIS de l'Agence nationale de sécurité sanitaires lié à la présence d'ions perchlorate dans les eaux destinées à la consommation humaine. ANSES‐Request No.2011‐SA‐0024, 21 pp.
  10. ANSES (l'Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail) , 2012. AVIS de l'Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail relatif aux études épidémiologiques portant sur les associations entre une exposition aux ions perchlorate dans l'eau de boisson et la fonction thyroïdienne dans des populations spécifiques. Saisine 2012‐SA‐0119, 16 pp.
  11. ANSES (l'Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail) , 2013. AVIS de l'Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail relatif à « la contamination des denrées alimentaires par les ions perchlorate». Saisine n. 2013‐SA‐0120, 12 pp.
  12. ANSES (l'Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail) , 2014. Opinion of the French Agency for Food, Environmental and Occupational Health and Safety on the presence of perchlorate in infant formula and in drinking water in France. Request Nos. 2011‐SA‐0208 and 2011‐SA‐0336, 52 pp.
  13. ATSDR (Agency for Toxic Substances and Disease Registry) , 2008. Toxicological profile for perchlorates. Atlanta, GA, United States Department of Health and Human Services, Public Health Service. Available at: www.atsdr.cdc.gov/toxprofiles/tp.asp?id=895&tid=181. [PubMed] [Google Scholar]
  14. Bernal J and Pekonen F, 1984. Ontogenesis of the nuclear 3,5,3′‐triiodothyronine receptor in the human fetal brain. Endocrinology, 114, 677–679. [DOI] [PubMed] [Google Scholar]
  15. BfR (Federal Institute for Risk Assessment) , 2013a. BfR recommendations on how to perform the consumer risk assessment for perchlorate in food. BfR opinion No.015/2013, 6.6.2013, 6 pp.
  16. BfR (Federal Institute for Risk Assessment) , 2013b. EU proposal for maximum percholorate concentrations in foods is inadequate. Updated BfR Opinion No. 027/2013, 9.7.2013, 11 pp.
  17. Bianco AC, Salvatore D, Gereben B, Berry MJ and Larsen PR, 2002. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocrine Reviews, 23, 38–89. [DOI] [PubMed] [Google Scholar]
  18. Blount BC, Pirkle JL, Osterloh JD, Valentin‐Blasini L and Caldwell KL, 2006. Urinary perchlorate and thyroid hormone levels in adolescent and adult men and women living in the United States. Environmental Health Perspectives, 114, 1865–1871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Blount BC, Rich DQ, Valentin‐Blasini L, Lashley S, Ananth CV, Murphy E, Smulian JC, Spain BJ, Barr DB, Ledoux T, Hore P and Robson M, 2009. Perinatal exposure to perchlorate. thiocyanate, and nitrate in New Jersey mothers and newborns. Environmental Science & Technology, 43, 7543–7549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Bogazzi F, Bartalena L, Tomisti L, Dell'Unto E, Cosci C, Sardella C, Tanda ML, Lai A, Gasperi M, Aghini‐Lombardi F and Martino E, 2008. Potassium perchlorate only temporarily restores euthyroidism in patients with amiodarone‐induced hypothyroidism who continue amiodarone therapy. Journal of Endocrinological Investigation, 31, 515–519. [DOI] [PubMed] [Google Scholar]
  21. Boyages SC, 2000. The neuromuscular system and brain in hypothyroidism. In: Werner and Ingbar's the thyroid: A fundamental and clinical text. Eds Braverman LE and Utiger RD. Lippincott Williams & Wilkins, Philadelphia, USA, 803–810. [Google Scholar]
  22. Brabant G, Bergmann P, Kirsch CM, Köhrle J, Hesch RD and von zur Mühlen A, 1992. Early adaptation of thyrotropin and thyroglobulin secretion to experimentally decreased iodine supply in man. Metabolism, 41, 1093–1096. [DOI] [PubMed] [Google Scholar]
  23. Brauer VF, Below H, Kramer A, Führer D and Paschke R, 2006. The role of thiocyanate in the etiology of goiter in an industrial metropolitan area. European Journal of Endocrinology, 154, 229–235. [DOI] [PubMed] [Google Scholar]
  24. Brandhuber P, Clark S and Morley K, 2009. A review of perchlorate occurrence in public water systems. Journal of American Water Works Association, 101, 63–73. [Google Scholar]
  25. Brauer VF, Below H, Kramer A, Führer D and Paschke R, 2006. The role of thiocyanate in the etiology of goiter in an industrial metropolitan area. European Journal of Endocrinology, 154, 229–235. [DOI] [PubMed] [Google Scholar]
  26. Braverman LE, He X, Pino S, Cross M, Magnani B, Lamm SH, Kruse MB, Engel A, Crump KS and Gibbs JP, 2005. The Effect of Perchlorate, Thiocyanate, and Nitrate on Thyroid Function in Workers Exposed to Perchlorate Long‐Term. Journal of Clinical Endocrinology and Metabolism, 90, 700–706. [DOI] [PubMed] [Google Scholar]
  27. Braverman LE, Pearce EN, He X, Pino S, Seeley M, Beck B, Magnani B, Blount BC and Firek A, 2006. Effects of six months of daily low‐dose perchlorate exposure on thyroid function in healthy volunteers. Journal of Clinical Endocrinology and Metabolism, 91, 2721–2724. [DOI] [PubMed] [Google Scholar]
  28. Brechner RJ, Parkhurst GD, Humble WO, Brown MB and Herman WH, 2000. Ammonium perchlorate contamination of Colorado River drinking water is associated with abnormal thyroid function in newborns in Arizona. Journal of Occupational and Environmental Medicine, 42, 777–782. [DOI] [PubMed] [Google Scholar]
  29. Brown GM and Gu B, 2006. The Chemistry of Perchlorate in the Environment. In: Perchlorate. Environmental Occurrence, Interactions and Treatment. Chapter 2. Eds Gu B and Coates JD, Springer Science, New York, Philadelphia, USA, 17–47. [Google Scholar]
  30. Buffler PA, Kelsh MA, Lau EC, Edinboro CH, Barnard JC, Rutherford GW, Daaboul JJ, Palmer L and Lorey FW, 2006. Thyroid function and perchlorate in drinking water: an evaluation among California newborns, 1998. Environmental Health Perspectives, 114, 798–804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Cao Y, Blount BC, Valentin‐Blasini L, Bernbaum JC, Phillips TM and Rogan WJ, 2010. Goitrogenic anions, thyroid‐stimulating hormone, and thyroid hormone in infants. Environmental Health Perspectives, 118, 1332–1337. Erratum in: Environmental Health Perspectives, 118, A470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Carr CW, 1952. Studies on the binding of small ions in protein solutions with the use of membrane electrodes. I. The binding of the chloride ion and other inorganic anions in solutions of serum albumin. Archives of Biochemistry and Biophysics, 40, 286–294. [DOI] [PubMed] [Google Scholar]
  33. CDC (Centers for Disease Control and Prevention) , 2009. Perchlorate. In: Fourth national report on human exposure to environmental chemicals. United States Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta, GA, USA, 243–246. [Google Scholar]
  34. Chang S, Crothers C, Lai S and Lamm S, 2003. Pediatric neurobehavioral diseases in Nevada counties with respect to perchlorate in drinking water: an ecological inquiry. Birth Defects Research A, 67, 886–892. [DOI] [PubMed] [Google Scholar]
  35. Charatcharoenwitthaya N, Ongphiphadhanakul B, Pearce EN, Somprasit C, Chanthasenanont A, He X, Chailurkit L and Braverman LE, 2014. The association between perchlorate and thiocyanate exposure and thyroid function in first‐trimester pregnant Thai women. Journal of Clinical Endocrinology and Metabolism, 99, 2365–2371. [DOI] [PubMed] [Google Scholar]
  36. Ciardelli R, Haumont D, Gnat D, Vertongen F and Delange F, 2002. The nutritional iodine supply of Belgian neonates is still insufficient. European Journal of Pediatrics, 161, 519–523. [DOI] [PubMed] [Google Scholar]
  37. Clewell RA, Merrill EA., Gearhart JM, Robinson PJ, Sterner TR, Mattie DR and Clewell HJ 3rd, 2007. Perchlorate and Radioiodide Kinetics Across Life Stages in the Human: Using PBPK Models to Predict Dosimetry and Thyroid Inhibition and Sensitive Subpopulations Based on Developmental Stage. Journal of Toxicology and Environmental Health Part A, 70, 408–428. [DOI] [PubMed] [Google Scholar]
  38. Clewell RA, Merrill EA, Narayanan L, Gearhart JM and Robinson PJ, 2004. Evidence for competitive inhibition of iodide uptake by perchlorate and translocation of perchlorate into the thyroid. International Journal of Toxicology, 23, 17–23. [DOI] [PubMed] [Google Scholar]
  39. Clewell RA, Merrill EA, Yu KO, Mahle DA, Sterner TR, Fisher JW and Gearhart JM, 2003b. Predicting neonatal perchlorate dose and inhibition of iodide uptake in the rat during lactation using physiologically‐based pharmacokinetic modeling. Toxicological Sciences, 74, 416–436. [DOI] [PubMed] [Google Scholar]
  40. Clewell RA, Merrill EA, Yu KO, Mahle DA, Sterner TR, Mattie DR, Robinson PJ, Fisher JW and Gearhart JM, 2003a. Predicting fetal perchlorate dose and inhibition of iodide kinetics during gestation: A physiologically‐based pharmacokinetic analysis of perchlorate and iodine kinetics in the rat. Toxicological Sciences, 73, 235–255. [DOI] [PubMed] [Google Scholar]
  41. Connell JM, 1981. Long‐term use of potassium perchlorate. Postgraduate Medical Journal, 57, 516–517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Contempre B, Jauniaux E, Calvo R, Jurkovic D, Campbell S and de Escobar GM, 1993. Detection of thyroid hormones in human embryonic cavities during the first trimester of pregnancy. Journal of Clinical Endocrinology and Metabolism, 77, 1719–1722. [DOI] [PubMed] [Google Scholar]
  43. Costa M, Zhitkovich A, Gargas M, Paustenbach D, Finley B, Kuykendall J, Billings R, Carlson TJ, Wetterhahn K, Xu J, Patierno S and Bogdanffy M, 1996. Interlaboratory validation of a new assay for DNA‐protein crosslinks. Mutation Research, 369, 13–21. [DOI] [PubMed] [Google Scholar]
  44. Crooks J and Wayne EJ, 1960. A comparison of potassium perchlorate, methylthiouracil, and carbimazole in the treatment of thyrotoxicosis. Lancet, 1, 401–404. [DOI] [PubMed] [Google Scholar]
  45. Crump C, Michaud P, Tellez R, Reyes C, Gonzalez G, Montgomery EL, Crump KS, Lobo G, Becerra C and Gibbs JP, 2000. Does perchlorate in drinking water affect thyroid function in newborns or school‐age children? Journal of Occupational and Environmental Medicine, 42, 603–612. [DOI] [PubMed] [Google Scholar]
  46. Crump KS and Gibbs JP, 2005. Benchmark calculations for perchlorate from three human cohorts. Environmental Health Perspectives, 113, 1001–1008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Dasgupta PK, Kirk AB, Dyke JV and Ohira S, 2008. Intake of iodine and perchlorate and excretion in human milk. Environmental Science & Technology, 42, 8115–8121. [DOI] [PubMed] [Google Scholar]
  48. Dasgupta PK, Martinelango PK, Jackson WA, Anderson TA, Tian K, Tock RW and Rajagopalan S, 2005. The origin of naturally occurring perchlorate: the role of atmospheric processes. Environmental Science & Technology, 39, 1569–1575. [DOI] [PubMed] [Google Scholar]
  49. de Benoist B, McLean E, Andersson M and Rogers L, 2008. Iodine deficiency in 2007: global progress since 2003. Food Nutrition Bulletin, 29, 195–202. [DOI] [PubMed] [Google Scholar]
  50. de Groef B, Decallonne BR, Van der Geyten S, Darras VM and Bouillon R, 2006. Perchlorate versus other environmental sodium/iodide symporter inhibitors: potential thyroid‐related health effects. European Journal of Endocrinology, 155, 17–25. [DOI] [PubMed] [Google Scholar]
  51. Dumont JE, Ermans AM, Maenhaut C, Coppée F and Stanbury JB, 1995. Large goitre as a maladaptation to iodine deficiency. Clinical Endocrinology, 43, 1–10. [DOI] [PubMed] [Google Scholar]
  52. Durand MJ, 1938. Recherches sur l'élimination des perchlorates, sur leur repartition dans les organes et sur leur toxicité. Bulletin de la Société de Chimie Biologique, 20, 428–435. [Google Scholar]
  53. ECHA (European Chemicals Agency) , 2014. Published information on the REACH Registration Dossier on ammonium perchlorate (CAS Number 7790‐98‐9). European Chemicals Agency. Available at: echa.europa.eu/information‐on‐chemicals/registered‐substances. [Google Scholar]
  54. EFSA (European Food Safety Authority) , 2006. Guidance of the Scientific Committee on a request from EFSA related to Uncertainties in Dietary Exposure Assessment. The EFSA Journal 2006, 438, 1–54. [Google Scholar]
  55. EFSA (European Food Safety Authority) , 2007. Reasoned opinion on the potential chronic and acute risk to consumers' health arising from proposed temporary EU MRLs. Available at: www.efsa.europa.eu.
  56. EFSA (European Food Safety Authority) , 2009. Guidance of the Scientific Committee on a request from EFSA on the use of the benchmark dose approach in risk assessment. The EFSA Journal 2009, 1150, 1–72. [Google Scholar]
  57. EFSA (European Food Safety Authority) , 2010. Management of left‐censored data in dietary exposure assessment of chemical substances. EFSA Journal 2010;8(3):1557, 96 pp. doi:10.2903/j.efsa.2010.1557. [Google Scholar]
  58. EFSA (European Food Safety Authority) , 2011a. Use of the EFSA Comprehensive European Food Consumption Database in Exposure Assessment. EFSA Journal 2011;9(3):2097, 34 pp. doi:10.2903/j.efsa.2011.2097. [Google Scholar]
  59. EFSA (European Food Safety Authority) , 2011b. Evaluation of the FoodEx, the food classification system applied to the development of the EFSA Comprehensive European Food Consumption Database. EFSA Journal 2011;9(3):1970, 27 pp. doi:10.2903/j.efsa.2011.1970. [Google Scholar]
  60. EFSA BIOHAZ Panel (EFSA Panel on Biological Hazards) , 2014. Scientific Opinion on the risk posed by pathogens in food of non‐animal origin. Part 2 (Salmonella and Norovirus in leafy greens eaten raw as salads). EFSA Journal 2014;12(3):3600, 118 pp. doi:10.2903/j.efsa.2014.3600. [Google Scholar]
  61. EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain) , 2011. Scientific Opinion on Tetrabromobisphenol A (TBBPA) and its derivatives in food. EFSA Journal 2011;9(12):2477, 67 pp. doi:10.2903/j.efsa.2011.2477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies) , 2014. Scientific Opinion on Dietary Reference Values for iodine. EFSA Journal 2014;12(5):3660, 57 pp. doi:10.2903/j.efsa.2014.3660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. EFSA SC (EFSA Scientific Committee) , 2012. Scientific Committee; Guidance on selected defaultvalues to be used by the EFSA Scientific Committee, Scientific Panels and Units in the absence ofactual measured data. EFSA Journal 2012;10(3):2579, 32 pp. doi:10.2903/j.efsa.2012.2579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. El Aribi H, Le Blanc YJ, Antonsen S and Sakuma T, 2006. Analysis of perchlorate in foods and beverages by ion chromatography coupled with tandem mass spectrometry (IC‐ESI‐MS/MS). Analytica Chimica Acta, 567, 39–47. [DOI] [PubMed] [Google Scholar]
  65. English P, Blount B, Wong M, Copan L, Olmedo L, Patton S, Haas R, Atencio R, Xu J and ValentinBlasini L. 2011. Direct measurement of perchlorate exposure biomarkers in a highly exposed population: a pilot study. PloS One 6 (3):e17015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Eskin BA, Shuman R, Krouse T and Merion JA, 1975. Rat mammary gland atypia produced by iodine blockade with perchlorate. Cancer Research, 35, 2332–2339. [PubMed] [Google Scholar]
  67. FAO/WHO (Food and Agriculture Organisation/World Health Organization) , 2004. Vitamin and mineral requirements in human nutrition: Joint FAO/WHO Expert Consultation on human vitamin and mineral requirements. 2nd edition. World Health Organization and Food and Agriculture Organization of the United Nations, Switzerland, Geneva, 341 pp. Available at: whqlibdoc.who.int/publications/2004/9241546123.pdf. [Google Scholar]
  68. FAO/WHO (Food and Agriculture Organisation/World Health Organization) , 2011. Safety evaluation of certain contaminants in food prepared by the Seventy‐second meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). WHO Food Additives Series 63, 685–762. Available at: www.inchem.org/documents/jecfa/jecmono/v63je01.pdf. [Google Scholar]
  69. FDA (US Food and Drug Administration) , 2013. Preliminary estimation of perchlorate dietary exposure based on FDA 2004/2005 exploratory data. Available at: www.fda.gov/Food/FoodborneIllnessContaminants/ChemicalContaminants/ucm077653.htm.
  70. Fernandez Rodriguez A, Galera Davidson H, Salguero Villadiego M, Moreno Fernandez A, Martin Lacave I and Fernandez Sanz J, 1991. Induction of thyroid proliferative changes in rats treated with antithyroid compound. Anatomia Histologia Embryologia, 20, 289–298. [DOI] [PubMed] [Google Scholar]
  71. Fernández‐Santos JM, De‐Miguel M, Gonzalez‐Campora R, Salguero‐Viladiego M, Cabrera JJ and Galera‐Davidson H, 2004. Ki‐ras mutational analysis in rat follicular‐cell proliferative lesions of the thyroid gland induced by radioactive iodine and potassium perchlorate. Journal of Endocrinological Investigation, 27, 12–17. [DOI] [PubMed] [Google Scholar]
  72. Ferreiro B, Bernal J, Goodyer CG and Branchard, CL , 1988. Estimation of nuclear thyroid hormone receptor saturation in human fetal brain and lung during early gestation. Journal of Clinical Endocrinology & Metabolism, 67, 853–856. [DOI] [PubMed] [Google Scholar]
  73. Fisher DA and Brown RS, 2000. Thyroid physiology in the perinatal period and during childhood. In: Werner and Ingbar's the thyroid: A fundamental and clinical text. Eds Braverman LE and Utiger RD. Lippincott Williams & Wilkins, Philadelphia, USA, 959–972. [Google Scholar]
  74. Fisher DA and Oddie TH, 1969. Thyroid iodine content and turnover in euthyroid subjects: validity of estimation of thyroid iodine accumulation from short‐term clearance studies. Journal of Clinical Endocrinology and Metabolism, 29, 721–727. [DOI] [PubMed] [Google Scholar]
  75. Fisher J, Lumen A, Latendresse J and Mattie D, 2012. Extrapolation of hypothalamic‐pituitary‐thyroid axis perturbations and associated toxicity in rodents to humans: case study with perchlorate. Journal of Environmental Science and Health Part C, 30, 81–105. [DOI] [PubMed] [Google Scholar]
  76. Fisher J, Todd P, Mattie D, Godfrey D, Narayanan L and Yu K, 2000. Preliminary development of a physiological model for perchlorate in the adult male rat: a framework for further studies. Drug and Chemical Toxicology, 23, 243–258. [DOI] [PubMed] [Google Scholar]
  77. Florencio Vicente MDR, 1990. Proliferative thyroid lesions: An experimental study. Dissertations Abstracts International C, 54, 176. [Google Scholar]
  78. Gärtner R, 2009. Autoregulation of thyroid growth and function by iodine: independent regulation of the thyroid gland by iodocompounds. In: Comprehensive handbook of iodine: nutritional, biochemical and therapeutic aspects. Eds Preedy VR, Burrow GN and Watson RW. Elsevier, 243–247. [Google Scholar]
  79. Gauss W, 1972. Physiological and histological criteria of thyroid gland function following a single or long‐term administration of potassium perchlorate in adult mice (Mus musculus L.). I. Long‐term experiments. Zeitschrift fur Mikroskopisch‐Anatomische Forschung, 85, 469–500. [PubMed] [Google Scholar]
  80. Gibbs JP, Narayanan L and Mattie DR, 2004. Crump et al. study among school children in Chile: subsequent urine and serum perchlorate levels are consistent with perchlorate in water in Taltal. Journal of Occupational and Environmental Medicine, 46, 516–517. [DOI] [PubMed] [Google Scholar]
  81. Gilbert ME and Sui L 2008. Developmental exposure to perchlorate alters synaptic transmission in hippocampus of the adult rat. Environmental Health Perspectives, 116, 752–760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Ginsberg GL, Hattis DB, Zoeller RT and Rice DC, 2007. Evaluation of the U.S. EPA/OSWER preliminary remediation goal for perchlorate in groundwater: focus on exposure to nursing infants. Environmental Health Perspectives, 115, 361–369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Goodman G, 2001. The conclusions of the Arizona perchlorate study require reexamination. Journal of Occupational and Environmental Medicine, 43, 305–309. [DOI] [PubMed] [Google Scholar]
  84. Greer MA, Goodman G, Pleus RC and Greer SE, 2002. Health effects assessment for environmental perchlorate contamination: the dose response for inhibition of thyroidal radioiodine uptake in humans. Environmental Health Perspectives, 110, 927–937. Erratum in: Environmental Health Perspectives, 2005, 113, A732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Greiner P, Mc Lellean C, Bennet D and Ewing A, 2008. Occurrence of perchlorate in sodium hypochlorite. Journal of Water Works Association, 100, 68–74. [Google Scholar]
  86. Hepperle J, Wolheim A, Kohlberg D, Wildgrube C and Kaufmann‐Horlacher I, 2013. Analysis of perchlorate in food samples of plant origin applying the QuPPe‐method and LC‐MS/MS. Aspects of Food Control and Animal Health, 2013, 1–16. [Google Scholar]
  87. Her N, Kim J and Yoon Y, 2010. Perchlorate in dairy milk and milk‐based powdered infant formula in South Korea. Chemosphere, 81, 732–737. [DOI] [PubMed] [Google Scholar]
  88. Hiasa Y, Kitahori Y, Kato Y, Ohshima M, Konishi N, Shimoyama T, Sakaguchi Y, Hashimoto H, Minami S and Murata Y, 1987. Potassium perchlorate, potassium iodide, and propylthiouracil: promoting effect on the development of thyroid tumors in rats treated with N‐bis(2‐hydroxypropyl)‐nitrosamine. Japanese Journal of Cancer Research, 78, 1335–1340. [PubMed] [Google Scholar]
  89. Huybrechts I, Sioen I, Boon PE, Ruprich J, Lafay L, Turrini A, Amiano P, Hirvonen T, de Neve M, Arcella D, Moschandreas J, Westerlund A, Ribas‐Barba L, Hilbig A, Papoutsou S, Christensen T, Oltarzewski M, Virtanen S, Rehurkova I, Azpiri M, Sette S, Kersting M, Walkiewicz A, Serra‐Majem L, Volatier J‐L, Trolle E, Tornaritis M, Busk L, Kafatos A, Fabiansson S, de Henauw S and Van Klaveren J, 2011. Dietary Exposure Assessments for Children in Europe (the EXPOCHI project): rationale, methods and design. Archives of Public Health, 69, 1–12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. Iannece P, Motta O, Tedesco R, Carotenuto M and Proto A, 2013. Determination of Perchlorate in Bottled Water from Italy. Water, 5, 767–779. [Google Scholar]
  91. Jackson WA, Joseph P, Laxman P, Tan K, Smith PN, Yu L and Anderson TA, 2005. Perchlorate accumulation in forage and edible vegetation. Journal of Agricultural and Food Chemistry, 53, 369–373. [DOI] [PubMed] [Google Scholar]
  92. Jain RB, 2013. Impact of pregnancy and other factors on the levels of urinary perchlorate, thiocyanate, and nitrate among females aged 15–44 years: data from National Health and Nutrition Examination Survey: 2003–2008. Chemosphere, 91, 882–887. [DOI] [PubMed] [Google Scholar]
  93. Josefsson M, Grunditz T, Ohlsson T and Ekblad E, 2002. Sodium/iodide‐symporter: distribution in different mammals and role in entero‐thyroid circulation of iodide. Acta Physiologica Scandinavica, 175, 129–137. [DOI] [PubMed] [Google Scholar]
  94. Kang N, Anderson TA and JacksonWA, 2006. Photochemical formation of perchlorate from aqueous oxychlorine anions. Analytica Chimica Acta, 567, 48–56. [DOI] [PubMed] [Google Scholar]
  95. Kang N, Jackson WA, Dasgupta PK and Anderson TA, 2008. Perchlorate production by ozone oxidation of chloride in aqueous and dry systems. The Science of the Total Environment, 405, 301–309. [DOI] [PubMed] [Google Scholar]
  96. Kannan K, Praamsma ML, Oldi JF, Kunisue T and Sinha RK, 2009. Occurrence of perchlorate in drinking water, groundwater, surface water and human saliva from India. Chemosphere, 76, 22–26. [DOI] [PubMed] [Google Scholar]
  97. Kelsh MA, Buffler PA, Daaboul JJ, Rutherford GW, Lau EC, Barnard JC, Exuzides AK, Madl AK, Palmer LG and Lorey FW, 2003. Primary congenital hypothyroidism, newborn thyroid function, and environmental perchlorate exposure among residents of a Southern California community. Journal of Occupational and Environmental Medicine, 45, 1116–1127. [DOI] [PubMed] [Google Scholar]
  98. Kessler FJ and Krüskemper HL, 1966. Experimental thyroid tumors caused by many years of potassium perchlorate administration. Klinische Wochenschrift, 44, 1154–1156. [DOI] [PubMed] [Google Scholar]
  99. Khan MA, Fenton SE, Swank AE, Hester SD, Williams A and Wolf DC, 2005. A mixture of ammonium perchlorate and sodium chlorate enhances alterations of the pituitary‐thyroid axis caused by the individual chemicals in adult male F344 rats. Toxicologic Pathology, 33, 776–783. [DOI] [PubMed] [Google Scholar]
  100. Kirk AB, Dyke JV, Martin CF, and Dasgupta PK, 2007. Temporal Patterns in Perchlorate, Thiocyanate, and Iodide Excretion in Human Milk. Environmental Health Perspectives, 115, 182–186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  101. Kirk AB, Dyke JV, Ohira S and Dasgupta PK, 2013. Relative source contributions for perchlorate exposures in a lactating human cohort. The Science of the Total Environment, 15, 939–943. [DOI] [PubMed] [Google Scholar]
  102. Kirk AB, Kroll M Dyke JV, Shin‐Ichi O, Dias RA and Dasgupta PK, 2012. Perchlorate, iodine supplements, iodized salt and breast milk iodine content. The Science of the Total Environment, 420, 73–78. [DOI] [PubMed] [Google Scholar]
  103. Kirk AB, Martinelango PK, Tian K, Dutta A, Smith EE and Dasgupta PK, 2005. Perchlorate and iodide in dairy and breast milk. Environmental Science & Technology, 39, 2011–2017. [DOI] [PubMed] [Google Scholar]
  104. Knudsen N, Bülow I, Jørgensen T, Laurberg P, Ovesen L and Perrild H, 2000. Goitre prevalence and thyroid abnormalities at ultrasonography: a comparative epidemiological study in two regions with slightly different iodine status. Clinical Endocrinology, 53, 479–485. [DOI] [PubMed] [Google Scholar]
  105. Knudsen N, Bülow I, Laurberg P, Ovesen L, Perrild H and Jørgensen T, 2002b. Association of tobacco smoking with goiter in a low‐iodine‐intake area. Archives of Internal Medicine, 162, 439–443. [DOI] [PubMed] [Google Scholar]
  106. Knudsen N, Bülow I, Laurberg P, Ovesen L, Perrild H and Jørgensen T, 2002a. Parity is associated with increased thyroid volume solely among smokers in an area with moderate to mild iodine deficiency. European Journal of Endocrinology, 146, 39–43. [DOI] [PubMed] [Google Scholar]
  107. Krohn K, Maier J and Paschke R, 2007. Mechanisms of disease: hydrogen peroxide, DNA damage and mutagenesis in the development of thyroid tumors. Nature Clinical Practice Endocrinology & Metabolism, 3, 713–720. [DOI] [PubMed] [Google Scholar]
  108. Krüskemper HL, 1960. Theoretische grundlagen und klinische ergebnisse der behandlung von hyperthyreosen mit perchlorat. Arzneimittel Forschung, 10, 13–17.14412229 [Google Scholar]
  109. Lamm SH, 2003. Perchlorate exposure does not explain differences in neonatal thyroid function between Yuma and Flagstaff. Journal of Occupational and Environmental Medicine, 45, 1131–1132. [DOI] [PubMed] [Google Scholar]
  110. Lamm SH, Braverman LE, Li FX, Richman K, Pino S and Howearth G, 1999. Thyroid health status of ammonium perchlorate workers: a cross‐sectional occupational health study. Journal of Occupational and Environmental Medicine, 41, 248–260. [DOI] [PubMed] [Google Scholar]
  111. Lamm SH and Doemland M, 1999. Has perchlorate in drinking water increased the rate of congenital hypothyroidism? Journal of Occupational and Environmental Medicine, 41, 409–411. [DOI] [PubMed] [Google Scholar]
  112. Lamm SH, Hollowell JG, Engel A and Chen R, 2007. Perchlorate, thiocyanate and low iodine association not seen with low creatinine‐adjusted urine iodine among women of childbearing age. Thyroid, 17, S51. [Google Scholar]
  113. Laurberg P and Andersen SL, 2014. Nutrition: Breast milk – a gateway to iodine‐dependent brain development. Nature Reviews Endocrinology, 10, 134–135. [DOI] [PubMed] [Google Scholar]
  114. Laurberg P, Cerqueira C, Ovesen L, Rasmussen LB, Perrild H, Andersen S, Pedersen IB and Carlé A, 2010. Iodine intake as a determinant of thyroid disorders in populations. Best Practice and Research Clinical Endocrinology & Metabolism, 24, 13–27. [DOI] [PubMed] [Google Scholar]
  115. Laurberg P, Nøhr SB, Pedersen KM and Fuglsang E, 2004. Iodine nutrition in breast‐fed infants is impaired by maternal smoking. Journal of Clinical Endocrinology and Metabolism, 89, 181–187. [DOI] [PubMed] [Google Scholar]
  116. Laurberg P, Pedersen IB, Carlé A, Andersen S, Knudsen N and Karmisholt J, 2009. The Relationship between Thiocyanate and Iodine. In: Comprehensive handbook of iodine: nutritional, biochemical and therapeutic aspects. Eds Preedy VR, Burrow GN and Watson RW, Elsevier Science, New York, Philadelphia, PA, USA, 275–281. [Google Scholar]
  117. Lawrence J, Lamm S and Braverman LE, 2001. Low dose perchlorate (3 mg daily) and thyroid function. Thyroid, 11, 295. [DOI] [PubMed] [Google Scholar]
  118. Lawrence JE, Lamm SH, Pino S, Richman K and Braverman LE, 2000. The effect of short‐term low‐dose perchlorate on various aspects of thyroid function. Thyroid, 10, 659–663. [DOI] [PubMed] [Google Scholar]
  119. Lazarus JH, 2014. Iodine status in Europe in 2014. European Thyroid Journal, 3, 3–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  120. Lee JW, Oh SH and Oh JE, 2012. Monitoring of perchlorate in diverse foods and its estimated dietary exposure for Korea populations. Journal of Hazardous Materials, 243, 52–58. [DOI] [PubMed] [Google Scholar]
  121. Leung AM, Braverman LE, He X, Schuller KE, Roussilhes A, Jahreis KA and Pearce EN, 2012. Environmental Perchlorate and Thiocyanate Exposures and Infant Serum Thyroid Function. Thyroid, 22, 938–943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  122. Leung AM, Pearce EN, Hamilton T, He X, Pino S, Merewood A and Braverman LE, 2009. Colostrum iodine and perchlorate concentrations in Boston‐area women: a cross‐sectional study. Clinical Endocrinology, 70, 326–330. [DOI] [PubMed] [Google Scholar]
  123. Levy O, Dai G, Riedel C, Ginter CS, Paul EM, Lebowitz AN and Carrasco N, 1997. Characterization of the thyroid Na+/I‐ symporter with an anti‐COOH terminus antibody. Proceedings of the National Academy of Sciences of the United States of America, 94, 5568–5573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  124. Levy O, de la Vieja A and Carrasco N, 1998. The Na+/I‐ symporter (NIS): recent advances. Journal of Bioenergetics and Biomembranes, 30, 195–206. [DOI] [PubMed] [Google Scholar]
  125. Li FX, Byrd DM, Deyhle GM, Sesser DE, Skeels MR, Katkowsky SR and Lamm SH, 2000b. Neonatal thyroid‐stimulating hormone level and perchlorate in drinking water. Teratology, 62, 429–431. [DOI] [PubMed] [Google Scholar]
  126. Li FX, Squartsoff L and Lamm SH, 2001. Prevalence of thyroid diseases in Nevada counties with respect to perchlorate in drinking water. Journal of Occupational and Environmental Medicine, 43, 630–634. [DOI] [PubMed] [Google Scholar]
  127. Li Z, Li FX, Byrd D, Deyhle GM, Sesser DE, Skeels MR and Lamm SH, 2000a. Neonatal thyroxine level and perchlorate in drinking water. Journal of Occupational and Environmental Medicine, 42, 200–205. [DOI] [PubMed] [Google Scholar]
  128. Lumen A, Mattie DR, Fisher JW, 2013. Evaluation of perturbations in serum thyroid hormones during pregnancy due to dietary iodine and perchlorate exposure using a biologically based dose‐response model. Toxicological Sciences, 133, 320–341. [DOI] [PubMed] [Google Scholar]
  129. Mahle DA, Yu KO, Narayanan L, Mattie DR and Fisher JW, 2003. Changes in cross‐fostered Sprague‐Dawley rat litters exposed to perchlorate. International Journal of Toxicology, 22, 87–94. [DOI] [PubMed] [Google Scholar]
  130. Martino E, Bartalena L, Bogazzi F and Braverman LE, 2001. The effects of amiodarone on the thyroid. Endocrinology Reviews, 22, 240–254. [DOI] [PubMed] [Google Scholar]
  131. McLanahan ED, Campbell JL, Jr. , Ferguson DC, Harmon B, Hedge JM, Crofton KM, Mattie DR, Braverman L, Keys DA, Mumtaz M and Fisher JW, 2007. Low‐dose effects of ammonium perchlorate on the hypothalamic‐pituitary‐thyroid axis of adult male rats pretreated with PCB126. Toxicological Sciences, 97, 308–317. [DOI] [PubMed] [Google Scholar]
  132. McLanahan ED, White P, Flowers L and Schlosser PM, 2014. The use of PBPK models to inform human health risk assessment: case study on perchlorate and radioiodide human lifestage models. Risk Analysis, 34, 356–66. [DOI] [PubMed] [Google Scholar]
  133. McLaughlin CL, Blake S, Hall T, Harman M, Kanda R, Hunt J and Rumsby PC, 2011. Perchlorate in raw and drinking water sources in England and Wales. Water and Environment Journal, 25, 456–465. [Google Scholar]
  134. MDEP (Massachusetts Department of Environmental Protection) , 2005. Draft Report – The Occurrence and sources of perchlorate in Massachusetts. Massachusetts Department of Environmental Protection, Boston, MA, USA, 48 pp. Available at: www.mass.gov/eea/docs/dep/cleanup/sites/percsour.pdf. [Google Scholar]
  135. Mendez W Jr. and Eftim SE, 2012. Biomarkers of perchlorate exposure are correlated with circulating thyroid hormone levels in the 2007–2008 NHANES. Environmental Research, 118, 137–144. [DOI] [PubMed] [Google Scholar]
  136. Merrill EA, Clewell RA, Gearhart JM, Robinson PJ, Sterner TR, Yu KO, Mattie DR and Fisher JW, 2003. PBPK Predictions of Perchlorate Distribution and Its Effect on Thyroid Uptake of Radioiodide in the Male Rat. Toxicological Sciences, 73, 256–269. [DOI] [PubMed] [Google Scholar]
  137. Merrill EA, Clewell RA, Robinson PJ, Jarabek AM, Gearhart JM, Sterner TR and Fisher JW, 2005. PBPK model for radioactive iodide and perchlorate kinetics and perchlorate‐induced inhibition of iodide uptake in humans. Toxicological Sciences, 83, 25–43. [DOI] [PubMed] [Google Scholar]
  138. Morgans ME and Trotter WR, 1960. Potassium Perchlorate in Thyrotoxicosis. British Medical Journal, 2, 1086–1087. [PMC free article] [PubMed] [Google Scholar]
  139. Morreale de Escobar G, Obregon MJ and Escobar del Rey F, 2004. Role of thyroid hormone during early brain development. European Journal of Endocrinology, 151, U25–37. [DOI] [PubMed] [Google Scholar]
  140. Murray CW, Egan SK, Kim H, Beru N and Bolger PM, 2008. US Food and Drug Administration's Total Diet Study: Dietary intake of perchlorate and iodine. Journal of Exposure Analysis and Environmental Epidemiology, 18, 571–580. [DOI] [PubMed] [Google Scholar]
  141. Nakamura S and Kosaka H, 1989. Genotoxicity of inorganic metal compounds with umu test. Japanese Journal of Industrial Health, 31, 430–431. [DOI] [PubMed] [Google Scholar]
  142. NRC (National Research Council) , 2005. Health implications of perchlorate ingestion. National Academics Press, Washington DC, 2005. Available at: www.nap.edu/openbook.php?isbn=0309095689. [Google Scholar]
  143. OEHHA (Office of Environmental Health Hazard Assessment) , 2012. Public Health Goal for perchlorate in drinking water (draft). Public Health Goal (PHG) Technical Support Document, 165 pp. Available at: www.oehha.ca.gov/water/phg/pdf/120612Perchloratedraft.pdf.
  144. Oldi JF and Kannan K, 2009a. Analysis of perchlorate in human saliva by liquid chromatography‐tandem mass spectrometry. Environmental Science & Technology, 43, 142–147. [DOI] [PubMed] [Google Scholar]
  145. Oldi JF and Kannan K, 2009b. Perchlorate in human blood serum and plasma: Relationship to concentrations in saliva. Chemosphere, 77, 43–47. [DOI] [PubMed] [Google Scholar]
  146. Oppenheimer JH and Schwartz HL, 1997. Molecular basis of thyroid hormone‐dependent brain development. Endocrine Reviews, 18, 462–475. [DOI] [PubMed] [Google Scholar]
  147. Ozpinar A, Golub MS, Poppenga RH, Blount BC and Gillespie JR, 2011. Thyroid status of female rhesus monkeys and preliminary information on impact of perchlorate administration. Laboratory Animals, 45, 209–214. [DOI] [PubMed] [Google Scholar]
  148. Pajer Z and Kalisnik M. 1991. The effect of sodium perchlorate and ionizing irradiation on the thyroid parenchymal and pituitary thyrotropic cells. Oncology, 48, 317–320. [DOI] [PubMed] [Google Scholar]
  149. Pearce EN, Alexiou M, Koukkou E, Braverman LE, He X, Ilias I, Alevizaki M and Markou KB, 2012. Perchlorate and thiocyanate exposure and thyroid function in first‐trimester pregnant women from Greece. Clinical Endocrinology, 77, 471–474. [DOI] [PubMed] [Google Scholar]
  150. Pearce EN, Lazarus JH, Smyth PP, He X, Dall'amico D, Parkes AB, Burns R, Smith DF, Maina A, Bestwick JP, Jooman M, Leung AM and Braverman LE, 2010. Perchlorate and thiocyanate exposure and thyroid function in first‐trimester pregnant women. Journal of Clinical Endocrinology and Metabolism, 95, 3207–3215. [DOI] [PubMed] [Google Scholar]
  151. Pearce EN, Leung AM, Blount BC, Bazrafshan HR, He X, Pino S, Valentin‐Blasini L and Braverman LE, 2007. Breast Milk Iodine and Perchlorate Concentrations in Lactating Boston‐Area Women. Journal of Clinical Endocrinology and Metabolism, 92, 1673–1677. [DOI] [PubMed] [Google Scholar]
  152. Pearce EN, Spencer CA, Mestman JH, Lee RH, Bergoglio LM, Mereshian P, He X, Leung AM and Braverman LE, 2011. Effect of environmental perchlorate on thyroid function in pregnant women from Còrdoba, Argentina, and Los Angeles, California. Endocrinology Practices, 17, 412–427. [DOI] [PubMed] [Google Scholar]
  153. Plummer LN, Böhlke JK and Doughten MW, 2006. Perchlorate in pleistocene and holocene groundwater in north‐central New Mexico. Environmental Science and Technology, 40, 1757–1763. [DOI] [PubMed] [Google Scholar]
  154. Rajagopalan S, Anderson TA, Fahlquist L, Rainwater KA, Ridley M and Jackson WA, 2006. Widespread presence of naturally occurring perchlorate in high plains of Texas and New Mexico. Environmental Science and Technology, 40, 3156–3162. [DOI] [PubMed] [Google Scholar]
  155. Rao B, Anderson TA, Orris GJ, Rainwater KA, Rajagopalan S, Sandvig RM, Scanlon BR, Stonestrom DA, Walvoord MA and Jackson WA, 2007. Widespread natural perchlorate in unsaturated zones of the southwest United States. Environmental Science and Technology, 41, 4522–4528. [DOI] [PubMed] [Google Scholar]
  156. Rao B, Anderson TA, Redder A and Jackson WA, 2010. Perchlorate formation by ozone oxidation of aqueous chlorine/oxy‐chlorine species: role of ClxOy radicals. Environmental Science & Technology, 44, 2961–2967. [DOI] [PubMed] [Google Scholar]
  157. San RHC and Clarke JJ, 1999. In vitro mammalian cell gene mutation test (L5178Y/TK±‐ mouse lymphoma assay). BioReliance study number G98BAO6.702. Perchlorate Study Group, Rockville, MD, USA, 9 pp. Available at: www.tera.org/ART/Perchlorate/2nd%20study%20protocol.pdf. [Google Scholar]
  158. Sanchez CA, Fonseca JM, Blount BC and Krieger RI, 2009. Hypochlorite treatments are not a significant source of perchlorate exposure in lettuce. Journal of Agriculture and food Chemistry, 57, 2320–2323. [DOI] [PubMed] [Google Scholar]
  159. Scatchard G and Black ES, 1949. The effect of salts on the isoionic and isoelectric points of proteins. The Journal of Physical and Colloid Chemistry, 53, 88–99. [PubMed] [Google Scholar]
  160. Schier JG, Wolkin AF, Valentin‐Blasini L, Belson MG, Kieszak SM, Rubin CS and Blount BC, 2010. Perchlorate exposure from infant formula and comparisons with the perchlorate reference dose. Journal of Exposure Analysis and Environmental Epidemiology, 20, 281–287. [DOI] [PubMed] [Google Scholar]
  161. Schreinemachers DM, 2011. Association between Perchlorate and Indirect Indicators of Thyroid Dysfunction in NHANES 2001–2002, a Cross‐Sectional, Hypothesis‐Generating Study. Biomarker Insights, 6, 135–146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  162. Scinicariello F, Murray HE, Smith L, Wilbur S and Fowler BA, 2005. Genetic factors that might lead to different responses in individuals exposed to perchlorate. Environmental Health Perspectives, 113, 1479–1484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  163. Selivanova LN, Boltromeyuk LP, Aref'eva ZS et al., 1986. Dynamics of the absorption and elimination of perchloric acid salts in laboratory animals and livestock. Khim Selsk Khoz 106, 43–45 (as cited by ATSDR, 2008). [Google Scholar]
  164. Siglin JC, Mattie DR, Dodd DE, Hildebrandt PK and Baker WH, 2000. A 90‐day drinking water toxicity study in rats of the environmental contaminant ammonium perchlorate. Toxicological Sciences, 57, 61–74. [DOI] [PubMed] [Google Scholar]
  165. Smanik PA, Ryu KY, Theil KS, Mazzaferri EL and Jhiang SM, 1997. Expression, exon‐intron organization, and chromosome mapping of the human sodium iodide symporter. Endocrinology, 138, 3555–3558. [DOI] [PubMed] [Google Scholar]
  166. Smellie JM, 1957. The Treatment of Juvenile Thyrotoxicosis with Potassium Perchlorate. Proceedings of the Royal Society of Medicine, 50, 1026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  167. Smith PN, Severt SA, Jackson JW and Anderson TA, 2006. Thyroid function and reproductive success in rodents exposed to perchlorate via food and water. Environmental Toxicology and Chemistry, 25, 1050–1059. [DOI] [PubMed] [Google Scholar]
  168. Snyder SA, Pleus RC, Vanderford BJ and Holady JC, 2006. Perchlorate and chlorate in dietary supplements and flavor enhancing ingredients. Analytica Chimica Acta, 567, 26–32. [DOI] [PubMed] [Google Scholar]
  169. Soldin OP, Braverman LE and Lamm SH, 2001. Perchlorate clinical pharmacology and human health: a review. Therapeutic Drug Monitoring, 23, 316–331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  170. Stanford BD, Pisarenko AN and Snyder SA, 2011. Perchlorate, broate and chlorate in hypochlorite solutions: guidelines for utilities. Journal of Water Works Association, 100, 1–13. [Google Scholar]
  171. Steinmaus C, Miller MD, Cushing L, Blount BC and Smith AH, 2013. Combined effects of perchlorate, thiocyanate, and iodine on thyroid function in the National Health and Nutrition Examination Survey 2007–08. Environmental Research, 123, 17–24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  172. Steinmaus C, Miller MD and Howd R 2007. Impact of smoking and thiocyanate on perchlorate and thyroid hormone associations in the 2001–2002 National Health and Nutrition Examination Survey. Environmental Health Perspectives, 115, 1333–1338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  173. Steinmaus C, Miller MD and Smith AH, 2010. Perchlorate in drinking water during pregnancy and neonatal thyroid hormone levels in California. Journal of Occupational and Environmental Medicine, 52, 1217–1524. [DOI] [PubMed] [Google Scholar]
  174. Stoker TE, Ferrell JM, Laws SC, Cooper RL and Buckalew A, 2006. Evaluation of ammonium perchlorate in the endocrine disruptor screening and testing program's male pubertal protocol: ability to detect effects on thyroid endpoints. Toxicology, 228, 58–65. [DOI] [PubMed] [Google Scholar]
  175. Sturniolo Gia, Gagliano E, Tonante A, Taranto F, Vermiglio F and Sturniolo Gio, 2013. Toxic multinodular goitre. Personal case histories and literature review. Il Giornale di Chirurgia, 34, 257–259. [PMC free article] [PubMed] [Google Scholar]
  176. Suh M, Abraham L, Hixon JG and Proctor DM, 2013. The effects of perchlorate, nitrate, and thiocyanate on free thyroxine for potentially sensitive subpopulations of the 2001–2002 and 2007–2008 National Health and Nutrition Examination Surveys. Journal of Exposure Science and Environmental Epidemiology, doi:10.1038/jes.2013.67. [DOI] [PubMed]
  177. Sungur Ş and Atan MM, 2013. Determination of nitrate, nitrite and perchlorate anions in meat, milk and their products consumed in Hatay region in Turkey. Food Additives & Contaminants. Part B, 6, 6–10. [DOI] [PubMed] [Google Scholar]
  178. Sungur Ş and Sangün MK, 2011. Ion chromatographic determination of perchlorate in foods consumed in Hatay region. Food Chemistry, 126, 326–331. [Google Scholar]
  179. Susarla S, Collette TW, Garrison AW, Wolfe NL and McCutcheon SC, 1999. Perchlorate identification in fertilizers. Environmental Science & Technology, 33, 3469–3472. [Google Scholar]
  180. Téllez RT, Michaud Chacón P, Reyes Abarca C, Blount BC, Van Landingham CB, Crump KS and Gibbs JP, 2005. Long‐term environmental exposure to perchlorate through drinking water and thyroid function during pregnancy and the neonatal period. Thyroid, 15, 963–975. [DOI] [PubMed] [Google Scholar]
  181. Thorpe‐Beeston JG, Nicolaides KH, Felton CV, Butler, J and McGregor AM, 1991. Maturation of the secretion of thyroid hormone and thyroid‐stimulating hormone in the fetus. The New England Journal of Medicine, 324, 532–536. [DOI] [PubMed] [Google Scholar]
  182. Thuett KA Roots EH, Mitchell LP, Gentles BA, Anderson TA, Kendall RJ and Smith EE. 2002a. In utero and lactational exposure to ammonium perchlorate in drinking water: effects on developing deer mice at postnatal day 21. Journal of Toxicology and Environmental Health. Part A, 65, 1061–1076. [DOI] [PubMed] [Google Scholar]
  183. Thuett KA Roots EH, Mitchell LP, Gentles BA, Anderson TA and Smith EE. 2002b. Effects of in utero and lactational ammonium perchlorate exposure on thyroid gland histology and thyroid and sex hormones in developing deer mice (Peromyscus maniculatus) through postnatal day 21. Journal of Toxicology and Environmental Health. Part A, 65, 2119–2130. [DOI] [PubMed] [Google Scholar]
  184. Tonacchera M, Pinchera A, Dimida A, Ferrarini E, Agretti P, Vitti P, Santini F, Crump K and Gibbs J, 2004. Relative potencies and additivity of perchlorate, thiocyanate, nitrate, and iodide on the inhibition of radioactive iodide uptake by the human sodium iodide symporter. Thyroid, 14, 1012–1019. [DOI] [PubMed] [Google Scholar]
  185. Toro Guillen M, 1991. Reversibility of proliferative thyroid lesions. Dissertation Abstracts International C, 54, 1186. [Google Scholar]
  186. Tran N, Valentín‐Blasini L, Blount BC, McCuistion CG, Fenton MS, Gin E, Salem A and Hershman JM, 2008. Thyroid‐stimulating hormone increases active transport of perchlorate into thyroid cells. American Journal of Physiology – Endocrinology and Metabolism, 294, E802–E806. [DOI] [PubMed] [Google Scholar]
  187. Trumpff C, de Schepper J, Tafforeau J, Van Oyen H, Vanderfaeillie J and Vandevijwere S, 2013. Mild iodine deficiency in pregnancy in Europe and its consequences for cognitive and psychomotor development of children: a review. Journal of Trace Elements in Medicine and Biology, 27, 174–183. [DOI] [PubMed] [Google Scholar]
  188. Trumpolt CW, Crain M, Cullison GD, Flanagan SJP, Siegel L and Lathrop S, 2005. Perchlorate: Sources, uses, and occurrences in the environment. Remediation Journal, 16, 65–89. [Google Scholar]
  189. Urbansky ET, 1998. Perchlorate Chemistry: Implications for Analysis and Remediation. Bioremediation Journal, 2, 81–95. [Google Scholar]
  190. Urbansky ET, 2002. Perchlorate as an Environmental Contaminant. Environmental Science and Pollution Research, 9, 187–192. [DOI] [PubMed] [Google Scholar]
  191. US‐EPA (United States Environmental Protection Agency) , 2005. Perchlorate and perchlorate salts. Integrated Risk Information System, 1007. Available at: www.epa.gov/iris/subst/1007.htm.
  192. US‐EPA (United States Environmental Protection Agency) , 2008. Interim Drinking Water Health Advisory for Perchlorate. Washington DC, Environmental Protection Agency, 1–41. [Google Scholar]
  193. Valentin‐Blasini L, Blount BC, Otero‐Santos S, Cao Y, Bernbaum JC and Rogan WJ, 2011. Perchlorate exposure and dose estimates in infants. Environmental Science & Technology, 45, 4127–4132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  194. Van den Hove MF, Beckers C, Devlieger H, de Zegher F and de Nayer P, 1999. Hormone synthesis and storage in the thyroid of human preterm and term newborns: effect of thyroxine treatment. Biochimie, 81, 563–570. [DOI] [PubMed] [Google Scholar]
  195. Völzke H, Schwahn C, Kohlmann T, Kramer A, Robinson DM, John U and Meng W, 2005. Risk factors for goiter in a previously iodine‐deficient region. Experimental and Clinical Endocrinology and Diabetes, 113, 507–515. [DOI] [PubMed] [Google Scholar]
  196. Wang Z, Forsyth D, Lau BP, Pelletier L, Bronson R and Gaertner D, 2009. Estimated dietary exposure of Canadians to perchlorate through the consumption of fruits and vegetables available in Ottawa markets. Journal of Agricultural and Food Chemistry, 57, 9250–9255. [DOI] [PubMed] [Google Scholar]
  197. Wang Z, Lau BP, Tague B, Sparling M and Forsyth D, 2011. Determination of perchlorate in infant formula by isotope dilution ion chromatography/tandem mass spectrometry. Food Additives & Contaminants. Part A, 28, 799–806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  198. Wenzel KW and Lente JR, 1984. Similar effects of thionamide drugs and perchlorate on thyroid‐stimulating immunoglobulins in Graves' disease: evidence against an immunosuppressive action of thionamide drugs. Journal of Clinical Endocrinology and Metabolism 58, 62–69. [DOI] [PubMed] [Google Scholar]
  199. WHO (World Health Organization) , 1998. Surface decontamination of fruits and vegetables eaten raw. Available at: apps.who.int/iris/bitstream/10665/64435/1/WHO_FSF_FOS_98.2.pdf?ua=1.
  200. WHO (World Health Organization) , 2007. Iodine deficiency in Europe – A continuing public health problem. Available at: www.who.int/nutrition/publications/VMNIS_Iodine_deficiency_in_Europe.pdf.
  201. WHO (World Health Organization) , 2009. Environmental Health Criteria 240. Principles and methods for the assessment of chemicals in food. Available at: www.who.int/iris/handle/10665/44065. [Google Scholar]
  202. WHO/IPCS ((World Health Organization – International Programme on Chemical Safety Evaluation) , 2008. Uncertainty and Data Quality in Exposure Assessment. Part 1: Guidance document on characterizingand communicating uncertainty in exposure assessment. Part 2: Hallmarks of data quality in chemical exposure assessment. Available at: www.who.int/ipcs/publications/methods/harmonization/exposure_assessment.pdf.
  203. Wolff J, 1998. Perchlorate and the thyroid gland. Pharmacological Reviews, 50, 89–105. [PubMed] [Google Scholar]
  204. Yifru DD and Nzengung VA, 2007. Uptake of perchlorate by vegetation growing at field sites in arid and subhumid climates. Remediation Journal, 17, 53–68. [Google Scholar]
  205. York RG, Barnett J Jr., Brown WR, Garman RH, Mattie DR and Dodd D, 2004. A Rat Neurodevelopmental Evaluation of Offspring, Including Evaluation of Adult and Neonatal Thyroid, from Mothers Treated with Ammonium Perchlorate in Drinking Water. International Journal of Toxicology, 23, 191–214. [DOI] [PubMed] [Google Scholar]
  206. York RG, Brown WR, Girard MF and Dollarhide JS. 2001b. Oral (drinking water) developmental toxicity study of ammonium perchlorate in New Zealand White rabbits. International Journal of Toxicology, 20, 199–205. [DOI] [PubMed] [Google Scholar]
  207. York RG, Brown WR, Girard MF and Dollarhide JS. 2001a. Two‐generation reproduction study of ammonium perchlorate in drinking water in rats evaluates thyroid toxicity. International Journal of Toxicology, 20, 183–197. [DOI] [PubMed] [Google Scholar]
  208. York RG, Funk KA, Girard MF, Mattie D and Strawson JE, 2003. Oral (Drinking Water) Developmental Toxicity Study of Ammonium Perchlorate in Sprague‐Dawley Rats. International Journal of Toxicology, 22, 453–464. [DOI] [PubMed] [Google Scholar]
  209. York RG, Lewis E, Brown WR, Girard MF, Mattie DR, Funk KA and Strawson JS, 2005a. Refining the effects observed in a developmental neurobehavioral study of ammonium perchlorate administered orally in drinking water to rats. I. Thyroid and reproductive effects. International Journal of Toxicology, 24, 403–418. [DOI] [PubMed] [Google Scholar]
  210. York RG, Lewis E, Brown WR, Girard MF, Mattie DR, Funk KA and Strawson JS, 2005b. Refining the effects observed in a developmental neurobehavioral study of ammonium perchlorate administered orally in drinking water to rats. II. Behavioral and neurodevelopment effects. International Journal of Toxicology, 24, 451–467. [DOI] [PubMed] [Google Scholar]
  211. Yu KO, Narayanan L, Mattie DR, Godfrey RJ, Todd PN, Sterner TR, Mahle DA, Lumpkin MH and Fisher JW, 2002. The pharmacokinetics of perchlorate and its effect on the hypothalamus‐pituitary‐thyroid axis in the male rat. Toxicology and Applied Pharmacology, 182, 148–159. [DOI] [PubMed] [Google Scholar]
  212. Yu L, Canas JE, Cobb GP, Jackson WA and Anderson TA, 2004. Uptake of perchlorate in terrestrial plants. Ecotoxicology and Environmental Safety, 58, 44–49. [DOI] [PubMed] [Google Scholar]
  213. Zeiger E, 1998a. Salmonella mutagenicity testing of ammonium perchlorate (memorandum with attachment to Annie Jarabek). Department of Health and Human Services, National Institute of Environmental Health Services, Research Triangle Park, NC, USA. [Google Scholar]
  214. Zeiger E, 1998b. Ammonium perchlorate MN test results [memorandum with attachment to Annie Jarabek]. Department of Health and Human Services, National Institute of Environmental Health Services Research; Triangle Park, NC, USA. [Google Scholar]
  215. Zoeller TR, 2003. Challenges confronting risk analysis of potential thyroid toxicants. Risk Analysis, 23, 143–162. [DOI] [PubMed] [Google Scholar]
  216. Zoeller TR, Dowling AL, Herzig CT, Iannacone EA, Gauger KJ and Bansal R, 2002. Thyroid hormone, brain development, and the environment. Environmental Health Perspectives 110 Suppl 3, 355–361. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from EFSA Journal are provided here courtesy of Wiley

RESOURCES