In an invited review article published on September 2, 2018, in the peer-reviewed journal Toxicology and Applied Pharmacology, Richard Pleus and Lisa Corey from the U.S. consulting agency Intertox evaluated “whether environmental levels of perchlorate are sufficient to cause the most sensitive adverse health effects.” The authors considered the “adverse impact on the developing fetal brain” to be the endpoint that is the “most significant to public health.” Therefore, they reviewed “animal studies, clinical studies, and population-based studies of children and pregnant women for evidence of perchlorate’s impact predominately on the thyroid gland,” which has “a key role in neurological development during gestation and post-natal development.” Following their analysis, the authors summarized that “the results from most populations report no consistent associations,” however, “a few studies report thyroidal effects at environmentally relevant levels of perchlorate.” The authors then discussed several reasons for these “mixed results” and inadvertently dismissed the population-based studies in favor of high-dose clinical studies, concluding that “health effects are expected to only occur at doses substantially higher than environmental levels.”
The most recent examples of epidemiological studies reporting associations between perchlorate exposure and health outcomes in the newborn include a cohort study by Bridget Knight and colleagues from the University of Exeter Medical School, Exeter, UK, that found a negative association between perchlorate levels in the urine of pregnant women and circulating levels of the free thyroxine (T4) hormone, suggesting a possibility of “an adverse impact on neurocognitive development of the fetus.” Yasemin Ucal and colleagues from the Department of Medical Biochemistry, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey, reported that urinary perchlorate levels in lactating mothers were associated with increased levels of thyroid-stimulating hormone (TSH) in their babies. Further, a study by Rainbow Rubin and colleagues from the School of Public Health, University of California, Berkeley, U.S., reported an association between urinary perchlorate levels in pregnant women and preterm births among male fetuses. The authors suggested that the observed “altered birth outcomes” could be followed by “long-term impacts,” requiring future research to understand these better. Pleus and Corey did not discuss the two latter studies. They also did not acknowledge the draft report released by the U.S. Environmental Protection Agency in 2017, that concluded that perchlorate exposure of pregnant women can negatively affect the brain development in the fetus (FPF reported).
Apart from neurodevelopmental effects, exposure to perchlorate could contribute to other diseases as well. In 2017, an article published in the peer-reviewed journal International Journal of Epidemiology reported on an analysis of 11,443 participants from the National Health and Nutritional Examination Survey (NHANES) in 2001-2014, finding that “higher urinary perchlorate levels are associated with an increased prevalence of diabetes mellitus, independent of traditional risk factors.” Lei Zhang and colleagues from the Key Laboratory of Food Safety Risk Assessment, Ministry of Health (CFSA) and China National Center for Food Safety Risk Assessment, Beijing, China, reported on a pair-matching case-control study that revealed an association between increased urinary levels of iodine and perchlorate and the risk of papillary thyroid cancer (PTC).
In the U.S., perchlorate is allowed to be used in food packaging and food processing equipment, what could have resulted in an increased perchlorate consumption by children (FPF reported). A study by Jenica McMullen and colleagues from the School of Medicine, New York University, New York, U.S., found that not only the newborns but also the “adolescent boys and girls represent vulnerable subpopulations to the thyroid-blocking effects.” In adults, a cross-sectional analysis performed by Jennifer Przybyla and colleagues from the School of Biological and Population Health, College of Public Health and Human Sciences, Corvallis, U.S., revealed a disruption of thyroid hormone levels by exposure to mixtures containing phenols, phthalates, and perchlorate. The non-governmental organization Environmental Defense Fund (EDF) has repeatedly asked the U.S. Food and Drug Administration to ban the use of perchlorate in food packaging (FPF reported).
In an article published on January 22, 2018, Katharina Vejdovszky and colleagues from the Department of Risk Assessment, Austrian Agency for Health and Food Safety (AGES), Vienna, Austria, reported on the dietary perchlorate exposure of the Austrian populations. The scientists used “analytical data of perchlorate occurrence in food products from the Austrian market” to calculate dietary exposure “for the three age classes of adults, children and infants,” followed by “a detailed risk assessment.” Compared to the tolerable daily intake (TDI) of 0.3 µg/kg body weight/day, confirmed by the European Food Safety Authority (EFSA) in 2015 (FPF reported), scenarios of average food consumption “did not indicate elevated health risks by dietary perchlorate uptake” for any age group. However, all age classes showed an exceeded TDI in the scenario of high consumption, with 132%, 161% and 156% exceedance calculated for adults, children and infants, respectively. The authors explained that “the major cause for this exceedance is the comparatively high perchlorate contamination of spinach, but also other leaf vegetables, legumes and pineapples, leading to elevated exposure of high consumers.” They further stated that “the current provisional intra-Union trade reference level for perchlorate in spinach of 0.2 mg/kg, advocated by the European Commission, is not sufficient to protect high consumers against possible health risks.” Therefore, they called for the “lowering of the regulatory maximum perchlorate concentrations” in order “to reduce health risks to a tolerable level for all consumers.”
In February 2018, the German Federal Institute for Risk Assessment (BfR) has suggested that perchlorate levels in the European food chain need to be reduced (FPF reported). In the 11th amendment to EU Regulation No 10/2011 on plastic food contact materials, published in June 2018, the specific migration limit (SML) for perchloric acid and its salts, perchlorates, was lowered from 0.05 mg/kg to 0.002 mg/kg (FPF reported).
References
Pleus R.C. and Corey L.M. (2018). “Environmental exposure to perchlorate: A review of toxicology and human health.” Toxicology and Applied Pharmacology 358:102-109.
Knight, B.A., et al. (2018). “Effect of perchlorate and thiocyanate exposure on thyroid function of pregnant women from South-West England: a cohort study.” Thyroid Research 11:9.
Rubin, R., et a. (2017). “Maternal perchlorate exposure in pregnancy and altered birth outcomes.” Environmental Research 158:72-81.
Ucal, Y., et al. (2018). “Exposure to perchlorate in lactating women and its associations with newborn thyroid stimulating hormone.” Frontiers in Endocrinology (Lausanne) 9:348.
U.S. EPA (2017). “Draft Report: Proposed approaches to inform the derivation of a maximum contaminant level goal for perchlorate in drinking water (Volume I – Main report).” EPA-HQ-OW-2016-0438
Vejdovszky, K., et al. (2018). “Risk assessment of dietary exposure to perchlorate for the Austrian population.” Food Additives & Contaminants: Part A 35:623-631.
Abt, E., et al. (2018). “Update on dietary intake of perchlorate and iodine from U.S. food and drug administration’s total diet study: 2008-2012.” Journal of Exposure Science & Environmental Epidemiology 28:21-30.
McMullen, J., et al. (2018). “Identifying subpopulations vulnerable to the thyroid-blocking effects of perchlorate and thiocyanate.” The Journal of Clinical Endocrinology & Metabolism 102:2637-2645.
Przybyla, et al. (2018). “A cross sectional study of urinary phthalates, phenols and perchlorate on thyroid hormones in US adults using structural equation models (NHANES 2007-2008).” Environmental Research 163:26-35.
Liu, G., et al. (2017). “Exposure to perchlorate, nitrate and thiocyanate, and prevalence of diabetes mellitus.” International Journal of Epidemiology 46:1913-1923.
Zhang, L., et al. (2018). “A case-control study of urinary levels of iodine, perchlorate and thiocyanate and risk of papillary thyroid cancer.” Environment International 120:388-393.
