PERCHLORATE

General Information


CAS number: 7790-98-9
Functional Class:
  • Food Contaminant
    • CONTAMINANT

Evaluations


Evaluation year: 2011
Comments: The key effect for perchlorate is its ability to competitively inhibit uptake of iodide by the thyroid gland, potentially causing hypothyroidism. The Committee selected a critical effect size of 50% inhibition of iodide uptake from a clinical study in healthy adults as the benchmark response, as data from healthy adults following both short-term and chronic exposure to perchlorate have shown that such a level of inhibition is not associated with any changes in TSH or thyroid hormone levels. The BMDL50 of 0.11 mg/kg bw/d from the clinical study was chosen as the point of departure. As perchlorate is rapidly cleared from the body, the Committee derived a PMTDI. The Committee concluded that it was not necessary to apply an uncertainty factor to account for the short duration of the pivotal study, as there are efficient homeostatic mechanisms to cope with short-term and long-term inhibition of iodide uptake, up to (at least) 50%, in healthy children and adults and there is at least a 4-fold margin between the value of the BMDL50 and the > 0.4 mg/kg bw/d of sustained exposure necessary to trigger hypothyroidism in normal adults. Applying a 10-fold factor to account for sensitive population subgroups to the BMDL50, a PMTDI of 0.01 mg/kg bw/d was established. The estimated dietary exposures of 0.7 μg/kg bw per day (highest) and 0.1 μg/kg bw per day (mean), including both food and drinking-water, are well below the PMTDI and not of health concern.
Intake: Estimated dietary exposure: High: 0.7 μg/kg bw/d (2-year old children); Mean: 0.1 μg/kg bw/d (>14 years old)
Tolerable Intake: PMTDI 0.01 mg/kg bw
Meeting: 72
Report: TRS 959-JECFA 72
Tox Monograph: 72nd_2011_perchlorate.pdf
Estimated exposure

Best estimate: 0.1-0.7 µg/kg bw/day

Toxicological study
Pivotal Study: Human clinical study by Greer et al. (2002): 16 male and 21 female healthy adults given perchlorate in drinking-water at doses of 0.007, 0.02, 0.1 or 0.5 mg/kg bw per day for 14 days. The uptake of iodide into the thyroid was measured at baseline before administration of perchlorate and on days 2 and 14 of administration at both 8 and 24 h after administration of radiolabelled iodine.
Animal specie: Human
Effect: Inhibition of iodide uptake
NOAEL: 0.007 mg/kg bw/day
PMTDI: 0.01 mg/kg bw/d
Point of departure: BMDL50: 0.11 mg/kg bw/day