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Background on Perchlorate
Perchlorate compounds have been widely used as solid rocket propellants and ignitable sources in munitions and fireworks. Perchlorates are also a laboratory waste by-product of perchloric acid. Perchlorate salts, particularly potassium perchlorate, have been used therapeutically to treat hyperthyroidism resulting from Graves’ disease and amiodorone-induced thyrotoxicosis. Recent advances in analytical chemistry for perchlorate have revealed that perchlorate is present in the public drinking water supply in several areas in California and also present in Lake Mead in Nevada. Therefore, State and Federal regulatory agencies are conducting risk assessments on perchlorate in order to develop drinking water standards to protect the public.
The perchlorate ion is a tetrahedron with four oxygen molecules at the corners and a chlorine atom at the center. The perchlorate ion, with a partial molal ionic volume of 44.5 at 25° C, is of a similar ionic size to iodide with a partial molal ionic volume of 36.7 (Wolff, 1998). Perchlorate competitively inhibits the active transport of iodide into the thyroid and also stimulates the discharge of unorganified iodide from the thyroid (Wolff, 1998; Stanbury and Wyngaarden, 1952 and others). Although perchlorate was used until the mid-1960s in the treatment of people who are hyperthyroid because of Graves’ disease (Connell,1981; Crooks and Wayne 1960; Godley and Stanbury, 1954; Morgans and Trotter,1960; Stanbury and Wyngaarden, 1952), very little data suitable for risk assessment purposes are available. Many studies have examined the effects of perchlorate in Graves’ patients but few have studied the effects in normal humans. The studies that were conducted in normal humans did not look at long-term exposure to perchlorate. Long-term studies in animals clearly show thyroid toxicity at high doses; but generally these studies did not examine targets other than the thyroid. No two-generation reproductive study in any species has been conducted prior to this experiment. In summary, the perchlorate database defines well the mechanisms by which perchlorate acts on the thyroid but provides little information on the dose-response of perchlorate or on the likely effects in normal humans after chronic exposure to low doses.
In 1997, Toxicology Excellence for Risk Assessment (TERA) convened an independent peer review panel that evaluated the suitability of the perchlorate database for developing a reference dose (RfD) for chronic environmental exposure by the oral route. Overall, the panel concluded that the database for perchlorate was insufficient to support the development of a RfD. Several major questions are left unanswered by the existing data including the shape of the dose-response curve in humans, the effects of perchlorate after long-term exposure, and the possibility of effects in organs or systems other than the thyroid. The panel recommended that additional studies of perchlorate be conducted (see http://www.tera.org/peer for a summary of discussions). As a result of this recommendation, a second panel of risk assessors, perchlorate experts, and thyroid experts was convened to develop a prioritized list of toxicological studies critical for the development of a RfD. That panel recommended that the following studies be conducted under current U.S. EPA guidelines: developmental neurotoxicity, 90-day rat toxicity, rabbit developmental toxicity, two-generation reproductive toxicity, mutagenicity/genotoxicity, immunotoxicity, and kinetics.
TERA, in association with the U.S. Air Force, U.S. EPA, the Perchlorate Study Group (PSG) and others, has helped develop a research program and protocols for studies on ammonium perchlorate that will fill in data gaps that currently exist in the toxicology database. Studies are being funded by the U.S. Department of Defense and the Perchlorate Study Group.
Several of these studies have been completed and were incorporated into a reassessment of the perchlorate RfD by the U.S. EPA in 1999. Additional studies are in progress and will be incorporated into a revised reassessment of the perchlorate RfD by the U.S. EPA in the fall of 2000.
© 2003 Toxicology Excellence for Risk Assessment
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Cincinnati OH 45211
Phone: 513-542-7475
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Email: TERA@TERA.org