Cabbage diets fed to rabbits by Chesney and his collegues in 1928, had a goitrogenic (suppression of thyroid function) effect due to the presence of cyanide in their leaves. Potassium thiocyanate administered to rats by Vanderlaan and Vanderlaan, caused discharge of iodide from the thyroid glands and prevented the accumulation of iodide in the gland. Five years later, Wyngaarden and his group, showed that potassium perchlorate also behaves like the potassium thiocyanate, although, it is more potent. Since then perchlorate has been extensively used in several studies as an antithyroid agent. Perchlorate inhibits the iodide uptake by blocking the Sodium-iodide symporter (a transporter for two ions usually in the same direction across the cell membrane).
An atom of chlorine bonded to four atoms of oxygen constitutes an anion of chlorate. The common cations that bind to the perchlorate anion include Ammonium NH4+, sodium Na+ and potassium K+. Perchlorate anion (ClO4-) has been found in drinking waters in Southwestern United States of America. Ammonium perchlorate salt is used in explosives, fireworks, airbags, flares, fertilizers, enamels and paints, besides its primary use as an oxidant in missile and rocket propulsion systems. This extensive use has led to elevated levels of these soluble ions in drinking water system. There has been a renewed concern on the perchlorate contamination and its entry into the food chain, through the use of contaminated water and Chilean fertilizers. The use of explosives should not be a major concern since, upon explosion, the chloride molecule no longer exists as chlorate. Instead chlorine anion forms an ionic bond with either sodium or potassium ions. . Even with incomplete detonation very less amounts of chlorate would remain as contaminant. The main sources of perchlorate contamination arise from the manufacturing companies that make perchlorate for rocket fuels, along the Colorado river, which supplies water to Arizona, Southern California and Southern Nevada. Because of lack of awareness of perchlorate contamination the wastes from these plants were allowed to seep into the ground water system for decades. Kerr-McGee Corp site still leaks about 900 pounds of perchlorate per day into the wash leading to the Colorado river. The Chilean fertilizer contaminated with perchlorate forced the closure of several wells in New York’s long island. The Committee to Assess the Health Implications of Perchlorate Ingestion [National Academy of Sciences (NAS)] recommends a reference dose (RfD) for perchlorate of 0.0007 mg/kg body weight in its final report [National Research Council (NRC) 2005] based on 14 days study of normal subjects, did not cause a statistically significant decrease in the group mean thyroid iodide uptake. However, there was no reference to effect of long term exposures to perchlorate on thyroid iodide uptake. Further, no significance has been attached to the effect of perchlorate contamination in milk and its effect on infant development, reproductive health and carcinogenicity in their report. Environmental Protection Agency (EPA) recommends a level no more than 24.5 ppb (parts per billion) for perchlorate in waters which is way below the levels of perchlorate found in the wells surrounding the perchlorate manufacturing companies and military sites.
While treating hyperthyroidism several groups reported the development of aplastic anemia (a condition where bone marrow does not produce enough new cells to replace the old cells), leading to a decreased count of all three blood cell types, red blood cells, white blood cell and platelets. Agranulocytosis or leucopenia (reduction in white blood cells) was also reported in some studies.
A toxicological study of threespine sticklebacks fish reared at the perchlorate contamination levels of 30, 60 and 100 ppm reported that atleast half of the offspring from these fishes (also raised in contaminated waters) died prematurely. The males of this group also showed loss of nuptial coloration and had no interest in the courtship behaviour or mating. Similar observations of effect of perchlorate on reproductive health were made in zebra fish in a different study. Although the concentration used in these studies are very low compared to that recommended by EPA, it is less compared to the levels of perchlorate detected at the military and manufacturing sites. The life span of these fishes is short and the total amount of exposure could be very less compared to humans who are exposed to this contaminant till their reproductive age and beyond. Further, drinking water perchlorate is reported to be in ppb, the levels reported in food vary from ppb to ppm. Thus it is likely that the present levels of perchlorate contamination in our water and food sources could similarly affect the reproductive health of men.
Sodium iodide symporters are expressed in mammary glands during lactation to aid in supply the iodide to the infants through milk. Potassium chlorate given to lactating mothers (animal models) reduces the levels of iodine in their milk though the blockade of the symporter. A minute fluctuation in the levels of thyroid hormone levels even within the normal levels are associated with lower intellectual and learning abilities during childhood. This effect could be compounded in women who consume low levels of iodine. These women would require endocrinological intervention even at low doses of perchlorate (5 ppb). According to the Centers for Disease Control estimates around two million women of childbearing age, could have thyroid deficiency because of perchlorate contamination.
Several studies, including retrospective and human volunteers, on perchlorate did not observe any significant effect on the function of thyroid. However, these studies were carried out without taking into consideration other factors such as genetic predisposition, iodine intake, that might affect the outcome of perchlorate mediated thyroid function inhibition. Chronic hypersecretion of thyroid stimulating hormone due to hypothyroidism caused by perchlorate also increases the risk for thyroid oncogenesis, although the evidence for such a mechanism is lacking.
Careful design and analysis of the effect of perchlorate on the health of humans is required to make a qualified judgment regarding the risk of perchlorate contamination and to provide appropriate remedies to correct the problem. While designing these studies other factors such as iodine intake, genetic predisposition need to be given utmost importance. More studies need to be carried out in animal models that are close to humans to access the effect of perchlorate on reproductive health, carcinogenesis (cancer development) and effect on behaviour, learning and memory. Whether we like it or not, perchlorate contamination is real and all of us will be affected by it. Thus, it does really matter that we take this issue seriously before it is too late and difficult to manage.
