19 Chemicals That Produced Thyroid Tumors in Animals: What About Humans? None Proven so Far
This seventy-ninth volume of IARC Monographs contains evaluations of the carcinogenic risk to humans of 19 chemicals that have produced thyroid tumours in rodents. Unless otherwise stated, the term ‘thyroid tumour’, as used in this volume, refers to neoplasms of thyroid follicular cell origin.
- Some are drugs.The ‘anti-thyroid’ agents (methimazole, methylthiouracil, propylthiouracil and thiouracil), sedatives (doxylamine succinate and phenobarbital), antifungal agents (griseofulvin), diuretics (spironolactone) and antibacterial agents (sulfamethazine and sulfamethoxazole).
- The others are or have been used in agriculture as pesticides (amitrole, chlordane, heptachlor, hexachlorobenzene and toxaphene), in foods or cosmetics (kojic acid), in hair dyes (2,4-diaminoanisole) and as industrial chemicals (N,N′-diethylthiourea, ethylenethiourea, and thiourea). Many of these agents have been evaluated previously in IARC Monographs, but some (N,N′-diethylthiourea, doxylamine succinate, kojic acid, methimazole and sulfamethazine) are evaluated for the first time.
Use of anti-thyroid drugs in humans
Thioureylene anti-thyroid drugs belong to the family of thionamides, which are heterocyclic thiourea derivatives that potently inhibit thyroid hormone synthesis. They were developed in the mid-1940s to early 1950s on the basis of observations that thiourea and thiocarbamide are goitrogenic in animals. Thiouracil was the first ‘anti-thyroid drug’ to be used clinically, but its use was short-lived because of toxicity and because other, more active drugs (i.e. propylthiouracil, methylthiouracil and methimazole) were soon developed (Astwood & VaanderLaan, 1945; Stanley & Astwood, 1949). In addition to propylthiouracil and methimazole, the 3-carbethoxy derivative of methimazole, carbimazole, is widely used in Europe and Asia. Carbimazole is metabolized in vivo to methimazole, which exerts the anti-thyroid effects. It has been estimated that 0.1–0.3% of the population in a number of developed countries is taking antithyroid drugs at any given time (Anon., 1988).
At present, the only clinical use of the thionamide anti-thyroid drugs is in the treatment of hyperthyroidism caused by Graves disease, toxic thyroid nodules, toxic multinodular goitre and several other rare causes of hyperthyroidism. In patients with Graves disease, anti-thyroid drugs are used in two contexts. In some patients, they are given for several months to normalize thyroid function prior to definitive therapy with either radioiodine or surgery. In other patients, they are given for 1–2 years, in the hope that the patient will enter a period of remission.
Thyroid cancer in humans caused by chemicals: None
Exposure to non-radioactive chemicals has not been shown to result in the development of thyroid carcinoma in humans.