Thyroid tumors, in rat

Case Study 2 An evaluation of the human relevance of the liver and thyroid tumors in rats induced by pyrethrins based on mode of action [118, 128-130]... 

The most important and extensively studied pesticides of this group (Fig. 10, Table 3) are Amitrole and several members of the family of s-triazines [89,151, 153,155,156]. Amitrole had been widely used as a herbicide,but its uses as a registered product for application on food crops were canceled starting in 1971 because it was suspected of inducing thyroid tumors in rats [157 -162]. Amitrole is soluble in water, with a weak basic character (PKb = 10) and behaves chemically as a typical aromatic amine. 

Chronic oral exposure of rats and mice to MDA and its dihydrochloride is carcinogenic. Treatment-related increases in the incidences of thyroid follicular cell adenomas and hepatocellular neoplasms were observed in mice after chronic ingestion of MDA in drinking water. In rats, increases in the incidences of thyroid follicular cell carcinoma and hepatic nodules were observed in males and thyroid follicular cell ademonas occurred in females. Although not statistically significant, certain uncommon tumors such as bile duct adenomas, papillomas of the urinary bladder, and granulosa cell tumors of the ovary also were reported. These tumors are of low incidence in historical controls. In another report, MDA acted as a promoter of thyroid tumors in rats. °... 

Hiasa Y, Kitahori Y, Enoki N, et al 4,4 -Diaminediphenylmethane Promoting effect on the development of thyroid tumors in rats treated with N-bis(2-hydroxypropyl) nitrosamine. J Natl Cancer Inst 72 471-476, 1984... 

Carcinogenesis There has been evidence of oncogenic activity in studies with oxytetracycline (adrenal and pituitary tumors) in rats and minocycline (thyroid tumors) in rats and dogs. 

There have been reports of increased incidence of urinary tract tumors and thyroid tumors in rats exposed chronically to trifluralin. Trifluralin is structurally similar to ethalfluralin, which is a known carcinogen in rats, and formulations contain N-nit-roso-di- -propylamine, an omnipresent contaminant, also a known carcinogen. Trifluralin has been classified as a group C (possible carcinogen) due to evidence of increased combined malignant and benign urinary bladder tumors in female rats and renal pelvis carcinomas in male rats. There is also evidence for an increased incidence of thyroid and follicular cell tumors in male rats. 

D5 has slightly different properties than D4, and it does not have any estrogenic activity [289]. It does, however, also have adverse effects on the reproductive system, much like D4, but also on the adipose tissue, bile production, and even immune system due to D5 s effect of reducing the prolactin levels [291]. In addition, it was determined that D5 causes a significant increase in uterine tumors in rats after a 160 ppm exposure. However, it is proposed that the tumors occur in rats through a mechanism that would not affect humans [291]. D5 also acts as a dopamine agonist and it can cause adverse effects on the nervous system in humans [291]. For exposures to D6 in rats, an increase in liver and thyroid mass and reproductive effects were observed [292]. 

Waritz RS, Steinberg M, Kinoshita FK, Kelly CM, Richter WR (1996) Thyroid function and thyroid tumors in toxaphene-treated rats. Regul Toxicol Pharmacol 24 184-192 Weeke J (1973) Circadian variation of the serum thyrotropin level in normal subjects. Scand J Clin Lab Invest 32 337... 

Ethylenethiourea, which produces thyroid carcinomas in rats and liver cell tumors in mice by ingestion, is formed from ethylenebisdithiocarbamates such as Maneb and Zineb by metabolic processes and cooking. 

Benign and malignant renal neoplasms have been observed in rats and mice fed diets with 100 or 1,000 mg of basic lead acetate per kg of diet. The results of these studies have been summarized [77]. Tumors in the testes and in the adrenal, thyroid, pituitary, and prostate glands have been noted in addition to renal neoplasms. Intraperitoneal and subcutaneous injections of lead phosphate have also caused the development of renal tumors in rats. Tetraethyl lead has been shown to produce malignant lymphomas in mice [77]. Dingwall-Fordyce and Lane [17] did not find any increase of malignant diseases in their follow-up study of 267 workers. 

To understand the MOA by which the thyroid tumors are produced, the effect of pyrethrins on rat thyroid gland, thyroid hormone levels, and hepatic thyroxine UDP-glucuronosyltransferase activity was also investigated [128]. The treatment of male rats with 8,000 ppm pyrethrins, female rats with 3,000 and 8,000 ppm pyrethrins, and both sexes with phenobarbital resulted in increased thyroid gland... 

It has been demonstrated that At is embryotoxic in pregnant mice, and there also exists a dose-related occurrence of associated fetal malformations (29, 30). Long-term studies in female rats that had received 0.5 /tCi g At systemically indicated a significant incidence of radiation-induced mammary carcinomata (39/45 44%) and endometrial polyps (43/55 76.4%) at 14 months after treatment. No thyroid tumors were found (50). Detailed macroscopic radiation dosimetric studies related to the biodistribution of At in animal models have been reported (29, 33, 39). 

Spontaneous thyroid tumors derived from the thyroid follicular cell occur in l%-3% of laboratory rats (adenomas and carcinomas combined in a variety of strains of rats aged 2 or more years). 

A recent study confirmed that ethylene thiourea was carcinogenic in male and female rats as shown by increased incidences of thyroid follicular cell neoplasms after treatment of up to 250 ppm in the diet for 2 years. In mice, concentrations ranging from 100 to 1000 ppm for 2 years caused liver and pituitary tumors in addition to thyroid tumors. Perinatal exposure up to 8 weeks followed by a control diet for 2 years was not carcinogenic in rats or mice. Combined perinatal-adult ETU exposures produced the same carcinogenic effects as adult-only exposures. 

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