ethylenethiourea and Body-Weight

Considerable public concern has developed regarding possible adverse reproductive outcomes resulting from exposure to power frequency magnetic fields (MF). To identify possible effects of MF exposure on fetal development, timed-pregnant female Sprague-Dawley rats (55/ group) received continuous exposure to linearly polarized, transient-free 60 Hz MF at field strengths of 0 Gauss (G; sham control), 0.02 G, 2 G, or 10 G, or intermittent (1 hr on/1 hr off) exposure to 10 G fields. Dams received MF or sham exposures for 18.5 hr/day on gestation days 6 through 19. A positive control group of 15 dams received daily oral doses of 85 mg ethylenethiourea (ETU)/kg body weight on gestation days 11, 12, and 13; positive control dams received no MF exposure. Ambient and experimentally generated MF were monitored continuously throughout the study. Experimentally generated MF were within 2% of the target field strengths at all times, and ambient MF to which sham controls were exposed did not exceed 0.7 mG at any point in the study. No evidence of maternal toxicity was identified in any MF-exposed dam; mean maternal body weight and organ weights in groups exposed to MF did not differ from those in sham controls. Comparisons of fetal viability and body weight demonstrated no biologically significant differences between MF-exposed groups and sham controls. Similarly, a battery of gross external, visceral, skeletal, and cephalic examinations demonstrated no significant differences in the incidence of fetal malformations or anomalies in MF-exposed groups vs. sham controls. By contrast, 100% of the fetuses in the positive control group treated with ETU demonstrated malformations and reduced body weight. Exposure of pregnant Sprague-Dawley rats to 60 Hz at field strengths up to 10 G during gestation days 6-19 did not produce biologically significant effects in either dams or fetuses. These results do not support the hypothesis that exposure to pure, linearly polarized 60 Hz MF is a significant risk factor for the developing fetus.

Topics: Abnormalities, Drug-Induced; Abnormalities, Radiation-Induced; Animals; Body Weight; Bone and Bones; Brain; Electromagnetic Fields; Embryonic and Fetal Development; Ethylenethiourea; Female; Male; Pregnancy; Rats; Rats, Sprague-Dawley; Reproduction

Chronic toxicity and carcinogenicity studies of ethylene thiourea (ETU), 97% pure, were conducted in F344/N rats and B6C3F1 mice of each sex. The major objective of the study was to determine if incorporation of perinatal exposure, in addition to the conventional exposure of young adult animals for 2 years, enhances the sensitivity of the bioassay in identification of the carcinogenic potential of chemicals when compared to the conventional exposure of animals to a chemical for 2 years, usually beginning at the age of 6-8 weeks. The studies were designed to determine (1) the toxic and carcinogenic effects of dietary ETU in rats and mice receiving perinatal exposure up to 8 weeks of age followed by control diet for 2 years, (2) the effects of ETU in rats and mice receiving exposure for 2 years beginning at the age of 8 weeks, and (3) the effects of combined perinatal/adult exposure to ETU (perinatal exposure to 8 weeks of age followed by the adult exposure for 2 years). During the perinatal period, rats were exposed to dietary ETU concentrations ranging from 9 to 90 ppm and adult exposure concentrations ranged from 25 to 250 ppm. In the mice, the perinatal exposure concentrations of ETU in the diet ranged from 33 to 330 ppm, and in the adults the concentrations were 100 to 1000 ppm. A total of eight exposure groups (including controls) were used with 60 animals in each group. Ten animals from each group were killed at Month 9 of the study for interim evaluation. The thyroid gland in rats and mice and the liver in mice were identified as target organs of ETU toxicity at the 9-month interim evaluation. The perinatal only exposure to ETU was not carcinogenic in rats or mice, while adult or perinatal/adult combination exposures to ETU were carcinogenic both in rats and in mice. The thyroid gland was the major site of ETU carcinogenicity both in rats and in mice. The liver and pituitary glands were other major sites of ETU carcinogenicity in mice. The carcinogenic effects of ETU were generally similar by adult and perinatal/adult combination protocols except that the incidences of thyroid tumors were slightly higher in the rats receiving the perinatal/adult combination of ETU exposure in the diet.

Topics: Animals; Body Weight; Carcinogens; Diet; Ethylenethiourea; Female; Hormones; Mice; Mice, Inbred C57BL; Neoplasms, Experimental; Organ Size; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Inbred F344; Species Specificity; Thyroid Hormones; Thyroid Neoplasms

Sprague-Dawley rats were administered ethylenethiourea (ETU), 1,3-dimethyl-2-thiourea (DMT), 1,3-dibutyl-2-thiourea (DBT), or 1,3-diphenyl-2-thiourea (DPT) by gavage from Days 6 to 20 of gestation. Daily dosage levels (mg/kg/day) were ETU at 0, 15, 25 and 35; DMT at 0, 15, 25, 50, 100, and 200; DBT at 0, 15, 25, 50, 100, and 200; and DPT at 0, 25, 50, 100, and 200. There was evidence of maternal toxicity at all doses of DMT and at doses greater than or equal to 50 mg DBT/kg/day. DPT was embryolethal at 200 mg/kg/day. Fetotoxicity was observed at doses greater than or equal to 15 mg DMT/kg/day, greater than or equal to 15 mg DBT/kg/day, and greater than or equal to 100 mg DPT/kg/day. ETU was the only chemical tested that proved to be teratogenic.

Topics: Animals; Behavior, Animal; Body Weight; Embryo, Mammalian; Ethylenethiourea; Female; Gestational Age; Intubation, Gastrointestinal; Pregnancy; Rats; Rats, Inbred Strains; Reproduction; Teratogens; Thiourea

Ethylene glycol dimethyl ether (EGdiME), diethylene glycol dimethyl ether (diEGdiME), triethylene glycol dimethyl ether (triEGdiME), diethylene glycol diethyl ether (diEGdiEE), ethylenethiourea (ETU), sodium selenite (SS), dimethyl phthalate (DMP), naphthalene (NAP), or p-nitrophenol (PNP) were administered by gavage for eight consecutive days to female CD-1 mice. Weight loss was insensitive as an index of sublethal adult toxicity and was inadequate for determining a maximum tolerated dose. LD50 values indicate that SS, NAP, and PNP were more toxic (8.4, 353.6, and 625.7 mg/kg, respectively) than the polyglycol ethers, ETU, and DMP (LD50 values ranged from 2525.8 to 6281.9 mg/kg). Each of the compounds was administered on d 7 through 14 to pregnant animals at a single dose estimated to be at or just below the threshold of adult lethality. In such a reproductive study, each of the compounds could be categorized on the basis of the pattern of maternal lethality and fetotoxicity which it produced. The number of dams with complete resorptions was significantly increased after administration of ETU, and no mice in the EGdiME-, diEGdiME-, or triEGdiME-treated groups delivered any viable offspring. Maternal lethality was significant in the EGdiME, triEGdiME, PNP, and NAP groups. There was a slight reduction in the average number of live pups per litter in the diEGdiEE- and PNP-treated groups and a significant reduction in the NAP group. The number dead per litter was increased with diEGdiEE. SS and DMP had no effect on maternal or fetal survival at the doses administered. Individual pup weight at d 1 postpartum was only significantly reduced by diEGdiEE, and no gross congenital abnormalities were detected in neonates from any treatment group. These results provide guidelines for the subsequent toxicity testing of these chemicals.

Topics: Administration, Oral; Analysis of Variance; Animals; Birth Weight; Body Weight; Drug Evaluation, Preclinical; Ethylene Glycols; Ethylenethiourea; Female; Fetal Death; Fetus; Imidazoles; Lethal Dose 50; Maternal-Fetal Exchange; Mice; Naphthalenes; Nitrophenols; Phthalic Acids; Pregnancy; Reproduction; Selenious Acid; Selenium

Thyrotoxicity of Ethylenthiourea (2-imidazolidinethione) (ETU) is well known: this paper examines the extent to which ETU alone may damage certain non-thyroid tissues, and the possible enhancement of its effects through synergism when it is taken with substances employed for medical or alimentary reasons. It was found that the lethality of ETU is augmented by accumulation of fractionated doses, particularly in male as opposed to female rats. When accompanied by ethanol, its harmfulness is increased, whereas phenobarbital provides a certain degree of protection. Liver secretion of triglycerides is greatly impaired (delta % = -31) by acute administration, which results in steatosis. This is not observed during subacute administration. Liver microsomal cytochrome P450 is significantly reduced (delta % = -32) after a long term administration. The 30 week treatment leads to a form of "selection". Some animals die (28.6%), whereas others survive despite: i) prolonged failure to put on weight, ii) alopecia (80% loss of hair), iii) severe conjuntivitis, iv) blepharitis, v) peripheral nervous system distress. These findings underscore the importance of investigating the relation between hazardous compounds and possible potentiating factors, on the one hand, and inclusion of organs not yet recognized as targets, on the other hand, when setting tolerance limits for ambient pollution.

Topics: Animals; Body Weight; Cytochrome P-450 Enzyme System; Ethylenethiourea; Female; Imidazoles; Lethal Dose 50; Lipid Metabolism; Liver; Male; Peripheral Nerves; Phenobarbital; Rats; Rats, Inbred Strains

Groups of 50 male and 50 female Sprague-Dawley rats were fed diets containing 0, 75, 100, or 150 ppm ethylenethiourea (ETU) for 7 weeks, at which time subgroups of 10 animals from each group were killed. Subsequent subgroups of 10, 10, and 20 animals were killed after an additional 2, 3, and 4 weeks, respectively, on the control diet in order to examine whether the toxicological effects induced by ETU were reversible. In both sexes, the mean body weight and feed consumption were significantly decreased in all treated groups, while the mean thyroid weight (absolute as well as relative to both body and brain weight) appeared to increase linearly with dose. Mean T4 blood levels in animals fed 150 ppm ETU were significantly below those in controls. The magnitude of the changes in body weight, thyroid weight, and T4 blood levels observed during the first 7 weeks of the study decreased after ETU was removed from the diet. The statistical procedures developed and applied here may be useful in other experiments designed to assess the reversibility of other toxicological endpoints.

Topics: Adenoma; Animals; Body Weight; Carcinoma; Diet; Dose-Response Relationship, Drug; Ethylenethiourea; Female; Imidazoles; Male; Models, Biological; Neoplasms, Experimental; Organ Size; Rats; Rats, Inbred Strains; Thyroid Gland; Thyroid Neoplasms; Thyroxine; Triiodothyronine

Ethylenethiourea (ETU) was given by gavage at a dose of 40 mg/kg/day from Days 7 through 15 of gestation to hypothyroid and euthyroid rats, and to rats given exogenous thyroxine, to determine whether ETU teratogenicity occurs through alteration of maternal thyroid function. At sacrifice on Day 20 of gestation 84-100% of the fetuses in all groups given ETU were malformed regardless of the thyroid status of the dams. Ten percent of the fetuses of dams thyroparathyroidectomized at 75 days of age that were not given ETU were malformed; no malformations were noted among the fetuses of the other groups not given ETU. Hence, ETU was found to induce teratogenicity in rats but not through alteration of maternal thyroid status. In addition, it was determined that ETU lowered serum thyroxine concentration, that hypothyroidism itself increased the background level of malformations in the rat, and that hypothyroidism qualitatively and quantitatively increased the incidence of specific malformations after ETU administration.

Topics: Animals; Body Weight; Ethylenethiourea; Female; Fertility; Hyperthyroidism; Hypothyroidism; Imidazoles; Organ Size; Pregnancy; Rats; Teratogens; Thyroid Gland

Topics: Animals; Body Weight; Bromides; Diet; Drug Interactions; Eating; Ethylenethiourea; Goiter; Imidazoles; Male; Organ Size; Rats; Thyroid Gland; Thyroxine