High temperatures and a broad pH range are stable for ethylene thiourea [1].

Ethylenethiourea (10-80 mg/kg; oral) is teratogenic in rats [1]. Ethylene thiourea (5-500 ppm; in diet; 12 months) promotes thyroid carcinoma in rats [2].

Animal/Disease Models: Virgin Wistar female rats [1]
Doses: 0, 5, 10, 20, 40 or 80 mg/kg
Route of Administration: Oral administration, from days 21-42 before conception to day 15 of pregnancy, and 6-15 days or 7-20 days of gestation.
Experimental Results: 10mg/kg or above induces meningoencephalocele, meningeal hemorrhage, meningeal leakage, hydrocephalus, neural tube occlusion, clubfoot, abnormal pelvic limb posture, short or curled tail.

Absorption, Distribution and Excretion
Dithiocarbamates and their metabolic products /including ETU/ are found in certain organs, such as the liver, kidneys, and, especially, the thyroid gland, but accumulation of these compounds does not take place because of their rapid metabolism. /Dithiocarbamate pesticides/
ETU is rapidly absorbed, metabolized, and excreted in mammals. Up to 90% is eliminated via the urine and only a small amount via the feces. Distribution of ETU in the body appears to be fairly uniform with the exception of a relative accumulation in the thyroid.
ETU is rapidly absorbed from the gastrointestinal tract and cleared from the body in all the mammalian species that have been tested. After only 5 min, ETU appeared in the blood of rats administered an oral dose of 100 mg (14)C-ETU/kg bw. Within 48 hr, 82 - 99% of an oral dose was eliminated via the urine and about 3% via the feces ... /Another study found/ approximately 70% was eliminated in the urine and 1% in the feces. Comparable results were found for mice while in monkeys, 55% was eliminated via the urine within 48 hr and less than 1.5% via the feces ...
To study the accumulation and elimination of radioactivity by the thyroid gland of rats dosed with (14)C-ETU, dose levels of 2 and 200 ug labeled ETU were administered daily for 14 days. In another study, rats were dosed with 0, 0.1, 1, 10, 50, or 100 mg (14)C-ETU/kg diet, daily, for 7 days. The first study showed that the concentration of ETU and/or its metabolites in the thyroid is dose-dependent, and the second that the level of (14)C in the thyroid did not increase appreciably when the daily dose was increased above 50 mg/kg diet. Withdrawal of ETU from the diet led to an 80 - 94% reduction in the radioactivity in the thyroid after 17 days ...
For more Absorption, Distribution and Excretion (Complete) data for Ethylene thiourea (13 total), please visit the HSDB record page.

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Metabolism / Metabolites
The metabolic decomposition of EBDCs in mammals is complex and results in the formation of carbon disulfide, EDA, a few ethylene bisthiuram disulfides, hydrogen sulfide, ethylene bisthiocyanate, and ETU. The latter is further broken down to moieties that are incorporated into compounds such as oxalic acid, glycine, urea, and lactose. /Dithiocarbamate pesticides/
After treating plants with dithiocarbamates, a large number of metabolites are found, including ETU, EU, imidazole derivatives, diisothiocyanates, diamines, disulfides, and other metabolites that are still unknown. /Dithiocarbamate pesticides/
The various metal derivatives of ethylene bisdithiocarbamic acid appear to be converted in the soil to /5,6-dihydro-3 H-imidazo [2,1-C]-1,2,4-dithiazole-3-thione/ (DIDT), ETU, carbon disulfide, hydrogen sulfide, and carbonyl sulfide ... The conversion by soil bacteria and fungi of DIDT into ETU has been demonstrated ... Even though ETU is slowly converted into EU in soil, pure cultures of soil bacteria and fungi were unable to effect this transformation. /Dithiocarbamate pesticides/
ETU is broken down to ethylene diamine (EDA), urea, carbon dioxide, or oxalic acid, or is transformed to imidazole derivatives in mammals, plants, and the environment.
For more Metabolism/Metabolites (Complete) data for Ethylene thiourea (12 total), please visit the HSDB record page.

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Biological Half-Life
ETU and its metabolites have been found to have a half-life of about 28 hr in monkeys, 9 - 10 hr in rats, and 5 hr in mice ...
240 mg/kg were administered to pregnant rats and mice by stomach tube. Maternal and fetal tissue levels were similar at 3 hr post treatment; thereafter mouse (maternal and fetus) showed less ETU than rat. /Half-life/ of elimination from maternal blood was 9.4 hr for rat and 5.5 hr for mouse.

Interactions
When the mutagenicity of ETU was assayed before and after nitrosation with sodium nitrite under acid conditions, nitrosation was found to cause a 160-fold increase in the number of revertant colonies of S. typhimurium TA 1535 ... The interactive mutagenicity of ETU and nitrite was also found in the mouse dominant lethal test ... However, no dominant-lethal mutations were induced in a group of mice treated with 30 mg ETU plus 10 mg nitrite/kg bw. A large increase in pre-implantation losses was noted 5 and 6 weeks after completing a 5-day treatment of males with a combined oral dose of 150 mg ETU/kg and 50 mg sodium nitrite/kg bw.
Administered alone /in rats/, sodium nitrite did not produce any teratogenic response in full-term fetuses, whereas ethylene thiourea produced a high incidence of various anomalies. However, the combined dosing resulted in the elimination of almost all the anomalies.
The effects of oral administration of ethylenethiourea (ETU) and sodium nitrite on endometrial adenocarcinoma development was investigated in female Donryu rats. At 10 week of age, groups 1 and 3 received a single dose of polyethylene glycol (PEG) into the uterine cavity, while groups 2 and 4 were given N-ethyl-N-nitrosourea (ENU) (15 mg/kg) solution, dissolved in PEG, in the same manner. ETU (80 mg/kg) and sodium nitrite (56 mg/kg) dissolved in distilled water were orally given to animals in groups 3 and 4 once a week from 11 to 51 weeks of age. Groups 1 and 2 received the vehicle alone. At termination (52 weeks of age), endometrial adenocarcinomas were observed in 29, 13 and 57% of rats in groups 2, 3 and 4, respectively, but not in group 1. Persistent estrus appeared earlier in groups 3 and 4 than in group 1. In groups 3 and 4, hyperplastic and neoplastic lesions of the digestive tract, especially the forestomach, were also observed. The results indicate that N-nitroso ETU formed in the stomach by concurrent oral administration of ETU and sodium nitrite, itself induces endometrial adenocarcinomas by its mutagenic action, as well as promoting their development after ENU-initiation, presumably by influencing the hormonal balance.
Aging effects on the susceptibility to chemical endometrial carcinogenesis were investigated in ICR female mice. The animals were divided into 3 groups of different ages: 1 month (young), 6 months (middle), and 12 months (old) at initiation of treatment. They received weekly oral administration of mixture of ETU (100 mg/kg body weight) and sodium nitrite (70 mg/kg body weight) for 6 months followed by a withdrawal period of 3 months. All animals were subjected to histopathology. The incidence of endometrial adenocarcinomas was highest in the middle age group (8/20), secondary in the old age group (4/20), and lowest in the young group (1/20). The incidence of atypical glandular hyperplasia, a precursor lesion of the tumor, was also higher in the middle age group. The endometrial adenocarcinomas showed morphological similarities among all age groups and the nuclei of tumor cells lost almost all staining reactivity to estrogen receptors. The labeling indices with bromodeoxyuridine (BrdU) were notably higher in the old age group than in the young and middle age groups. A further investigation on the aging process of female genital organs in control mice revealed that their senility seemed to be preceded by the formation of ovarian cysts which first appeared at 6 months of age with a concomitant elevation of plasma 17 beta-estradiol level. These results indicate that the susceptibility of the mouse endometrium to the carcinogenic effects of N-nitroso ETU could be closely linked with the stage of aging process of the genital organs and it appears to be most susceptible when initiated at around 6 months of age. However, the mitotic activity of neoplastic endometrial glandular cells seems to be higher in older mice than younger ones.
For more Interactions (Complete) data for Ethylene thiourea (6 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 545 mg/kg bw
LD50 Rat oral 900 mg/kg bw
LD50 Rat oral 1832 mg/kg
LD50 Mouse oral 3000 mg/kg
For more Non-Human Toxicity Values (Complete) data for Ethylene thiourea (7 total), please visit the HSDB record page.

[1]. Khera KS. Ethylenethiourea: teratogenicity study in rats and rabbits. Teratology. 1973 Jun;7(3):243-52.

[2]. Effects of one-year administration of ethylenethiourea upon the thyroid of the rat. J Agric Food Chem. 1973 May-Jun;21(3):324-9.

Ethylene Thiourea can cause cancer according to The World Health Organization's International Agency for Research on Cancer (IARC) and The National Toxicology Program. It can cause developmental toxicity according to an independent committee of scientific and health experts.
Ethylene thiourea appears as white to pale green crystals or an off-white solid. Odorless when pure, but technical product may have an amine odor. (NTP, 1992)
Ethylenethiourea is a member of imidazolidines.
Ethylene thiourea is used in the rubber industry and in the production of some fungicides. No information is available on the acute (short-term) or chronic (long-term) effects of ethylene thiourea in humans. In rodents chronically exposed to ethylene thiourea in their diet, effects on the thyroid have been observed. Ethylene thiourea has been shown to be a potent teratogen (causes birth defects) in rats orally or dermally exposed. A study of female workers occupationally exposed to ethylene thiourea did not report an increased incidence of thyroid cancer. In a study by the National Toxicology Program (NTP), an increased incidence of thyroid tumors in rats, and thyroid, liver, and pituitary gland tumors in mice exposed to ethylene thiourea were noted. EPA has classified ethylene thiourea as a Group B2, probable human carcinogen.
Ethylene Thiourea is a greenish, crystalline compound with a faint amine smell and emits toxic fumes of nitrogen oxides and sulfur oxides when heated to decomposition. Ethylene thiourea is mainly used as an accelerator in the production of rubber, and in the manufacture of ethylene bisdithiocarbamate pesticides. This substance is teratogenic in animals and is reasonably anticipated to be a human carcinogen based on evidence of carcinogenicity in experimental animals. (NCI05)
Ethylenethiourea is an organosulfur compound. It is an example of an N-substituted thiourea. This compound is be synthesized by treating ethylenediamine with carbon disulfide.
A degradation product of ethylenebis(dithiocarbamate) fungicides. It has been found to be carcinogenic and to cause THYROID hyperplasia.

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Mechanism of Action
Ethylenebisdithiocarbamates (EBDCs) maneb and zineb are widely used fungicides the final metabolite of which is ethylenethiourea (ETU). EBDCs distort the humoral activity of the thyroid gland, and ETU is especially active in this respect. Male Wistar rats were exposed either to exogenous (100 ng ip) or endogenous (+4 degrees C) TRH stimulation. ETU (100-500 mg/kg i.p.) caused no changes in serum TSH levels whereas zineb (70-500 mg/kg ip) significantly decreased the bursts induced by cold or exogenous TRH. Maneb (20-200 mg/kg ip) significantly decreased the cold-induced TSH response while it had no effect on the TRH-stimulated TSH secretion. None of the agents caused significant changes in serum T3 or T4 levels. It seems that maneb, and zineb, but not ETU, inhibit rat TSH secretion through an action on the endogenous TRH at the hypothalamic or pituitary level. The mechanism behind this action may be the inhibition of dopamine-beta-hydroxylase.
The biochemical changes induced by antithyroid drugs include reduced production of thyroid hormones (T3 and T4), followed by increased production of TSH in response to low thyroid hormone levels in the blood. Pathological changes in the thyroid gland begin with diffuse microfollicular hyperplasia and are followed by diffuse and nodular hyperplasia and later by nodular hyperplasia with papillary and cystic changes induced by the TSH. If hyperstimulation of the thyroid by TSH is severe and prolonged, it provides conditions conducive to the formation of tumors. Antithyroid drugs can inhibit T4 production in various ways. The chemical similarity of ETU to thiourea and thiouracil suggests that ETU acts by blocking the iodination of thyroxine precursors, thus reducing the synthesis of the thyroid hormones. Iodide peroxidase catalyses the iodination of tyrosine and the coupling of the resultant iodotyrosyl residues to produce the active hormones T3 and T4 ... ETU /was found to/ inhibit iodide peroxidase in vitro. The resulting decreased level of thyroid hormones causes stimulatory feedback of the pituitary gland and consequently an increased release of TSH ... The influence of ETU in pregnant hypothyroid and euthyroid rats /was studied/ to determine whether ETU teratogenicity occurs as a result of altered maternal thyroid function. Doses of 40 mg ETU/kg bw, administered on days 7 - 15 of gestation, resulted in 84 - 100% of the fetuses in all treated groups being malformed, regardless of the thyroid status of the dams ... /It was/ concluded that the thyroid status of the mother is not of importance in causing teratogenic effects ... The effects of feeding rats 125 - 625 mg ETU/kg diet for 2 - 12 weeks, which included thyroid hyperplasia and dose related suppression of serum T3 and T4 (with corresponding TSH elevation), were reversible within 22 weeks of placing on control diets. Long-term studies using ETU showed significantly increased thyroid/bw ratios in rats fed 125, 250, or 500 mg/kg diet for periods of up to 2 years ... This effect was not reversed in rats placed on a control diet after 66 weeks of continuous exposure to 5 - 500 mg ETU/kg diet. It is likely that by that time the thyroid was severely damaged ... Decreased levels of serum thyroid hormones and increased thyroid weights were reversed in Sprague Dawley rats fed diets containing 0, 75, 100, or 150 mg ETU/kg diet for 7 weeks. The reversibility of microscopic changes in the thyroids of male rats exposed to ETU was /also/ studied. The rats were fed diets containing 75 or 150 mg ETU/kg diet for 7 - 82 weeks and then returned to a control diet for periods ranging from 2 to 42 weeks. The severity and extent of reversibility of thyroid hyperplasia were found to depend on the duration of exposure to ETU. Above a certain threshold, hyperplasia did not regress significantly. Numerous studies with ETU suggest that the rat is more sensitive than other species to the effects of the thyroid. A recent study with propylthiouracil, a thyroid inhibitor with a mode of action similar to that of ETU, has confirmed that monkeys are much less sensitive than rats. The sensitivity difference was not quantified in vivo, but in an in vitro study, the concentration of inhibitor required to produce the same level of thyroid peroxidase inhibition was approximately 100 times greater for monkey enzyme than it was for rat enzyme ...

C3H6N2S

102.1581

102.025

96-45-7

Ethylenethiourea-d4;352431-28-8

2723650

White to off-white solid powder

1.3±0.1 g/cm3

148.3±23.0 °C at 760 mmHg

196-200 °C(lit.)

43.5±22.6 °C

4.3±0.3 mmHg at 25°C

1.626

-0.66

2

1

0

6

63.2

0

PDQAZBWRQCGBEV-UHFFFAOYSA-N

InChI=1S/C3H6N2S/c6-3-4-1-2-5-3/h1-2H2,(H2,4,5,6)

imidazolidine-2-thione

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)