Biomonitoring Summary

Ethylene thiourea

CAS No. 96-45-7
Metabolite, degradation product, and contaminant of select ethylene bisdithiocarbamate fungicides

Propylene thiourea

CAS No. 2122-19-2
Metabolite, degradation product, and contaminant of the fungicide propylene bisdithiocarbamate (propineb)

General Information

Ethylene thiourea (ETU) is a metabolite and an environmental degradation product common to several fungicides classified as ethylene bisdithiocarbamates (EBDCs), which are formulated either as zinc or manganese salts (zineb, maneb), or as polymeric metal-coordinated complexes (metiram, mancozeb). Propylene thiourea (PTU) is the metabolite and degradation product of the polymeric zinc-coordinated complex of propylene bisdithiocarbamate (propineb). ETU and PTU are also synthesis contaminants in these commercial fungicide products. The EBDCs and propineb are contact fungicides and do not act systemically. These fungicides can be applied to fruits, vegetables, field crops, and ornamental plants, but they are not registered for residential applications. EBDCs may also be added to paints, fabrics, and leather. ETU also has been used as a vulcanization accelerator, and used in electroplating baths, in dyes, synthetic resins, and pharmaceuticals and as a scavenger in waste water treatment. Propineb is not currently registered for use in the U.S. but is used in other countries that import fruits and vegetables into the U.S. (U.S. EPA, 2012)

EBDCs and propineb are water insoluble, highly bound to soil, and breakdown quickly to ETU and PTU in the environment. In contrast, ETU is water soluble and readily taken up by plant roots. Residual ETU is microbiologically degraded in soil and photo-oxidized in water within a few days (IPCS, 1988). ETU and PTU do not bioaccumulate or persist in the environment, but both can be toxic to fish and aquatic invertebrates at high concentrations such as may occur in contaminated streams and waterways. ETU has been rarely detected in surveys of groundwater (U.S. EPA 2005a, 2005b).

General population exposure to ETU and PTU occurs by consuming foods that have been treated with EBDC fungicides or propineb, respectively. Most ingested ETU and PTU originates either as a contaminant in the applied fungicide or from degradation of the parent fungicide, and ETU can be produced when food contaminated with an EBDC is heated (Lentza-Rizos, 1990). Food surveys in the U.S. have indicated that the potential for human exposure to ETU is low (U.S. EPA, 2005a, 2005b, 2005c). Because past risk estimates identified toddlers and athletes as potentially exposed through physical contact with treated sod (e.g., transplanted onto residential settings or athletic fields), there have been specific restrictions for sod treatments (U.S. EPA, 2005a, 2005b). Workers involved in the production or application of EBDCs or propineb may also be exposed to the ETU or PTU, respectively, as a synthetic contaminant or degradation product. Workers in industries that use ETU in production processes also may be exposed.

Human health effects from ETU or PTU at low environmental doses or at biomonitored levels from low environmental exposures are unknown. The EBDCs and propineb are absorbed following ingestion, inhalation, and dermal exposure. EBDCs applied to the skin or inhaled can produce irritation, but neither EBDCs nor propineb are highly toxic to humans or animals (IPCS, 1988). These fungicides breakdown rapidly in the body, so that the toxic effects of primary concern are from ETU and PTU, respectively. In animal studies ETU was well absorbed from the gastrointestinal tract and rapidly excreted in the urine as unchanged ETU and several oxidative metabolites (Allen et al., 1978; Camoni et al., 1984; Houeto et al., 1995; Iverson et al., 1980). Propineb administered to animals is rapidly metabolized and urinary metabolites include PTU. In animal testing, ETU and PTU, as well as the respective parent fungicides, have produced thyroid hyperplasia, decreased serum thyroxine levels, and increased thyroid stimulating hormone levels; these effects were attributed to inhibition of the enzyme thyroid peroxidase (FAO/WHO, 1999; NTP, 1992; U.S. EPA 2005a). A small number of rubber manufacturing workers exposed to ETU were reported to have lower serum levels of thyroxine (Smith, 1984). Increases in animal thyroidal follicular cell adenomas and carcinomas, liver and pituitary tumors have followed prolonged ETU dosing (NTP, 1992). Animals fed high doses (10-1000 mg/kg) of PTU long-term developed liver and pituitary tumors, but thyroid tumors were inconsistently noted (IPCS, 1988; FAO/WHO, 1999). ETU is a known animal teratogen and produced musculoskeletal and craniofacial teratogenic anomalies, particularly in the pregnant rat which is more sensitive than other species (NTP, 1992). Behavioral and anatomic anomalies in the central nervous system were related to impaired neural tube formation (Daston et al., 1989; Khera, 1987), which may have resulted from necrosis of neuronal cells (Khera and Tryphonas, 1985). The offspring of PTU-treated pregnant rats showed teratogenic effects of the skeletal system, and in addition at higher doses, brain malformations and enlarged thyroid glands (FAO/WHO, 1999).

ETU was negative in most mutagenic assays (Dearfield, 1994), and PTU was not mutagenic or genotoxic (IPCS, 1993). EPA considers maneb, mancozeb, and metiram fungicides and ETU as probable human carcinogens. ETU is considered by IARC as unclassifiable with regard to human carcinogenicity, and NTP considers that ETU is reasonably anticipated to be a human carcinogen. PTU was reported not to be carcinogenic in some animal studies (FAO/WHO, 1999), but carcinogenic potential was suggested by liver tumors and thyroid effects observed in mice and rat studies (IPCS, 1988). Propineb produced thyroid cancers in laboratory animals (Hasegawa et al., 1993) but has no rating as to human carcinogenicity. Additional information about external exposure (i.e., environmental levels) is available from U.S. EPA web site at: icon.

Biomonitoring Information

Urinary ETU and PTU levels reflect recent exposure. The presence of ETU in urine may indicate exposure to one of the parent ethylene bisdithiocarbamate fungicides or more likely, to ETU. PTU in urine may indicate exposure to propineb or more likely, to PTU. In the NHANES 2003-2004 and 2005-2006 survey periods, ETU was detectable only at the 90th percentile, and PTU was not detected in the subsample (CDC, 2013). Dietary intake of ETU from fruits, vegetables, and wine was correlated with urinary ETU excretion in five volunteers whose levels ranged from 0.6 to 6.7 µg/g creatinine (Aprea et al., 1997). ETU and PTU were measured in urine samples from 499 largely Hispanic pregnant women and children residing in the California agricultural area of the Salinas Valley. The geometric mean urine ETU was 0.71 µg/L(detection frequency, 22.6%) and for PTU was 0.34 µg/L (detection frequency, 0.2%) (Montesano et al., 2007).Italian adults living in an agricultural area where EBDC aerial spraying was common had higher urinary ETU concentrations (0.9-61.4 µg/L) and detection frequency (37%) compared with adults living in urban areas, 0.8-8.3 µg/L and 24%, respectively (Aprea et al., 1996). In another report of 69 Italian adults without occupational exposure, approximately 22% had detectable urinary ETU concentrations, ranging as high as 7.2 µg/day (Saieva et al., 2004). Mancozeb formulators had a geometric mean urinary ETU level of 65.3 μg/g creatinine with 644.4 μg/g creatinine as the highest level (Aprea et al., 1998). Of 272 urine specimens collected from French farmers during the season when EBDC fungicides were applied, 49% had no ETU detected and the highest 5% had levels ranging 30-100 μg/L (El Balkhi et al., 2005). In 14 potato farmers applying different ethylene dithiobiscarbamate fungicides, urinary ETU levels ranged up to 22 μg/g creatinine on the day of exposure and decreased with an approximate half-life of 100 hours (Kurttio et al., 1990). A small study of Italian vineyard workers who used mancozeb demonstrated an increase in urinary ETU at the end of the work shift that was about 20 times greater than the pre-shift concentrations (Colosio et al., 2002). A recent review summarizes urinary ETU concentrations reported in biomonitoring studies conducted in agricultural workers and control groups (Montesano and Wang, 2011)

Finding measurable amounts of ETU or PTU in urine does not imply that the levels of ETU or PTU cause an adverse health effect. Biomonitoring studies on urinary ETU or PTU provide physicians and public health officials with reference values so that they can determine whether people have been exposed to higher levels of ETU or PTU than are found in the general population. Biomonitoring data can also help scientists plan and conduct research on exposure and health effects.


Allen JR, Van Miller JP, Seymour JL. Absorption, tissue distribution and excretion of 14C ethylenethiourea by the rhesus monkey and rat. Res Commun Chem Pathol Pharmacol 1978;20(1):109-15.

Aprea C, Betta A, Catenacci G, Colli A, Lotti A, Minoia C, et al. Urinary excretion of ethylenethiourea in five volunteers on a controlled diet (multicentric study). Sci Total Environ 1997;203(2):167-79.

Aprea C, Betta A, Catenacci G, Lotti A, Minoia C, Passini W, et al. Reference values of urinary ethylenethiourea in four regions of Italy (multicentric study). Sci Total Environ 1996;192(1):83-93.

Aprea C, Sciarra G, Sartorelli P, Mancini R, Di Luca V. Environmental and biological monitoring of exposure to mancozeb, ethylenethiourea, and dimethoate during industrial formulation. J Toxicol Environ Health A 1998;53(4):263-81.

Camoni I, Cicero AM, Di Muccio A, Dommarco R. Monitoring urinary excretion of ethylenethiourea (ETU) in rats treated with Zineb. Med Lav 1984;75(3):207-14.

Centers for Disease Control and Prevention (CDC). Fourth National Report on Human Exposure to Environmental Chemicals. Updated Tables, 2013. [online] Available at URL: 4/1/13

Colosio C, Fustinoni S, Birindelli S, Bonomi I, De Paschale G, Mammone T, et al. Ethylenethiourea in urine as an indicator of exposure to mancozeb in vineyard workers. Toxicol Lett 2002;134(1-3):133-40.

Daston GP, Yonker JE, Powers JF, Heitmeyer SA. Difference in teratogenic potency of ethylenethiourea in rats and mice: relative contribution of embryonic and maternal factors. Teratology 1989;40(6):555-66.

Dearfield KL. Ethylene thiourea (ETU). A review of the genetic toxicity studies. Mutat Res 1994;317:111-32.

El Balkhi S, Sandouk P, Galliot-Guilley M. Determination of ethylene thiourea in urine by HPLC-DAD. J Anal Toxicol 2005;29(4):229-33.

FAO/WHO. Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food, Toxicological Evaluations- Propylene thiourea. 1999. Available at URL: icon.4/1/13

Hasegawa R, Cabral R, Hoshiya T, Hakoi K, Ogiso T, Boonyaphiphat P, et al. Carcinogenic potential of some pesticides in a medium-term multi-organ bioassay in rats. Int J Cancer 1993;54(3):489-93. Erratum in: Int J Cancer 1993 Sep30;55(3):528.

Houeto P, Bindoula G, Hoffman JR. Ethylenebisdithiocarbamates and ethylenethiourea: possible human health hazards. Environ Health Perspect 1995;103(6):568-73.

International Programme on Chemical Safety (IPCS). Environmental Health Criteria 78: Dithiocarbamate pesticides, ethylenethiourea, and propylenethiourea:a general introduction. 1988. Available at URL: icon.4/1/13

International Programme on Chemical Safety (IPCS). Propineb (Pesticide residues in food: 1993 evaluations Part II Toxicology). 1993. Available at URL: icon. 4/1/13

Iverson F, Khera KS, Hierlihy SL. In vivo and in vitro metabolism of ethylenethiourea in the rat and the cat. Toxicol Appl Pharmacol 1980;52(1):16-21.

Khera KS, Tryphonas L. Nerve cell degeneration and progeny survival following ethylenethiourea treatment during pregnancy in rats. Neurotoxicol 1985;6(3):97-102.

Khera KS. Ethylenethiourea:A review of teratogencity and distributions studies and an assessment of reproduction risk. Crit Rev Toxicol 1987;18:129-39.

Kurttio P, Vartiainen T, Savolainen K. Environmental and biological monitoring of exposure to ethylenebisdithiocarbamate fungicides and ethylenethiourea. Br J Ind Med 1990;47(3):203-206.

Lentza-Rizos C. Ethylenethiourea (ETU) in relation to use of ethylenebisdithiocarbamate (EBDC) fungicides. Rev Environ Contam Toxicol 1990;115:1-37.

Montesano MA, Olsson AO, Kuklenyik P, Needham LL, Bradman A, Barr DB. Method for determination of acephate, methamidophos, omethoate, dimethoate, ethylenethiourea and propylenethiourea in human urine using high-performance liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry. J Expo Sci Environ Epidemiol 2007;17:321-30.

Montesano MA, Wang R. Biomonitoring of contemporary pesticides: ethylenethiourea in occupational settings. Chap 9. In: Styocheva M, ed. Pesticides in the Modern World-Effects of Pesticides Exposure. InTech—Open Access Company. DOI:10.5772/18387. 2011.Available at URL: icon. 4/1/13

National Toxicology Program (NTP) Toxicology and Carcinogenesis Studies of Ethylene Thiourea (CAS: 96-45-7) in F344 Rats and B6C3F1 Mice (Feed Studies). Natl Toxicol Program Tech Rep Ser 1992;388:1-256. Available at URL: iconexternal icon. 4/1/13

Saieva C, Aprea C, Tumino R, Masala G, Salvini S, Frasca G, et al. Twenty-four-hour urinary excretion of ten pesticide metabolites in healthy adults in two different areas of Italy (Florence and Ragusa). Sci Total Environ 2004;332(1-3):71-80.

Smith DM. Ethylene thiourea: thyroid function in two groups of exposed workers. Br J Ind Med 1984;41(3):362-6.

U.S. Environmental Protection Agency (U.S. EPA). Multi-year workplan for registration of conventional pesticide¬¬–new chemicals. Updated October 22, 2012. Available at URL: icon.4/1/13

U.S. Environmental Protection Agency (U.S. EPA). Reregistration Eligibility Decision for Maneb. August 2005a. EPA 738 R 05-XXX. Available at URL: iconexternal icon. 4/1/13

U.S. Environmental Protection Agency (U.S. EPA). Reregistration Eligibility Decision for Mancozeb. September 2005b. EPA 738 R 04-012. Available at URL: iconreregistration/REDs/mancozeb_red.pdf.4/1/13

U.S. Environmental Protection Agency (U.S. EPA). Reregistration Eligibility Decision for Metiram. August 2005c. EPA 73 R 05-017. Available at URL: iconexternal icon. 4/1/13

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