3-(3,5-다이클로로페닐)-5-에텐일-5-메틸-2,4-옥사졸리딘다이온

Pesticide -> EPA IRIS

Fungicides

Active substance -> EU Pesticides database: Not approved

Pesticides -> Fungicides

Environmental transformation -> Pesticides (parent, predecessor)

Fungicides

log Kow = 3.10

3.1

Colorless crystals

Crystalline solid

Colorless to white crystalline solid

White solid. MP 106-109 °C. Solubility in toluene 10.9; acetone33.4, methanol 1.54 (mg/L, 20 °C) (technical)

In water, 2.6 mg/L at 20 °C

In acetone = 435; benzene = 146; chloroform = 319; ethyl acetate = 253 (g/kg)

In methanol 1.54, acetone 33.4, ethyl acetate 23.3, n-heptane 0.45, toluene 10.9, dichloromethane 47.5 (all in g/100 mL at 20 °C).

Danger

H317: May cause an allergic skin reaction [Warning Sensitization, Skin]

P203, P261, P272, P273, P280, P302+P352, P318, P321, P333+P317, P362+P364, P391, P405, and P501 (click each P-code to see the statement)

Danger

H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]

P203, P261, P272, P273, P280, P302+P352, P318, P321, P333+P317, P362+P364, P391, P405, and P501 (click each P-code to see the statement)

Hazard Traits - Carcinogenicity; Developmental Toxicity; Reproductive Toxicity

Regulation (EC) No 1107/2009 (amended)

Vinclozolin is listed in the dataset of EPA Human Health Benchmarks for Pesticides under the Safe Drinking Water Act (40 eCFR 141)

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

A skin sensitizer; Has antiandrogenic activity; A metabolite is a potential carcinogen; [EPA REDs] A skin and eye irritant; Possible skin sensitizer; [Merck Index] A moderate skin and mild mucous membrane irritant, based on animal studies; [HSDB] Causes adverse effects on testis and genital tract development after pregnant animals fed >100 mg/kg/day; No human data; [REPROTOX] May cause skin sensitization; [eChemPortal: ESIS]

USEPA/Office of Prevention, Pesticides and Toxic Substances; Reregistration Eligibility Decision Document - Vinclozolin EPA 738-R-00-023 (October 2000). The RED summarizes the risk assessment conclusions and outlines any risk reduction measures necessary for the pesticide to continue to be registered in the USA.[Available from, as of January 31, 2017: http://www.epa.gov/pesticides/reregistration/status.htm]

U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) on Vinclozolin (50471-44-8).[Available, as of February 24, 2017: https://www.epa.gov/iris]

Tolerances are established for the combined residues of the fungicide vinclozolin (3-(3,5-dichlorophenyl)-5-ethenyl-5-methyl-2,4-oxazolidinedione) and its metabolites containing the 3,5-dichloroaniline moiety in or on the food commodities in the table below. There are no USA registrations for grape (wine) as of July 30, 1997.[Table#6235]

Revoked tolerances subject to the channel of trade provisions. The following table lists commodities with residues of vinclozolin resulting from lawful use /that/ are subject to the channels of trade provisions of section 408(l)(5) of the FFDCA:[Table#6236]

Based on the reviews of the generic data for the active ingredient in this case, the Agency has sufficient information on the health effects and on the environmental fate and effects of vinclozolin. The Agency has determined that vinclozolin products, if labeled and used as specified in this Reregistration Eligibility Decision, will not pose unreasonable risks or adverse effects to humans or the environment. Under the Food Quality Protection Act, the Agency has determined that there is reasonable certainty that no harm will result to infants and children or the general population for aggregate exposure to vinclozolin. Therefore, the Agency concludes that all products containing vinclozolin are eligible for reregistration.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer saftey standards, such as those described in the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern than those on List C, and with List C containing pesticides of greater concern than those on List D. Vinclozolin is found on List B. Case No: 2740; Pesticide type: Fungicide; Case Status: OPP is reviewing data from the pesticide's producers regarding its human health and/or environmental effects, or OPP is determining the pesticide's eligibility for reregistration and developing the Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): 3-(3,5-dichlorophenyl)-5-ethenyl-5-methyl-2,4-oxazolidinedione; Data Call-in (DCI) Date(s): 06/28/91, 03/03/95, 10/13/95, 12/21/95, 09/18/96; AI Status: The producers of the pesticide have made commitments to conduct the studies and pay the fees required for reregistration, and are meeting those commitments in a timely manner.

A halogenated dicarboximide. Organic amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx).

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

ACCIDENTAL RELEASE MEASURES Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging: Dispose of as unused product.

Do not discharge effluent containing this product into lakes, streams, ponds estuaries, oceans or other waters unless in accordance with the requirements of a National Pollutant Discharge Elimination System (NPDES) permit and the permitting authority has been notified in writing prior to discharge.

ACCIDENTAL RELEASE MEASURES Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

For more Preventive Measures (Complete) data for Vinclozolin (17 total), please visit the HSDB record page.

Tolerances are established for the combined residues of the fungicide vinclozolin (3-(3,5-dichlorophenyl)-5-ethenyl-5-methyl-2,4-oxazolidinedione) and its metabolites containing the 3,5-dichloroaniline moiety in or on the food commodities in the table below. There are no USA registrations for grape (wine) as of July 30, 1997.[Table#6229]

Revoked tolerances subject to the channel of trade provisions. The following table lists commodities with residues of vinclozolin resulting from lawful use /that/ are subject to the channels of trade provisions of section 408(l)(5) of the FFDCA:[Table#6230]

Excerpt from ERG Guide 171 [Substances (Low to Moderate Hazard)]:

Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

For more Personal Protective Equipment (PPE) (Complete) data for Vinclozolin (9 total), please visit the HSDB record page.

... We tested the hypothesis that the antiandrogenic activity of mixtures of azole fungicides can be predicted by the concentration addition (CA) model. The antiandrogenic activity was assessed in MDA-kb2 cells. Following assessing single compounds activities mixtures of azole fungicides and vinclozolin were investigated. Interactions were analyzed by direct comparison between experimental and estimated dose-response curves assuming CA, followed by an analysis by the isobole method and the toxic unit approach. The antiandrogenic activity of pyrethroids deltamethrin, cypermethrin, fenvalerate and permethrin was weak, while the azole fungicides tebuconazole, propiconazole, epoxiconazole, econazole and vinclozolin exhibited strong antiandrogenic activity. Ten binary and one ternary mixture combinations of five antiandrogenic fungicides were assessed at equi-effective concentrations of EC25 and EC50. Isoboles indicated that about 50% of the binary mixtures were additive and 50% synergistic. Synergism was even more frequently indicated by the toxic unit approach. Our data lead to the conclusion that interactions in mixtures follow the CA model. However, a surprisingly high percentage of synergistic interactions occurred. Therefore, the mixture activity of antiandrogenic azole fungicides is at least additive ...

Endocrine disruptors may play substantial roles in the high incidence of breast cancer. We previously described how early exposure to the mixture of phytoestrogen genistein (G) and the anti-androgen vinclozolin (V) affects peripubertal mammary development. This study evaluates the carcinogenic potential of exposure to V alone or associated with G from conception until weaning in Wistar rats. Dams were exposed to V, G or GV during pregnancy/lactation. At PND50 offspring were treated with DMBA[7,12-dimethylbenz(a)anthracene]. V or GV maternal exposure decreased number of DMBA-induced mammary tumors in the offspring, without significant modifications in tumor incidence, multiplicity and latency. G exposure decreased number of tumors, incidence and multiplicity. Unexpectedly, GV exposure increased tumor volume (p=0.04 vs controls) and epithelial proliferation (p=0.001 vs controls; p=0.005 vs G,V only). All tumors were in situ carcinomas. Concluding, maternal gestation/lactation exposure to a vinclozolin and genistein mixture significantly increases offspring tumor growth without changes in carcinogenesis susceptibility.

... In the present study, the effects of two model androgen receptor (AR) antagonists, flutamide (FLU), and vinclozolin (VIN), were first determined individually in male Japanese medaka using the transcriptional response for genes associated with the hypothalamic-pituitary-gonadal axis. The fish were further exposed to binary mixtures of VIN and 17beta-trenbolone (TRE, AR agonist) to confirm the theoretical opposing effects of the AR antagonist and agonist. The results showed that exposure to FLU or VIN alone induced very similar transcriptional responses, demonstrating that gene transcription analysis could be successfully employed in identifying the action of single chemicals. For example, both exposures increased the transcription of cyp17b but decreased that of cyp19b in the gonad, demonstrating the compensatory response for AR blockage. However, in the case of exposure to mixtures, although the joint antagonistic action of TRE and VIN affected the most genes, the transcription profiles after exposure to mixtures were not consistent with expectations based on the results for individual chemicals, such as hepatic vtg, and star or cyp19a in gonads ...

Bisphenol-A (BPA), dichrolodiphenyltrichloroethane (DDT) and vinclozolin were found able to induce abnormal uterine contraction ... We hypothesized that the effect of these compounds were mediated via the uterotonin pathways. Therefore, in this study, effects of BPA, vinclozolin and DDT-only and in combination with uterotonins (PGF-2alpha, acetylcholine and oxytocin) on the force and pattern of uterine contraction were observed. Uteri were harvested from intact adult female rats 24 hours after a single injection (1 mg/kg/bw) of estrogen to synchronize their estrous cycle. The uterine horns were subjected for ex-vivo contraction studies in an organ bath connected to Powerlab data acquisition system. Different doses of BPA, vinclozolin and DDT were added into the bathing solution and changes in the pattern and strength of uterine contraction were recorded. Further, increasing doses of uterotonins were concomitantly administered with these compounds and changes in the force and pattern of contraction were observed. In the absence of uterotonins, uterine contractile force decreased with increasing doses of BPA and DDT. However, vinclozolin induced sharp increase in the contractile forces which then gradually decrease. Administration of BPA, DDT and vinclozolin alone reduced the force of uterine contraction following stimulation of contraction by uterotonins. However, BPA, vinclozolin or DDT effects were relieved upon co-administration with uterotonins at increasing doses. The antagonizing effect of uterotonins on BPA, vinclozolin and DDT actions could explain the mechanism underlying the adverse effect of these compounds on uterine contraction.

For more Interactions (Complete) data for Vinclozolin (10 total), please visit the HSDB record page.

LC50; Species: Anas platyrhynchos (Mallard duck) age 14 days; dietary >5629 ppm for 8 days

LC50; Species: Colinus virginianus (Northern bobwhite) age 14 days; dietary >5620 ppm for 8 days

LC50; Species: Colinus virginianus (Northern bobwhite) age 20 weeks; dietary >5620 ppm for 8 days

LD50; Species: Colinus virginianus (Northern bobwhite) age 20 weeks; oral via capsule >2510 mg/kg

For more Ecotoxicity Values (Complete) data for Vinclozolin (21 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values ranging from 100 to 735(2) indicate that vinclozolin is expected to have moderate to low mobility in soil(SRC). Volatilization of vinclozolin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.7X10-8 atm-cu m/mole(SRC), derived from its vapor pressure, 2.6X10-6 mm Hg(3), and water solubility, 2.6 mg/L(2). Vinclozolin is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(3). Hydrolysis half-lives ranging from 541 hours at pH 4.3 to 0.62 hours at pH 8.3(4) suggest hydrolysis may be important in some soils(SRC). In aerobic soil studies, vinclozolin exhibited 50% degradation, following second and third fungicide applications, after 4 to 30 days and 2.5 to 7 days, respectively(5), indicating that under certain conditions biodegradation is expected to be an important fate process in soil(SRC).

TERRESTRIAL FATE: Utilizing aerobic soil field studies, vinclozolin demonstrated dissipation half-lives between 34 to 94 days, while half-lives for the total system (including metabolites) were between 179 to less than 1000 days(1).

AQUATIC FATE: Based on a classification scheme(1), Koc values ranging from 100 to 735(2) indicate that vinclozolin may adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.4X10-8 atm-cu m/mole(SRC), derived from its vapor pressure, 2.6X10-6 mm Hg(4), and water solubility, 2.6 mg/L(2). According to a classification scheme(5), an estimated BCF range of 52 to 1,260(6,7), derived from its log Kow of 3.10(8), suggest the potential for bioconcentration in aquatic organisms is moderate to very high(SRC), provided the compound is not metabolized by the organism(SRC). Hydrolysis is affected by pH with half-lives at 35 °C ranging from 541 hours at pH 4.5 to half-lives of 0.62 hours at pH 8.3(9). In aerobic soil studies, vinclozolin exhibited 50% degradation, following second and third fungicide applications, after 4 to 30 days and 2.5 to 7 days, respectively(10), indicating that under certain conditions biodegradation may be an important fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), vinclozolin, which has a vapor pressure of 2.6X10-6 mm Hg at 20 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase vinclozolin is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 4 hours(SRC), calculated from its rate constant of 3.3X10-11 cu cm/molecule-sec at 25 °C(SRC), that was derived using a structure estimation method(3). Particulate-phase vinclozolin may be removed from the air by wet and dry deposition(SRC). Irradiation of vinclozolin for 8 hours under UV light (>290 nm) resulted in a 10% degradation of the chemical; irradiation for 8 hours under artificial sunlight in the presence of humic acid resulted in 55% degradation(4), suggesting the potential for direct photolysis(SRC).

In FDA total diet studies analyzing foods as part of the pesticide monitoring program during the fiscal years 2011 through 2013, vinclozolin was not detected in food items examined. However for fiscal years 2008 and 2009 vinclozolin was listed as a pesticide found although it was not quantified(1). Vinclozolin was detected in the following food assessed an FDA total diet study from 2004 to 2005 (times found, mean concn in ppm): iceberg lettuce (2 of 8; 0.00018), green beans (2 of 8; 0.0063), green beans canned (3 of 8; 0.00104), honey (1 of 8; 0.00013), green beans baby food (3 of 8; 0.00025), mixed frozen vegetables (4 of 8; 0.00098), leaf lettuce (2 of 8; 0.00121), and was not detected in: lima beans (0 of 8) or strawberries (0 of 8)(2).

Vinclozolin was detected in 9 of 936 samples from the U.S. FDA's 1990 Total Diet Study(1,2). Vinclozolin was detected in 3 of 201 adult foods, mainly strawberries, in the U.S. FDA's Total Diet Study conducted between April 1982 to April 1984 and in June 1984 to April 1986(3,4). Vinclozolin was detected in 90 of 6,391 domestic agricultural commodities (kiwi fruit, iceberg lettuce, strawberries) and in 160 of 12,044 imported agricultural commodities (apples, apricots, blackberries, grapes, kiwi fruit, mache greens, bell peppers, raspberries, strawberries, tomatoes) sampled by the U.S. FDA's Los Angeles District between Oct 1981 to Sept 1986(5). Vinclozolin was detected in 68 of 13,980 food samples analyzed during Fiscal year 1988; in 57 of 13,085 food samples analyzed in Fiscal year 1989(6). In a U.S. survey of produce (approx 80% domestic, 20% foreign) conducted from 1989 to 1991 vinclozolin was detected in 28 of 6,970 samples, including grapes, onions, peppers, and strawberries(7). In 1992 to 1993, the U.S. FDA detected vinclozolin in 3 of 1,219 domestic tomato samples at a maximum concentration of 0.04 ppm(8).

Samples of fruits and vegetables from eight local markets in Egypt were collected in 1995, where vinclozolin was detected in 2 out of 47 cucumbers, and one out of 13 oranges at mean concentrations of 0.17 (range of 0.02 to 0.31) and 0.02 mg/kg, respectively(1). In 1996, vinclozolin was detected one time each in 43 onions, 56 squash, and 38 strawberries, at concentrations of 0.1, 0.3 and 0.87 mg/kg, respectively, from eight local markets in Egypt(2). Over a 10-year study period from 1982 to 1991, vinclozolin was detected 55 times in 6 ready-to-eat foods at an average concentration of 0.0443 ug/g; 0.0023 ug/g in boiled green beans, 0.0073 in canned green beans, 0.0170 in plain cake type donuts, 0.0432 in purple or green grapes, and 0.1918 in raw strawberries(3). Vinclozolin was detected in the following foods from the Danish National Pesticide Monitoring Program in 1996 (times found/total samples analyzed): pear (1/33), nectarine (2/20), plum (1/23), grape (1/50), strawberry (10/72), kiwi (10/31), carrot (1/54), tomato (1/48), pepper (2/31), squash (1/30), and Chinese cabbage (1/40)(4).

Vinclozolin was detected in the following foods in the Belgian total diet from 1991 to 1993(1,2):[Table#6237]

For more Food Survey Values (Complete) data for Vinclozolin (6 total), please visit the HSDB record page.

IDENTIFICATION AND USE: Vinclozolin is a solid. It is a non-systemic fungicide used to control various blights and rots caused by fungal pathogens. HUMAN EXPOSURE AND TOXICITY: There was no evidence of any health effects induced by vinclozolin among employees with potential long term exposure. In particular, no antiandrogenic effects were found. Vinclozolin did not prompt sister-chromatid exchange (SCE)-inducing activities in human lymphocytes in vitro with or without metabolic activation. ANIMAL STUDIES: Vinclozolin has been shown to be strong antiandrogen in rats when exposure occurs in utero. At low dose levels in rats (>3 mg/kg/day), the most androgen sensitive effects are noted, such as decreased prostate weight, weight reduction in other sex organs, nipple/areolas development, and decreased ano-genital distance in male rats. At higher dose levels, the reduction in male sex organ weight is exacerbated, and sex organ malformations are seen, such as reduced penis size, ectopic testes, vaginal pouches, hypospadias, and additional ambiguities of the urogenital system. In some studies reduced fertility from the hypospadias, delayed puberty and kidney stones were noted. Vinclozolin and/or its metabolites cause Leydig cell (testicular) tumors in rats. There is also evidence in the published literature that vinclozolin may affect the development and function of the neuroendocrine system. Vinclozolin has been shown to alter sexual behavior in rats. When vinclozolin (98%) was tested at 0, 100, 500, 2500, 5000, 7500 or 10,000 ug/plate with and without metabolic activation in Salmonella strains TA98, TA100, TA1535, TA1537 and TA1538, no mutagenicity was reported. Vinclozolin (98.1%) was tested in sister chromatid exchange (in vivo) with Chinese hamsters, no increase in SCE was reported. ECOTOXICITY STUDIES: In adult Japanese quail steroid levels were unaltered by vinclozolin treatment, the display of male reproductive behavior seemed delayed, with the number of mounts and the number of cloacal contacts being significantly lower in the treated males. In mammals, vinclozolin is known as anti-androgen, which causes male infertility via androgen receptor antagonism. In aquatic animals, vinclozolin effects on reproductive functions are largely unknown and results are somewhat contradictory. In invertebrates, vinclozolin can modulate gene expression, leading to possible significant endocrine alterations of the insect endocrine system.

Vinclozolin and some of its metabolites have antiandrogenic activity. Vinclozolin's main toxic effects are related to its antiandrogenic activity. They compete with androgens for the androgen receptor, inhibit androgen receptor-DNA binding, and alter androgen-dependent gene expression.

FOOD: The daily intake per unit of body weight of vinclozolin in Fiscal Years 1979 and 1981/82 was 0.003 ug/kg of body weight/day(1). Average daily intake of vinclozolin was determined as 0.01 mg/kg, for Danish farmers assuming a body weight of 60 kg(2).

FOOD: Daily intake of vinclozolin in the US(1).[Table#6231]

FOOD: Daily intake of vinclozolin per unit of body weight in the US(1).[Table#6232]

FOOD: Daily intake of vinclozolin per unit of body weight in the US(1).[Table#6233]

/BIRDS and MAMMALS/ In a one-generation reproduction study, the major agricultural fungicide vinclozolin was administered to adult Japanese quail for a period of 6 weeks at dietary levels of 125 and 500 ppm. Fertility and reproductive performance were not affected up to the highest concentration, although the examination of additional endpoints in the drakes (spermatid count, histology of the testis) provided some evidence of an inhibition of spermatogenesis at both dietary concentrations. Likewise, there were no indications of systemic toxicity in the adult birds. Plasma hormone concentrations (estradiol, testosterone, progesterone, T3, and T4) showed a large interindividual variance but treatment-related differences between the groups could not be established. There were no clear-cut indications of antiandrogenic effects in quail, although a limited transfer of the test substance into the eggs was proven.

/BIRDS and MAMMALS/ ... The effects of vinclozolin (VIN), an antiandrogenic fungicide, on sexual differentiation and maturation were investigated in Japanese quail (Coturnix coturnix japonica). On day 4 of incubation, embryos were exposed /by direct injection into the egg/ to no treatment, oil, or 25, 50, or 100 ppm of VIN. Endpoints measured included adult male reproductive behavior, hypothalamic gonadotropin-releasing hormone I (GnRH-I) content in hatchlings and adults, plasma steroid levels in hatchlings and adults, proctodeal gland growth during maturation, and relative testicular weight at seven weeks of age. Results showed that exposure to VIN significantly (p<0.05) altered GnRH-I in male hatchlings, whereas GnRH-I levels in females remained unaffected. Although steroid levels were unaltered by any VIN treatment, the display of male reproductive behavior seemed delayed, with the number of mounts and the number of cloacal contacts being significantly (p<0.05) lower in the VIN-treated males. This could have an extreme negative impact on wild avian species that are routinely exposed to similar EDCs.

/AQUATIC SPECIES/ Vinclozolin, a widely used fungicide, has been characterized as a potent androgen antagonist. In this study, the effects of vinclozolin on the interrenal system of the rare minnow (Gobiocypris rarus) were evaluated. The results revealed a decline of the renal somatic index (RSI) and the presence of histopathological effects, including shrinkage of the glomerulus and expansion of the Bowman's space in the kidneys, in rare minnows exposed to vinclozolin. Elevated plasma cortisol concentrations in females exposed to >/= 2 ug/L vinclozolin and males exposed to >/= 10 ug/L vinclozolin (p<0.05) suggested that endocrine stress was evoked by vinclozolin exposure. Significant decreases in mRNA levels of interrenal crf, pomc, gr, and nka in females and gr and nka in males were observed after exposure to >/= 0.5 ug/L and 2 ug/L vinclozolin (p<0.05), respectively; however, no changes in expression of these genes were observed in the brain of males (p>/=0.159) or females (p>/=0.053) compared with the control. The results indicated that female rare minnows were more sensitive than males to vinclozolin exposure. In conclusion, vinclozolin exposure evoked endocrine stress on the hypothalamic-pituitary-interrenal axis in the rare minnow, and the interrenal tissue was more sensitive than the brain tissue to stress caused by vinclozolin exposure ...

/AQUATIC SPECIES/ ... This study aimed at identifying windows of sensitivity to endocrine disruptors (EDs) along the life-cycle of the freshwater snail Lymnaea stagnalis, a candidate species for the development of forthcoming test guidelines. Juveniles, sub-adults, young adults and adults were exposed for 21 days to the fungicide vinclozolin (VZ). Survival, growth, onset of reproduction, fertility and fecundity were monitored weekly. Data were analyzed using standard statistical analysis procedures and mixed-effect models. No deleterious effect on survival and growth occurred in snails exposed to VZ at environmentally relevant concentrations. A significant impairment of the male function occurred in young adults, leading to infertility at concentrations exceeding 0.025 ug/L. Furthermore, fecundity was impaired in adults exposed to concentrations exceeding 25 ug/L. Biological responses depended on VZ concentration, exposure duration and on their interaction, leading to complex response patterns. The use of a standard statistical approach to analyze those data led to underestimation of VZ effects on reproduction, whereas effects could reliably be analyzed by mixed-effect models. L. stagnalis may be among the most sensitive invertebrate species to VZ, a 21-day reproduction test allowing the detection of deleterious effects at environmentally relevant concentrations of the fungicide ...

For more Ecotoxicity Excerpts (Complete) data for Vinclozolin (20 total), please visit the HSDB record page.

Vinclozolin was detected in vegetation (Salsola sp., Avena sp., Malva sp., and Heliotropium sp.) collected near Karak raw wastewater disposal site, Jordan, in October 1998, at concentrations ranging from 11.8 to 190.7 ppb, with an average of 46.9 ppb(1).

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of December 8, 2016: http://actor.epa.gov/dashboard/]

Vinclozolin was detected in wastewater samples taken from Karak raw wastewater disposal site, Jordan, in October 1998, at concentrations ranging from 12.1 to 110.5 ppb, with an average of 46.3 ppb(1). Vinclozolin was detected in the biodegradable fraction of household waste collected in 1995, its 5-month compost, anaerobic mesophilic digestates after 30 days and anaerobic thermophilic digestates after 19 days at average concentrations of 14, 5.1, 4.5 and 4.9 ng/g, respectively(2).

Tolerances are established for the combined residues of the fungicide vinclozolin (3-(3,5-dichlorophenyl)-5-ethenyl-5-methyl-2,4-oxazolidinedione) and its metabolites containing the 3,5-dichloroaniline moiety in or on the food commodities in the table below. There are no USA registrations for grape (wine) as of July 30, 1997.[Table#6235]

Revoked tolerances subject to the channel of trade provisions. The following table lists commodities with residues of vinclozolin resulting from lawful use /that/ are subject to the channels of trade provisions of section 408(l)(5) of the FFDCA:[Table#6236]

Based on the reviews of the generic data for the active ingredient in this case, the Agency has sufficient information on the health effects and on the environmental fate and effects of vinclozolin. The Agency has determined that vinclozolin products, if labeled and used as specified in this Reregistration Eligibility Decision, will not pose unreasonable risks or adverse effects to humans or the environment. Under the Food Quality Protection Act, the Agency has determined that there is reasonable certainty that no harm will result to infants and children or the general population for aggregate exposure to vinclozolin. Therefore, the Agency concludes that all products containing vinclozolin are eligible for reregistration.

As the federal pesticide law FIFRA directs, EPA is conducting a comprehensive review of older pesticides to consider their health and environmental effects and make decisions about their continued use. Under this pesticide reregistration program, EPA examines newer health and safety data for pesticide active ingredients initially registered before November 1, 1984, and determines whether the use of the pesticide does not pose unreasonable risk in accordance to newer saftey standards, such as those described in the Food Quality Protection Act of 1996. Pesticides for which EPA had not issued Registration Standards prior to the effective date of FIFRA '88 were divided into three lists based upon their potential for human exposure and other factors, with List B containing pesticides of greater concern than those on List C, and with List C containing pesticides of greater concern than those on List D. Vinclozolin is found on List B. Case No: 2740; Pesticide type: Fungicide; Case Status: OPP is reviewing data from the pesticide's producers regarding its human health and/or environmental effects, or OPP is determining the pesticide's eligibility for reregistration and developing the Reregistration Eligibility Decision (RED) document.; Active ingredient (AI): 3-(3,5-dichlorophenyl)-5-ethenyl-5-methyl-2,4-oxazolidinedione; Data Call-in (DCI) Date(s): 06/28/91, 03/03/95, 10/13/95, 12/21/95, 09/18/96; AI Status: The producers of the pesticide have made commitments to conduct the studies and pay the fees required for reregistration, and are meeting those commitments in a timely manner.

Vinclozolin, a dicarboximide fungicide, alters morphological sex differentiation in male rats following perinatal exposure. The occurrence of these abnormalities correlates with the in vivo formation of two antiandrogenic metabolites of vinclozolin, (i.e. 2-(((3,5-dichlorophenyl)-carbamoyl)oxy)-2-methyl-3-butenoic acid (M1) and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2)), which are potent inhibitors of rat androgen receptor binding. As steroid hormone receptors exhibit promiscuity in their ability to bind different ligands, the present study evaluated the ability of these vinclozolin metabolites to bind to the estrogen (ER) and progesterone (PR) receptors in vitro, and to alter estrogen receptor and progesterone receptor function following in vivo exposure. To this end, in vitro ligand binding assays demonstrated that both 2-(((3,5-dichlorophenyl)-carbamoyl)oxy)-2-methyl-3-butenoic acid and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide can compete with endogenous ligand for binding to the progesterone receptor (Ki = 400 and 60 uM, respectively). In contrast, neither metabolite exhibited the ability to bind estrogen receptor. Subsequent in vivo studies to evaluate the potential of vinclozolin to alter estrogen receptor or progesterone receptor function demonstrate that, (1) the estrogen-dependent increases in uterine weight and progesterone receptor induction were not altered by vinclozolin; (2) the distribution of nuclear and cytosolic progesterone receptor was not altered following short-term vinclozolin exposure: and (3) vinclozolin did not disrupt ovulation in cycling female rats. These studies indicate that although vinclozolin metabolites can compete for binding to the PR in vitro, concentrations of these metabolites do not reach sufficient levels to disrupt female reproductive function following short-term in vivo exposure to vinclozolin ...

Vinclozolin is a fungicide that has been shown to cause Leydig cell tumors and atrophy of the accessory sex glands in adult rodents. In addition, exposure of rats during pregnancy causes a pattern of malformations in the male urogenital tract. A wealth of standard toxicological studies and targeted research efforts is available related to this adverse effect, and these were used to evaluate the Human Relevance Framework (HRF) for noncancer health effects. Vinclozolin and two of its metabolites, designated M1 and M2, have been shown to bind and inhibit the function of the rat and human androgen receptor. Other means of interfering with androgen receptor function (e.g., by exposure to the pharmaceutical agent flutamide) lead to similar adverse health outcomes. There is direct in vivo evidence in the rat prostate that androgen-dependent gene expression changes occur after exposure to vinclozolin. There are no proposed alternatives to the androgen receptor-mediated mode of action. Based on what is known about kinetic and dynamic factors, confidence is high that the animal mode of action (MOA) for vinclozolin-induced malformation of the male reproductive tract is highly plausible in humans.

Compounds with antiandrogenic effect appear to compete with the normal negative feedback effect of testosterone at hypothalamic receptors, resulting in excessive release of gonadotropin-releasing hormone from the hypothalamus. This is followed by excessive release of hormones from the anterior pituitary (notably of LH), resulting in excessive stimulation of testicular interstitial cells. The overstimulation results in interstitial cell tumors.

... Plasma half-lives following single oral doses of 10 to 200 mg/kg/day vinclozolin were estimated at 23 and 36 hr for M and F, respectively. Similarly, half life after a 12-hr peak plateau following dietary administration was about 40 hr.

Vinclozolin (V) is a fungicide with antiandrogenic properties. To determine the pharmacokinetics and dosimetry of V, adult male rats were administered an oral dose of V (100 mg/kg) in corn oil and sacrificed over time after dosing. ...At 2 hr, V serum concentration peaked; whereas only trace levels were detected at 24 hr (t(1/2 elim) = 3.6 hr). V was detected in all tissues and preferentially accumulated in fat. M1 serum levels increased until 8 hr, being at least 2-fold higher than those of V at this time, and then declined with a t(1/2) = 3.3 hr. ... At 48 hr, M5 remained the main metabolite (t(1/2 elim) = 13.1 hr).

The mechanism of antiandrogenic activity of vinclozolin was investigated using recombinant human androgen receptor (AR). The two primary metabolites of vinclozolin in plants and mammals are M1 (2-[[3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid) and M2 (3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide). Both metabolites, in a dose-dependent manner, target androgen receptor to the nucleus and inhibit androgen-induced transactivation mediated by the mouse mammary tumor virus promoter. 3',5'-Dichloro-2-hydroxy-2-methylbut-3-enanilide is a 50-fold more potent inhibitor than (2-[[3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid) and only 2-fold less than hydroxyflutamide. In the presence of dihydrotestosterone (50 nM), 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (0.2-10 uM) inhibits androgen-induced androgen receptor binding to androgen response element DNA. In the absence of dihydrotestosterone, concentrations of 10 uM 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide or hydroxyflutamide promote androgen receptor binding to androgen response element DNA and activation of transcription. Agonist activities of 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide and hydroxyflutamide occur at 10-fold lower concentrations with the mutant androgen receptor (Thr877 to Ala) endogenous to LNCaP human prostate cancer cells. The results indicate that androgen antagonists can act as agonists, depending on ligand binding affinity, concentration, and the presence of competing natural ligands.

Vinclozolin (V) is a fungicide used in agricultural settings. V administered to rats is hydrolyzed to 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1) and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2). V, M1 and M2 have antiandrogenic properties by interacting with the androgen receptor ... Our objective was to characterize V metabolism by rat liver microsomes. V was incubated with non-treated adult male Long-Evans rat liver microsomes and NADPH. Several metabolites were detected following the extraction of incubate with acetonitrile and analysis by HPLC/DAD/MSD. One metabolite was identified as [3-(3,5-dichlorophenyl)-5-methyl-5-(1,2-dihydroxyethyl)-1,3-oxazolidine-2,4-dione] (M4), which was gradually converted to 3',5'-dichloro-2,3,4-trihydroxy-2-methylbutylanilide (M5). Both co-eluted in the same HPLC peak. Another metabolite ([M7]) was detected by UV but was unstable for mass spectral analysis. The K(M app) for co-eluted M4/M5 and [M7] was 53.7 and 135.4 ?M, the V(max app) was 0.812 and 0.669 nmoles/min/mg protein, and CL(int) was 15.1 and 4.9 mL/min/g protein, respectively. Pilocarpine, orphenadrine and proadifen and anti-rat cytochrome P450 (CYP)2A, 2B and 3A antibodies inhibited M4/M5 and [M7] formation. These results indicate that V is efficiently metabolized by CYP ...

The major metabolite in urine, feces, and bile was N-(3,5-dichlorophenyl)-2-methyl-2,3,4-trihydroxybutyramide (in the case of urine and bile, this compound was conjugated as the glucuronide). The percentage of recovered label found in bile of cannulated rats was variable, but ranged as high as 71% of recovered radioactivity. Comparatively high tissue levels were found in liver and kidney. In either tissue, N-(3,5-dichlorophenyl)-2-methyl-2,3,4-trihydroxybutyramide was the major metabolite (not conjugated).

Metabolite is buteonic acid derivative and an enanilide metabolite

Vinclozolin (V) is a fungicide with antiandrogenic properties. To determine the pharmacokinetics and dosimetry of V, adult male rats were administered an oral dose of V (100 mg/kg) in corn oil and sacrificed over time after dosing. V and its metabolites were analyzed in serum and tissues by high performance liquid chromatography/diode array detector/mass spectrometer. V, 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), and five other metabolites were detected in serum and tissues. One metabolite was identified as 3',5'-dichloro-2,3,4-trihydroxy-2-methylbutylanilide (M5). The mean serum concentration data for V were fitted to a one-compartment model for kinetic analysis. At 2 hr, V serum concentration peaked; whereas only trace levels were detected at 24 hr (t(1/2 elim) = 3.6 hr). V was detected in all tissues and preferentially accumulated in fat. M1 serum levels increased until 8 hr, being at least 2-fold higher than those of V at this time, and then declined with a t(1/2) = 3.3 hr. M5 was the main metabolite in serum and tissues. Serum M5 levels were 5-fold higher than V and 2-fold greater than M1 at all times. At 48 hr, M5 remained the main metabolite (t(1/2 elim) = 13.1 hr). Liver and kidney exhibited the highest levels of M5, V, and M1. M2 and 3,5-dichloroaniline had the lowest levels of V metabolites in serum and tissues. V is well absorbed, extensively metabolized and widely distributed. M5, the most abundant V metabolite, may be used as an exposure biomarker for pharmacokinetic modeling ...

Compounds which inhibit or antagonize the biosynthesis or actions of androgens.

Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc.

Vinclozolin (V) is a fungicide with antiandrogenic properties. To determine the pharmacokinetics and dosimetry of V, adult male rats were administered an oral dose of V (100 mg/kg) in corn oil and sacrificed over time after dosing. V and its metabolites were analyzed in serum and tissues by high performance liquid chromatography/diode array detector/mass spectrometer. V, 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), and five other metabolites were detected in serum and tissues. One metabolite was identified as 3',5'-dichloro-2,3,4-trihydroxy-2-methylbutylanilide (M5). The mean serum concentration data for V were fitted to a one-compartment model for kinetic analysis. At 2 hr, V serum concentration peaked; whereas only trace levels were detected at 24 hr (t(1/2 elim) = 3.6 hr). V was detected in all tissues and preferentially accumulated in fat. M1 serum levels increased until 8 hr, being at least 2-fold higher than those of V at this time, and then declined with a t(1/2) = 3.3 h. M5 was the main metabolite in serum and tissues. Serum M5 levels were 5-fold higher than V and 2-fold greater than M1 at all times. At 48 hr, M5 remained the main metabolite (t(1/2 elim) = 13.1 hr). Liver and kidney exhibited the highest levels of M5, V, and M1. M2 and 3,5-dichloroaniline had the lowest levels of V metabolites in serum and tissues. V is well absorbed, extensively metabolized and widely distributed. M5, the most abundant V metabolite, may be used as an exposure biomarker for pharmacokinetic modeling. These results may clarify the relationship between toxicity and tissue dose of V and its metabolites.

Male Wistar rats were dosed with 0.002, 0.02, 0.2, or 2 mg vinclozolin/sq m skin (nominal doses of 0.13, 1.3, 13, or 130 mg vinclozolin/kg b.w.) in CMC vehicle on shaved, unabraded skin of the back for up to 10 hr or until time of sacrifice (if earlier than 10 hr), at which time excess material was washed off with water. Rats were sacrificed at 0.5, 1, 2, 4, 10, or 72 hr after application. Total absorbed was defined as the sum of % of administered dose recovered in urine, cagewash, feces, and tissues plus remaining carcass. Percent absorption went down with increased dose, so that at 72 hr, total percent absorbed dose in 0.002, 0.02, 0.2, or 2 mg/sq m groups was 27, 20, 3, and 1%, respectively. In general, urine accounted for most of the label recovered. Feces generally contained about half as much label as urine for a given group. Most of the label was removed in the washing step in all groups, but the highest percentage recovery in washing was obtained from the higher dose animals.

Used as non-systemic agricultural fungicide (exhibits protective action); [HSDB] Banned in the EU for use as pesticide for plant protection; [eChemPortal: ESIS] Used on raspberries, chicory, lettuce, kiwi, canola, snap beans, dry bulb onions, ornamentals, and turf; Also on imported wine, sweet peppers, and cucumbers; [EPA REDs]

Farming (Pesticides) [Category: Industry]

For vinclozolin (USEPA/OPP Pesticide Code: 113021) there are 0 labels match. /SRP: Not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Vinclozolin is a non-systemic fungicide used to control various blights and rots caused by fungal pathogens.

Vinclozolin (VZ) is a dicarboximide fungicide widely used on fruits, vegetables and wines, effective against fungi plagues.

Agricultural fungicide.

Vinclozolin is produced by reaction of 3,5-dichlorophenyl isocyanate with an alkyl ester of 2-hydroxy-2-vinylpropionic acid, followed by ring closure is achieved at elevated temperature, or by reaction of methyl vinyl ketone with sodium cyanide, 3,5-dichloroaniline, and phosgene.

Preparation: D. Mangold et al., German patent 2207576 (1973 to BASF).

Vinclozolin is formulated as a 50% extruded granule (EG) sold only in water-soluble packets and as a 50% dry flowable (DF) formulation for open pour. In 1998, BASF requested voluntary cancellation of the 41% liquid flowable (FL) product and the wettable powder (WP) product. A minimal amount of these formulated products may still exist in the channels of trade.

Dry flowable, water dispersible granule, flowable, wettable powder in water soluble bags.

Wettable powder; suspension concentrate; dustable powder; smoke tin.

Premix Partners: Carbendazim; Chlorothalonil; Thiophanate-methyl; Thiram.

Fungicides

Environmental transformation -> Pesticides (parent, predecessor)

The WHO Recommended Classification of Pesticides by Hazard identifies Vinclozolin as unlikely to present an acute hazard in normal use; Main Use: Fungicide, other than for seed treatment.

In 1997, previously registered uses were cancelled for the following: tomatoes, plums, prunes, and grapes (except wine grapes). To reduce exposure to children, residential uses of vinclozolin were deleted and turf and ornamental applications limited to commercial and industrial sites.