Vinclozolin

Last updated
Vinclozolin
Vinclozolin.svg
Names
IUPAC name
(RS)-3-(3,5-Dichlorophenyl)-5-methyl-5-vinyloxazolidine-2,4-dione
Other names
Vinclozoline
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.051.437 OOjs UI icon edit-ltr-progressive.svg
KEGG
PubChem CID
UNII
  • InChI=1S/C12H9Cl2NO3/c1-3-12(2)10(16)15(11(17)18-12)9-5-7(13)4-8(14)6-9/h3-6H,1H2,2H3 Yes check.svgY
    Key: FSCWZHGZWWDELK-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C12H9Cl2NO3/c1-3-12(2)10(16)15(11(17)18-12)9-5-7(13)4-8(14)6-9/h3-6H,1H2,2H3
    Key: FSCWZHGZWWDELK-UHFFFAOYAN
  • O=C2OC(C(=O)N2c1cc(Cl)cc(Cl)c1)(C=C)C
Properties
C12H9Cl2NO3
Molar mass 286.11 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Vinclozolin (trade names Ronilan, Curalan, Vorlan, Touche) is a common dicarboximide fungicide used to control diseases, such as blights, rots and molds in vineyards, and on fruits and vegetables such as raspberries, lettuce, kiwi, snap beans, and onions. It is also used on turf on golf courses. [1] Two common fungi that vinclozolin is used to protect crops against are Botrytis cinerea and Sclerotinia sclerotiorum . [2] First registered in 1981, vinclozolin is widely used but its overall application has declined. As a pesticide, vinclozolin is regulated by the United States Environmental Protection Agency (U.S. EPA). In addition to these restrictions within the United States, as of 2006 the use of this pesticide was banned in several countries, including Denmark, Finland, Norway, and Sweden. [3] It has gone through a series of tests and regulations in order to evaluate the risks and hazards to the environment and animals. Among the research, a main finding is that vinclozolin has been shown to be an endocrine disruptor with antiandrogenic effects.[ citation needed ]

Contents

Use in the United States

Vinclozolin is manufactured by the chemical company BASF and has been registered for use in the United States since 1981. The following is a compilation of data indicating the national use of vinclozolin per crop (lbs AI/yr) in 1987: apricots, 124; cherries, 3,301; green beans, 13,437; lettuce, 24,779; nectarines, 1,449; onions, 829; peaches, 15,203; plums, 163; raspberries, 3,247; and strawberries, 41,006. [4] In 1997, two applications totaling 285 pounds each, were applied to kiwifruit in California to prevent the gray mold and soft rot caused by Botrytis cinerea. [5] In general, the United States has seen an overall decline in the national use of vinclozolin. In 1992, a total of approximately 135,000 pounds were used. However, in 1997 this number dropped to 122,000 and in 2002 it was down to 55,000 pounds. [6]

Preparation and application

The following chemical reactions are used to make vinclozolin: [7] One method combines methyl vinyl ketone, sodium cyanide, 3,5-dichloroaniline, and phosgene. This process involves formation of the cyanohydrin, followed by hydrolysis of the nitrile. [4] Vinclozolin is also prepared by the reaction of 3,5-dichlorophenyl isocyanate with an alkyl ester of 2-hydroxy-2-vinylpropionic acid. Ring closure is achieved at elevated temperature. [4]

Vinclozolin is then formulated into a dry flowable or extruded granular. It can be applied by through the air (aerial), through irrigation systems (chemigation), or by ground equipment. Vinclozolin is also applied to some plants, such as decorative flowers, as a dip treatment where the plant is dipped into the fungicide solution and then dried. It is also common to spray a vinclozolin solution using thermal foggers in greenhouses. [1]

History of regulations in the US

All pesticides sold or distributed in the United States must be registered by U.S. EPA. Pesticides that were first registered before November 1, 1984, were reregistered so that they can be retested using the now more advanced methods. Because vinclozolin was released in 1981, it has gone through both preliminary and a subsequent reregistration. [1] Below is a list of the history of regulations for vinclozolin:

Means of exposure

The U.S. EPA has examined dietary (food and water), non-dietary, and occupational exposure to vinclozolin or its metabolites. In general, fungicides have been shown to circulate through the water and air, and it possible for them to end up on untreated foods after application. Consumers alone cannot easily reduce their exposure because fungicides are not removed from produce that is washed with tap water. [9] A key example of exposure to vinclozolin is through wine grapes which is considered to account for about 2% of total vinclozolin exposure. [10] It has been determined that people may be exposed to residues of vinclozolin and its metabolites containing the 3,5-dichloroaniline moiety (3,5-DCA) through diet, and thus tolerance limits have been established for each crop. [1] Although vinclozolin is not registered for use by homeowners, it is still possible for people to come into contact with the fungicide and its residues. For example, golfers playing on treated golf courses, and families playing on sod which has been previously treated may be at risk for exposure. [1] Occupationally, workers can be exposed to vinclozolin while doing activities such as loading and mixing. [1]

Environmental and health impacts

Antiandrogen

As part of the reregistration process, the U.S. EPA reviewed all toxicity studies on vinclozolin. The main effect induced by vinclozolin is related to its antiandrogenic activity and its ability to act as a competitive antagonist of the androgen receptor.[ citation needed ] Vinclozolin can mimic male hormones, like testosterone, and bind to androgen receptors, while not necessarily activating those receptors properly. There is evidence that vinclozolin itself binds weakly to the androgen receptor but that at least two of its metabolites are responsible for much of the antiandrogenic activity. [8] When male rats were given low dose levels (>3 mg/kg/day) of vinclozolin, effects such as decreased prostate weight, weight reduction in sex organs, nipple development, and decreased ano-genital distance were noted. At higher dose levels, male sex organ weight decreased further, and sex organ malformations were seen, such as reduced penis size, the appearance of vaginal pouches and hypospadias. [8] In the rat model, it has been shown that the antiandrogenic effects of vinclozolin are most prominent during the developmental stages. [8] In utero, this sensitive period of fetal development occurs between gestation days 16-17. [11] Embryonic exposure to vinclozolin can influence sexual differentiation, gonadal formation, and reproductive functions. [12] In bird models, vinclozolin and its metabolites were shown in vitro and in vivo to inhibit androgen receptor binding and gene expression. Vinclozolin caused reduced egg laying, reduced fertility rate, and a reduction in successful hatches. [1] Androgens also play a role in puberty, and it has been shown an antiandrogen like vinclozolin can delay pubertal maturation. [11] Antiandrogenic toxins are also known to alter sexual differentiation and reproduction in the rabbit model. Male rabbits exposed to vinclozolin in utero or during infancy did not show a sexual interest in females or did not ejaculate. [11] Since the androgen receptor is widely conserved across species lines, antiandrogenic effects would be expected in humans. [8] In vertebrates, vinclozolin also acts as a neuroendocrine disruptor, affecting behaviors tied to locomotion, cognition, and anxiety. [13]

Progesterone and estrogen effects in rats

In rats, vinclozolin has been shown to affect other steroid hormone receptors, such as those of progesterone and estrogen. Just as with androgens, the timing of the exposure to vinclozolin determines the magnitude of the effects related to these hormones. In a study with rats, in vitro research showed the ability of two vinclozolin metabolites to bind to the progesterone receptor. However, the same study in vivo using adult male rats showed no effects. [14] When mice experienced vinclozolin exposure in utero, male offspring exhibited up-regulated estrogen receptor and up-regulated progesterone receptor. In females, vinclozolin down-regulated expression of estrogen receptors and up-regulated progesterone receptor expression. This result causes virilization and the feminization of males and masculinization of females. [14]

Transgenerational effects

In rats, vinclozolin has been demonstrated to have trangenerational effects, meaning that not only is the initial animal affected, but effects are also seen in subsequent generations. One study demonstrated that vinclozolin impaired male fertility not only in the first generation that was exposed in utero, but in males born for three generations and beyond. [15] Furthermore, when affected males were mated with normal females, some of the offspring were sterile and some had reduced fertility. After three generations, male offspring continued to show low sperm count, prostate disease and high rates of testicular cell apoptosis. [15] [16] Other studies conducted experiments where rat embryos were exposed to vinclozolin during sex determination. F1 (first generation) vinclozolin treated males were bred with F1 vinclozolin treated females. This pattern continued for three generations. The initial F0 mother was the only subject that was directly exposed to doses of vinclozolin. F1-F4 generation males all showed an increase in the prevalence of tumors, prostate disease, kidney disease, test abnormalities and immune failures when compared to the control group. F1-F4 females also showed an increased incidence of tumors and kidney disease. [12] Furthermore, transgenerationally transmitted changes in mate preference and anxiety behavior have also been observed in rats following exposure to vinclozolin. [17] It has been reported that these transgenerational reports correlate with epigenetic changes, specifically, an alteration in DNA methylation in the male germ line. [17] However, these transgenerational changes have not been successfully reproduced by BASF scientists, the manufacturer of vinclozolin [18]

The U.S. EPA has classified vinclozolin as a possible human carcinogen. Vinclozolin induces an increase in leydig cell tumors in rats. The 3,5-DCA metabolite is thought to possess a mode of tumor induction based on its similarity to p-choroaniline. [8]

Environment

Laboratory test indicate that vinclozolin easily breaks down and dissipates in the environment with the help of microbes. Of its several metabolites 3,5-dichloroaniline resists further degradation. [8] In terrestrial field dissipation studies conducted in various states, vinclozolin dissipated with a half-life between 34 and 94 days. Half-lives including residues can reach up to 1,000 days. Residues may accumulate and be available for future crop uptake. [8]

Alternative fungicides

Since the phase-out of vinclozolin, farmers are faced with fewer options to control gray and white mold. The New York State Agricultural Experiment Station has carried out efficacy trials for gray and white mold. Research has showed potential alternatives to vinclozolin. Trifloxystrobin (Flint), iprodione (Rovral), and cyprodinil plus fludioxonil (Switch) control gray mold. Thiophanate-methyl (Topsin M) was as effective as vinclozolin in controlling white molds. Switch was the most promising alternative to vinclozolin for controlling both gray and white mold on pods and for increasing marketable yield. [19]

Related Research Articles

<span class="mw-page-title-main">Pesticide</span> Substance used to destroy pests

Pesticides are substances that are used to control pests. They include herbicides, insecticides, nematicides, fungicides, and many others. The most common of these are herbicides, which account for approximately 50% of all pesticide use globally. Most pesticides are used as plant protection products, which in general protect plants from weeds, fungi, or insects. In general, a pesticide is a chemical or biological agent that deters, incapacitates, kills, or otherwise discourages pests. Target pests can include insects, plant pathogens, weeds, molluscs, birds, mammals, fish, nematodes (roundworms), and microbes that destroy property, cause nuisance, or spread disease, or are disease vectors. Along with these benefits, pesticides also have drawbacks, such as potential toxicity to humans and other species.

<span class="mw-page-title-main">Cypermethrin</span> Chemical compound

Cypermethrin (CP) is a synthetic pyrethroid used as an insecticide in large-scale commercial agricultural applications as well as in consumer products for domestic purposes. It behaves as a fast-acting neurotoxin in insects. It is easily degraded on soil and plants but can be effective for weeks when applied to indoor inert surfaces. Exposure to sunlight, water and oxygen will accelerate its decomposition. Cypermethrin is highly toxic to fish, bees and aquatic insects, according to the National Pesticides Telecommunications Network (NPTN). It is found in many household ant and cockroach killers, including Raid, Ortho, Combat, ant chalk, and some products of Baygon in Southeast Asia.

<span class="mw-page-title-main">Carbofuran</span> Toxic carbamate pesticide

Carbofuran is a carbamate pesticide, widely used around the world to control insects on a wide variety of field crops, including potatoes, corn and soybeans. It is a systemic insecticide, which means that the plant absorbs it through the roots, and from there the plant distributes it throughout its organs where insecticidal concentrations are attained. Carbofuran also has contact activity against pests. It is one of the most toxic pesticides still in use.

<span class="mw-page-title-main">Chlorpyrifos</span> Chemical compound

In organic chemistry, chlorpyrifos (CPS), also known as chlorpyrifos ethyl, is an organophosphate pesticide that has been used on crops, animals, and buildings, and in other settings, to kill several pests, including insects and worms. It acts on the nervous systems of insects by inhibiting the acetylcholinesterase enzyme. Chlorpyrifos was patented in 1966 by Dow Chemical Company.

<span class="mw-page-title-main">Atrazine</span> Herbicide

Atrazine is a chlorinated herbicide of the triazine class. It is used to prevent pre-emergence broadleaf weeds in crops such as maize (corn), soybean and sugarcane and on turf, such as golf courses and residential lawns. Atrazine's primary manufacturer is Syngenta and it is one of the most widely used herbicides in the United States, Canadian, and Australian agriculture. Its use was banned in the European Union in 2004, when the EU found groundwater levels exceeding the limits set by regulators, and Syngenta could not show that this could be prevented nor that these levels were safe.

<span class="mw-page-title-main">Fipronil</span> Chemical compound

Fipronil is a broad-spectrum insecticide that belongs to the phenylpyrazole chemical family. Fipronil disrupts the insect central nervous system by blocking the ligand-gated ion channel of the GABAA receptor and glutamate-gated chloride (GluCl) channels. This causes hyperexcitation of contaminated insects' nerves and muscles. Fipronil's specificity towards insects is believed to be due to its greater binding affinity for the GABAA receptors of insects than to those of mammals, and for its action on GluCl channels, which do not exist in mammals. As of 2017, there does not appear to be significant resistance among fleas to fipronil.

<span class="mw-page-title-main">Chlorothalonil</span> Fungicide

Chlorothalonil (2,4,5,6-tetrachloroisophthalonitrile) is an organic compound mainly used as a broad spectrum, nonsystemic fungicide, with other uses as a wood protectant, pesticide, acaricide, and to control mold, mildew, bacteria, algae. Chlorothalonil-containing products are sold under the names Bravo, Echo, and Daconil. It was first registered for use in the US in 1966. In 1997, the most recent year for which data are available, it was the third most used fungicide in the US, behind only sulfur and copper, with 12 million pounds used in agriculture that year. Including nonagricultural uses, the United States Environmental Protection Agency (EPA) estimates, on average, almost 15 million lb (6.8 million kg) were used annually from 1990 to 1996.

<span class="mw-page-title-main">Phosmet</span> Organophosphate non-systemic insecticide

Phosmet is a phthalimide-derived, non-systemic, organophosphate insecticide used on plants and animals. It is mainly used on apple trees for control of codling moth, though it is also used on a wide range of fruit crops, ornamentals, and vines for the control of aphids, suckers, mites, and fruit flies.

<span class="mw-page-title-main">Dicarboximide fungicides</span>

Dicarboximidefungicides are a family of agricultural fungicides that include vinclozolin, iprodione, and procymidone. Dicarboximides are believed to inhibit triglyceride biosynthesis in sclerotia-forming fungi, including Botrytis cinerea. These fungicides turn into 3,5-dichloroaniline in soil rapidly. Repeated use of dicarboximides over several years reduce their effectiveness. Resistance has developed against all dicarboximides in many plant species, including vines, strawberries and protected crops, and are recommended to be used in conjunction with other fungicides.

<span class="mw-page-title-main">Organophosphate poisoning</span> Toxic effect of pesticides

Organophosphate poisoning is poisoning due to organophosphates (OPs). Organophosphates are used as insecticides, medications, and nerve agents. Symptoms include increased saliva and tear production, diarrhea, vomiting, small pupils, sweating, muscle tremors, and confusion. While onset of symptoms is often within minutes to hours, some symptoms can take weeks to appear. Symptoms can last for days to weeks.

<span class="mw-page-title-main">Procymidone</span> Chemical compound

Procymidone is a pesticide. It is often used for killing unwanted ferns and nettles, and as a dicarboximide fungicide for killing fungi, for example as seed dressing, pre-harvest spray or post-harvest dip of lupins, grapes, stone fruit, strawberries. It is a known endocrine disruptor which interferes with the sexual differentiation of male rats. It is considered to be a poison.

<span class="mw-page-title-main">Acetamiprid</span> Chemical compound

Acetamiprid is an organic compound with the chemical formula C10H11ClN4. It is an odorless neonicotinoid insecticide produced under the trade names Assail, and Chipco by Aventis CropSciences. It is systemic and intended to control sucking insects (Thysanoptera, Hemiptera, mainly aphids) on crops such as leafy vegetables, citrus fruits, pome fruits, grapes, cotton, cole crops, and ornamental plants. It is also a key pesticide in commercial cherry farming due to its effectiveness against the larvae of the cherry fruit fly.

<span class="mw-page-title-main">Health effects of pesticides</span> How pesticides affect human health

Health effects of pesticides may be acute or delayed in those who are exposed. Acute effects can include pesticide poisoning, which may be a medical emergency. Strong evidence exists for other, long-term negative health outcomes from pesticide exposure including birth defects, fetal death, neurodevelopmental disorder, cancer, and neurologic illness including Parkinson's disease. Toxicity of pesticides depend on the type of chemical, route of exposure, dosage, and timing of exposure.

<span class="mw-page-title-main">Chlormequat</span> Chemical compound

Chlormequat is an organic compound with the formula ClCH
2CH
2N(CH
3)+
3 that is used as a plant growth regulator. It is typically sold as the chloride salt, chlormequat chloride (C5H13Cl2N), a colorless hygroscopic crystalline substance that is soluble in water and ethanol. It is an alkylating agent and a quaternary ammonium salt. Chlormequat is one of the onium-type growth regulators.

<span class="mw-page-title-main">Terbufos</span> Chemical compound

Terbufos is a chemical compound used in insecticides and nematicides. It is part of the chemical family of organophosphates. It is a clear, colourless to pale yellow or reddish-brown liquid and sold commercially as granulate.

<span class="mw-page-title-main">Fluxapyroxad</span> Chemical compound

Fluxapyroxad is a broad-spectrum pyrazole-carboxamide fungicide used on a large variety of commercial crops. It stunts fungus growth by inhibiting the succinate dehydrogenase (SQR) enzyme. Application of fluxapyroxad helps prevent many wilts and other fungal infections from taking hold. As with other systemic pesticides that have a long chemical half-life, there are concerns about keeping fluxapyroxad out of the groundwater, especially when combined with pyraclostrobin. There is also concern that some fungi may develop resistance to fluxapyroxad.

<span class="mw-page-title-main">David Crews</span> American zoologist

David Pafford Crews is the Ashbel Smith Professor of Zoology and Psychology at the University of Texas at Austin. He has been a pioneer in several areas of reproductive biology, including evolution of sexual behavior and differentiation, neural and phenotypic plasticity, and the role of endocrine disruptors on brain and behavior.

Antiandrogens in the environment have become a topic of concern. Many industrial chemicals, including phthalates and pesticides, exhibit antiandrogen activity in animal experiments. Certain plant species have also been found to produce antiandrogens. In animal studies, environmental antiandrogens can harm reproductive organ development in fetuses exposed in utero as well as their offspring.

<span class="mw-page-title-main">5α-Dihydronorethisterone</span> Chemical compound

5α-Dihydronorethisterone is a major active metabolite of norethisterone (norethindrone). Norethisterone is a progestin with additional weak androgenic and estrogenic activity. 5α-DHNET is formed from norethisterone by 5α-reductase in the liver and other tissues.

<span class="mw-page-title-main">6α-Methylprogesterone</span> Chemical compound

6α-Methylprogesterone (6α-MP) is a progestin which was never marketed. It has 150% of the progestogenic potency of progesterone. In addition, and in contrast to progesterone, 6α-MP has weak androgenic, antiandrogenic, and synandrogenic actions. 6α-MP is structurally related to medroxyprogesterone acetate and megestrol acetate, which possess androgenic and/or antiandrogenic activity to varying degrees similarly. MPA is more androgenic than 6α-MP and MGA.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 "R.E.D Facts Vinclozolin" (PDF). EPA. Retrieved 22 October 2011.
  2. ↑ "Vinclozolin" (PDF). Santa Cruz Biotechnology, Inc. Retrieved 31 October 2011.
  3. ↑ Boyd, David R. (October 2006). The Food We Eat: An International Comparison of Pesticide Regulations (PDF). Vancouver, BC, Canada: David Suzuki Foundation. p. 12. ISBN   0-9737599-9-2. Archived from the original (PDF) on 2015-07-14. Retrieved 9 February 2015.
  4. 1 2 3 Vinclozolin from PubChem
  5. ↑ "Crop Profile for Kiwi in California" (PDF). UC Davis. Archived from the original (PDF) on 30 April 2012. Retrieved 2 November 2011.
  6. ↑ "Pesticide Use in U.S. Crop Production: 2002 Fungicides and Herbicides" (PDF). Crop Life Foundation. Archived from the original (PDF) on 27 September 2011. Retrieved 2 November 2011.
  7. ↑ Franz Müller, Peter Ackermann and Paul Margot "Fungicides, Agricultural, 2. Individual Fungicides" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim. doi : 10.1002/14356007.o12_o06
  8. 1 2 3 4 5 6 7 8 "Reregistration Eligibility Decision: Vinclozolin" (PDF). EPA. Retrieved 22 October 2011.
  9. ↑ Colbert, Nathan K.W.; Pelletier, Nicole C.; Cote, Joyce M.; Concannon, John B.; Jurdak, Nicole A.; Minott, Sara B.; Markowski, Vincent P. (2005). "Perinatal Exposure to Low Levels of the Environmental Antiandrogen Vinclozolin Alters Sex-Differentiated Social Play and Sexual Behaviors in the Rat". Environmental Health Perspectives. 113 (6): 700–7. doi:10.1289/ehp.7509. PMC   1257594 . PMID   15929892.
  10. ↑ Environmental Protection Agency (26 March 2003). "Vinclozolin; Notice of Filing a Pesticide Petition To Establish a Tolerance for a Certain Pesticide Chemical in or on Food". Federal Register: 14628–14635. Retrieved 8 February 2015.
  11. 1 2 3 Gray, L. E.; Ostby, J; Furr, J; Wolf, C. J.; Lambright, C; Parks, L; Veeramachaneni, D. N.; Wilson, V; Price, M; Hotchkiss, A; Orlando, E; Guillette, L (2001). "Effects of environmental antiandrogens on reproductive development in experimental animals". Human Reproduction Update. 7 (3): 248–64. doi: 10.1093/humupd/7.3.248 . PMID   11392371.
  12. 1 2 Anway, Matthew D.; Leathers, Charles; Skinner, Michael K. (2006). "Endocrine Disruptor Vinclozolin Induced Epigenetic Transgenerational Adult-Onset Disease". Endocrinology. 147 (12): 5515–23. doi:10.1210/en.2006-0640. PMC   5940332 . PMID   16973726.
  13. ↑ León-Olea, Martha; Martyniuk, Christopher J.; Orlando, Edward F.; Ottinger, Mary Ann; Rosenfeld, Cheryl S.; Wolstenholme, Jennifer T.; Trudeau, Vance L. (1 July 2014). "Current concepts in neuroendocrine disruption". General and Comparative Endocrinology. 203: 158–173. doi:10.1016/j.ygcen.2014.02.005. PMC   4133337 . PMID   24530523.
  14. 1 2 Buckley, Jill; Willingham, Emily; Agras, Koray; Baskin, Laurence (2006). "Embryonic exposure to the fungicide vinclozolin causes virilization of females and alteration of progesterone receptor expression in vivo: an experimental study in mice". Environmental Health: A Global Access Science Source. 5 (1): 4. Bibcode:2006EnvHe...5....4B. doi: 10.1186/1476-069X-5-4 . PMC   1403752 . PMID   16504050.
  15. 1 2 Gilbert, Scott; Epel, David (2009). Ecological Developmental Biology[Integrating Epigenetics, Medicine, and Evolution]. MA: Sinauer Associates. p. 231. ISBN   978-0-87893-299-3.
  16. ↑ Skinner, Michael K.; Anway, Matthew D. (2007). "Epigenetic Transgenerational Actions of Vinclozolin on the Development of Disease and Cancer". Critical Reviews in Oncogenesis. 13 (1): 75–82. doi:10.1615/CritRevOncog.v13.i1.30. PMC   5940343 . PMID   17956218.
  17. 1 2 Gaetano, Carlo; Guerrero-Bosagna, Carlos; Settles, Matthew; Lucker, Ben; Skinner, Michael K. (2010). "Epigenetic Transgenerational Actions of Vinclozolin on Promoter Regions of the Sperm Epigenome". PLOS ONE. 5 (9): e13100. Bibcode:2010PLoSO...513100G. doi: 10.1371/journal.pone.0013100 . PMC   2948035 . PMID   20927350.
  18. ↑ Schneider, Steffen; Marxfeld, Heike; Gröters, Sibylle; Buesen, Roland; van Ravenzwaay, Bennard (2013). "Vinclozolin—No transgenerational inheritance of anti-androgenic effects after maternal exposure during organogenesis via the intraperitoneal route". Reproductive Toxicology. 37: 6–14. doi:10.1016/j.reprotox.2012.12.003. PMID   23313085.
  19. ↑ "Alternatives to Vinclozolin (Ronilan) for Controlling Gray and White Mold on Snap Bean Pods in New York" (PDF). Plant Management Network. Archived from the original (PDF) on 25 April 2012. Retrieved 12 December 2011.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.