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.
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.
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. 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.
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. 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.
Preparation and application
The following chemical reactions are used to make vinclozolin. 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. Vinclozolin is also prepared by the reaction of 3,5-dichlorophenyl isocyanate with an alkyl ester of 2-hydroxy-2-methylbut-3-enoic acid. Ring closure is achieved at elevated temperature.
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.
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.
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. A key example of exposure to vinclozolin is through wine grapes which is considered to account for about 2% of total vinclozolin exposure. 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. Embryonic exposure to vinclozolin can influence sexual differentiation, gonadal formation, and reproductive functions. 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.
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. 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. 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. 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. It has been reported that these transgenerational reports correlate with epigenetic changes, specifically, an alteration in DNA methylation in the male germ line.
Links to cancer
In 2025, International Agency for Research on Cancer (IARC) classified vinclozolin as "probably carcinogenic to humans" (Group 2A).
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.
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.