Disease relevance of Ornalin

• Pregnant rabbits were dosed orally with vinclozolin (10 mg/kg body weight) or carrot paste vehicle once daily for 6 wk beginning at midgestation and continuing through nursing until Postpartum Week 4 [1].
• Environmental hormone disruptors: evidence that vinclozolin developmental toxicity is mediated by antiandrogenic metabolites [2].
• Dosing the animals with a combination of a 1:1 mixture of vinclozolin and procymidone resulted in a weight reduction in the reproductive organs and an increase of serum LH and FSH as early as with 10 mg/kg combined dose [3].
• Perinatal administration of 100 or 200 mg vinclozolin (V) kg-1 day-1 during sexual differentiation in rats induces female-like anogenital distance (AGD), retained nipples, cleft phallus with hypospadias, suprainguinal ectopic scrota/testes, a vaginal pouch, epididymal granulomas, and small to absent sex accessory glands in male offspring [4].
• We therefore investigated the effect of 1- and 24-h treatments with vinclozolin at concentrations of 25, 50, 100 microg/ml and iprodione at concentration of 62.5, 125, 250 microg/ml on malonaldehyde and free radical production and on reduced glutathione levels in the human HepG2 hepatoma cell line [5].

High impact information on Ornalin

• Antiandrogenic environmental disrupting chemicals, such as 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene, vinclozolin, or nitrofen, also disrupted the intranuclear fluorescence foci [6].
• The mechanism of antiandrogenic activity of vinclozolin (3-(3,5-dichlorophenyl)-5-methyl-5-vinyloxazolidine-2,4-dione), a dicarboximide fungicide under investigation for its potential adverse effects on human male reproduction, was investigated using recombinant human androgen receptor (AR) [7].
• 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 [8].
• The expression pattern of several of the genes during embryonic development were found to be altered in the vinclozolin F(1) and F2 generation testis [9].
• Analysis of the transgenerational epigenetic effects on the male germline (i.e. sperm) identified 25 candidate DNA sequences with altered methylation patterns in the vinclozolin generation sperm [9].

Chemical compound and disease context of Ornalin

• Repeated 28-day oral toxicity study of vinclozolin in rats based on the draft protocol for the "Enhanced OECD Test Guideline No. 407" to detect endocrine effects [10].

Biological context of Ornalin

• All assays detected and quantified the antiandrogenic effect of vinclozolin [median inhibitory concentration (IC50) values ranging from 1.1 times symbol 10(-7) M to 4.7 times symbol 10(-7) M] [11].
• Sex differences and the development of the rabbit brain: effects of vinclozolin [1].
• Vinclozolin is a fungicide thought to be an environmental antiandrogen, which disrupts masculine sexual behavior when administered to rabbits during development [1].
• Recently, the effects of an antiandrogen, vinclozolin, on the brain and behavior were cited as a special concern by the U.S. Environmental Protection Agency in its risk assessment of this pesticide [12].
• DHT-induced luciferase gene expression was inhibited by nonsteroidal antiandrogens, hydroxyflutamide, flutamide, bicalutamide, and vinclozolin [13].

Anatomical context of Ornalin

• In both sexes, exposure to vinclozolin significantly increased calbindin expression in the ventral POA/AH and significantly decreased number of GnRH neurons selectively in the region of the organum vasculosum of the lamina terminalis (OVLT) but not more caudally in the POA/AH [1].
• Previous work in our laboratory showed that perinatal administration of vinclozolin to rats results in malformations of the external genitalia, permanent nipples, reduced anogenital distance (AGD), and reduced seminal vesicle, ventral prostate, and epididymal weights [14].
• This suggestion was supported by reference to unpublished data on the antiandrogen vinclozolin which indicated reductions in the weight of accessory sex organs [15].
• In addition, apoptotic germ cell number in testis of vinclozolin exposed animals was higher in adult P60 animals [16].
• Adaptation to oxidative stress: effects of vinclozolin and iprodione on the HepG2 cell line [5].

Associations of Ornalin with other chemical compounds

• Capillary electrophoresis with ultraviolet detection (CE/UV) of selected fungicides (carbendazim, metalaxyl, propiconazole, and vinclozolin) using different buffer compositions was investigated [17].
• For vinclozolin, calculated antiandrogenic potencies relative to bicalutamide (RAAPs) differed no more than a factor of 10, and IC50 values matched those of bicalutamide [11].
• Peripubertal exposure to the antiandrogenic fungicide, vinclozolin, delays puberty, inhibits the development of androgen-dependent tissues, and alters androgen receptor function in the male rat [18].
• A base-line separation of vinclozolin and its degradation products was found with symmetrical peak shapes on an XTerratrade mark MS C(18) column using 10mM ammonium bicarbonate at pH 9.2 and acetonitrile as mobile phase [19].
• The pesticides vinclozolin, procymidone, linuron and DDT are AR antagonists [20].

Gene context of Ornalin

• Vinclozolin does not alter progesterone receptor (PR) function in vivo despite inhibition of PR binding by its metabolites in vitro [21].
• The result suggested that induction of CYP1A1 by vinclozolin account for its enhancing effect on genotoxicity caused by BaP [22].
• In general, however, Vinclozolin has a complex pattern of induction and suppression of CYP-dependent enzymes, as shown from the reduced expression of various monooxygenases depending upon dose, sex or organ considered [23].
• Several environmental chemicals, including metabolites of the fungicide vinclozolin and the pesticide DDT, disrupt male reproductive development and function by inhibiting androgen receptor mediated events [24].
• We found no in vivo effect of vinclozolin on androgen receptor expression [25].

Analytical, diagnostic and therapeutic context of Ornalin

• In the antagonist version of the assay using vinclozolin and p,p'-DDE, 0.2 mg/kg/day of testosterone propionate was coadministered by subcutaneous injection [26].
• A specific high-performance liquid chromatography method has been developed for simultaneous detection of vinclozolin and its degradation products (M(1), M(2), and M(3)) [19].
• Vinclozolin is quantified by capillary gas chromatography with electron-capture and mass spectrometric detection [27].
• In this regard, the present study was designed to examine the effects of peripubertal oral administration of vinclozolin (0, 10, 30, or 100 mg kg-1 day-1) on morphological landmarks of puberty, hormone levels, and sex accessory gland development in male rats [18].
• Vinclozolin treatment at 50 and 100 mg kg-1 day-1 induced reproductive tract malformations and reduced ejaculated sperm numbers and fertility [4].

References