Return to Epoxiconazole Index Page

Activity: Fungicide (conazole)
Structure:

Adverse Effects:
Body Weight Decrease
Bone
Carcinogenic: LIVER
Endocrine: Adrenal
Endocrine: Ovary
Endocrine: Pituitary-Adrenal axis
Endocrine: Suspected Disruptor
Liver
Environmental

Body Weight Decrease (click on for all fluorinated pesticides)

iii. An oncogenicity study in mice fed dosages of 0, 0.17, 0.81, 35.3, and 70.4 (males) or 205.4 (females) mg/kg/day with a NOAEL of 0.81 mg/kg/day for male and female mice based on the following effects: a. Highly significant decreased body weights were observed in both male and/or female mice at the mid-high and highest dose tested.
Ref: Federal Register: September 22, 2000. [Page 57338-57344]. Notice of Filing Pesticide Petitions to Establish Tolerances for Certain Pesticide Chemicals in or on Food.
http://www.fluoridealert.org/pesticides/Epoxiconazole.FR.Sept.2000.htm

Bone (click on for all fluorinated pesticides)

A developmental study was conducted via oral gavage in rats resulted in dosages of 0, 5, 15, and 45 mg/kg/day HDT with a developmental toxicity NOAEL of 5 mg/kg/day and a maternal toxicity of 5 mg/kg/day based on the following:.. d. A significant number of fetuses with skeletal variations (especially rudimentary cervical and/or accessory 14th rib(s)) in the high dose group tested were observed. However, no malformations were observed in any pups in this study. iii. In a second developmental study in rats via dermal exposure for 6 hours/day on intact skin with dosages of 0, 100, 400, and 1,000 mg/kg/day (HDT) with a development toxicity NOAEL of 400 mg/kg/day and a maternal toxicity of 400 mg/kg/day based on increased placental weights and a slight increase in the number of fetuses with skeletal variations was observed at the highest dose tested."
Ref: Federal Register. September 22, 2000. [PF-961; FRL-6737-8].
http://www.fluoridealert.org/pesticides/Epoxiconazole.FR.Sept.2000.htm

Carcinogenic (click on for all fluorinated pesticides)

"Likely to be Carcinogenic to Humans." Combined hepatocellular tumors in male or female mice.
Ref: April 26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs. From: Jess Rowland, Chief Science Information Management Branch Health Effect Division (7509C) Office of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf

Endocrine: Adrenal (click on for all fluorinated pesticides)

Endocrine disruption. A series of mechanistic studies were performed to elucidate and define the aromatase enzyme inhibition properties of epoxiconazole. The following conclusions can be drawn from the in vivo data: The effects on the ovaries are assessed to be the result of the following: Decreasing aromatase enzyme activity which is responsible for converting both testosterone and adrostendione (male sex-steroids) into female sex steroids (e.g., estradiol). This action would result in decreased estradiol (i.e., estrogen) and increased androgen. As a consequence of reduced estradiol levels, measured LH and FSH concentrations are slightly altered. The increased incidences of neoplasms in the ovaries are considered to be the result of a continuous cell proliferation by these stimulating [[Page 57342]] hormones of the regulating hormones of the pituitary-gonadal axis (LH and FSH). The changes adrenals are assessed to be the result of the following: Decreasing adrenal-cortical enzyme activity. This action would result in decreased adrenal hormones such as corticosterone levels. As a consequence of reduced corticosterone levels, pronounce ACTH concentrations are found. The increased incidences of neoplasms in the adrenals are considered to be the result of a continuos cell proliferation by these stimulating hormones of the pituitary-adrenal axis ACTH.
Ref: Federal Register: September 22, 2000 [Page 57338-57344]. Notice of Filing Pesticide Petitions to Establish Tolerances for Certain Pesticide Chemicals in or on Food. http://www.fluoridealert.org/pesticides/Epoxiconazole.FR.Sept.2000.htm

Endocrine: Ovary (click on for all fluorinated pesticides)

Endocrine disruption. A series of mechanistic studies were performed to elucidate and define the aromatase enzyme inhibition properties of epoxiconazole. The following conclusions can be drawn from the in vivo data: The effects on the ovaries are assessed to be the result of the following: Decreasing aromatase enzyme activity which is responsible for converting both testosterone and adrostendione (male sex-steroids) into female sex steroids (e.g., estradiol). This action would result in decreased estradiol (i.e., estrogen) and increased androgen. As a consequence of reduced estradiol levels, measured LH and FSH concentrations are slightly altered. The increased incidences of neoplasms in the ovaries are considered to be the result of a continuous cell proliferation by these stimulating [[Page 57342]] hormones of the regulating hormones of the pituitary-gonadal axis (LH and FSH). The changes adrenals are assessed to be the result of the following: Decreasing adrenal-cortical enzyme activity. This action would result in decreased adrenal hormones such as corticosterone levels. As a consequence of reduced corticosterone levels, pronounce ACTH concentrations are found. The increased incidences of neoplasms in the adrenals are considered to be the result of a continuos cell proliferation by these stimulating hormones of the pituitary-adrenal axis ACTH.
Ref: Federal Register: September 22, 2000 [Page 57338-57344]. Notice of Filing Pesticide Petitions to Establish Tolerances for Certain Pesticide Chemicals in or on Food. http://www.fluoridealert.org/pesticides/Epoxiconazole.FR.Sept.2000.htm

Endocrine: Pituitary (click on for all fluorinated pesticides)

Endocrine disruption. A series of mechanistic studies were performed to elucidate and define the aromatase enzyme inhibition properties of epoxiconazole. The following conclusions can be drawn from the in vivo data: The effects on the ovaries are assessed to be the result of the following: Decreasing aromatase enzyme activity which is responsible for converting both testosterone and adrostendione (male sex-steroids) into female sex steroids (e.g., estradiol). This action would result in decreased estradiol (i.e., estrogen) and increased androgen. As a consequence of reduced estradiol levels, measured LH and FSH concentrations are slightly altered. The increased incidences of neoplasms in the ovaries are considered to be the result of a continuous cell proliferation by these stimulating [[Page 57342]] hormones of the regulating hormones of the pituitary-gonadal axis (LH and FSH). The changes adrenals are assessed to be the result of the following: Decreasing adrenal-cortical enzyme activity. This action would result in decreased adrenal hormones such as corticosterone levels. As a consequence of reduced corticosterone levels, pronounce ACTH concentrations are found. The increased incidences of neoplasms in the adrenals are considered to be the result of a continuos cell proliferation by these stimulating hormones of the pituitary-adrenal axis ACTH.
Ref: Federal Register: September 22, 2000 [Page 57338-57344]. Notice of Filing Pesticide Petitions to Establish Tolerances for Certain Pesticide Chemicals in or on Food. http://www.fluoridealert.org/pesticides/Epoxiconazole.FR.Sept.2000.htm

Endocrine: Suspected Disruptor (click on for all fluorinated pesticides)

Suspected Endocrine Disruptor
Ref: June 14, 2001 - Implementation of the Community Strategy for Endocrine Disruptors - a range of substances suspected of interfering with the hormone systems of humans and wildlife. Communication from the Commission to the Council and the European Parliament. Commission of the European Communities, Brussels COM (2001) 262 final.
http://www.fluoridealert.org/pesticides/Endocrine.Disruptors.EC2001.pdf
(More information available at: http://europa.eu.int/eur-lex/en/com/cnc/2001/com2001_0262en01.pdf)

"Epoxyconazole 106325-08-0 Banned. Low degradability, toxic to water-living organisms and endocrine effects. 1997."
Definition: "Banned. A substance which for health or environmental reasons by an authority decision is either no longer approved for any area of application, or for which an approval or registration has been denied from the first instance."
Ref: Euopean Commission. Appendix 5. Substances which may not be included as active ingredients in approved pesticide products, Chapter 15, Section 2, subsection one.
http://www.kemi.se/lagar_eng/pdf/app5_8.pdf

Liver (click on for all fluorinated pesticides)

"Likely to be Carcinogenic to Humans." Combined hepatocellular tumors in male or female mice.
Ref: April 26, 2006 . Chemicals Evaluated for Carcinogenic Potential by the Office of Pesticide Programs. From: Jess Rowland, Chief Science Information Management Branch Health Effect Division (7509C) Office of Pesticide Programs, USEPA.
http://www.fluorideaction.org/pesticides/pesticides.cancer.potential.2006.pdf

-- Dose levels 23 mg/kg/day resulted in maternal death, clinical signs, clinical chemical effects, liver effects (i.e., damage), histopathology, and limited number of pregnancy and pups with reduced body weights which increased in severity to the upper dose levels, this also indicated that doses above 23 mg/kg/day were considered to be beyond the maximum tolerated dose (MTD) for pregnant rats.
--Chronic toxicity. i. A series of two 1-year dog studies (study A dose levels were 0, 1.6, 15, and 49 mg/kg/day for which a NOAEL was established in females, and study B dose levels were 0, 0.3, 0.6, 0.9, and 1.1 mg/kg/day to determine a NOAEL in males. The NOAEL was established as 1.1 mg/kg/day based on the following effects: a. Mortality in the 49.0 mg/kg/day dose group with severe clinical signs and evidence of liver damage in those dogs which were sacrificed for humane reasons.
-- Separate chronic feeding and oncogenicity studies in rats were performed to assess the chronic toxicity and oncogenic potential of epoxiconazole. The chronic toxicity study was conducted at dose levels of 0 and approximately 2, 8, 38, and 78 mg/ [[Page 57341]] kg/day. The oncogenicity study was conducted at dose levels of 0 and approximately 2, 7, 40, and 80 mg/kg/day. The results from the 2 studies are combined and summarized as follows: c. Increased absolute and relative liver weights were seen for males and/or females at dose levels 38 mg/kg/day. d. Microscopic findings were observed in the liver for male and/or female rats at dose levels 38 mg/kg/day, in female adrenals at the highest dose test, and in the ovaries at dose levels 38 mg/kg/day.
-- It has been determined that liver tumor effects observed at the 70.4 and 205.4 mg/ kg/day dose levels clearly exceeded the MTD. The liver necrosis observed in the male and female mice, further support the finding that the MTD was exceeded in the 70.4 and 205.4 mg/kg/day dose levels. A series of mechanistic studies were performed to elucidate and define the liver promotion properties of epoxiconazole. The following conclusions can be drawn from the data: The material is a potent inducer of the hepatic cytocrome P-450 enzyme system, similar to the drug-phenobarbital. The material induced proliferation of the smooth endoplasmatic reticulum in the liver centrolobular hypertrophy and induction of phase 1 and phase 2 enzymes of the xenobiotic metabolism. The material was determined not to be an initiator of the carcinogenic process, but a promoter of initiated cells in the tumorgenesis as has been similarly shown with drug--phenobarbital.
Ref: September 22, 2000. Federal Register. [Notices] [Page 57338-57344]. Notice of Filing Pesticide Petitions to Establish Tolerances for Certain Pesticide Chemicals in or on Food.
http://www.fluorideaction.org/pesticides/epoxiconazole.fr.sept.2000.htm