Suspected Endocrine Disruptors
Fluorinated and Fluoride Pesticides
 
 

The Endocrine System:

Illustration by K. Born in Our Stolen Future (1996)
by Theo Colborn, Dianne Dumanoski and JP Myers

Note: This is not an exhaustive list.
When time allows more information will be added.

Bifenthrin - Insecticide, Acaricide- CAS Nos. 82657-04-3 (Cis); 83322-02-5 (Trans)

"Suspected Endocrine Disruptor"
Ref: PAN Pesticides Database

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

Cyhalothrin - Acaricide, Insecticide - CAS No. 68085-85-8

"Suspected Endocrine Disruptor"
Ref: PAN Pesticides Database

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

Cyhalothrin, gamma - Insecticide - CAS No. 76703-62-3

Suspected Endocrine Disruptor
Ref: PAN Pesticides Database

Cyhalothrin, lambda - Insecticide - CAS No. 91465-08-6

Suspected Endocrine Disruptor
Ref: PAN Pesticides Database

Dichlofluanid - Wood Preservative, Antifoulant, Fungicide, Acaricide - CAS No.1085-98-9

Dichlofluanide has been reported as a hormonal active substance in the environment in a review of the German Umweltbundesambt (Schramm et al., 1996). However, a concentration range for which this "hormonal activity" was found, was not reported (page 44).
[Schramm K.-w., thumm W. * Kettrup A. (1996). Hormonal active substances in the environment: exposition, impact and detection. Expert Round. Endocrinically active chemicals in the environment. UBA Texte 3/96. Umweltbundesamt, Germay.]

Ref: RIVM report 601506005. BIOCIDES (II). Refined aquatic environmental risk assessment of 28 priority biocides. B.J.W.G. Mensink. November 2000. RIVM = Rijksinstituut voor Volksgezondheid en Milieu. National Institute of Public Health and the Environment.

http://www.rivm.nl/bibliotheek/rapporten/601506005.pdf

Diflubenzuron - Insecticide, Acaricide - CAS No. 35367-38-5

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.pd
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Epoxiconazole - Fungicide - CAS No. 135319-73-2 (formerly CAS No. 106325-08-0)

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

Fipronil - Acaracide, Insecticide, Wood Preservative - CAS No.120068-37-3

Endocrine disruption. Data from the reproduction/ developmental toxicity and short- and long-term repeated dose toxicity studies with fipronil in the rat, rabbit, mouse, or dog, do not suggest any endocrine disruption activity. This information is based on the absence of any treatment-related effects from the histopathological examination of reproductive organs as well as the absence of possible effects on fertility, reproductive performance, or any other aspect of reproductive function, or on growth and development of the offspring. Evidence of offspring toxicity was observed only in the presence of significant parental toxicity. Fipronil disrupts the thyroid-pituitary axis. However, mechanistic studies have demonstrated that fipronil decreases thyroid hormone levels in long-term studies via increased clearance, rather than a direct effect on the thyroid. Concerns related to long-term exposure of fipronil are addressed in human risk estimates, as the chronic RfD (0.0002 mg/kg/day) is based on endpoints that include thyroid hormone related effects in rats.
Ref: August 24, 2005. Federal Register. Fipronil; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food.
http://www.fluorideaction.org/pesticides/fipronil.fr.aug.24.2005.html

Abstract: The purpose of the present study was to investigate possible reproductive adverse effects of fipronil (Frontline TopSpot) in female Wistar rats. The pesticide was topically applied to rats (single dose) at different concentrations (70, 140 and 280 mg/kg) and hormonal analysis, estrous cycle, and pregnancy and outcome data were determined. Treatment with fipronil altered cyclicity of female rats lengthening the estrous cycle (days) after a single topic administration of 70 mg/kg (9.7+/-1.18) or 280 mg/kg (14.5+/-1.45) when compared to control (4.8+/-0.17). In the mating study fipronil reduced the pregnancy index (67%) in the highest dose group (280 mg/kg). Plasma progesterone and estradiol levels, obtained in different periods after treatment with fipronil (70 mg/kg), were significantly different 96 h after treatment, when compared to controls. In summary, the results of the present study indicate that fipronil may alter the normal functioning of the endocrine system and cause adverse reproductive effects in female rats.
Ref: Reproductive adverse effects of fipronil in Wistar rats. Ohi M, Dalsenter PR, Andrade AJ, Nascimento AJ. Toxicol Lett. 2004 Jan 15;146(2):121-7.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14643964

Abstract: Vitellogenin (VTG) has been widely used as a biomarker of estrogenic exposure in fish, leading to the development of standardized assays for VTG quantification. However, standardized quantitative assays for invertebrate, particularly crustacean, lipovitellin (also known as vitellin [VTN]) are lacking. In this study, a fluorescence-based VTN enzyme-linked immunosorbent assay (ELISA) was developed to quantify microquantities of VTN in the estuarine, sediment-dwelling copepod Amphiascus tenuiremis. This ELISA utilizes a VTN-specific polyclonal antibody developed against amphipod (Leptocheirus plumulosus) embryo VTN and exhibits specificity toward female copepod proteins. In routine assays, the working range of the ELISA was 31.25 to 1,000 ng/ml (75-25% specific binding/maximum antibody binding [B/B0]) with a 50% B/B0 intra- and interassay variation of 3.9% (n = 9) and 12.5% (n = 26), respectively. This ELISA is capable of detecting VTN as low as 2 ng/ml, and can accurately detect VTN in as few as four copepods. The ELISA significantly discriminated positive (gravid female) and negative (male) samples, and was suitable for screening endocrine toxicity in copepods. Stage-I juvenile copepods were individually reared to adults in aqueous microvolumes of the phenylpyrazole insecticide, fipronil, and whole-body homogenate extracts were assayed for VTN levels. Fipronil-exposed virgin adult females, but not males, exhibited significantly higher levels of VTN relative to control males and females. This crustacean VTN ELISA is likely useful for evaluating endocrine activity of environmental toxicants in copepods and other crustacean species.
Ref: Environ Toxicol Chem. 2004 Feb;23(2):298-305.
An enzyme-linked immunosorbent assay for lipovitellin quantification in copepods: a screening tool for endocrine toxicity; by Volz DC, Chandler GT.

The purpose of the present study was to investigate possible reproductive adverse effects of fipronil (Frontline TopSpot) in female Wistar rats. The pesticide was topically applied to rats (single dose) at different concentrations (70, 140 and 280 mg/kg) and hormonal analysis, estrous cycle, and pregnancy and outcome data were determined. Treatment with fipronil altered cyclicity of female rats lengthening the estrous cycle (days) after a single topic administration of 70 mg/kg (9.7+/-1.18) or 280 mg/kg (14.5+/-1.45) when compared to control (4.8+/-0.17). In the mating study fipronil reduced the pregnancy index (67%) in the highest dose group (280 mg/kg). Plasma progesterone and estradiol levels, obtained in different periods after treatment with fipronil (70 mg/kg), were significantly different 96 h after treatment, when compared to controls. In summary, the results of the present study indicate that fipronil may alter the normal functioning of the endocrine system and cause adverse reproductive effects in female rats.
Ref: Toxicol Lett. 2004 Jan 15;146(2):121-7. Reproductive adverse effects of fipronil in Wistar rats; by Ohi M, Dalsenter PR, Andrade AJ, Nascimento AJ.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14643964

"Suspected Endocrine Disruptor"
Ref: PAN Pesticides Database

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

Fluazifop-butyl - Herbicide - CAS No. 69806-50-4

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

Flusilazole - Fungicide (azole) - CAS No. 85509-19-9

Abstract: Azoles (imidazoles and triazoles) are used as antifungal agents in agriculture and in medicine, and also for antiestrogen therapy, e.g., for breast cancer treatment. Antifungal activity is based on inhibition of fungal CYP51 (lanosterol 14alpha-demethylase), and estrogen biosynthesis reduction is due to azole inhibition of CYP19 (aromatase). Inhibition of aromatase by antifungal agents is usually an unwanted side effect and may cause endocrine disruption. A fluorimetric assay based on human recombinant CYP19 enzyme with dibenzylfluorescein as a substrate was used to compare the inhibitory potency of 22 azole compounds. Dose responses were established and duplicate datasets were analyzed with a nonlinear mixed-effects model with cumulative normal distribution for the logarithm of concentration. IC50 values (50% inhibitory concentration) of 13 fungicides used in agriculture ranged more than 700-fold, starting from 0.047 microM. The potency of seven human drugs spanned more than 7000-fold, starting from 0.019 microM. Most potent fungicides included prochloraz, flusilazole, and imazalil, and most potent medicinal antifungals were bifonazole, miconazole, and clotrimazole. These in vitro data indicate that the top-ranking azoles used as antifungal agents or drugs are as potent inhibitors of aromatase as are antiestrogen therapeutics used to treat breast cancer. These putative effects of azole agents and drugs on steroid biosynthesis and sex hormone balance should be considered when used in human subjects and also in wildlife exposed to azole fungicides used in agriculture.
Ref: Comparative assessment of the inhibition of recombinant human CYP19 (aromatase) by azoles used in agriculture and as drugs for humans. Trosken ER, Scholz K, Lutz RW, Volkel W, Zarn JA, Lutz WK. Endocr Res. 2004 Aug;30(3):387-94.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15554355

• Definition of aromatase inhibition: Prevention of the formation of estradiol, a female hormone, by interfering with an aromatase enzyme. Aromatase inhibition is a type of hormone therapy used in postmenopausal women who have hormone-dependent breast cancer.

Fluvalinate - Acaricide, Insecticide - CAS No. 69409-94-5

Suspected Endocrine Disruptor
Ref: PAN Pesticides Database

Hydramethylnon - Insecticide - CAS No. 67485-29-4

EPA may require further testing of this active ingredient and end use products for endocrine disruptor effects.
Ref: Federal Register. March 4, 1998. Pesticide tolerances for emergency exemptions. Final Rule.
http://www.fluoridealert.org/pesticides/hydramethylnon.fr.mar4.1998.htm

Prodiamine - Herbicide - CAS No. 29091-21-2

"Suspected Endocrine Disruptor"
Ref: PAN Pesticides Database

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

Tembotrione - Herbicide - CAS No. 335104-84-2

• Certain changes in multiple organs seen in the subchronic, chronic, dermal, and reproduction studies (e.g., microscopic changes in the thyroid gland, adrenal gland, and pancreas; increased number of corpora lutea in the ovary, and delayed preputial separation) may be due to various mechanisms including possible liver-pituitary-thyroid homeostatic disruption or inhibition of steroid synthesis (page 6).
• When additional appropriate screening and/or testing protocols being considered under the Agency’s EDSP have been developed, tembotrione may be subjected to further screening and/or testing to better characterize effects related to endocrine disruption (page 29).
Reference: Tembotrione. Human-Health Risk Assessment for Proposed Uses on Field Corn, Sweet Corn and Popcorn. USEPA. September 7, 2007.

TFM (3-Trifluoro-Methyl-4-Nitro-Phenol) - Lampricide, Piscicide - CAS No. 88-30-2

-- TFM treatments have been associated with induction of hepatic mixed function oxyganase activity and altered levels of circulating steroids in fish and induced hepatic vitellogenesis in primary cultures of rainbow trout hepatocytes (Hewitt et al. 1997). As such, TFM acts as an estradiol agonist and has a demonstrated endocrine disrupting effect...
-- Abundance of sea lamprey peaked in several Great Lakes before chemical control began. The sex ratio in these peak populations were predominately males (68-71%). Following a decade of lampricide treatments, populations of sea lampreys showed marked declines and the sex ratios in these populations shifted toward a predominance of females accounting for 72% of the population (Henrich, et al, 1979). This publication by Henrich concludes that lampricides reduced the populations of sea lampreys in the Great Lakes and contributed to the sequential shifting of the sex composition from a predominance of males to a predominance of females. There are no data to support that the endocrine mediated effect associated with TFM is related to the observed sex-ratio shifts among TFM-treated populations of sea lamprey [page 23].
Ref: November 1999 US EPA's Reregistration Eligibility Decision (RED) for 3-Trifluoro-Methyl-4-Nitro-Phenol and Niclosamide). http://www.fluoridealert.org/pesticides/tfm.red.1999.pdf

Abstract: BIOSIS COPYRIGHT: BIOL ABS. Recent laboratory studies with nontarget fish species have shown that the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) exhibits estrogenic activity through binding to rainbow trout (Oncorhynchus mykiss) hepatic estrogen receptors and induction of vitellogenin in hepatocyte cultures. In addition, mixed function oxygenase (MFO) activity associated with exposure to field formulations has been attributed in part to the presence of chloro-nitrotrifluoromethyl-dibenzo-p-dioxin impurities. To investigate the environmental effects associated with these findings, the temporal and spatial patterns of MFO activity and vitellogenin induction were monitored in three nontarget fish species following a TFM field treatment. Elevated MFO activity was detected as early as 1 day in caged rainbow trout and activity in trout, wild white sucker (Catostomus commersoni), and longnose dace (Rhinichthys cataractae) peaked 2 or 3 days after treatment. Highest activities were observed in fish
Ref: HEWITT LM et al. (1998). Hepatic mixed function oxygenase activity and vitellogenin induction in fish following a treatment of the lampricide 3-trifluoromethyl-4-nitrophenol (TFM). CANADIAN JOURNAL OF FISHERIES AND AQUATIC SCIENCES; 55 (9). 1998. 2078-2086.

Thiazopyr - Herbicide - CAS No. 117718-60-2

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

Tributyltin fluoride - Antifoulant, Fungicide, Microbiocide - CAS No. 1983-10-4

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

Table 9 Organotin compounds suspected of being endocrine disruptors.
Common name CAS-no. Y /g l 1 log P ow
Bis(tributyltin)oxide 56-35-9 8000 10 000 3.62
Triphenyltinhydroxide 76-87-9 400 -
Tributyltin fluoride 1983-10-4 - -
Ysat :Water solubility in seawater at 22 C.
P ow :Partition coefficient octanol/water.
Ref: Endocrine Disruptors in the Environment (IUPAC Technical Report). Prepared for publication by J.LINTELMANN et al. INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY. Pure Appl.Chem.,Vol.75,No.5,pp.631 681,2003. 2003 IUPAC. Full report available at
http://www.iupac.org/publications/pac/2003/pdf/7505x0631.pdf

Trifluralin - Herbicide - CAS No. 1582-09-8

Suspected Endocrine Disruptor
Ref: PAN Pesticides Database

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

 
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