Return to Flucythrinate Index Page

Activity: Acaricide; Insecticide (pyrethroid) ]
Structure:

Adverse Effects:
Ataxia
Body Weight Decrease
Bone
Brain
Cancer: Potential for tumor promotion
Endocrine: Breast
Endocrine: Pituitary
Endocrine: Testicular
Endocrine: Uterus
Heart
Kidney
Liver
Lung
Sciatic Nerve
Spleen
Environmental

Ataxia (click on for all fluorinated pesticides)

-- Groups of 20 male and 20 female SPF (Sprague-Dawley derived) rats received 0, 30, 60, 120, or 240 ppm technical flucythrinate (85.4% pure) in the diet for 6 months. Males and females that received 240 ppm flucythrinate exhibited symptoms of decreased motor activity and ataxia, characterized by weakness in the extremities and gait disturbances. One control and 1 male and 4 females of the 240-ppm group died during the study. Males receiving 240 ppm and females receiving 240 and 120 ppm flucythrinate exhibited weight loss attributable to decreased food consumption. Water intake was depressed in males and females receiving 240 ppm. Leucocyte counts were slightly depressed in males receiving 120 and 240 ppm. Organ weights were in accord with body weights. An increased incidence of brown pigmentation in the spleen was observed in high- dose males and females (Shirasu, 1983)...
-- Short-term studies Rat Groups of CD (Sprague-Dawley derived) rats received technical flucythrinate (86% pure) in the diet daily for 28 days at 0, 6, 30 ppm (8 male and 8 female rats per group) or at 150 or 300 ppm (12 male and 12 female rats per group). Some survivors from the 150 and 300 ppm groups were used to study reversibility of toxicity. Animals receiving 300 ppm exhibited severe hind limb ataxia, diuresis, hypersensitivity and salivation typical of pyrethroid intoxication. Animals receiving 150 ppm were much less affected, while females generally exhibited greater sensitivity to flucythrinate than males. Five females of the 300 ppm group died without apparent cause...
Ref: 1985 World Health Organization Review for FLUCYTHRINATE.
http://www.fluoridealert.org/pesticides/Flucythrinate.1985.WHO.htm

Body Weight Decrease (click on for all fluorinated pesticides)

CHRONIC TOXICITY No adverse effects were observed when rats and dogs were fed flucythrinate for 90 days at doses of up to 3 mg/kg for rats and 3.75 mg/kg for dogs (5). Dogs fed 7.5 mg/kg/day for 2 years exhibited vomiting and decreased body weight gain. The NOEL for this study was 0.75 mg/kg/day (12). Rats fed 6 mg/kg/day for 2 years also exhibited decreased body weight gain. The systemic NOEL for this study was 3 mg/kg/day (12).
Ref: E X T O X N E T Pesticide Information Profile Flucythrinate.
http://www.fluoridealert.org/pesticides/Flucythrinate.Profile.PMEP.htm

-- In an apparently treatment-related manner, 1 dam treated at 4 mg/kg died, while 19 died at 8 mg/kg, but the cause of death was not determined. Absolute body weights were reduced at 4 and 8 mg/kg as were body-weight gains. Incomplete recovery of body weight had occurred by day 20 (termination).
-- Groups of twenty female New Zealand white rabbits were artifically inseminated after induction of ovulation with chorionic gonadotropin on 2 consecutive days. Technical flucythrinate (80% pure) was administered in corn oil at 0, 10, 30, or 60 mg/kg daily from days 6-18 (inclusive) of gestation and were maintained without treatment until sacrificed at day 29... Depression of maternal body weight and faecal scouring were observed in the high-dose (60 mg/kg) group up to day 18. Maternal weight gain was significantly reduced in the mid- and high-dose groups and its recovery in the high-dose group was incomplete at day 29 (termination).
-- Short-term studies Rat Groups of CD (Sprague-Dawley derived) rats received technical flucythrinate (86% pure) in the diet daily for 28 days at 0, 6, 30 ppm (8 male and 8 female rats per group) or at 150 or 300 ppm (12 male and 12 female rats per group). Some survivors from the 150 and 300 ppm groups were used to study reversibility of toxicity. Animals receiving 300 ppm exhibited severe hind limb ataxia, diuresis, hypersensitivity and salivation typical of pyrethroid intoxication. Animals receiving 150 ppm were much less affected, while females generally exhibited greater sensitivity to flucythrinate than males. Five females of the 300 ppm group died without apparent cause. Absolute weight and weight gain were markedly depressed for males and females in the groups receiving 150 and 300 ppm. All symptoms in the two highest-dose groups were reversed in 48 hours, while the weight loss, relative to controls, was regained within 4 weeks after cessation of exposure. Weight loss in the two highest-dosage groups was attributable to decreased food intake. Plasma urea nitrogen was elevated for females receiving 300 ppm. Absolute and relative liver weights were elevated in females receiving 300 ppm. Based on the findings of weight loss, a no-effect level of 30 ppm was determined (Fischer, 1979).
- Rat Groups of 50 male and 50 female CD (Sprague-Dawley derived) rats received technical flucythrinate (80% pure) in the diet at 0, 30, 60 or 120 ppm daily for 24 months. Skin lesions consistent with scratching of the head, neck and thorax were observed in all mid- and high-dose groups throughout the study. Mortality was decreased in high-dose males. Terminal body weights were decreased in treated animals, but especially in high-dose males and females. This was possibly related to a depression of food intake. A very mild anaemia was observed in the 3rd months for both high-dose males and females...
Ref: Flucythrinate. 1985 World Health Organization Review.
http://www.fluoridealert.org/pesticides/Flucythrinate.1985.WHO.htm

Bone (click on for all fluorinated pesticides)

Increases in the incidence of 14th rudimentary ribs and incomplete ossification of sternebrae and other bones were observed at 8 mg/kg. The results of this study indicate that daily treatment up to 4 mg/kg was without effect, while daily treatment up to 8 mg/kg, which produced severe maternal toxicity in the rat, produced no teratogenic effect (Rodwell et al., 1979).
Ref: 1985 World Health Organization Review.
http://www.fluoridealert.org/pesticides/Flucythrinate.1985.WHO.htm

Brain (click on for all fluorinated pesticides)

-- Groups of 50 male and 50 female CD-1 mice received technical flucythrinate (80% pure) in the diet at 0, 30, 60, or 120 ppm daily for 18 months. Skin lesions (abrasions, ulceration and scabs) were observed in high-dose males and females. No treatment-related symptoms or treatment-related changes in survival were found. No haematology, clinical chemistry or urinalysis were undertaken. At necropsy, hepatocellular adenomas were found in all control and treated groups. The incidence was variable and statistically- significant only in high-dose males. Hepatocellular adenocarcinoma and hepatocellular carcinoma were found in low incidence in all male groups, but only in control and low-dose female mice. The incidences of these neoplasms were similar to those previously found in mice and were apparently unrelated to treatment. Mild sciatic nerve degeneration occurred in all groups, but at slightly increased incidence in treated groups, especially high-dose males. There was no apparent dose-response relationship. The incidence of mild axonal degeneration was similar in all groups. The no-effect level for this study was therefore set at 30 ppm (Lang, 1981b).
Ref: 1985 World Health Organization Review for Flucythrinate.
http://www.fluoridealert.org/pesticides/Flucythrinate.1985.WHO.htm

• Note from FAN: "Interestingly, although about 30% of individuals with HIV/AIDS will develop the symptoms of sensory neuropathy, axonal degeneration is almost universal at autopsy."
Ref: Griffin, et al., Peripheral neuropathy in AIDS: New Investigative Approaches. Technical advances in AIDS. In: Major E, ed. Research in Human Nervous System. Plenum Press: 1994. - http://www.hopkins-aids.edu/publications/report/may01_2.html

Cancer: Potential for tumor promotion (click on for all fluorinated pesticides)

Abstract: Male Sprague-Dawley rats dosed with N-nitrosodiethylamine (NDEA) 24 h after two-thirds partial hepatectomy were treated with the pyrethroid insecticides fenvalerate, flucythrinate or cypermethrin in the diet for 20 weeks. Altered hepatic foci were analyzed by quantitative stereology from paraffin-embedded sections stained for gamma-glutamyltranspeptidase (GGT) or glutathione S-transferase P (GST-P). The present results demonstrate that the pyrethroids tested all enhance the development of NDEA-initiated, GGT-positive foci in rat liver at non-hepatotoxic doses. On the contrary, the volume fractions of GST-P-positive foci were not elevated as compared to the control group. The three pyrethroids tested all inhibited the transfer of Lucifer Yellow CH between WB-F344 rat liver epithelial cells in culture, supporting the increase of GGT-positive foci and suggesting that these substances can act as tumour promoters. The discrepancy between the results from analyses using GGT or GST-P as markers emphasizes the importance of understanding the mechanism underlying the expression of different markers for preneoplastic lesions and the importance of such effects in tumour promotion.
Ref: Enhancement of altered hepatic foci in rat liver and inhibition of intercellular communication in vitro by the pyrethroid insecticides fenvalerate, flucythrinate and cypermethrin; by Hemming H, Flodstrom S, Warngard L. Carcinogenesis 1993 Dec;14(12):2531-5
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7903603&dopt=Abstract

Endocrine: Breast (click on for all fluorinated pesticides)

-- Groups of 50 male and 50 female CD (Sprague-Dawley derived) rats received technical flucythrinate (80% pure) in the diet at 0, 30, 60 or 120 ppm daily for 24 months... At autopsy, high-dose females exhibited an increased incidence of cystic uterus... The uterine cysts found at autopsy in the high-dose females were characterized as endometrial cysts. In the high-dose females, further slight increases in uterine pathology were described histologically, namely etritis/endometritis, cystic endometrial hyperplasia and uterine fibrovascular polyps. Mammary fibroadenomas occurred at similar incidences in all female groups. The incidence of mammary adenomas in treated females exceeded that of controls, but not in a dose-related manner. Mammary adenocarcinomas occurred at higher incidence at 60 and 120 ppm, but not in a dose-related manner. The latter incidences remained within the range of historical control data. The variable incidences and lack of dose-response relationships contraindicate a neoplastic response, but in view of the observed weight losses, especially in high-dose groups, these findings cannot be discounted entirely...
Ref: 1985 World Health Organization Review for Flucythrinate.
http://www.fluoridealert.org/pesticides/Flucythrinate.1985.WHO.htm

Endocrine: Pituitary (click on for all fluorinated pesticides)

-- Groups of 6 male and 6 female Beagle dogs received technical flucythrinate (87.3% pure) in the diet at 0, 30, 100, or 300 ppm daily for 24 months... At sacrifice, the relative liver, kidney, and pituitary weights were increased in both high-dose males and females, while increases in relative spleen, testis and lung weights were noted for high-dose males only... ((Spicer et al., 1984).
Ref: 1985 World Health Organization Review for Flucythrinate.
http://www.fluoridealert.org/pesticides/Flucythrinate.1985.WHO.htm

Endocrine: Testicular (click on for all fluorinated pesticides)

-- Groups of 6 male and 6 female Beagle dogs received technical flucythrinate (87.3% pure) in the diet at 0, 30, 100, or 300 ppm daily for 24 months... At sacrifice, the relative liver, kidney, and pituitary weights were increased in both high-dose males and females, while increases in relative spleen, testis and lung weights were noted for high-dose males only... (Spicer et al., 1984).
Ref: 1985 World Health Organization Review for Flucythrinate.
http://www.fluoridealert.org/pesticides/Flucythrinate.1985.WHO.htm

Endocrine: Uterus (click on for all fluorinated pesticides)

-- Groups of 50 male and 50 female CD (Sprague-Dawley derived) rats received technical flucythrinate (80% pure) in the diet at 0, 30, 60 or 120 ppm daily for 24 months... At autopsy, high-dose females exhibited an increased incidence of cystic uterus... The uterine cysts found at autopsy in the high-dose females were characterized as endometrial cysts. In the high-dose females, further slight increases in uterine pathology were described histologically, namely etritis/endometritis, cystic endometrial hyperplasia and uterine fibrovascular polyps. Mammary fibroadenomas occurred at similar incidences in all female groups. The incidence of mammary adenomas in treated females exceeded that of controls, but not in a dose-related manner...
-- -- Groups of 50 male and 50 female CD (Sprague-Dawley derived) rats received technical flucythrinate (80% pure) in the diet at 0, 30, 60 or 120 ppm daily for 24 months... At autopsy, high-dose females exhibited an increased incidence of cystic uterus... ((Brewer et al., 1981).
Ref: 1985 World Health Organization Review for Flucythrinate.
http://www.fluoridealert.org/pesticides/Flucythrinate.1985.WHO.htm

G-Proteins (click on for all fluorinated pestic

Note from EC: I've added this abstract to this section as the authors concluded that flucythrinate "inhibits intercellular communication."
Abstract: The effects of the pyrethroids flucythrinate (70124775), cyfluthrin (68359375), bioallethrin (584792) and resmethrin (10453868) were compared with the effects of tetradecanoyl-phorbol-acetate (TPA) and DDT on metabolic cooperation between Chinese-hamster-V79 cells to determine if pyrethroid structure was associated with ability to inhibit intercellular communication. Addition of flucythrinate (structurally related to fenvalerate and DDT) to cocultures of 6-thioguanine resistant cells and 6-thioguanine sensitive cells significantly increased mutant cell recovery, indicating inhibition of intercellular communication; other tested pyrethroids produced no such effect. Addition of TPA, together with increasing doses of flucythrinate or fenvalerate, produced a synergistic response. Various combinations of fenvalerate, flucythrinate, and DDT exposure indicated additive responses. The authors conclude that flucythrinate inhibits intercellular communication and that the p-substituted phenyl group may play an important role; there appear to be different pathways of action for TPA and the halogenated insecticides investigated in this study.
Ref: Effects of Tetradecanoyl Phorbol Acetate, Pyrethroids and DDT in the V79; by Warngard L, Flodstrom S. Cell Biology and Toxicology, Vol. 5, No. 1, pages 67-75, 27 references, 1989.

Heart (click on for all fluorinated pesticides)

"Chronic Dietary Toxicity Study in Dogs." (IRDC, 1/5/84.) Flucythrinate (85.4%) fed in the diet at 0, 30, 100 and 300 ppm of 24 months; eye exam included; 6/sex/group; NOEL stated in report = 100 ppm (emesis); reviewerÕs NOEL = 30 ppm (emesis, others); adverse "pharmacological" effect on heart (arrythmia, slower rate); ACCEPTABLE, Possible adverse effect. JG, 7/14/86.
Ref: Summary of Toxicological Data for Flucythrinate. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch. July 18, 1986 Revised August 12, 1987. Also available at
http://www.cdpr.ca.gov/docs/toxsums/pdfs/2168.pdf

Kidney (click on for all fluorinated pesticides)

-- Groups of 50 male and 50 female CD (Sprague-Dawley derived) rats received technical flucythrinate (80% pure) in the diet at 0, 30, 60 or 120 ppm daily for 24 months... Absolute and relative kidney weights were significantly elevated in mid- and high- dose males while only the relative kidney weight was elevated in high- dose females.... (Brewer et al., 1981).
-- Groups of 6 male and 6 female Beagle dogs received technical flucythrinate (87.3% pure) in the diet at 0, 30, 100, or 300 ppm daily for 24 months... At sacrifice, the relative liver, kidney, and pituitary weights were increased in both high-dose males and females, while increases in relative spleen, testis and lung weights were noted for high-dose males only... ((Spicer et al., 1984).
Ref: 1985 World Health Organization Review for Flucythrinate.
http://www.fluoridealert.org/pesticides/Flucythrinate.1985.WHO.htm

Liver (click on for all fluorinated pesticides)

Groups of 50 male and 50 female CD-1 mice received technical flucythrinate (80% pure) in the diet at 0, 30, 60, or 120 ppm daily for 18 months. Skin lesions (abrasions, ulceration and scabs) were observed in high-dose males and females. No treatment-related symptoms or treatment-related changes in survival were found. No haematology, clinical chemistry or urinalysis were undertaken. At necropsy, hepatocellular adenomas were found in all control and treated groups. The incidence was variable and statistically- significant only in high-dose males. Hepatocellular adenocarcinoma and hepatocellular carcinoma were found in low incidence in all male groups, but only in control and low-dose female mice. The incidences of these neoplasms were similar to those previously found in mice and were apparently unrelated to treatment.
Ref: 1985 World Health Organization Review for Flucythrinate.
http://www.fluoridealert.org/pesticides/Flucythrinate.1985.WHO.htm

Abstract: Male Sprague-Dawley rats dosed with N-nitrosodiethylamine (NDEA) 24 h after two-thirds partial hepatectomy were treated with the pyrethroid insecticides fenvalerate, flucythrinate or cypermethrin in the diet for 20 weeks. Altered hepatic foci were analyzed by quantitative stereology from paraffin-embedded sections stained for gamma-glutamyltranspeptidase (GGT) or glutathione S-transferase P (GST-P). The present results demonstrate that the pyrethroids tested all enhance the development of NDEA-initiated, GGT-positive foci in rat liver at non-hepatotoxic doses. On the contrary, the volume fractions of GST-P-positive foci were not elevated as compared to the control group. The three pyrethroids tested all inhibited the transfer of Lucifer Yellow CH between WB-F344 rat liver epithelial cells in culture, supporting the increase of GGT-positive foci and suggesting that these substances can act as tumour promoters. The discrepancy between the results from analyses using GGT or GST-P as markers emphasizes the importance of understanding the mechanism underlying the expression of different markers for preneoplastic lesions and the importance of such effects in tumour promotion.
Ref: Carcinogenesis 1993 Dec;14(12):2531-5. Enhancement of altered hepatic foci in rat liver and inhibition of intercellular communication in vitro by the pyrethroid insecticides fenvalerate, flucythrinate and cypermethrin. Hemming H, Flodstrom S, Warngard L.

Lung (click on for all fluorinated pesticides)

-- Groups of 6 male and 6 female Beagle dogs received technical flucythrinate (87.3% pure) in the diet at 0, 30, 100, or 300 ppm daily for 24 months... At sacrifice, the relative liver, kidney, and pituitary weights were increased in both high-dose males and females, while increases in relative spleen, testis and lung weights were noted for high-dose males only... Upon histological examination, mid- and high-dose groups exhibited increased evidence of interstitial pneumonia, compared to controls... ((Spicer et al., 1984).
Ref: 1985 World Health Organization Review for Flucythrinate.
http://www.fluoridealert.org/pesticides/Flucythrinate.1985.WHO.htm

Sciatic Nerve (click on for all fluorinated pesticides)

Long-term studies. Mouse. Groups of 50 male and 50 female CD-1 mice received technical flucythrinate (80% pure) in the diet at 0, 30, 60, or 120 ppm daily for 18 months... Mild sciatic nerve degeneration occurred in all groups, but at slightly increased incidence in treated groups, especially high-dose males. There was no apparent dose-response relationship. The incidence of mild axonal degeneration was similar in all groups. The no-effect level for this study was therefore set at 30 ppm (Lang, 1981b).
Ref: Flucythrinate. 1985 World Health Organization Review.
http://www.fluoridealert.org/pesticides/flucythrinate.1985.who.htm

Abstract: The neurotoxic action of six pyrethroid insecticides, four type II, (flucythrinate, deltamethrin, fenvalerate, fluvalinate) and two type I (cis- and trans-permethrin) was compared on the isolated sciatic nerve of frog. The nerve was exposed to pyrethroids for 30 min and action potentials were recorded for more than 45 hr after exposure. From the plots of the amplitude of the compound action potential vs time, it was possible to estimate, for each compound, the minimum effective concentration, the concentration which is required to reduce the amplitude of the compound action potential to 50% of its control value (mEC50). Flucythrinate was the most toxic compound, while toxicity decreased in the value: deltamethrin > fenvalerate > fluvalinate >> cis-permethrin > trans-permethrin. Low neurotoxicity of cis-permethrin and trans-permethrin (type I pyrethroids) was expected. The neurotoxicity of type I pyrethroids is mainly due to an action at the synapse, which are not present in the frog sciatic nerve preparation. The relative potencies of the four type II compounds agree with their acute toxicity estimated using the LD50.
Ref: Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 1997 Sep;118(1):97-103. Neurotoxic action of six pyrethroid insecticides on the isolated sciatic nerve of a frog (Rana ridibunda).
Theophilidis G, Benaki M, Papadopoulou-Mourkidou E.

Spleen (click on for all fluorinated pesticides)

-- Groups of 6 male and 6 female Beagle dogs received technical flucythrinate (87.3% pure) in the diet at 0, 30, 100, or 300 ppm daily for 24 months... At sacrifice, the relative liver, kidney, and pituitary weights were increased in both high-dose males and females, while increases in relative spleen, testis and lung weights were noted for high-dose males only... ((Spicer et al., 1984).
Ref: 1985 World Health Organization Review for Flucythrinate.
http://www.fluoridealert.org/pesticides/Flucythrinate.1985.WHO.htm