Adrenal Glands - Adverse Effects
Fluorinated and Fluoride Pesticides
 
 

A little information on Adrenal Glands:
The adrenal glands are orange-colored endocrine glands which are located on the top of both kidneys. The adrenal glands are triangular shaped and measure about one-half inch in height and 3 inches in length. Each gland consists of a medulla (the center of the gland) which is surrounded by the cortex. The medulla is responsible for producing epinephrine and norepinephrine (adrenaline). The adrenal cortex produces other hormones necessary for fluid and electrolyte (salt) balance in the body such as cortisone and aldosterone. The adrenal cortex also makes sex hormones but this only becomes important if overproduction is present.
Ref:
http://www.endocrineweb.com/adrenal.html



The use of high doses increases the likelihood that potentially significant toxic effects will be identified. Findings of adverse effects in any one species do not necessarily indicate such effects might be generated in humans. From a conservative risk assessment perspective however, adverse findings in animal species are assumed to represent potential effects in humans, unless convincing evidence of species specificity is available.

-- Food and Agricultural Organization of the United Nations

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

Chlorodifluoromethane - Insecticide, Fungicide, Propellant - CAS No. 75-45-6

Increased kidney, adrenal and pituitary weights... The female rats in the 50,000-ppm group exhibited a statistically significant increase in liver (absolute and relative), kidney (absolute), adrenal (absolute), and pituitary (absolute, at interim sacrifice--pituitaries were not weighed at terminal sacrifice) weights. No nonneoplastic histopathological changes attributable to exposure to HCFC-22 were observed. The liver weight effect was not considered adverse because it did not exceed a 10% weight change and there was no histopathology observed. Based on effects on kidney, adrenal, and pituitary weight, a NOAEL of 10,000 ppm [NOAEL(HEC) = 5260 mg/cu.m] and a LOAEL of 50,000 ppm [LOAEL(HEC) = 26,300 mg/cu.m] can be estimated.
Ref: US EPA IRIS for Chlorodifluoromethane.

http://www.fluoridealert.org/pesticides/Chlorodifluoromethane.IRIS.htm

CTFT Chlorotrifluorotoluene, 4-,Alpha,Alpha,Alpha- Intermediate used in herbicides - CAS No. 98-56-6

In 14-day toxicity studies, 1 of 10 female rats given the top dose of 1000 mg/kg CTFT in corn oil died on day 8; no deaths of male rats or of mice of either sex were attributable to the administration of CTFT. Body weight gains in all groups of rats and mice were similar with the exception of the top dose (1000 mg/kg) groups of male and female rats, which lost weight during the first week and resumed weight gain during the second. CTFT was found to accumulate in the kidneys of male rats, and there was a linear relationship between the kidney CTFT concentrations and the kidney levels of a2u-globulin, as determined by an ELISA assay. Microscopic changes in male rats included a dose-related toxic nephropathy consistent with that previously described as "hyaline droplet nephropathy." Dosed male and female rats also had hepatocyte hypertrophy and cytoplasmic vacuolization of the adrenal cortex. Clinical pathology findings suggested a mild anemia and cholestasis in rats. In contrast to rats, mice did not show appreciable CTFT concentrations in any tissue evaluated, suggesting a more rapid elimination of the chemical. However, hepatocellular hypertrophy, and clinical pathology findings consistent with cholestasis and mild liver injury, were noted in mice in the 400 and 1000 mg/kg dose groups. These studies demonstrated that oral doses of CTFT of 400 mg/kg or higher caused liver hypertrophy in rats and mice and adrenal changes in rats. Doses of 50 mg/kg or higher caused "hyaline droplet nephropathy" in male rats. The results were similar with CTFT administered either in corn oil or in -CD (although absorption of CTFT was somewhat more rapid with -CD), suggesting that -CD may be an appropriate vehicle for toxicity studies with other chemicals.
Ref: National Toxicology Program. July 1992. Toxicity Studies of p-Chloro-,,Trifluorotoluene (CAS NO: 98-56-6) Administered in Corn Oil and -Cyclodextrin to F344/N Rats and B6C3F1 Mice in 14-Day Comparative Gavage Studies.

http://www.fluoridealert.org/pesticides/CTFT.NTP.ToxicityStudy.1992.htm

Cyfluthrin - Insecticide - CAS No. 68359-37-5

-- Subchronic toxicity-- i. 28-Day oral toxicity study in rats. Cyfluthrin was administered to SPF-Wistar rats via gavage at 0, 5, 20, or 80 (40) mg/kg/day. The high dose was 80 mg/kg/day during the first and third weeks and 40 mg/kg/day during the second and fourth weeks. The LOEL was 80 (40) mg/kg/day in both sexes based on clinical signs of nerve toxicity, decreases in body weight gain, and changes in liver and adrenal weights. The NOEL was 20 mg/kg/day. This study was classified as core minimum.
Ref: Federal Register: November 26, 1997. Cyfluthrin; Pesticide Tolerances. Final Rule.
http://www.fluoridealert.org/pesticides/Cyfluthrin.FR.Nov.26.1997.htm

-- Rats Four groups of 30 male and 24 female Mura:SPRA (SPF 68 Han) rats received 14C radiolabelled cyfluthrin as either oral doses of 0.5 or 10 mg/kg bw or intravenous or intraduodenal doses of 0.5 mg/kg bw. Another group received unlabelled cyfluthrin orally once a day for 14 consecutive days, followed by a single oral dose of 0.5 mg/kg bw 14C-cyfluthrin... The residues found in the organs and tissues were influenced by the route of administration, as the mean relative concentration of cyfluthrin in the bodies of males and females at sacrifice was lower after oral administration (0.013) than after intravenous injection (0.06). Female rats had higher plasma concentrations after oral administration of the single high or low dose; 48 h after administration, lower concentrations were detected in the bone and muscle of animals of each sex and in the testes of males rats. The sciatic nerve showed a similar relative concentration value, which may explain the toxic effects observed on the peripheral nervous system. Higher concentrations were detected in the spleen, adrenal glands, liver, and plasma of both males and females and in the ovaries. The renal fatty tissue concentration was about seven times higher after either oral or intravenous administration, whereas the mean concentration in brain was significantly lower ( p = 0.0006-0.006) (Klein et al., 1983).
-- Groups of 28 male and 28 female Sprague-Dawley rats received diets containing 0, 100, 300, or 1000 mg/kg cyfluthrin (purity, 95%) incorporated into the powdered diet on a 0.4% maximum clay carrier, daily for three months... The food consumption and body-weight gains of females and males at the highest dose were significantly lower than those of the control group. The body-weight gain depression in females appeared to recover after cessation of treatment, while that of the males remained significantly low... The absolute weights of the liver, heart, and lung were decreased in male rats at the high dose, and females at this dose had depressed liver, kidney, adrenal, and ovarian weights. In both males and females at the high dose, the relative weight of the submaxillary gland was increased...
Ref: Cyfluthrin. Toxicological evaluation of certain veterinary drug residues in food. WHO FOOD ADDITIVES SERIES 39 Prepared by: The forty-eighth meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). World Health Organization, Geneva 1997.
http://www.fluoridealert.org/pesticides/Cyfluthrin.WHO.Tox.Eval.97.htm

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

Chloroaniline, p (or 4-chloraniline) is a metabolite of Diflubenzuron. In 2006, USEPA classified chloroaniline, p as a "Group B2 -- Probable Human Carcinogen." "Spleen (fibrosarcomas, hemangiosarcomas & osteosarcomas) (M); Adrenal (pheochromocytomas (M & F); F344/N rats. Hepatocellular adenomas/carcinomas (M); Hemangiosarcomas in spleen and/or liver (M) in B6C3F1 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

-- PCA [p-chloroaniline; a metabolite of Diflubenzuron] was administered 5 days/week by oral gavage, as a hydrochloride salt in water, to male and female F344/N rats at doses of 0, 2, 6, or 18 mg/kg/day. Mean body weights of dosed rats were generally within 5% of those of controls throughout the study. High dose animals generally showed mild hemolytic anemia and dose-related methemoglobinemia. Non- neoplastic lesions seen were bone marrow hyperplasia, hepatic hemosiderosis, and splenic fibrosis, suggesting treatment-related effects on the hematopoietic system. Adrenal medullary hyperplasia was observed in high dose female rats. The incidence of uncommon sarcomas of the spleen was significantly increased in high dose male rats. A marginal increase in pheochromocytomas of the adrenal gland was seen in high dose male and female rats. It was concluded that, under the conditions of this 2-year gavage study, there was clear evidence of carcinogenic activity of PCA hydrochloride for male F344/N rats and equivocal evidence of carcinogenic activity of PCA hydrochloride for female F344/N rats.
Ref: Federal Register: December 14, 2001. (Volume 66, Number 241)] [Notices] [Page 64823-64828]. Notice of Filing Pesticide Petitions to Establish a Tolerance for a Certain Pesticide Chemical in or on Food.
http://www.fluoridealert.org/pesticides/Diflubenzuron.FR.Dec14.2001.htm

(p-Chloroaniline: Metabolite of Diflubenzuron): A marginally increased incidence of pheochromocytomas was also observed in the adrenal gland of male and female rats at 18 mg/kg/day. For male rats, the incidence was 13/49, 14/48, 15/48 and 26/49 and for female rats was 2/50, 3/50, 1/50 and 6/50 at dose levels of 0, 2, 6 and 18 mg/kg/day respectively.
Ref: US EPA Reregistration Eligibility Decision (RED) Diflubenzuron. EPA 738-R-97-008. August 1997.

Dithiopyr - Herbicide - CAS No. 97886-45-8

The following results were presented by a Monsanto scientist.
-- Thirteen-week Feeding Study in Rats. Dithiopyr was administered via the diet to groups of 12 male and 12 female F-344 rats for 13 weeks at concentrations of 0, 10, 100, 1000 and 5000 ppm.. Other findings included [no concentrations listed] multiple organ weight effects, thyroid follicular hypertrophy, adrenal cortical hypertrophy, and pulmonary foam cell aggregation. The subchronic NOEL in rats is considered to be 10 ppm. (The Institute of Environmental Toxicology, 1988)
-- Four-week Feeding Study in Mice. Dithiopyr was administered via the diet to groups of 6 male and 6 female CD-1 mice for 4 weeks at concentrations of 0, 300, 1000, 3000, 10,000 and 30,000 ppm... [No concentrations listed for the following effects:]-- Liver enlargement and discoloration, adrenal enlargement, and atrophy of the thymus, spleen, seminal vesicles, ovaries and uterus were noted on gross post-mortem examination... (The Institute of Environmental Toxicology, 1987)
-- Thirteen-week Feeding Study in Mice. Dithiopyr was administered via the diet to groups of 12 male and 12 female CD-1 mice for 13 weeks at concentrations of 0, 10, 100, 1000 and 5000 ppm... Other findings included [no concentrations listed]: multiple organ weight effects, adrenal cortical hypertrophy and ovarian atrophy. The subchronic NOEL in mice is considered to be 10 ppm. (The Institute of Environmental Toxicology, 1989)
-- Eighteen-month Feeding Study in Mice. In an oncogenicity study, dithiopyr was administered via the diet to groups of 70 male and 70 female CD-1 mice for 78 weeks at concentrations of 0, 3, 30 and 300 ppm... Other findings included [no concentrations listed]: increased adrenal weights, adrenal cortical swelling, spleen enlargement and increased splenic extramedullary hematopoiesis. The chronic NOEL in mice is considered to be 3 ppm (equivalent to a daily intake of 0.31 mg/kg b.w. in males and 0.37 mg/kg b.w. in females). (The Institute of Environmental Toxicology, 1989)
-- REPRODUCTION AND DEVELOPMENTAL TOXICITY STUDIES 1. Two-generation Reproduction Study in Rats •Dithiopyr was administered via the diet to groups of 24 male and 24 female S-D rats over 2 consecutive generations at concentrations of 0, 25, 250 and 2500 ppm... Other findings included [no concentrations listed]: increased kidney weight, focal renal tubular atrophy, thyroid follicular hypertrophy, and adrenal cortical hypertrophy... (The Institute of Environmental Toxicology, 1989)
Ref: Summary of Toxicology Studies With Dithiopyr. Dennis P. WARD. Toxicology Department, The Agricultural Grop, A Unit of Monsanto Company (Received February 20, 1993). Also available at

http://wwwsoc.nii.ac.jp/pssj2/tec_info/dithiopy.pdf

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

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

"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

Etoxazole - Acaricide - CAS No. 153233-91-1

Subchronic toxicity. Effects observed at high dose levels consisted primarily of anemia and histological changes in the adrenal gland, liver and kidneys.
Ref: August 13, 2003. [Federal Register: August 13, 2003 (Volume 68, Number 156)] [Notices]. Etoxazole; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food.

http://www.fluorideaction.org/pesticides/etoxazole.fr.aug.13.2003.htm

Reproduction and fertility effects (rat). Parental/Systemic NOAEL = 20 mg/kg/ day LOAEL = 100 mg/kg/ day (M/F), based upon increased liver weights in the P and F1 males and increased adrenal weights in the P females Offspring/Systemic NOAEL = 20 mg/kg/ day LOAEL = 100 mg/kg/ day (M/F), based upon pup mortality Reproductive NOAEL = 100 mg/kg/day LOAEL = not determined.
Ref: Federal Register: September 26, 2003. Etoxazole; Pesticide Tolerance. Final Rule.
http://www.fluorideaction.org/pesticides/etoxazole.fr.sept.26.2003.htm

Flonicamid - Insecticide - CAS No. 158062-67-0

-- In the multi-generation rat reproduction study, the NOAEL was 300 ppm for both parental animals (13.5-32.8 and 16.3-67.0 mg/kg/day, respectively, for males and females) and their offspring. The effects at the highest dose of 1,800 ppm included the following: increased kidney weights and gross and histopathological alterations in the kidney. Findings noted in the top dose females included delayed vaginal opening and increased liver, kidney and spleen weights in the F1 generation and reduced ovary and adrenal weights in the parental generation and decreased uterine weights in the F1 female weanlings. There was an increase in the FSH and LH levels in F1 females tested for these endpoints. These findings did not affect the reproductive performance or survival of offspring in the study.
-- Endocrine disruption. No special studies investigating potential estrogenic or other endocrine effects of flonicamid have been conducted. Some suggestions of possible endocrine effects were reported at the highest dose tested (1,800 ppm) in the multi-generation reproduction study which showed increased FSH and LH levels, a delay in the time to vaginal opening in the F1 generation, and reduced ovary and adrenal weights in the parental generation. However, there were no effects on reproductive performance or survival of the offspring in the study. At levels that are expected to be found in the environment, flonicamid will not cause any endocrine-related effects.
Ref: Federal Register: May 23, 2003 (Volume 68, Number 100)] [Notices] [Page 28218-28222]. Flonicamid; Notice of Filing a Pesticide Petition to Establish a Tolerance for a Certain Pesticide Chemical in or on Food.
http://www.fluorideaction.org/pesticides/Flonicamid.FR.May23.2003.htm

-- 90-Day oral toxicity (nonrodents- dogs). NOAEL is 8 mg/kg/day in males and 20 mg/kg/day for female. LOAEL is 20 mg/kg/day in males and 50 mg/kg/day in females, based on acute clinical signs in males and females (vomiting, first observed on Day 1 and last observed on Day 90), clinical pathology at 7 weeks (increased total protein levels in males, lower red blood cells and higher reticulocytes counts in females), increased adrenal weights in males, decreased thymus gland weights in males, and increased kidney tubular vacuolation in females at study termination.
Ref: August 31, 2005. Flonicamid; Pesticide Tolerance. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/
flonicamid.fr.aug.31.2005.html

Floransulam - Herbicide - CAS No. 145701-23-1

Short term toxicity. Target / critical effect: Anemia, hepatotoxicity , renal hypertrophy epithelial cells, collecting ducts, adrenal vacuolation(dog ) Lowest relevant oral NOAEL / NOEL: 1 y & 90 d dog (oral feed) ; 5 mg/kg bw/d;...
Ref: September 18, 2002 - Review report for the active substance florasulam. European Commission Health & Consumer Protection Directorate-General
.
http://www.fluoridealert.org/pesticides/Florasulam.EU.Sept.2002.pdf

-- The subchronic and chronic toxicity of florasulam was investigated in the mouse, rat and dog. A 28-d repeat dose dermal toxicity study was also carried out in rats. In the subchronic and chronic studies, treatment-related findings were observed in the kidney in all species and in the liver and adrenal glands in dogs. In the kidney, hypertrophy of the epithelial cells of the collecting ducts occurred in all species tested.
-- In subchronic and chronic dietary studies, treatment-related findings were observed in the kidneys in mice, rats and dogs and in the liver and adrenal glands in the dog. In the kidney, hypertrophy of the epithelial cells of the collecting duct was observed in all species tested. In rats, hypertrophy of the epithelial cells correlated with elevated serum bicarbonate levels, urinary acidification, decreased urinary specific gravity and increased kidney weights. In dogs, treatment-related findings associated with the liver included increased ALP activity, decreased serum albumin and protein levels, increased liver weights and increased incidence or severity of hepatic vacuolation. Dogs also exhibited slight vacuolization of the zona reticularis and zona fasciculata in the adrenal glands; however, in the absence of any associated inflammation, necrosis or other changes, the toxicological significance was uncertain. The most appropriate NOAEL for subchronic and chronic toxicity end points is 5.0 mg/kg bw/d in the 90-d and 1-year dietary studies in dogs. At the LOAEL, 50 mg/kg bw/d, treatment-related findings were observed in the kidneys and liver in the 90-d and 1-year dietary studies and in the adrenal glands in the 1-year dietary study.

Ref: Florasulam EF-1343 Suspension Concentrate Herbicide. REF2001-12. September 21, 2001. Canadian Pest Management Regulatory Agency. Health Canada.

http://www.hc-sc.gc.ca/pmra-arla/english/pdf/reg/reg2001-12-e.pdf

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

**411-083 069476 Virgo, D. M., “Fluazifop-butyl: 55 week oral toxicity study in beagle dogs,” Life Science Research, Stock, Essex, England, 10/15/82. LSR Report No. 81/ILK019/620. Six dogs/sex/group were dosed for 55 weeks with Fluazifop-butyl, 99.6% purity, by gelatin capsules at dose levels of 0, 5, 25, and 125 mg/kg/day in a chronic study. Test article within capsules was dissolved in 0.4 ml/kg corn oil vehicle. NOEL = 5 mg/kg/day. The degree of adrenal gland cortical fatty degeneration evident in one mid-dose female was sufficiently greater than that of any of the control dogs that investigators attributed this finding to treatment. Cortical fatty degeneration of moderate to severe degree was observed in one high dose male and in all high dose females. All other noteworthy findings were limited to the high dose group, as follows... Male reproductive toxicity included testicular tubular degeneration and reduced/absent spermatozoa in epididymides. Possible adverse effects (many-faceted toxicity, including mortalities, at 125 mg/kg/day). Acceptable. Aldous, 5/20/02.
Ref: May 20, 2002. SUMMARY OF TOXICOLOGY DATA FLUAZIFOP-P-BUTYL. California EPA. Department of Pesticide Regulation. Medical Toxicology Branch.

http://www.fluoridealert.org/pesticides/Fluazifop-P-butyl.CAepa.02.pdf

Flufenoxuron - Acaricide, Insecticide, Herbicide - CAS No. 101463-69-8

Carcinogenicity. Rat. Groups of 50/sex/group Fischer 344 rats were administered 0, 500, 5000 or 50000 ppm flllufenoxuron in the diet for 24 months... In males relative spleen weight was reduced in all treatment groups (respectively 14, 29 and 32 %)...In the females there was a significant increase in adrenal weight in all treatment groups (respectively 9, 7 and 15%).
Ref: December 1995. Evaluation of Flufenoxuron use as a public hygiene insecticide. UK: Health and Safety Executive, Biocides & Pesticides Assessment Unit. Available at
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm

Flumioxazin - Herbicide - CAS No. 103361-09-7

-- "Three-Month Subacute Toxicity Study of S-53482 by Dietary Administration in Rats"; (Haruhiko Adachi; Sumitomo Chemical Co., Environmental Health Science Laboratory,, Ltd., Osaka, Japan; Study No. 1760; 4/26/91); Sixteen Crj:CD (SD) rats/sex/group were treated in the diet with 0, 30, 300, 1000 or 3000 ppm of S-53482 (lot no. PYG-89021-M, purity: 94.8%). Six of these animals/sex/group were treated for 5 weeks. The remaining 10 animals/sex/group were treated for 13 weeks ((M): 0, 1.94, 19.4, 65.2, 197.3 mg/kg/day, (F) 0, 2.22, 22.4, 72.8, 218.4 mg/kg/day)... Other noted lesions for the 3000 ppm females were... atrophy of the thymus and the presence of thymal foam cells (0:0/10 vs. 3000: 3/10), sinus histiocytosis in the mesenteric lymph node (0:0/10 vs. 3000: 3/10), and cytoplasmic vacuolation in the adrenal cortex (0:0/10 vs. 3000: 3/10)...
Ref: January 32, 2003 (revised) - Summary of Toxicological Data. California EPA, Department of Pesticides Regulation, Medical Toxicology Branch.

Fluometuron - Herbicide - CAS No. 2164-17-2

-- CHRONIC TOXICITY. Rats were fed 7.5, 75, or 750 mg/kg/day for 90 days. At the 750 mg/kg dose, decreased body weight and congestion in the spleen, adrenals, liver, and kidneys were evident. The NOAEL for this study was 7.5 mg/kg/day (100 ppm). When doses of 1.5, 15 or 150 mg/kg/day were fed to puppies for 90 days, congestion of the liver, kidneys and spleen occurred at the 150 mg/kg dose. No effects were seen at 15 mg/kg/day (400 ppm) (20).
Ref: Flumeturon. EXTOXNET. Pesticide Information Profile. March 1994.

http://pmep.cce.cornell.edu/profiles/extoxnet/dienochlor-glyphosate/fluometuron-ext.html

Fluoxastrobin - Fungicide - CAS No. 193740-76-0

• 90-Day oral toxicity-rats. reduced body weight gain and food intake, vacuolation in the zona fasciculate of the adrenal cortex, calculi in the urethra and kidney, and histological lesions in kidney, urinary bladder, and urethra;
Ref: Federal Register. September 16, 2005. Fluoxastrobin; Pesticide Tolerances. Final Rule.

http://www.fluorideaction.org/pesticides/fluoxastrobin.fr.sept16.05.html

Fluroxypyr - Herbicide - CAS No. 69377-81-7

-- Chronic toxicity. EPA has established the RfD for fluroxypyr at 0.5 mg/kg/day. This RfD is based on histopathological lesions in the kidneys, decreased testes weights, and increased adrenal weights in both sexes observed in a 4-week range-finding feeding study in the dog with a NOAEL of 50 mg/kg/day. An uncertainty factor of 100 was used in calculating the RfD to account for both inter- and intra-species variations.
-- A 90-day feeding study in Wistar rats (10/sex/group) administered fluroxypyr (98.5% a.i.) in the diet at 0, 80, 750, 1,000 or 1,500 milligrams/kilogram/day (mg/kg/day) for 13 weeks. Significant nephrotoxicity and deaths were observed at 1,000 and 1,500 mg/kg/day in both sexes, and in males at 750 mg/kg/day. Death was due to renal papillary necrosis. Also observed were signs of ill health, emaciation, decreased food intake, increased kidney weight, histopathological lesions and decreased renal function. Histological changes were observed in the adrenals in both sexes at 1,000 and 1,500 mg/kg/day. In males the NOAEL for this study is 80 mg/kg/day, and the LOEL is 750 mg/ kg/day based on kidney effects and death. In females the NOAEL is 750 mg/kg/day, with the LOEL at 1,000 mg/kg/day based on kidney effects and death.
-- A 28-day feeding study in Beagle dogs administered Fluroxypyr 98.0% a.i. in the diet at levels of 0, 50, 150 or 450 mg/kg/day for 28 days. Dogs at 500 mg/kg/day exhibited ataxia and hind limb weakness as well as decreases in body weight and food consumption and were sacrificed on days 16/17 of the study. Histopathology showed moderate acute tubular nephrosis and a slight to moderate acute gastroenteritis. Some early signs of acute tubular nephrosis were also seen in both sexes of dogs at 150 mg/kg/day. The NOAEL for the study was 50 mg/kg/ day, the LOEL was 150 mg/kg/day based on histopathological lesions in the kidneys, decreased testes weights, and increased adrenal weights in both sexes.
Ref: Federal Register: September 30, 1998. Fluroxypyr; Pesticide Tolerance. Final Rule.

http://www.fluoridealert.org/pesticides/Fluroxypyr.FR.Sept.30.1998.htm

Fluroxypyr 1-methylheptyl ester - Herbicide - CAS No. 81406-37-3

Reproductive toxicity study. In the 2-generation reproductive toxicity study in rats, the maternal (systemic) NOAEL was 100 mg/kg/ day, based on increased kidney weights and kidney histopathology at the LOAEL of 500 mg/kg/day. The developmental (pup) NOAEL was 500 mg/kg/ day, based on decreased body weight at the LOAEL of 1,000 mg/kg/day. The reproductive NOAEL was 1,000 mg/kg/day (HDT).... Chronic dietary all populations: 28-day dog range- finding feeding study LOAEL = 150 mg/kg/day based on histopathological lesions in the kidneys, decreased testes weights, and increased adrenal weights in both sexes...
Ref: Federal Register. September 17, 2001. Fluroxypyr 1-Methylheptyl Ester; Pesticide Tolerances for Emergency Exemptions. Final Rule.

http://www.fluoridealert.org/pesticides/Fluroxypyr.FR.Sept.17.2001.htm

Flurprimidol - Plant Growth Regulator - CAS No. 56425-91-3

-- A l-year dog study treated with flurprimidol at doses of 0, 0.5, 1.5, 7.0 and 30.0 mg/kg/day, the NOEl was 7.0 mg/kg/day and the LEL was 30.0 mg/kg/day Highest Dose Tested (HDT) based on adrenal changes including decreased plasma cortisol response to ACTH stimulation (males and degenerative changes of the adrenal cortex (males and females). The histopathology was limited to the zona fasciculata of the adrenal cortex and was characterized by eosinophilic degeneration, vacuolation and cortical atrophy. There was a slight increase in hepatic p-nitroanisole 0-demethylase activity (males).
Ref: EPA Pesticide Fact Sheet for Flurprimidol. Reason for Issuance: New Chemical Registration. Date Issued: FEB 22 1989. Fact Sheet Number: 202.

http://www.fluoridealert.org/pesticides/Flurprimidol.EPA.Facts.1989.htm

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

- On May 28, 1998, the Agency’s Cancer Peer Review Committee concluded that the dose levels of 100 ppm in males, and 50 ppm in females were adequate to assess the carcinogenic potential of hydramethylnon in rats.... The statistically significant increases in tumors observed in the uterus (adenomatous polyps) and adrenals (medullary adenomas) were not considered to be biologically significant since they were seen at excessive doses (i.e., at 200 ppm). Under the conditions of this study, the NOAEL was 50 ppm (2.4 mg/kg/day in males, 3.0 mg/kg/day in females), and the LOAEL was 100 ppm (4.9 mg/kg/day in males, 6.2 mg/kg/day in females) based on small, soft testes, decreased testicular weights, and testicular atrophy in males; and decreased body weight gain in females. This study is classified as acceptable and satisfies guideline requirement 83-5 for a chronic feeding/carcinogenicity study in rodents.
Ref: US EPA. Reregistration Eligibility Decision (RED) Hydramethylnon. EPA 738-R-98-023. December 1998.

http://www.fluoridealert.org/pesticides/Hydramethylnon.RED.1998.pdf

Lactofen - Herbicide - CAS No. 77501-63-4

Dog chronic toxicity LOAEL = 3.96 mg/kg/day based on increased incidence of
proteinaceous casts in the kidneys, and statistically significant increases in the absolute weights of the thyroid and adrenal glands in males.
Ref: Sept 24, 2004. Lactofen. Pesticide Tolerance. Final Rule. Federal Register.
http://www.fluorideaction.org/pesticides/lactofen.fr.sept.24.2004.htm

-- Subchronic feeding-- Mice-- 3-month. Groups of Male and female mice were fed diets containing Lactofen Technical at concentrations of 0, 40, 200, 1,000, 5,000, and 10,000 for 13-weeks. At week 5, the dosage of the 40 ppm groups was increased to 2,000 ppm. Treatment related mortality occurred at dosages above 1,000 ppm. The LOEL was 200 ppm based on: increased WBC; decreased hematocrit, hemoglobin and RBC; increased alkaline phosphatase, SGOT, SGPT, cholesterol and total serum protein levels; increased weights or enlargement of the spleen, liver, adrenals, heart and kidney; histopathological changes of the liver, kidney, thymus, spleen, ovaries and testes. In general, effects were slight in the 200 ppm groups, and moderate to severe in the 1,000 ppm groups.
Ref: Federal Register: February 25, 1998 [Page 9532-9540]. Notice of Filing of Pesticide Petition.

http://www.fluoridealert.org/pesticides/Lactofen.FR.Feb.1998.htm

Novaluron - Insecticide - CAS No. 116714-46-6

Chloroaniline, p (or 4-chloraniline) is a metabolite of Novaluron. In 2006, USEPA classified chloroaniline, p as a "Group B2 -- Probable Human Carcinogen." "Spleen (fibrosarcomas, hemangiosarcomas & osteosarcomas) (M); Adrenal (pheochromocytomas (M & F); F344/N rats. Hepatocellular adenomas/carcinomas (M); Hemangiosarcomas in spleen and/or liver (M) in B6C3F1 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

Noviflumuron - Insecticide - CAS No. 121451-02-3

-- “XDE-007: One-Year Dietary Toxicity Study in Beagle Dogs,” (Stebbins, K.E., Day, S.J., Thomas, J.; Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI; Laboratory Project Study ID #: 142640; 3/5/04). XDE-007 (97.9% pure) was fed in diet to Beagle dogs (4/sex/dose) for 1 year at 0, 0.003, 0.03 or 0.225% (equivalent to 0, 0.74, 9.3 and 69 mg/kg/day - Males and 0, 0.94, 8.7 and 70 mg/kg/day - females)... There was a statistically significant increase in absolute adrenal weights (analyzed across both sexes) at 0.225% without histological findings.
-- “XDE-007: One-Generation Dietary Reproduction Toxicity Study With CrossFostering in CD Rats,” (Marty, M.S., Zablotny, C.L., Liberacki, A.B., Yano, B.L.;Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI; Laboratory Project Study ID: 011221; 3/23/04). XDE -007 (97.9% pure) was fed in diet to Crl:CD (SD) IGS BR rats (30/sex/dose) at 0, 0.5, 5 and 100 mg/kg/day continuously from pre-mating (10 weeks) of parental generation, through breeding (2 weeks), gestation (3 weeks) and lactation through weaning of F1 offspring. Although designed as a 2 generation reproduction study, it was terminated after 1 generation due to excessive F1 pup mortality at 100 mg/kg/day. Subsequently a Cross-fostering Study was performed to determine whether the decreased survival in pups from XDE-007 treated P1 rats resulted from in utero or lactational exposure. Parental Systemic NOEL = 0.5 mg/kg/day (Tonoclonic convulsions were observed in 2/30 males and 1/24 females at 100 mg/kg/day. Males had statistically significantly decreased food consumption from day 8 until termination at 100 mg/kg. Females had statistically significantly decreased food consumption during lactation. Male P1 premating body weights were statistically significantly decreased at 100 mg/kg/day. Mean gestational body weight gain in females was statistically significantly decreased GD 0 - 7 (but not GD 0 - 21) and lactation days 7 - 13 at 100 mg/kg/day.) Reproduction and Fertility NOEL = 0.5 mg/kg/day (P1 female gestation survival was decreased and gestation length was increased at 100 mg/kg. Pup NOEL = 0.5 mg/kg (F1 survival was drastically decreased throughout lactation at 100 mg/kg. Clinical effects were increased in pups at 100 mg/kg, primarily tonoclonic convulsions, no milk in stomach, entire litter loss and death. Pup weights were statistically significantly decreased at 100 mg/kg. Cross-fostering data indicate the proximate toxicant (either XDE-007 and/or its metabolites) led to decreased pup survival through the maternal milk and not through exposure in utero. Possible adverse effect indicated: excessive neonatal/pup mortality and increased tonoclonic convulsions in pups (17/24 litters) at 100 mg/kg. These data are supplemental. M. Silva, 7/20/04
-- “XDE-007: Two-Generation Dietary Reproduction Toxicity Study in CD Rats,” (Carney, E.W., Zablotny, C.L., Liberacki, A.B., Yano, B.L.;Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI; 3/22/04). XDE -007 (97.9% pure) was fed in diet to Crl:CD (SD) IGS BR rats (30/sex/dose/generation) at 0, 0.5, 5 or 25 mg/kg/day continuously from pre-mating of parental generation 1 (P1) through weaning of offspring through 2 generations (2 matings for P2 generation) to F2b weaning. Parental Systemic NOEL = 5.0 mg/kg/day (There were increased absolute and relative liver weights in both sexes of P1 and P2 adults at 25 mg/kg and in P1 female liver weights at 5.0 mg/kg. P1 male relative kidney weights, P2 female absolute kidney weights, P2 male relative spleen and thyroid weights and P2 female absolute and relative adrenal weights were increased at 25 mg/kg.) ...
Ref: August 2005 - Summary of toxicological data. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch.
http://www.fluorideaction.org/pesticides/noviflumuron.ca.epa.2005.pdf

Oxyfluorfen - Herbicide - CAS No. 42874-03-3

Absolute and relative thymus weights were decreased in mid-dose males (-14%/-10%)and high-dose males (-32%/- 18%)...Vacuolation of the adrenal cortex was present in high-dose females. Thymic atrophy occurred in high-dose males and females.... Fine vacuolation of adrenal glands (slight) and cortical atrophy of the thymus (slight) were increased in high-dose males... Absolute and/or relative organ weights in the high-dose groups that showed statistically significant changes relative to control weights (thyroid gland in both sexes and kidney in females at 12 months and brain, pituitary, and spleen in females sacrificed at 24 months) had no microscopic correlates and are not considered toxicologically significant.
Ref: US EPA. Toxicology Chapter for RED. August 8, 2001
.
http://www.epa.gov/oppsrrd1/reregistration/oxyfluorfen/oxytoxchapter.pdf

Picolinafen - Herbicide - CAS No. 137641-05-5

In the 78-week dietary study, there was no evidence to indicate that picolinafen was oncogenic in the mouse. In the rat 2-year dietary study, there was a non-statistically significant, increased incidence of benign neoplasms (benign pheochromocytomas) in the adrenal gland medullary region for males at 500 ppm (highest dose tested). The incidence was within recent historical control data for benign medullary neoplasms. In addition, there was no decrease in the time-to-appearance of the induced tumour and no dose-response relationship in proliferative changes usually associated with neoplasms, benign or malignant, in the adrenal medulla. Published literature indicates that proliferative lesions of the adrenal medulla in male rats occurs at relatively high incidences and can be spontaneous (age-related) in nature. Based on these findings, the slight increased incidence of benign neoplasms in the adrenal gland medullary region noted for males at 500 ppm, was most likely spontaneous in nature and not treatment-related. The weight of evidence suggests that picolinafen is not likely to be oncogenic in humans.
Ref: February 17, 2003 - Canada. Picolinafen. Regulatory Note REG2003-02. Alternative Strategies and Regulatory Affairs Division, Pest Management Regulatory Agency.
http://www.fluorideaction.org/pesticides/picolinafen.canada.feb.2003.pdf

PFOS - PFOA - Insecticide, US EPA List 3 Inert

Adverse signs of toxicity observed in Rhesus monkey studies included anorexia, emesis, diarrhea, hypoactivity, prostration, convulsions, atrophy of the salivary glands and the pancreas, marked decreases in serum cholesterol, and lipid depletion in the adrenals. The dose range for these effects was reported between 1.5-300 mg/kg/day. No monkeys survived beyond 3 weeks into treatment at 10 mg/kg/day or beyond 7 weeks into treatment at doses as low as 4.5 mg/kg/day.
Ref: November 21, 2002 report: Hazard Assessment of Perfluorooctane sulfonate (PFOS) and its salts. Organisation for Economic Co-operation and Development. ENV/JM/RD(2002)17/FINAL.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf

In the second study, Goldenthal et al. (1978a) administered rhesus monkeys, 2/sex/group, doses of 0, 0.5, 1.5 or 4.5 rng/kg/day PFOS (FC-95) in distilled water by gavage for 90 days... All monkeys in the 4.5 mg/kg/day group died or were sacrificed in extremis between week 5 and 7 of the study. Beginning on the first or second day of the study, these monkeys exhibited signs of gastrointestinal tract toxicity including anorexia, emesis, black stool and dehydration. All of the monkeys had decreased activity and just prior to death showed marked to severe rigidity, convulsions, generalized body trembling and prostration. The mean body weight decreased from 3.44 kg at the beginning of the study to 2.7 kg at week 5 . After 30 days of treatment, there was a significant reduction in serum cholesterol and a 50% reduction in serum alkaline phosphatase activity. At necropsy, mean organ weights were comparable among the control and treated monkeys. Histologic examination showed several treatment related lesions. All the male and females had marked diffuse lipid depletion in the adrenals. One male and two females had moderate diffuse atrophy of the pancreatic exocrine cells with decreased cell size and loss of zymogen granules. Two males and one female had moderate diffuse atrophy of the serous alveolar cells characterized by decreased cell size and loss of cytoplasmic granules.
Ref: Sulfornated Perfluorochemicals in the Environment: Sources, Dispersion, Fate and Effects. Prepared by 3M. March 1,2000.

3.5 Reproductive Toxicity Studies in Animals
York (2002) conducted an oral two-generation reproductive toxicity study of APFO, which is summarized below. Although this preliminary risk assessment focuses on developmental toxicity, the summary below of the two generation reproductive toxicity study includes all endpoints. Five groups of 30 Sprague-Dawley rats per sex per dose group were administered APFO by gavage at doses of 0,1,3,10, and 30 mg/kg/day six weeks prior to and during mating. Treatment of the F0 male rats continued until mating was confirmed,and treatment of the F0 female rats continued throughout gestation, parturition, and lactation....
Parental Males (F0)... No treatment-related effects were seen at necropsy or upon microscopic examination of the reproductive organs, with the exception of increased thickness and prominence of the zona glomerulosa and vacuolation of the cells of the adrenal cortex in the 10 and 30 mg/kg/day dosegroups.
F1 Males ... The absolute weight of the prostate, brain and left adrenal gland were significantly decreased in the 30 mg/kg/day dosage group. The ratios of the weights of the seminal vesicles, with and without fluid, liver and left and right kidneys to the terminal body weights were significantly increased in all treated groups... Histopathologic examination of the reproductive organs was unremarkable; however, treatment-related microscopic changes were observed in the adrenal glands of high-dose animals (cytoplasmic hypertrophy and vacuolation of the cells of the adrenal cortex) and in the liver of animals treated with 3,10,and 30 mg/kg/day (hepatocellular hypertrophy). No other treatment- related effects were reported.
Ref:
April 10, 2003: Preliminary Risk Assessment of the Developmental Toxicity associated with Exposure to Perfluorooctanoic Acid and its Salts. US EPA Office of Pollution Prevention and Toxics. 63 pages.

Pyridalyl - Insecticide - CAS No. 179101-81-6

Subchronic toxicity.
-- Pyridalyl technical was tested in rats in a 3-month feeding study. Effects included decreased body weight gain, altered blood biochemistry, increased relative liver weight and
histopathological changes in the liver, ovary, adrenal and lung. The NOAEL is 100 ppm (5.56 mg/kg/day in males and 6.45 mg/kg/day in females).
-- A 13-week feeding study in mice was conducted. Effects included decreased body weight gain, hematological and blood biochemical effects,increased liver weight, decreased kidney and ovary weights and histopathological changes in liver, kidney, ovary and adrenal. The NOAEL is 70 ppm in males (8.169 mg/kg/day) and 700 ppm in females (86.78 mg/kg/day).
-- A 13-week oral (capsule) toxicity study was conducted in
dogs. Effects included decreased body weight gain, clinical signs indicative of respiratory distress, hematological and blood biochemistry effects, increased liver, lung and kidney weights and histopathological alterations of the lung, kidney, adrenal and liver. The NOAEL was 10 mg/kg/day.
Ref: Federal Register: December 5, 2003. Pyridalyl; Notice of Filing a Pesticide Petition.
http://www.fluorideaction.org/pesticides/pyridalyl.fr.dec.5.2003.htm

Sulfuryl fluoride - Fumigant insecticide - CAS No. 2699-79-8

- (870.4100) Chronic toxicity--rodents. NOAEL = 3.5 for M and 16 for F mg/kg/ day
LOAEL = 20 ppm or 14 for M and 80 ppm or 62 for F mg/kg/day based on dental fluorosis* in males and for females greatly increased mortality (due mostly to severe kidney toxicity which led to kidney failure); and histopathology in brain (vacuolation in cerebrum and thalmus/ hypothalmus), adrenal cortex, eyes, liver, nasal tissue and respiratory tract; and, dental fluorosis*.
- (870.4300) 2-Year combined chronic/carcinogenicity--rat. NOAEL = 3.5 for M and 16 for F mg/kg/day. LOAEL = 20 ppm or 14 for M and 80 ppm or 62 for F mg/kg/day based on dental fluorosis* in males and for females greatly increased mortality (due mostly to severe kidney toxicity which led to kidney failure); and histopathology in brain (vacuolation in cerebrum and thalmus/hypothalmus), adrenal cortex, eyes, liver, nasal tissue and respiratory tract; and, dental fluorosis*.
Ref: January 23, 2004. Sulfuryl Fluoride; Pesticide Tolerance.
40 CFR Part 180 [OPP-2003-0373; FRL-7342-1]. Final Rule. Federal Register

Transfluthrin - Insecticide - CAS No. 118712-89-3

3.2.4 Carcinogenicity Studies. ... In a combined chronic toxicity and carcinogenicity study, groups of 60 Wistar rats (strain Bor:WISW (SPF Cpb) of both sexes were administered transfluthrin (94.5-95% pure) in the diet at concentrations of 0, 20, 200 or 2000 ppm for 109 weeks. In addition, groups of 10 male and 10 female rats were treated identically for full interim necropsy at 52 weeks... Benign adrenal tumours seen in males are within the control ranges for Wistar rats...
Ref: Evaluation on: Transfluthrin Use as a Public Hygiene Insecticide. September 1997. Prepared by: the UK Health and Safety Executive, Biocides & Pesticides Assessment Unit, Magdalen House, Stanley Precinct, Bootle, Merseyside L20 3QZ. Available from: Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7PX. UK.
Also at
http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm
• Note: This was transcribed from the copy available on the web. While one can easily read this report on the web, the report is inaccessible, or locked, to any attempt to copy it. Any errors are mine. EC.

 
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