Kidney - Adverse Effects
Fluorinated and Fluoride Pesticides

beginning with
A-E • F-G H-P Q-Z
See short description and definitions on kidney

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.

Ammonium bifluoride - Wood Preservative - CAS No. 1341-49-7

-- Ingestion: May cause salivation, nausea, vomiting, diarrhea, and abdominal pain, followed by symptoms of weakness, tremors, shallow respiration, carpopedal spasm, convulsions, and coma. May cause brain and kidney damage. Affects heart and circulatory system. Death may be caused by respiratory paralysis. Lethal dose estimated at between 1 teaspoonful and 1 oz.
-- Aggravation of Pre-existing Conditions: Populations that appear to be at increased risk from the effects of fluoride are individuals that suffer from diabetes insipidus or some forms of renal impairment.
Ref: Analytyka. Material Safety Data Sheet. Online as of September 15, 2003.

Acifluorfen, sodium - Herbicide - CAS No. 62476-59-9

A 2-generation reproduction study in rats fed diets containing 0, 25, 500 or 2,500 ppm with no adverse effect on adult reproductive performance observed under the conditions of the study. The NOEL was established at 25 ppm (equivalent to 1.25 mg/kg of body weight/day) based on decreased viability and increased incidence of kidney lesions in high dose offspring.
Ref: Federal Register. April 17, 1996. Sodium Salt of Acifluorfen; Pesticide Tolerance. Proposed Rule.

The chronic feeding toxicity study in rats, mice, and dogs demonstrated that acifluorfen induced liver toxicity (acidophilic cells in the liver and increased liver weight) and kidney toxicity (nephritis/pyelonephritis and increased kidney weight). An increase in the incidence of stomach ulcer was also seen in chronic feeding study in rats.
Ref: US EPA Toxicology Chapter for RED. November 10, 1999

Ammonium fluoride - Wood Preservative - CAS No. 12125-01-8

Ingestion: May cause salivation, nausea, vomiting, diarrhea, and abdominal pain, followed by weakness, tremors, shallow respiration, cardopedal spasm, convulsions, and coma. May cause brain and kidney damage. Death may be caused by respiratory paralysis. Affects heart and circulatory system.
Aggravation of Pre-existing Conditions: Populations that appear to be at increased risk from the effects of fluoride are individuals that suffer from diabetes insipidus or some forms of renal impairment.
Ref: 1999 Material Safety Data Sheet prepared by Mallinckrodt Baker, Inc.

Benfluralin (Benefin) - Herbicide - CAS No. 1861-40-1

COMBINED, RAT **208-079 167288, "Benefin: Two-Year Dietary Chronic Toxicity/Oncogenicity Study in Fischer 344 Rats", (Michael R. Moore, Corning Hazleton Inc, Vienna, VA., Laboratory ID # CHV 174-133, Sponsor Report # DR-0097-3397-005, 1 July 1996). Fifty CDF ® (F-344)CrlBR rats per sex per group received benefin in the diet at 0, 10, 100, 2500, and 5000 ppm for 2 yr. An additional 10 per sex per group at the same dose levels were designated for 1-yr interim sacrifice. Estimated achieved dosages were 0, 0.5, 5.4, 136, and 275 mg/kg/day in males, and 0, 0.7, 6.8, 168, and 331 mg/kg/day in females, respectively over weeks 1-104. Chronic NOEL = 10 ppm (0.5 and 0.7 mg/kg/day in M and F), based on increased hyaline droplets in kidneys of both sexes at 100 ppm and above, increased and tubular cell karyomegaly and transitional cell hyperplasia in kidneys of males, hepatocellular hypertrophy and increased hepatocellular pigmentation in females, and calculus of renal pelvis in females. Substantial toxicity prompted investigators to determine that the two highest dose levels “exceeded the maximum tolerated dose and therefore should not be used for risk assessment”. The study design, with no dose levels between 100 and 2500 ppm, gave no opportunity to characterize dose-response in this range of primary interest. These were major changes at the highest two dose levels (in both sexes, unless indicated), in addition to the findings for the NOEL (above) applying to both sexes. Body weights were reduced over time (in males, primarily in last few weeks of the study), so that at termination the deficits of 2500 and 5000 ppm groups compared to controls were 8 and 17% in males, and 18 and 28% in females, respectively. In females only, this was accompanied by approximately 10% food consumption reductions at each of the higher dose levels. There were reductions in the main hematology parameters (RBC counts, HCT, and Hb levels). Incidence and/or degree of chronic progressive nephropathy was increased. The majority of these rats had “slight” to “minimal” degeneration of sciatic nerve and skeletal muscle (thigh). Males had elevated incidence of single cell necrosis in liver. Chronic inflammation of the lungs was seen in the majority of these rats, whereas low incidences of congestion of the abdominal cavity, and urinary bladder hyperplasia were limited to these dose levels. Numerous clinical chemistry changes mirrored the above pathology in kidneys, liver, and perhaps other tissues at the higher two dose levels. Tumor incidence: thyroid follicular tumors (adenomas and carcinomas) increased in males (incidences of 1, 1, 1, 7, and 8 in controls through high dose, respectively) and females (incidences of 0, 0, 1, 5, and 4). Hepatocellular tumors (primarily adenomas) were increased in males (incidences of 2, 2, 1, 5, and 11 in controls through high dose, respectively). There were no statistically significant increases in epithelial cell tumors in kidneys nor urinary bladder, however the low incidences of transitional cell papilloma and tubule cell adenoma or carcinoma were predominantly found in 2500 and 5000 ppm groups (compare to the congener, trifluralin). Study is acceptable. Tumors are possible adverse effects, which should be evaluated in perspective of the many indications of excessive exposures at effective dose levels. Green and Aldous, 4/11/00.
Ref: Summary of Toxicological Data: Benefin. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch. Revised April 21, 2000.

Benthiavalicarb-isopropyl - Fungicide - CAS No. 177406-68-7

. In a chronic/oncogenicity study Fisher rats received 0, 50, 200, 5,000, or 10,000 ppm of benthiavalicarb- isopropyl for up to 104 weeks. The NOAEL was 200 ppm (9.9 mg/kg/day and 12.5 mg/kg/day in males and females respectively), based on a variety
of toxic effects, primarily in the liver and kidney, and adenocarcinomas of the uterus at 5,000 ppm.

In an oncogenicity study in mice, the dietary doses were 0, 20, 100, 2,500 or 5,000 ppm. The NOAEL was 100 ppm (13.7 mg/kg/day and 18.6 mg/kg/day in males and females, respectively) based on a variety of toxic effects, primarily in the liver and kidney, and hepatocellular blastoma and carcinoma at 2,500 ppm.
Ref: March 9, 2005. Petition for the establishment of Tolerances on Imported Grapes and Tomatoes. Federal Register: March 9, 2005.

Benzotrifluoride - (also known as Trifluoromethylbenzene) - Insecticide - CAS No. 98-08-8

-- Trifluoromethylbenzene was studied for oral toxicity in Crj:CD (SD) rats in an OECD combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 20, 100 and 500 mg/kg/day. With regard to repeated dose toxicity, effects on liver and kidney were observed in both sexes given more than 100 mg/kg, indicating a NOEL is of 20 mg/kg/day for both sexes. In the reproductive/developmental toxicity study, there were no effects of the test article on the reproductive performance of the parents. Depression of body weight gain in offspring of all treatment groups was observed without any necropsy findings. The NOELs are considered to be 500 mg/kg/day for reproductive performance of the parents and less than 20 mg/kg/day for offspring development.
-- Test Results: ... As necropsy findings, renal hypertrophy and discoloration were observed in males of the 500 mg/kg group. Increase kidney weights in males given more than 100 mg/kg and in females of the 500 mg/kg group, and increased liver weights in males given more than 100 mg/kg were observed. On histopathological examination, centrilobular hepatocyte hypertrophy in both sexes, and hyaline droplets, necrosis, basophilic change and dilatation of renal proximal tubules in males were noted in the 100 and 500 mg/kg groups. Therefore, the NOEL is considered to be 20 mg/kg/day for both sexes.

Ref: 1988. GINC: Global Information Network on Chemicals. The Databases of Chemicals.

Boron Trifluoride - Fumigant - CAS No. 7637-07-2

-- Exposure of 6 animal species to 100 ppm, 4-7 hr/day, 5 days/wk in a 30 day experiment killed all animals, most within the test period. Guinea pigs were most susceptible ... dogs least ... The primary site of damage was the lung ... Kidney damage ... also occurs. [Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) PublicationNo. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981.
-- An acute study of boron trifluoride (BF3) in rats indicated the 4 hr LC50 to be 1.21 mg/l. In a 2 week study, all animals exposed to 180 mg/cu m died prior to the sixth exposure, rats exposed at concn of 66 and 24 mg/cu m showed clinical signs of respiratory irritation, body weight gain depressions, increased lung weights, and depressed liver weights. Histopathology showed necrosis and pyknosis of the proximal tubular epithelium of the kidneys. This effect was limited to the high-concn exposure group. Based on the results of these studies, Fischer 344 rats were exposed 6 hr/day, 5 days/week for 13 weeks to a respirable, liquid aerosol of BF3 at concn of 0, 2.0, 6.0, and 17 mg/cu m. One rat in the high exposure group died. The most significant finding in this group was necrosis of the proximal tubular epithelium of the kidneys....
-- Boron trifluoride is primarily a respiratory irritant which predisposed the exposed /guinea pigs/ to respiratory infection. Exposure at 100 ppm (277 mg/cu m) was fatal to all animals. Physiological responses prior to death included respiratory irritation and infection, kidney damage, retarded growth, and severe progressive fluorosis in rat teeth...
Ref: TOXNET profile from Hazardous Substances Data Bank for Boron Trifluoride.

-- The principal acute effect in animals is irritation of the mucous membranes of the respiratory tract and eyes; post mortem examination also revealed pneumonia and degenerative changes in renal tubules. The kidneys are most severely affected because boric acid concentrates in this organ.
Ref. USEPA/OPPT. Support Document for the Health and Ecological Toxicity Review of TRI Expansion Chemicals. U. S. Environmental Protection Agency, Washington, DC (1993). As cited by US EPA in: Federal Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition of Certain Chemicals; Toxic Chemical Release Reporting; Community Right-to-Know; Proposed Rule.

Carfentrazone-ethyl - Herbicide - CAS No. 128639-02-1

-- Repeat-dose studies indicate that the primary targets for carfentrazone-ethyl toxicity are the liver, kidney, and the red blood cell forming system... Increased kidney weight and the presence of pigment in kidney cells typified kidney toxicity in rats and dogs...
Ref: April 2000 - Australia. Evaluation of the new active CARFENTRAZONE-ETHYL in the product AFFINITY 400 DF HERBICIDE. National Registration Authority for Agricultural and Veterinary Chemicals. NRA Ref. 51555.
Also available at

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.

Chlorotrifluorotoluene, 4-,Alpha,Alpha,Alpha - (CTFT) - 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.

Clodinafop-propargyl - Herbicide - CAS No. 105512-06-9

Reproductive and developmental toxicity... Target organs were liver (adults) and kidney (adults and pups). The treatment had no effect on reproductive organs. The NOAEL for toxicity to the parental rats and offspring was 50 ppm, corresponding to a mean daily intake of 3.2 mg/kg clodinafop-propargyl. The NOAEL for reproductive toxicity was 1,000 ppm (64.2 milligram/kilogram body weight/day (mg/kg bw/day))... The EPA HIARC concluded that based on hepatocellular hypertrophy and kidney findings, the NOAEL was 1 ppm (0.031 in males and 0.034 in females.
Ref: Federal Register. April 26, 2000. [PF-938; FRL-6554-2]

-- 870.4300 Chronic/ Oncogenicity in the Rat. NOAEL = M:0.03 mg/kg/day ; F: 0.03 mg/kg/day LOAEL = M: 0.3 mg/kg/day; F: 0.4 mg/kg/day based on hepatocytic hypertrophy,
chronic progressive nephropathy, and tubular pigmentation. Under the conditions of this study, treatment with clodinafop-propargyl increased the incidence of prostate and ovarian tumors in rats at 750 ppm. For males, an increased incidence of prostate adenoma was seen in the high-dose group. The chemical was administered at a dose sufficient to test its carcinogenic potential.
Ref: US EPA Pesticide Fact Sheet. Reason for Issuance: Conditional Registration.
June 6, 2000.

Cloransulam-methyl - Herbicide - CAS No. 147150-35-4

... Cloransulam-methyl 84% DF was not found to be carcinogenic, teratogenic or to cause reproductive effects. In-vitro and animal mutagenicity studies were negative. Target organ effects have been reported in the blood, kidney, liver, testes and thyroid gland...
Ref: Material Safety Data Sheet for Gauntlet Herbicide. MSDS Ref. No: F18-20-2. Date Approved: 09/25/2000. Revision No. 1. FMC Corporation, Agricultural Products Group, 1735 Market Street, Philadelphia, PA 19103, USA.
Also available at

-- In the rat Chronic Feeding / Carcinogenicity study the NOEL was equal to 75 mg/kg/day and the Lowest Observed Effect Level (LOEL) was 325 mg/kg/day based on significant increase in hemoglobin, hematocrit, and red cell count in males, activities of the liver enzymes aspartate and alanine aminotransferase as well as alkaline phosphatase were decreased in males, cholesterol was decreased in females, specific gravity of urine was decreased in females, increased relative wight in liver and relative weight of testes in males, males exhibited an increased incidence of collecting duct hypertrophy and females exhibited increased incidence of vacuolation in the kidney. There was no evidence of carcinogenicity for cloransulam-methyl in this study. In the mouse carcinogenicity study the NOEL was 10 mg/kg/day and the LOEL was 108 mg/kg/day based on based on a decrease in renal tubule vacuolation in male mice, increased size of centrilobular and midzonal hepatocytes accompanied by altered tinctorial properties in females and centrilobular hepatocyte hypertrophy in males. Total tumor incidence (adenoma + carcinoma) was not increased by dosing with cloransulam-methyl.
-- Two Generation Reproduction (rat): Parental Systemic NOEL = 10 mg/kg/day Parental Systemic LOEL = 100 mg/kg/day based on hypertrophy of the collecting ducts and vacuolation consistent with fatty changes. Reproductive and Developmental NOEL = 100 mg/kg/day Reproductive and Developmental LOEL = 500 mg/kg/day based on decreased live pups and increased pup deaths.
-- Chronic Feeding/ Carcinogenicity (rat): NOEL = 75 mg/kg/day LOEL = 325 mg/kg/day based on significant increase in hemoglobin, hematocrit, and red cell count in males, activities of the liver enzymes aspartate and alanine aminotransferase as well as alkaline phosphatase were decreased in males, cholesterol was decreased in females, specific gravity of urine was decreased in females, increased relative wight in liver and relative weight of testes in males, males exhibited an increased incidence of collecting duct hypertrophy and females exhibited increased incidence of vacuolation in the kidney. There was no evidence of carcinogenicity for cloransulam-methyl in this study.
-- Carcinogenicity (mouse): NOEL = 10 mg/kg/day LOEL = 108 mg/kg/day based on a decrease in renal tubule vacuolation in male mice, increased size of centrilobular and midzonal hepatocytes accompanied by altered tinctorial properties in females and centrilobular hepatocyte hypertrophy in males. Total tumor incidence (adenoma + carcinoma) was not increased by dosing with cloransulam-methyl.
Ref: USEPA. Pesticide Fact sheet. Cloransulam-methyl. Reason for Issuance: Conditional Registration Date Issued: October 29, 1997.

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

A 24 month chronic feeding/carcinogenicity study in rats demonstrated a NOAEL of 2.5 mg/kg/bwt/day and LEL of 6.2 mg/kg/bwt/day, based on decreased body weights in males, decreased food consumption in males, and inflammatory foci in the kidneys in females... 4. Subchronic toxicity. Thirteen-week dietary toxicity studies in rats, mice and dogs were conducted. The primary target organs identified in these studies were the kidneys (rat), and the liver (rat, mouse and dog)... Chronic toxicity. In a 2-year combined chronic toxicity/ oncogenicity study in the rat, the NOAEL for chronic toxicity was 5 mg/ kg/day based upon kidney effects characterized as slight, subtle alteration in kidney tubular morphology, mostly within the corticomedullary junction which likely represented more a physiologic adaptation than a pathological change indicative of a toxic injury... In a 2-year dietary feeding study in B6C3F1 mice conducted at 50, 100, 250 and 500 mg/kg/ day, 50 mg/kg/day was considered the NOAEL in males and the NOAEL in females based upon histologic changes in the kidney. The lesion noted in male mice was a reduced vacuolation of the kidney tubular epithelium at all dose levels. Decreased absolute and relative kidney weights were seen at 100 mg/kg/day and above. In female mice, focal dilation with hyperplasia of the lining epithelium of the renal cortical tubules was seen at 100 mg/kg/day and above.
Ref: Federal Register. November 20, 1998. [PF-836; FRL-6030-9]

Cyhalofop-butyl - Herbicide - CAS No. 122008-85-9

-- Chronic dietary all populations: Carcinogenicity in mice based on kidney effects in females including tubular dilatation, chronic glomerulonephritis, and hyaline casts. LOAEL = 10.06 mg/kg/day.
Ref: Federal Register. September 27, 2001. Cyhalofop-butyl; Pesticide Tolerances for Emergency Exemptions. Final Rule.

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

-- In the chronic studies, the most consistent findings were cranial osteosclerosis in the rat, and findings consistent with fluorosis in a 2-year mouse study. Clinical chemistry findings with supportive histopathology were observed in a 1-year study in the dog which were indicative of renal and liver damage. A detailed assessment of cranial osteosclerosis was performed in a 2-year study in the rat; a LOEL was established at 10-14 mg kg -1 d -1..
-- A detailed assessment of cranial osteosclerosis was performed in a rat 2-year study (summarised in section in which a LOEL was established at 10-14 mg kg -1 d -1 . A clear increase in the incidence of cranial osteosclerosis was observed in the low- and middle-dose groups, with almost all animals affected at the top dose. These findings are likely to be secondary to fluorosis in these animals. In terms of interspecies comparisons, in a mouse 2- year study, thickening of both the appositional bone of the cranial vault and nasal turbinates, and tooth alveolitis were observed at the top dose of 1,731-1,873 mg kg -1 d -1 . These findings are also considered to be a secondary consequence of fluorosis in these animals. No evidence of fluorosis was observed in the dog studies. It is considered that these findings are likely to represent a fluoride mediated perturbation of bone metabolism but are not considered to be of concern for human health. It is considered that the observed liver and renal damage is of concern to human health.
-- In a 1-year dog study clinical chemistry findings with supportive histopathology, indicative of nephrotoxicity and liver damage, were observed. In this study a NOAEL of 2.5 mg kg -1 d -1 was established.
-- Two-year Study The following study is considered to be flawed due to the lack of histopathological evaluation and it was not GLP compliant. Beagles (4/sex/group) received dietary administration of either 0, 100, 300, 1000 or 3000 ppm dichlofluanid (90 % purity); equivalent to 3.6, 10.5, 34 and 107 mg kg -1 d -1 (males) and 3.4, 11, 34 and 101.4 mg kg -1 d -1 (females) respectively, for a two year study period. Interim blood sampling was carried out at 6 weeks, 6 months and 12 months for haematology, with interim clinical chemistry analysis being performed at 12 months... Changes reported in clinical chemistry parameters at 3000 ppm including increased ALP, ALT, bilir
ubin, cholesterol levels and BSP retention time, indicative of impaired hepatic function... Against a background of variable data, increases in serum creatinine (27 % males and 33 % females, at 3000 ppm) and urea levels (34 % males and 50 % females, at 3000 ppm) were reported, this being suggestive of impaired renal function. Direct measurements of kidney function at study termination revealed a decrease in both p-aminohippuric acid (PAH) and inulin clearance; (5 and 17 %) in males and (19 and 32 %) females at 24 months at 3000 ppm. These data provide further evidence for impaired renal function... The relative kidney and liver weights were elevated at both 1000 (21 and 3.4 %) and 3000 ppm (18 and 10 %).
Ref: January 2003 - Evaluation on: Booster biocides in antifouling products. Full review of Dichlofluanid. No. 206. Evaluation of Fully Approved or Provisionally Approved Products. Prepared by : The 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 available at:

1,1-Difluoroethane - Propellent, EPA List 2 Inert - CAS No. 75-37-6

McAlack, J.W. and P.W. Schneider, Jr. 1982. Two-year inhalation study with ethane, 1,1-difluoro (FC-152a) in rats. E.I. Du Pont de Nemours and Co., Inc. Haskell Laboratory for Toxicology and Industrial Medicine. Haskell Laboratory Report No. 8-82. CD rats (30/sex/group) were exposed to 0, 2000, 10,000, or 25,000 ppm 1,1- difluoroethane (HCFC-152a) (99.88% pure) (0, 5399, 26,994, or 67,485 mg/cu.m, respectively) for 6 hours/day, 5 days/week, for 2 years (McAlack and Schneider, 1982). Duration-adjusted concentrations are 0, 964, 4821, or 12,051 mg/cu.m, respectively. Interim sacrifices were performed on 10 rats/sex/group after 3 or 12 months of exposure. The animals were exposed in 4.6-cu.m stainless steel and glass chambers using a one-pass, flow-through mode of air flow (air flow rate = 1200 L/minute). The test atmosphere was generated by diluting HCFC-152a vapor with air. The concentration of the test atmosphere was analyzed approximately every 30 minutes during each exposure period by gas chromatography, and mean chamber concentrations were found to be within 15% of nominal concentrations. Animals were observed twice daily and several times during exposure for clinical signs of toxicity and moribundity. Body weights and food consumption were measured biweekly for the first 14 weeks and monthly thereafter. Hematology, clinical chemistry, and urinalysis were conducted at 1, 3, 6, 12, 18, and 24 months on 10 rats/sex/group. Gross and microscopic evaluation of approximately 40 tissues was conducted in all animals at terminal sacrifice and in the high-concentration and control animals at the 3- and 12-month sacrifices (10 rats/sex). Kidney and nasal tissues from the low- and intermediate-concentration groups were also examined microscopically. The number of cross-sections examined in the nasal tissue ranged from three to six (Trochimowicz, 1992). ... Urinary fluoride was increased statistically in both sexes at all concentrations, indicating metabolism of HCFC-152a. Biochemical changes (significant increases in serum creatinine in the females exposed to 10,000 and 25,000 ppm HCFC-152a), increased urine volume, and decreased urine osmolality seen throughout the study suggested renal toxicity. The only organ weight or histopathology data to support this functional deficit was decreased kidney weight and renal tubular damage noted in the high-concentration animals at the 3-month sacrifice. The tubular lesions were reported in the original report as "slight cytoplasmic vacuolation, luminal dilation, and the presence of occasional vesiculated nuclei" and were seen in 4/10 males and 7/10 females. These changes were not seen at the other scheduled evaluations, however, and a subsequent peer review of these data (Bruner, 1992) determined that the renal tubular changes reported at the 3-month sacrifice were artifactual changes due to tissue processing rather than a treatment-related nephrotoxicity.
Ref: US EPA IRIS for 1,1-Difluoroethane.,1-difluoroethane.epa.iris.htm

1,2-Difluoroethane (Freon 152) - List 3 Inert - CAS No. 624-72-6

Abstract: The inhalation toxicity of a series of fluorinated ethanes which are metabolized to fluoroacetate (144490) were studied in the male CD-rat. When the rats were exposed by inhalation to 1,2-difluoroethane (624-72-6), 1-chloro-2-fluoroethane (762505), 1-bromo-2-fluoroethane (762492), or 1-chloro-1,2-difluoroethane (338647) for 4 hours, the lethal concentrations for each compound were less than 100 parts per million (ppm). Tests with 1,1-difluoroethane (75376) showed a 4 hour median lethal dose of over 400,000ppm in rats. Clinical signs of fluoroacetate toxicity were noted including lethargy, hunched posture, and convulsions. Concentrations of citrate increased in serum and heart tissue on exposure to 1,2-difluoroethane, 1-chloro-2-fluoroethane, 1-chloro-1,2-difluoroethane, and 1-bromo-2-fluoroethane. Fluoroacetate was present in the urine of rats exposed to each of the toxic compounds. Rats exposed to 1,2-difluoroethane showed fluorocitrate in the kidneys. Rats exposed to 1,2-difluoroethane showed a concentration related elevation of serum and heart citrate up to 1000ppm of the compound. Serum citrate was up five fold and heart citrate 11 fold over control levels. The authors suggest that the metabolism of the toxic fluoroethane was initiated at the carbon/hydrogen bond, with metabolism to fluoroacetate via an aldehyde or an acyl fluoride. The authors conclude that 1-(di)halo-2-fluoroethanes are highly toxic to rats and should be viewed as a hazard to humans.
Ref: Fluoroacetate-Mediated Toxicity of Fluorinated Ethanes; by Keller DA, Roe DC, Lieder PH. Fundamental and Applied Toxicology, Vol. 30, No. 2, pages 213-219, 1996.

Dichlorofluoromethane (CFC-21) - Propellant, EPA List 2 Inert - CAS No. 75-43-4

-- /GUINEA PIGS/ ... EXPOSED /UP TO 2 HR/ @ CONCN OF 10.2% DIED &, ON AUTOPSY, CONGESTED LUNGS, CONGESTED KIDNEYS, CONGESTED LIVER, DISCOLORED SPLEEN, & HIGHLY CONTRACTED HEART WERE FOUND. [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values for Substances in Workroom Air. Third Edition, 1971. Cincinnati, Ohio: AmericanConference of Governmental Industrial Hygienists, 1971. (Plus supplements to 1979) 81
Ref: TOXNET profile from Hazardous Substances Data Base for DICHLOROFLUOROMETHANE

Diclosulam - Herbicide - CAS No. 145701-21-9

Based on oral feeding studies, the primary target organs are the liver and kidney. In a subchronic rat feeding study, the primary target organ is the liver including increased relative organ weight, hepatocellular hypertrophy, and slight multifocal necrosis. Decreased body weight and kidney lesions were also noted. Liver effects were also noted in a subchronic dog study and included increased relative liver weight, centrilobular hepatocellular changes, and hepatocellular necrosis accompanied by elevated ALP, AST, and ALT... In a chronic toxicity/oncogenicity study in the rat, the kidney is identified as a target organ... The kidney was also a target organ in a mouse carcinogenicity study. Among the observed kidney effects were reduced vacuolization in the tubular epithelium, lower absolute and relative kidney weights, and focal dilatation with hyperplasia of the epithelial lining in the cortical tubules.
Ref: Federal Register. March 8, 2000. Diclosulam; Pesticide Tolerance. Final Rule.

Diflufenzopyr - Herbicide - CAS No. 109293-97-2

Chronic toxicity. A 52-week feeding study in the dog at doses of 0, 1, 5, 40, or 80 mg/kg. Liver and kidney were identified as target organs and the NOEL was established at 5 mg/kg... A 90-day feeding study in the dog at approximate doses of 0, 0.25, 1, 5, 50, 150, or 400 mg/kg/day. Liver, kidney, stomach, and thymus were identified as target organs. The NOEL was 50 mg/kg/day. The maximum tolerated dose was exceeded at > 150 mg/kg/day...
Ref: Federal Register. November 21, 1997. [PF-778; FRL-5755-4]

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

... In a 13-week dog feeding study, increased alkaline phosphatase, discolored livers, and cholestasis was observed at 10 mg/kg/day (LOEL). The NOEL was 1 mg/kg/day. In addition, at 30 mg/kg/day, increased serum glutamic-pyruvic transaminase and serum glutamic oxaloacetic transaminase, increased liver and kidney weights, and decreased cholesterol and albumin were observed. EPA believes that there is sufficient evidence for listing dithiopyr on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available hepatic and renal toxicity data.
Ref: USEPA/OPP. Support Document for the Addition of Chemicals from Federal Insecticide, Fungicide, Rodenticide Act (FIFRA) Active Ingredients to EPCRA Section 313. U. S. Environmental Protection Agency, Washington, DC (1993). As cited by US EPA in: Federal Register: January 12, 1994. Part IV. 40 CFR Part 372. Addition of Certain Chemicals; Toxic Chemical Release Reporting; Community Right-to-Know; Proposed Rule.

The following results were presented by a Monsanto scientist.
-- Four-week Feeding Study in Rats. Dithiopyr was administered via the diet to groups of 6 male and 6 female Fischer-344 (F-344) rats for 4 weeks at concentrations of 0, 300, 1000, 3000, 10,000 and 30,000 ppm. Decreased body weight and food consumption, as well as clinical signs of toxicity were observed at the higher dose levels. Liver enlargement and discoloration, thymic atrophy, emaciation, and increased liver, kidney and thyroid/parathyroid weights were noted on gross postmortem examination. Due to an elevation in liver and kidney weights at the low dose level, the no observable effect level (NOEL) is considered to be less than 300 ppm. (The Institute of Environmental Toxicology, 1986)
-- 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... Postmortem examination revealed primarily liver and kidney toxicity. Elevated plasma AP, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen and cholesterol levels were indicative of cholestasis and liver toxicity. These biochemical changes were accompanied by a significant increase in liver weight, hepatocellular swelling, vacuolation and necrosis, dissociation of hepatocellular cords, and bile duct proliferation. Increased kidney weights, decreased urine protein and specific gravity, and acidophilia of proximal tubular cells were indicative of mild renal toxicity... (The Institute of Environmental Toxicology, 1989)
-- CHRONIC TOXICITY AND ONCOGENICITY STUDIES. Twenty-four-month Feeding Study in Rats •In a combined chronic toxicity and oncogenicity study, dithiopyr was administered via the diet to groups of 90 male and 90 female F-344 rats for 104 weeks at concentrations of 0, 3, 10, 100 and 300 ppm... Postmortem examination provided evidence of liver and kidney toxicity. There were no statistically significant or biologically significant increases in neoplastic lesions.
-- Twelve-month Oral Study in Dogs •Dithiopyr was administered orally via gelatin capsule to groups of 6 male and 6 female beagle dogs for 52 weeks at dose levels of 0, 0.5, 5 and 25 mg/kg/day... Postmortem examination revealed liver toxicity and cholestasis. Specific findings included : increased AP levels in plasma, liver enlargement and discoloration, the presence of black sandy materials in the gallbladder, hepatocellular necrosis and fibrosis, pseudo-bile duct formation, bile duct proliferation, and increased mucoidal secretion in the gallbladder. Brown pigment deposition was also found in the bile canaliculi, Kupffer cells and the kidneys. The chronic NOEL in dogs is considered to be 0.5 mg/kg/day. (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... Postmortem examination of parental animals revealed primarily liver toxicity, consisting of organ enlargement and discoloration, hepatocellular swelling and necrosis, and bile stasis. Other findings included : 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)

Ethalfluralin - Herbicide - CAS No. 55283-68-6

Group C -- Possible Human Carcinogen. Mammary tumors (F); Suggestion of bladder tumors (F) and kidney tumors (M & F); Fischer 344 rats.
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.

Ethylene fluorohydrin - Rodenticide - CAS No. 371-62-0

REPRODUCTIVE HAZARDS: An increase in sternebral ossification defects, hydronephrosis, runting (pup weight less than 2.7 g), variant rib ossifications, extra vertebral ossification centers, cardiac septal defects, and intrauterine growth retardation were noted in rats.
Ref: TOXNET profile from Hazardous Substances Data Base.
HYDRONEPHROSIS - Pathological chronic enlargement of the collecting channels of a kidney, leading to compression and eventual destruction of kidney tissue, and diminishing kidney functionning.

Etoxazole - Acaracide - 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.

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