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

Acrinathrin - Acaricide, Insecticide - CAS No. 103833-18-7

SUBCHRONIC TOXICITY STUDIES 1. Rats Study by Dietary Repeat Dose for 90 Days Followed by a 28-Day Recovery Period Group of 20 male and 20 female CD (SD) rats were fed diet containing 0, 30, 100 or 300 ppm of acrinathrin for 90 days... Other microscopic findings observed were lymphoid deletion in the spleen and thymus in 5 females of the 300 ppm group and medullar [marrow] atrophy in 2 females of the 300 ppm group... The No Observed Effect Level (NOEL) for this study was considered to be 30 ppm (male: 2.4 mg/kg/day; female: 3.1 mg/kg/day) (Centre International de Toxicologie, 1988).
Ref: Summary of Toxicological Studies on Acrinathrin Market Development, AgrEvo Japan Limited (Received January 26, 1998 ; Accepted March 20, 1998).
http://www.fluoridealert.org/pesticides/acrinathrin.tox.studys.1998.pdf

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

"Benefin: 13-Week Oral Toxicity Study in Beagle Dogs", (D.W. Dalgard, Hazleton Washington, HWA 174-135, 12/28/93). Benefin, purity 95.8%, administered via capsule at concentrations of 0, 5, 25, 125 mg/kg/day to 4 Beagle dogs/sex/group for 13 weeks. Emesis (compound colored) was slightly increased at all dose levels for females and for mid and high dose males. Liver weights was increased for high dose males; and the incidence of hepatocellular hypertrophy was increased for high dose males and females. Increased incidence of hemosiderin pigment was observed in the liver at the high dose and the spleen at mid and high dose levels. NOAEL = 5 mg/kg/day. Acceptable (Kishiyama, J., and P. Iyer, 5/12/98).
Ref: Summary of Toxicology Data for Benefin. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch
http://www.cdpr.ca.gov/docs/toxsums/pdfs/53.pdf

Butafenacil - Herbicide - CAS No. 134605-64-4

Some excerpts from Table 2.--Subchronic, Chronic, and Other Toxicity Ref: Butafenacil; Pesticide Tolerance. Final Rule. Federal Register. September 19, 2003. http://www.fluorideaction.org/pesticides/butafenacil.fr.sept.19.2003.htm
Study type [Guideline number]	Results
90-Day oral (capsule) toxicity in non- rodents (dog) - [870.3150]	NOAEL = 200 mg/kg/ day M/F LOAEL = 1,000 mg/kg/ day M/F, based on decreases in MCV and MCH in males; increases in RDW, HDW, platelets and triglycerides in males; and hemosiderosis in spleen and liver and extramedullary hematopoiesis the spleen in males
Mechanistic studies - [870.7485]	Effects on porphyrin profile in rats; treatment induced porphyria, consisting of accumulation of selected porphyrins in the liver, spleen, and plasma and increased excretion in urine and feces
Mechanistic studies - [870.7485]	Test substance interferes with heme biosynthesis in rats, as evidenced by dose- dependent, pronounced porphyria in the liver, spleen, and plasma; increased porphyrin excretion, and decreased activity of various isoenzymes of the hepatic microsomal cytochrome P450 system

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

-- Short-Term Studies In mice fed carfentrazone-ethyl at concentrations up to 20000 ppm for 28 days, decreased defecation was observed at 14000 and 20000 ppm. Blood haemoglobin concentration was reduced in females at concentrations ¥ 4000 ppm and mean corpuscular volume and mean corpuscular haemoglobin were reduced at the highest concentration. Liver weight was increased in both males and females at concentrations ¥ 8000 ppm and spleen weights were reduced in males at the highest concentration.
-- Short-Term Studies... The body weight of dogs (1/sex) given 1000 mg/kg bw/day carfentrazone-ethyl in capsules for 14 days was reduced; food consumption of the female also reduced. Mean corpuscular haemoglobin and mean corpuscular volume were reduced. In the female, haematocrit was also reduced with white blood cell counts and neutrophils increased. The female had a pale kidney and the male had reduced relative spleen and testes weights.
-- Short-Term Studies... In mice fed up to 20 000 ppm dietary carfentrazone-ethyl for 90 days, a pink/brown staining of the litter tray was observed at concentrations ¥ 14000 ppm. Although red blood cell counts were increased in males at concentrations ¥ 14000 ppm, mean corpuscular volume and mean corpuscular haemoglobin were reduced in males at concentrations ¥ 8000 ppm and in females at concentrations ¥14000 ppm. In addition, mean corpuscular haemoglobin concentration was reduced in females at the highest concentration. Aspartate aminotransferase and alanine aminotransferase activities were increased at 20000 ppm and albumin was increased in females at concentrations ¥ 1400 ppm. Liver weights were increased at concentrations ¥ 8000 ppm and spleen weights were decreased in all treated females... A NOEL was not established for this study, because a reduction in spleen weights was observed in females at the lowest concentration tested (1000 ppm, equivalent to 150 mg/kg bw/day)
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.
http://www.fluorideaction.org/pesticides/carfentrazone-e.aus.2000rpt.pdf
Also available at http://www.apvma.gov.au/publications/prscar.pdf

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

*** Note: Effects attributed to diflubenzuron metabolites : PCA and CPU ***
-- In a 28-day feeding study technical grade diflubenzuron was administered in the diet to rats at dose levels of 0 (control), 800, 4000, 20000 or 100000 ppm (equivalent to 0, 40, 200, 1000 or 5000 mg/kg/day). Methemoglobin was increased in males at all dose levels and in females at dose levels of 200 mg/kg/day and higher. Sulfhemoglobin was increased in all treated males and females. At 5000 mg/kg/day males and females experienced decreased erythrocyte counts, packed cell volumes and hemoglobin. Dose-related increases in spleen weights at all dose levels and in liver weights at dose levels of 200 mg/kg/day and higher were also observed. No NOEL was established in this study since treatment-related effects were observed at 40 mg/kg/day, the lowest dose level tested. The LEL is 40 mg/kg/day, based on increased methemoglobin in males, increased sulfhemoglobin in males and females and increased spleen weights in males and females. (MRID 00070018)
-- At all dose levels, histopathological examinations indicated dose related increases of hemosiderosis and congestion of the spleen, hemosiderosis and chronic hepatitis of the liver, and mild erythroid hyperplasia of the bone marrow... Male rats at 6 and 18 mg/kg/day and female rats at 18 mg/kg/day had blue extremities indicative of cyanosis. Histopathological examinations indicated non-neoplastic treatment-related effects in the spleen, liver, bone marrow and adrenal gland... (National Toxicology Program (NTP) Report No. 351; July, 1989)..."
Ref: US EPA RED. August 1997.
http://www.fluoridealert.org/pesticides/diflubenzuron.red.pdf

-- A 91-week carcinogenicity study in CFLP mice was conducted at doses of 0, 16, 80, 400, 2,000, and 10,000 ppm. There was no increase in tumor incidence as a result of diflubenzuron administration. Target organ effects included: Increased methemoglobin and sulfhemoglobin values, Heinz bodies, increased liver and spleen weight, hepatocyte enlargement, and vacuolation, extramedullary hemopoiesis in the liver and spleen, siderocytosis in the spleen and pigmented Kupffer cells. A NOAEL for these effects was 16 ppm (2 mg/kg/day).
- 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.
-- PCA [p-chloroaniline; a metabolite of Diflubenzuron] hydrochloride was administered 5 days/week by oral gavage to male and female B6C3F1 mice at doses of 0, 3, 10, or 30 mg/kg/day. Mean body weights of high dose male and female mice were generally within 5% of those of controls throughout the study. The incidence of hepatocellular adenomas or carcinomas (combined) was increased in a non-dose-dependent manner in treated male mice. Metastasis of carcinoma to the lung was seen in the high dose group. An increased incidence of hemangiosarcomas of the liver or spleen was seen in high dose male mice. It was concluded that, under the conditions of this 2-year gavage study, there was some evidence of carcinogenic activity of PCA hydrochloride for male B6C3F1 mice and no evidence of carcinogenic activity of PCA hydrochloride for female B6C3F1 mice.
-- In addition to PCA, 4-chlorophenylurea (CPU) is also a potential minor metabolite of diflubenzuron. By association with PCA, EPA has concluded that CPU has carcinogenic potential and the same carcinogenic potency (q\1\*) as PCA. In the NTP report of the PCA bioassay, it is proposed that PCA undergoes N-hydroxylation to form the corresponding N-hydroxylamine [[Page 64827]] metabolites; N-hydroxylation of aromatic amines is a well know mechanism of aromatic amine carcinogenicity. This metabolite, or proximate carcinogen, is then conjugated to form the ultimate carcinogen capable of ionizing and reacting with DNA to form adducts which result in splenic tumor formation. An alternate mechanism involving toxicity resulting in erythrocyte damage, splenic scavenging, hemorrhage, hyperplasia and fibrosis and ultimately splenic tumor formation is also proposed, but both mechanisms are based on the formation of N-hydroxy PCA.
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

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

Chronic toxicity--i. 1-Year non-rodent (dog). Beagle dogs were dosed with diflufenzopyr at 0, 750, 7,500 and 15,000 ppm in the diet for one year. The NOEL was determined to be 750 ppm (26 mg/kg/day) in males and (28 mg/kg/day) in females. The LOAEL was 7,500 ppm (299 mg/ kg/day) in males and (301 mg/kg/day) in females. This is based on an erythropoietic response in bone marrow and increased hemosiderin deposits in spleen, liver and kidneys.
Ref: Federal Register: November 21, 1997 (Volume 62, Number 225) [Notices] [Page 62304-62308]. Notice of Filing of Pesticide Petitions
http://www.fluoridealert.org/pesticides/diflufenzopyr.fr.nov21.1997.htm

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

The following results were presented by a Monsanto scientist.
-- 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... 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)
-- 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 : 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)
Ref: Summary of Toxicology Studies With Dithiopyr Dennis P. WARD. Toxicology Department, The Agricultural Grop, A Unit of Monsanto Company (Received February 20, 1993)
http://wwwsoc.nii.ac.jp/pssj2/tec_info/dithiopy.pdf

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.
-- In a 13-week mouse study, the NOAEL was 100 ppm (15.25 mg/kg/day in males and 20.1 mg/kg/day in females). The LOAEL is 1,000 ppm (153.9 mg/kg/day in males and 191.5 mg/kg/day in females) based on hematology effects and changes in glucose, creatinine, bilirubin, sodium, chloride and potassium levels, increased liver and spleen weights and histopathology findings in the bone marrow, spleen and kidney.
-- In the 18-month mouse study, effects were observed in the lung, liver, spleen and bone marrow at 250 ppm or higher. Findings included, centrilobular hepatocellular hypertrophy, extramedullary hematopoiesis and pigment deposition in the spleen and decreased cellularity (hypocellularity) in the bone marrow...
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 rodents (mice). LOAEL is 1,000 ppm in (males: 153.9 mg/kgbw/day; females: 191.5 mg/kg bw/ day) based on extramedullary hematopoiesis of the spleen. Many of the tissues/organs recommended by Guideline 870.3100 were not histologically examined in any dose group, but this study is not required and serves as a range-finding study for the mouse carcinogenicity study.Therefore, it is classified as acceptable, non-guideline study.
Ref: August 31, 2005. Flonicamid; Pesticide Tolerance. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/flonicamid.fr.aug.31.2005.html

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

Fluazifop butyl was evaluated for reproductive and developmental effects in 2 successive generations of Charles River Wistar strain rats (30/sex/group) exposed continuously to 0, 10, 80 and 250 ppm in the diet. Each respective parent generation had received treatment for a minimum of 100 days (F0) and 120 days (F1) prior to mating. F0 and F1 dams weaned their progeny for 25 days postpartum to time of offspring selection for mating and continued study (F1) or sacrifice (F1, F2). Thirty days after sacrifice of their offspring, the surviving F1 females and select F1 males were sacrificed and with representative F1 and F2 offspring were examined histologically.... F2 female progeny of 250 ppm exposed parents were found with significantly increased absolute and relative spleen weights... [ICI AMERS INC; Fluazifop butyl: Effects Upon Reproductive Performance of Rats Treated Continuously Through 2 Generations (Final Report); 03/17/81; EPA Doc No. 88-920006849; Fiche No. OTS05543854]
Ref: TOXNET profile from Hazardous Substances Data Bank for FLUAZIFOP-BUTYL.
http://www.fluoridealert.org/pesticides/fluazifop-butyl.toxnet.hsdb.htm

Fluazifop-P-butyl - Herbicide - CAS No. 79241-46-6

Reproductive Effects: In a 3-generation reproductive study in rats, effects included reductions in weight gain, fetal weight, ossification, testicular weight, spleen weight, increased prostate weight and gestational length. No Effect Level (NEL) was 1 mg/kg/day...
Chronic/Subcrhonic Toxicity Studies: Chronic toxicity studies in rodents have shown liver changes (cellular hypertrophy). The No Effect Level (LEL) in rats is 10 ppm (0.5 mg/kg/day). Long term feeding studies in dogs produced a range of potentially serious effects at high dose rates (red cell, bone marrow and lymphadenopathy changes and liver and spleen damage) with a No Effect Level of 25 mg/kg/day.
Target Organs: Liver, skin, kidney, eye, bone marrow, blood, reproductive system.
Ref: Material Safety Data Sheet for Fusilade DX (active indredient Fluazifop-P-Butyl). Syngenta. January 21, 2002.
http://www.fluoridealert.org/pesticides/fluazifop-p-butyl.msds.pdf

Flubendiamide - Insecticide - CAS No. 272451-65-7

Results of a reproductive toxicity study in rats (exposure route not stated):
Thyroid, liver, uterine, thymus, and spleen weight changes in 2000 and 20000 ppm F1 and F2 pups.
Ref: TSCA Health & Safety Study Cover Sheet "Public Display Copy"
http://www.epa.gov/opptintr/tsca8e/doc/8ehq/2004/november04/8ehq-1004-15768a.pdf
•• This document was cited at EPA's site: "TSCA 8(e) and FYI Submissions Received from 11-15-04-11-26-04". It is important to note this as the document itself does not identify flubendiamide or its CAS No.
•• This study was conducted in the laboratory of The Institute of Environmental Toxicology - Japan
•• Source of Data/Study Sponsor: Bayer Material Science Corporation, 100 Bayer Road, Pittsburg PA 15205

Flucythrinate - Acaracide, Insecticide - CAS No. 70124-77-5

-- 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

Fludioxonil - Fungicide - CAS No. 131341-86-1

A carcinogenicity study in mice administered in the diet nominal dose levels at 0, 10, 100, 1,000, and 3,000 ppm (0, 1.1, 11.3, 112, and 360 mg/kg/day for male mice; 0, 1.4, 13.5, 133, and 417 mg/kg/day for female mice). Male mice at the 3,000 ppm level exhibited clinical toxicity in the form of an incidence of male mice which ``convulsed'' when handled. No significant effects on body weight, weight gain, food consumption, hematology, or microscopic non-neoplastic pathology was reported in either sex. Increased liver weight (9%) and spleen weight (34%) were observed in male mice at the 3,000 ppm dose level, which correlated with the macroscopic observations of enlarged spleen and raised foci of their liver. Female mice showed a statistically significant increase in liver weight at the 3,000 ppm dose level, and this is also supported by the macroscopic observation of enlarged liver at the 3,000 ppm dose level in female mice. Other macroscopic changes in female mice were an increased incidence of enlarged thymus, spleen, mediastinal lymph node, and liver, and an increased incidence of lymphoma in these organs.
Ref: Federal Register: October 29, 1997 (Volume 62, Number 209) [Rules and Regulations] [Page 56075-56082]. 4-(2,2-difluoro-1,3-benzodioxol-4-yl)-1H-pyrrole-3-carbonitrile; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/fludioxonil.fr.oct.29.1997.htm

Flufenacet - Herbicide - CAS No. 142459-58-3

Chronic feeding studies in dog and rat showed structural or functional alterations in liver, kidney, haematology, spleen, and thyroid. Flufenacet induces neuropathogical changes in the brain and spinal cord (axonal swelling) in rat and dog. The overall evaluation of the observed changes demonstrates that these effects occur only after repeated and prolonged exposure to high dose levels of flufenacet, which saturate metabolic pathways, and exceed the animal capacity to rapidly metabolise and excrete it. The liver was considered the primary target organ, with increases in organ weight, cell size and number, and/or associated changes in liver function tests.
Ref: European Commission, Health & Consumer Protection Directorate-General, Scientific Committee on Plants, October 17, 2001. SCP/FLUFEN/002-Final.
http://europa.eu.int/comm/food/fs/sc/scp/out112_ppp_en.pdf

-- In the rat chronic feeding / carcinogenicity study the NOEL was less than 1.2 mg/kg/day in males and less than 1.5 mg/kg/day in females and the LOEL was 1.2 mg/kg/day in males and 1.5 mg/kg/day in females based on methemoglobinemia and multi-organ effects in blood, kidney, spleen, heart, and uterus. Under experimental conditions the treatment did not alter the spontaneous tumor profile. In the mouse carcinogenicity study the NOEL was less than 7.4 mg/kg/day in males and was 9.4 mg/kg/day for females and the LOEL was 7.4 mg/kg/day for males and was 38.4 mg/kg/day for females based on cataract incidence and severity. There was no evidence of carcinogenicity for flufenacet in this study.
Ref: US EPA. Pesticide Fact Sheet. Flufenacet Reason for Issuance: Conditional Registration Date Issued: April 1998.
http://www.epa.gov/opprd001/factsheets/flufenacet.pdf

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

-- Repeat dose mammalian studies. Studies submitted were 28 d rat, 90 d rat/mouse/dog, 12 and 24 month rat, and 12 month dog. In both the rat and dog there was evidence of regenerative anaemia and increased methaemoglobin levels with NELs of 5 mg.kg-1 (rat 28- and 90- day) and 2.5 mg.kg-1.d-1 (dog 12 month). In mice the NEL was 7.5 mg.kg-1.d-1 based on increased plasma bilirubin. Plasma bilirubin was also increased in rats (24 month). Evidence of regenerative anaemia (increased methaemoglobin, decreased erythrocyte parameters, increased reticulocytes, increased marrow cellularity and increased spleen weight) was seen in most studies. In addition at higher doses triglycerides were decreased and heart weight increased in the rat.
-- 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%).
-- Carcinogenicity data. Adequately conducted carcinogenicity studies in the rat and mouse have been reported. Flufenoxuron was not carcinogenic in the rat. The NOEL for non-neoplastic effects (body weight and relative spleen weight changes) was 25 mg-1.kg-1.d-1. In the mouse there was an increased incidence of haemangiosarcoma in the liver (males) and spleen (females) at 50000 ppm, and an apparent increase in hepatocellular carcinoma in males at all dose levels. The apparent increase in liver tumors was due to an abnormally low control incidence, and therefore flufenoxuron had no significant carcinogenic activity in the mouse. No NEL was established in this study.
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

Flumethrin - Acaricide - CAS No. 69770-45-2

-- IN GLP repeated-dose toxicity study, groups of 20/sex/dose Wistar rats were fed diets containing 0, 10, 40 or 160 mg/kg feed flumethrin for up to 15 weeks. During mixing of the diets, 1% peanut oil was added to minimise dust formation. At 160 mg/kg feed, body weight gain was significantly reduced. Sever skin lesions were observed in the 160 mg/kg feed group. Some mild skin lesions were also observed in the 40 mg/kg feed group. Decreased red cell values and increased leucocyte counts in the 160 mg/kg feed group were probably associated with the skin lesions. At termination, histopathological examination revealed ulcerative skin lesions in all rats given 160 mg/kg feed and some rats from the 40 mg/kg feed group. Increased extramedullary haematopoiesis and reduced haemosiderin storage in the spleen were also observed in the 160 mg/kg feed group. The NOEL was 10 mg/kg feed, equivalent to 0.7/0.8 mg/kg bw per day in males/females respectively..
Ref: Committee for Veterinary Medicinal Products. Flumethrin. Summary Report (1). June 1998. EMEA/MRL/469/98-FINAL. The European Agency for the Evaluation of Medicinal Products.
http://www.fluorideaction.org/pesticides/flumethrin.eu.june.1998.pdf

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

The spleen, kidney, and liver appear to be the organs consistently affected following exposure to moderate doses of fluometuron in rats and dogs in subchronic, chronic, developmental, and reproductive studies. (page 8)
Ref. February 1, 2005. US EPA: Fluometuron: Revised HED Risk Assessment for Phase III of the Reregistration Eligibility Decision. Docket Identification Number: OPP-2004-0372-0008. 
http://www.fluorideaction.org/pesticides/fluometuron.opp-2004-0372-0008.pdf

E. Subchronic Studies. Subchronic feeding studies were conducted to determine the two concentrations (referred to in this report as "low" and "high" doses) to be used in the chronic studies. Fluometuron was administered in the diet for 90 days at doses of 0, 250, 500, 1,000, 2,000, 4,000, 8,000, or 16,000 ppm to groups consisting of 10 males and 10 females of each species (Tables 1 and 2) (page 5) ... A second 90-day subchronic study, described in Table 3, was undertaken to investigate in-depth the effects of feed containing 0 to 4,000 ppm fluometuron on the spleens of rats.... Gross lesions observed at necropsy included varying degrees of splenomegaly in all dosed groups. This change was dose related with the spleens being larger, heavier, darker, and firmer than the control spleens. In male rats, an increase in the mean weights of spleens occurred at 1,000 ppm, and the mean spleen weight at 4,000 ppm was twice that of the control. In female rats, the mean weight of spleens in the group receiving 250 ppm was greater than that of the control, and those of the groups receiving 2,000 ppm or 4,000 ppm were respectively twice and almost three times that of the control. A dose-related increased incidence of red blood cells with polychromasia and anisocytosis was observed for both male and female rats. Microscopically, the pathologic changes were congestion of the red pulp with corresponding decrease of white pulp. (page 8)
Reference: 1980. Bioassay of fluometuron for possible carcinogenicty. NCI-CG-TR-195. NTPO-80-11. National Cancer Institute. Carcinogenesis. Technical Report Series No. 195. NTP No. 80-11.
http://www.fluorideaction.org/pesticides/fluometuron.ntp.1980.pdf

-- 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

Combined chronic toxicity / carcinogenicity--rats. decreased body weight, decreased body weight gain, and decreased food efficiency in both sexes; decreased spleen weight in males; and microscopic lesions in the uterus of females. The apparent increase in tumors in the uterus and thyroid were addressed and resolved by an Agency committee, which concluded that no carcinogenic concern exists for fluoxastrobin.
Ref: Federal Register. September 16, 2005. Fluoxastrobin; Pesticide Tolerances. Final Rule.
http://www.fluorideaction.org/pesticides/fluoxastrobin.fr.sept16.05.html

Flurtamone - Herbicide - CAS No. 96525-23-4

-- Two-year dietary study in mice. In a carcinogenicity study, groups CD-1 mice (60/sex/dose) were fed diets containing 0, 30, 300, 3500 and 7000 ppm flurtamone (91.9% purity) for at least 78 weeks... The mean intake of flurtamone for males and females was estimated to be 4.5, 45, 525 and 1050 mg/kg bwday at 30, 300, 3500 and 7000 ppm, respectively. After 78 weeks of treatment, the mortality rate for the 7000 ppm female mice was significantly higher than controls and a significant negative survival trend was found in both sexes. The test laboratory pathologist considered systemic amyloidosis to be the major cause of death (Table 5.34) [page 102]... The severity and incidence of extramedullary haematopoiesis was increased in the spleens of the 7000 ppm males and females [page 104]..
Ref: December 2000 . Evaluation on: Flurtamone. No. 196. Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7PX, UK. Available online at http://www.pesticides.gov.uk/citizen/evaluations/evallist_alphabet.htm

Flutolanil - Fungicide - CAS No. 66332-96-5

Subchronic toxicity. A 84-day rat feeding study with a No Observed Effect Level ( NOEL) less than 100 ppm [6.0 mg/kg/day] for males and a NOEL of 100 ppm [7.2 mg/kg/day] for females and with a Lowest Observed Effect Level (LOEL) of 100 ppm [6.8 mg/kg/day] for males based on suppression of thyroxine (T4) level and a LOEL of 400 ppm [28.8 mg/kg/day] for females based on hematology and clinical chemistry findings. A 13-week mouse feeding study with a NOEL of 100 ppm [18.2 mg/kg/day for males and 24.5 mg/kg/day for females] and a LOEL of 400 ppm [64.2 mg/kg/day for males and 91.3 mg/kg/day for females] based on histopathology of the liver, spleen and thyroid. A 13-week dog dietary study with a NOEL of 50 ppm [1.70 mg/kg/day for males and 1.67 mg/kg/day for females] and a LOEL of 200 ppm [6.90 mg/ kg/day for males and 7.20 mg/kg/day for females] based on evidence that the bio-transformation capacity of the liver has been exceeded, (as indicated by increase in LDH, liver weight, ALK and hepatomegaly), globulin and spleen pigment in females, decreased T4 and [[Page 34180]] ALT values in both sexes, decreased albumin in males, and decreased serum glucose in females. A 21-day rabbit dermal study with the dermal irritation NOEL of 1,000 mg/kg/day for males and females and a systemic NOEL of 20 mg/kg/day for males and 150 mg/kg/day for females and a systemic LOEL of 150 mg/kg/day for males and 1,000 mg/kg/day for females based on clinical chemistry data (decreased T4 and FT4 levels in both sexes) and centrilobular hepatocytomegaly in females.
Ref: Federal Register: June 23, 1998 [Page 34176-34184]. Notice of Filing of Pesticide Petitions.
http://www.fluoridealert.org/pesticides/flutolanil.fr.june.23.1998.htm

Gliftor - Rodenticide - Rodenticide - CAS No. 8065-71-2

Abstract. The single administration of gliftor (I; internally, 40-160 mg/kg) caused considerable destructive changes and circulatory disorders in the internal organs of rats. The maximum tolerance dose of I (60 mg/kg) caused hyperplasia of the cells of the RES in the spleen, proliferation of local cells, and inflammatory cellular infiltration of the alveolar walls in the lungs.
Ref: Morphological changes of internal organs of experimental animals after oral administration of gliftor; by KNYSH VS, TKACH NZ, TSAREVSKII LP. TR INST KRAEV PATOL AKAD NAUK KAZ SSR; 22 1971 28-30. [Abstract from Toxline at Toxnet.]

Abstract. Rats were subjected to the single inhalation effect of vapors of the zoocide gliftor (I; 50, 100, 350, 520, and 1100 mg/m-3). Morphological changes were noted beginning with a concentration of 350 mg/m-3. In a chronic experiment (4 mo.) the rats were subjected to I poisoning in a concentration of 10, 13, 64, and 110 mg/m-3. Distinct morphological changes in the organs were noted under the effect of concentrations 64 and 110 mg/m-3. Under the chronic effect of I there were considerable circulatory disorders and destructive changes of the interanl organs, especially in the liver, lungs, spleen, and kidneys.
Ref: Pathomorphological changes in internal organs of white rats under the inhalation effect of gliftor; by KNYSH VS, TKACH NZ, TSAREVSKII LP, MILOVANOVA VI. TR INST KRAEV PATOL AKAD NAUK KAZ SSR; 22 1971 23-28. [Abstract from Toxline at Toxnet.]

Indoxacarb - Insecticide - CAS No. 173584-44-6

The haemosiderin deposits in spleen and liver, and spleen and bone marrow hyperplastic response should be considered to be secondary physiological responses to the increased RBC turn over. The very shallow dose-response curve also indicates that the compensatory mechanism of the haemopoietic system was not overcome (except at high doses in the dog) and the effect of indoxacarb in rats and dogs can be described as a compensated haemolytic effect.
July 18, 2002: Opinion of the Scientific Committee on Plants on specific questions from the Commission concerning the evaluation of Indoxacarb. European Commission. Health & Consumer Protection Directorate-General.
http://www.fluorideaction.org/pesticides/indoxacarb.eu.july.18.2002.pdf

COMBINED, RAT **52425-054 162226 "Combined Chronic Toxicity/Oncogenicity Study with DPX-JW062-106 (50% DPX-KN128, 50% DPX-KN127) Two-Year Feeding Study in Rats" (Frame, S. 835-E. I. du Pont de Nemours and Company, Haskell Laboratory, Elkton Road, Newark, Delaware, Study HLR 1174-96, 11/19/97). DPX-JW062-106 technical (Batch DPX-JW062-106, 47.5% DPX-KN128) was given in the diet daily to males at 0, 20, 40, 60, 125 or 250 ppm and females at 0, 10, 20, 40, 60 or 125 ppm for 24 months. Deaths of one female at 60 ppm and seven at 125 ppm during the first year were associated with bone marrow atrophy, splenic lymphoid depletion and thymic necrosis. Decreases in mean body weight/weight gain in males at 125 and 250 ppm and females at 60 and 125 ppm correlated with decreased food consumption. Hemolytic anemia at 60 ppm and above (males) and 40 ppm and above (females): RBC mass, hemoglobin and hematocrit were decreased and linked with increased reticulocyte counts and increased MCV. Bone marrow regenerative response was increased bone marrow hyperplasia in the one-year interim sacrifice 125 ppm females. Spleen weights were increased in both sexes at the respective high-dose levels and other non-neoplastic changes were secondary physiological responses to test substance-related hemolysis; increased pigment observed within the Kupffer cells of female livers (125 ppm) and the macrophages of the spleen (both sexes at 60 ppm and above) indicated increased RBC turnover. Increased hematopoiesis was reported in the spleen of interim sacrifice males at 125 ppm and above and in the bone marrow of high-dose males and females. After two years, secondary changes were seen in the liver, spleen, bone marrow, kidneys and thymus in high dose groups. Increased pigment was observed in the Kupffer cells of female livers at 40 ppm and above; in males, increases were noted at 250 ppm only. Increased splenic pigment was seen in all compound-treated male groups and in females at 60 ppm and above; a slight increase in splenic congestion was seen in 250 ppm males. No evidence of an oncogenic effect was reported. NOEL(M)= 40 ppm; (F)=20 ppm (M: 1.59 mg/kg/day; F: 1.04 mg/kg/day based on hemolytic anemia). Acceptable. Kellner, 1/29/99.
-- **52425-047 162215 "Chronic Toxicity Study of DPX-JW062-106 (50% DPX-KN128, 50% DPX-KN127) One Year Feeding Study in Dogs" (Mertens, J. 831-WIL Research Laboratories, Inc. Ashland, Ohio. Study HLO 885-96, 11/19/97). DPX-JW062-106 technical (Batch DPX-JW062- 106, 47.5% DPX-KN128) was administered orally (via the feed) to 5 Beagle dogs/sex/dose at levels of 0, 40, 80, 640 and 1280 ppm for 52 weeks... Microscopic changes in groups 40 ppm and above included increased pigment (hemosiderin) in liver Kupffer cells, kidney tubule epithelium, spleen and bone marrow and increased extramedullary hematopoiesis in the spleen and bone marrow hyperplasia. NOEL (M/F)=40 ppm (males: 1.1 mg/kg/day; females: 1.3 mg/kg/day based on biologically significant hemolytic anemia at 80 ppm and above). Acceptable. Kellner, 1/12/99.
-- REPRODUCTION, RAT **52425-046 162214 "Two Generation Reproduction/Fertility Study with DPX-JW062-106 in Rats" (Breslin, W. 834-MPI Research, Mattawan, MI, Report# HLO 115-96, 11/3/97). DPX-JW062- 106 (Batch no. DPX-JW062-106, 47.7% DPX-KN128, dissolved in acetone) was administered orally via the feed to 26 Crl:CD ¨ VAF/Plus ¨ rats/sex/dose at levels of 0, 20, 60, 100 ppm beginning 70 days prior to mating and continuing until euthanasia for 2 generations... Necropsy findings included increased spleen weights in the F0 and F1 males at 100 ppm and in the F0 and F1 females at 60 and 100 ppm. Maternal NOEL= 20 ppm (0.856-4.141 mg/kg/day, based on increased spleen weights in females at 60 and 100 ppm). There were no apparent compound-related effects on gonad function, estrous cycling or mating behavior in either the F0 or F1 animals. In F1 females at 100 ppm, slight decreases in fecundity and fertility index were noted. While mean F1 pup weights in the 60 and 100 ppm groups were statistically reduced during the lactation period, corresponding weights in the F2 generation showed no compound-related effect. Developmental NOEL= 20 ppm (based on decreased F1 pup weights during lactation at 60 and 100 ppm). No Adverse Effects; decrease in F1 fecundity and fertility indices were not statistically significant, not seen during F0 mating and not accompanied by effects in sperm or estrous cycle evaluations. Reproductive NOEL= 60 ppm (1.734-11.610 mg/kg/day; based on slight reduction in F1 fertility index at 100 ppm). Acceptable. Kellner,
-- ** 034; 162199; "Subchronic Oral Toxicity:90-Day Study with DPX-MP062 (Approximately 75% DPX-KN128, 25% DPX-KN127) Feeding Study in Rats" (MacKenzie, S.A., Haskell Laboratory for Toxicology and Industrial Medicine, E.I. du Pont de Nemours and Company, Newark, DE, Laboratory Project ID DuPont HL-1997-00056, 3/24/97). 821. DPX-MP062 (Batch No. DPX-MP062- 51A, 74.7% DPX-KN128) was admixed to the feed at concentrations of 0, 10, 25 (females only), 50, 100, or 200 (males only) ppm (0, 0.620, 3.09, 6.01, or 15.0 mg/kg/day, respectively, for males and 0, 0.760, 2.13, 3.78, or 8.94 mg/kg/day, respectively, for females) and fed to 10 Crl:CD ¨ (SD)BR rats per sex per dose level for approximately 90 days. 5 females at 100 ppm died or were sacrificed in extremis. No dose-related clinical signs were observed in males; among females at 100 ppm, ataxia (in 2 of the mortalities), weakness (in 4 animals), and tremors (in 1 of the mortalities) were observed. Treatment-related decreased mean body weight and decreased mean body weight gain in males at 200 ppm and in females at 50 and 100 ppm were observed. Statistically significant and dose-related decreases in mean red blood cell, hemoglobin, and hematocrit levels in males beginning at 100 ppm, 50 ppm, and 100 ppm, respectively, and in females beginning at 25 ppm, 10 ppm, and 10 ppm, respectively, were observed. Microscopic examination revealed treatment-related increased pigment and increased extramedullary hematopoiesis in the spleen in males at 50, 100, and 200 ppm, and in females at all dose levels. No adverse effects. NOEL (M)=0.620 mg/kg/day (10 ppm) and (F)< 0.760 mg/kg/day (10 ppm) [based on treatment-related decreased mean hemoglobin (males and females) and hematocrit (females) levels and histologic effects in the spleen). Acceptable. (Corlett, 1/19/99
-- ** 035; 162200; "Subchronic Oral Toxicity:90-Day Study with DPX-JW062-34 (50% DPX-KN128, 50% DPX-KN127) Feeding Study in Mice" [Malek, D.E., Haskell Laboratory for Toxicology and Industrial Medicine, E.I. du Pont de Nemours and Company, Newark, DE, Haskell Laboratory Report No. 750-93 (Revision No. 1), 1/22/97]. 821. DPX-JW062-34 Technical (Batch No. DPX-JW062-34, 47.4% DPX-KN128) was admixed to the feed at concentrations of 0, 10/300 (started at 10 ppm and increased to 300 ppm on Day 42 of feeding), 35, 75, or 150 ppm (0, 1.7/44, 5.5, 12, or 23 mg/kg/day, respectively, for males and 0, 2.1/51, 7.0, 16, or 30 mg/kg/day, respectively, for females) and fed to 10 Crl:CD-1 ¨ (ICR)BR mice per sex per dose level for approximately 90 days. One male at 300 ppm was found dead on day 85. Treatment-related clinical signs included animals leaning to one side (in males at 300 ppm and in females at 150 and 300 ppm), abnormal gait or mobility (in females at 300 ppm), and tremors (in one male at 300 ppm). Treatment-related decreases in mean body weight (in males at 300 ppm), mean body weight gain (in males at 300 ppm), and mean daily food consumed per mouse (in males at 300 ppm and in females at 150 and 300 ppm) were observed. Treatment-related increases in mean reticulocyte (in males and females at 300 ppm), mean cell volume (in males at 300 ppm and in females at 150 and 300 ppm), and mean white blood cell (in males and females at 300 ppm) levels, and the treatment-related presence of Heinz bodies (in males and females at 150 and 300 ppm) were observed. Microscopic examination revealed treatment-related increased pigment in the spleen in males and females beginning at 75 ppm. No adverse effects. NOEL (M)=5.5 mg/kg/day (35 ppm) and (F)=7.0 mg/kg/day (35 ppm) (based on treatment-related increased pigment in the spleen). Acceptable. (Corlett, 1/28/99)
-- ** 036; 162201; "Subchronic Oral Toxicity:90-Day Study with DPX-JW062-106 (Approximately 50% DPX-KN128, 50% DPX-KN127) Feeding Study in Dogs" (Mertens, J.J.W.M., WIL Research Laboratories, Inc., Ashland, OH, Haskell Laboratory Project ID: HLO 494-95, Performing Laboratory Project ID: WIL-189016, 11/19/97). 821. DPX-JW062 Technical (Batch No. DPX-JW062- 106, 47.5% DPX-KN128) was admixed to the feed at concentrations of 0, 40, 80, 160, or 640 ppm (0, 1, 2, 5, or 18 mg/kg/day, respectively, for males, and 0, 1, 3, 5, or 17 mg/kg/day, respectively, for females) and fed to 4 outbred beagle dogs per sex per dose level for 13 weeks. No animals died during the study interval. No treatment-related clinical signs were observed. Statistically significant and treatment-related decreases in mean red blood cell and hemoglobin levels in males at 160 and 640 ppm, and females at 640 ppm and statistically significant and dose-related increases in mean cell volume in males beginning at 160 ppm and in females beginning at 80 ppm and percent reticulocytes in males at 640 ppm and in females at 160 and 640 ppm were observed. Treatment-related increases in Heinz bodies and mean total bilirubin levels were observed in males and females at 160 and 640 ppm. Microscopic examination revealed a treatment-related increase in pigment in the spleen beginning in males at 40 ppm and in females at 80 ppm, increased extramedullary hematopoiesis in the spleen beginning in males and females at 160 ppm, treatment-related erythrocytic hyperplasia and an increase in pigment in the bone marrow in males beginning at 80 ppm and in females beginning at 40 ppm, and a treatment-related increase in pigment in the liver in males and females beginning at 80 ppm. No adverse effects. NOEL (M/F)< 1 mg/kg/day (40 ppm) (based on a treatment-related increase in pigment in the spleen in males, and on a treatment-related increase in extramedullary hematopoiesis in the spleen, and treatment-related erythrocytic hyperplasia and a treatment-related increase in pigment in the bone marrow in females). Acceptable. (Corlett, 2/10/99)
Ref: March 11, 1999: Summary of Toxicology Data - Indoxycarb. California EPA Department of Pesticide Regulation, Medical Toxicology Branch.
http://www.fluorideaction.org/pesticides/indoxacarb.ca.epa.1999.pdf

28-Day dermal toxicity -- rats: DPX--MP062 / NOAEL = 50 mg/kg/day LOAEL = 500 mg/kg/ day based on decreased body weights, body weight gains, food consumption, and food efficiency in F, and changes in hematology parameters (increased reticulocytes), the spleen (increased absolute and relative weight M only, gross discoloration), clinical signs of toxicity in both sexes in rats.
Ref: Federal Register: September 29, 2000. Indoxacarb; Pesticide Tolerance. Final Rule.
http://www.epa.gov/EPA-PEST/2000/September/Day-29/p25052.htm

In a 2-generation rat reproduction study, the parental NOEL was 1.3 and 1.5 mg/kg/day for males and females, respectively. The parental NOEL was based on observations of reduced weight gain and food consumption for the higher concentration groups of the F0 generation and potential treatment-related changes in spleen weights for the higher groups of the F1 generation.
Ref: Federal Register: April 16, 1998 [Page 18912-18919]. Notice of Filing of Pesticide Petitions.
http://www.fluoridealert.org/pesticides/dpx-mp062.fr.apr16.1998.htm

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

-- 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.
-- Reproduction-- Rats. Groups of male and female rats were fed 0, 50, 500 or 2,000 ppm of Lactofen Technical continuously in their diets for 2-generations. Adult systemic toxicity (mortality, reduced body weight, increased liver and spleen weight, decreased kidney weight and histological changes in the liver and testes) was observed at levels of 500 ppm and greater.
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

Mefluidide and its potassium and diethanolamine salts - Herbicide, Plant growth regulator - CAS Nos. 53780-34-0, 53780-36-2, 83601-83-6)

21-Day Dermal toxicity - rabbit (4 rabbits/sex/dose). Acceptable/Non-guideline (NOAEL was not observed). Systemic LOAEL = 240 mg/kg/day, based on clinical chemistry (increased alkaline phosphatase and alanine aminotransferase) and organ weights (decreased spleen weight in females and increased liver weights in males). Edema and swelling with myelin loss in sciatic nerve was seen in 720 and 2400 mg/kg/day dose group. Dehydration observed at 2400 mg/kg/day dose. Dermal and systemic NOAELs were not established.
Ref: USEPA. Mefluidide - Toxicology section for the Reregistration Eligibility Decision Document (RED) (January 31, 2007)
http://www.fluoridealert.org/pesticides/docket/EPA-HQ-OPP-2007-0431-0009.pdf

Norflurazon - Herbicide - CAS No. 27314-13-2

- A two-year carcinogenicity study was conducted in male and female CD-1 HaM/ICR Swiss mice in which 125 mice/sex/dose were administered technical norflurazon in the diet at dose levels of 0, 85, 340, or 1360 ppm (0, 12.8, 58.7, or 218.8 mg/kg/day) for 100-104 weeks. No significant effects were observed on body weight, body weight gain, clinical toxicity, or food consumption at any dose level tested. Liver weight was increased by 9% and 15% in male and female mice at the 340 ppm dose level, and by 27% and 21% at the 1360 ppm dose level, respectively. The liver to body weight ratio was increased by 19% and 4% in male and female mice at the 340 ppm dose level, and by 43% and 19% at the 1360 ppm dose level, respectively. Increased incidences of enlarged spleen, nephritis, swollen/enlarged liver, and nodular enlargement of the liver were observed in high dose male mice, while increased incidences of pyelonephritis, enlarged liver, and cystic ovaries were observed in high dose female mice. Carcinogenic potential was evidenced by an increased incidence of hepatic adenoma and combined adenoma/carcinoma in high dose male mice. The systemic NOEL was determined to be 12.8 mg/kg/day (85 ppm) for male mice, and 58.7 mg/kg/day (340 ppm) for female mice. The systemic LEL was determined to be 58.7 mg/kg/day (340 ppm) for male mice, based on the increased incidence of enlarged spleen, increased absolute and relative liver weight, and increased incidence of nephritis. The systemic LEL was determined to be 218.8 mg/kg/day (1360 ppm) for female mice, based on the increased incidence of enlarged liver and cystic ovaries, the increased absolute and relative liver weight, and the increased incidence of pyelonephritis (guideline ¤83-2; MRID 00111649).
-- A chronic toxicity and carcinogenicity study was conducted in Sprague-Dawley rats. In this study, technical norflurazon was administered in the diet at dose levels of 0, 125, 375, or 1025 ppm (0, 6.25, 18.75, or 51.25 mg/kg/day) for 104 weeks.,, Other microscopic alterations observed at the high dose included an increased incidence of parathyroid hyperplasia (both sexes), hemosiderin pigment deposition in the spleen (males only) and liver (both sexes), and endometritis and squamous metaplasia of the uterus (females). The systemic NOEL was determined to be 375 ppm (18.75 mg/kg/day) for both sexes...
Ref: US EPA REREGISTRATION ELIGIBILITY DECISION NORFLURAZON. LIST A. CASE 0229.
http://www.fluoridealert.org/pesticides/norflurazon.red.epa.pdf

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

-- SUBCHRONIC STUDIES (Oral) 52846-002; 174427; " 'Rimon' Technical: Toxicity Study by Dietary Administration to CD Rats for 13 Weeks Followed by a 4 Week Reversibility Period":; (P.W. East; Huntingdon Life Sciences Ltd, Eye, Suffolk, England; Report No. MAK399/972319; 4/2/98); Ten CD rats/sex/group were fed 0, 50, 100, 10000 or 20000 ppm of Rimon Technical (Novaluron Technical) (batch no. 031068069, purity: 99.8% (pre-study analysis)) in the diet for 13 weeks ((M): 0, 4.2, 8.3, 818.5, 1666.9 mg/kg/day, (F): 0, 4.7, 8.9, 871.0, 1820.6 mg/kg/day). An additional 5 animals/sex/group in the 0, 50 and 20000 ppm groups were maintained for 4 more weeks after the termination of dosing in order to assess the reversibility of treatment-related effects... Microscopic examination of the spleen revealed increased extramedullary erythropoesis (50 ppm and above) and increased hemosiderosis (M) 10000 ppm and above (p<0.01), (F) 50 ppm and above (p<0.05 at 50 ppm). In the livers of the 10000 and 20000 ppm females, pigmented Kupffer cells were noted (p<0.05 at 10000 ppm). At the conclusion of the 4 week recovery period, the methemoglobin levels were still slightly elevated for the 20000 ppm group (p<0.05), the relative spleen weight was increased for the 20000 ppm females (p<0.05), and there was still increased hemosiderosis in the spleen of the 20000 ppm females (p<0.01). No adverse effect indicated. NOEL: (M/F) < 50 ppm ((M) 4.2 mg/kg/day, (F) 4.7 mg/kg/day (based upon the increased incidence of splenic extramedullary erythropoesis noted for the 50 ppm treatment group); Study acceptable. (Moore, 11/1/00)
Ref: 2001. Summary of Toxicology Data for Novaluron. California Environmental Protection Agency, Department of Pesticide Regulation, Medical Toxicology Branch. Chemical Code # 5754, Tolerance # 52846 3/23/01.
http://www.fluoridealert.org/pesticides/novaluron.caepa.toxtst.2001.pdf

-- Short-term incidental oral (1-30 days); Intermediate-term incidental oral (1-6 months); and Intermediate-term inhalation (1 to 6 months): 90-day feeding study in rat. LOAEL = 8.64 mg/kg/day based on clinical chemistry (decreased hemoglobin, hematocrit and RBC counts) and histopathology (increased hematopoiesis and hemosiderosis in spleen and liver).
-- Reproduction and fertility- rat. Parental NOAEL= Not established; LOAEL
(M/F)= 74.2/84.0 mg/kg/day based on increased absolute and relative spleen weights. Offspring NOAEL= Not established; LOAEL (M/F)= 74.2/84.0 mg/
kg/day based on increased absolute and relative spleen weights.
Re: June 2, 2004. Novaluron; Pesticide Tolerance. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/novaluron.fr.june.2.2004.htm

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

-- REPRODUCTION, RAT. “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. . ... . F2a male weanlings had statistically significantly decreased body weights, relative brain and absolute spleen weights at 25 mg/kg. Neonates at 25 mg/kg in both F1 and F2 generations showed tonoclonic convulsions, as well as in 1 litter of F2a at 5.0 mg/kg. P2 females (1, 1, 5 and 7 at 0, 0.5, 5.0 and 25 mg/kg, respectively) failed to litter, so the female is considered to be an affected sex.) Possible adverse effects on reproduction, fertility and pup survival, along with numerous other toxicologically relevant effects. M. Silva, 6/18/04
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

PFOS - PFOA - Insecticide, US EPA List 3 Inert

The effects of peroxisome proliferators on the immune system of male C57B1/6 mice have been investigated. Significant atrophy of the thymus and spleen was observed in animals treated with potent peroxisome proliferators (e.g. perfluorooctanoic acid (PFOA), di(2-ethylhexyl)phthalate (DEHP), Wy-14643 and nafenopin), whereas the effects of a moderate peroxisome proliferator (i.e. acetylsalicylic acid (ASA)) were relatively weak. The time course of thymic and splenic atrophy caused by PFOA was found to resemble the time course of the increase in liver weight and of peroxisome proliferation... Interestingly, in vitro exposure to PFOA for up to 24 h did not produce analogous effects in either thymocytes or splenocytes. Thus, the thymic and splenic atrophy caused by PFOA appears to involve an indirect pathway."
Ref: 2000. Clin Exp Immunol Nov;122(2):219-26. Effects of peroxisome proliferators on the thymus and spleen of mice; by Yang Q, Xie Y, Depierre JW.

In the rat subchronic study, Goldenthal et al. (1978b) administered CD rats, 5/sex/group, dietary
levels of 0, 30, 100, 300, 1000 or 3000 ppm PFOS (FC-95) for 90 days. The males weighed 196-
232 g and the females weighed 165-206 g at study initiation. The dietary levels were equivalent
to doses of 0, 2, 6, 18, 60 and 200 mg/kg/day... The rats were sacrificed after 90 days of treatment and a gross necrospy was conducted... All of the rats in the 300, 1000 and 3000 ppm groups died. Death occurred between days 13-25 and days 18-28 for the males and females, respectively, in the 300 ppm group...
The rats in all groups showed signs of toxicity including emaciation, convulsions following
handling, hunched back, red material around the eyes, yellow material around the anogenital
region, increased sensitivity to external stimuli, reduced activity and moist red material around
the mouth or nose. Three males and two females in the 100 ppm group died prior to scheduled sacrifice. Two of the males and the two females died during week 5 and the third male died during week 11 of the study... All rats in the 30 ppm group survived until the end of the study... Histologic examination also showed lesions in all treated groups. Centrilobular to midzonal cytoplasmic hypertrophy of hepatocytes and focal necrosis was observed in the liver; the incidence and relative severity were greater in the males. In addition, especially among rats in the 300, 1000 and 3000 ppm groups, treatment related histologic lesions were noted in the primary (thymus, bone marrow) and secondary (spleen, mesenteric lymph nodes) lymphoid organs, stomach, intestines, muscle and skin. In the thymus, this consisted of depletion in the number and size of the lymphoid follicles and in the bone marrow hypocellularity was noted. The spleen was slightly atrophied with a corresponding decrease in the size and number of lymphoid follicles and cells and a similar depletion was noted in the mesenteric lymph nodes.
Ref: August 31, 2000. MEMORANDUM. SUBJECT: Hazard Assessment of PFOS. FROM: Jennifer Seed, Branch Chief, Existing Chemical Assessment Branch, Risk Assessment Division (7403). THRU: Oscar Hernandez , Division Director, Risk Assessment Division (7403). TO: Charlie Auer, Division Director, Chemical Control Division (7405).

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

-- Fat, liver and kidneys contained the highest amounts of picolinafen metabolites labelled on the pyridine ring, whereas the blood, liver, spleen and lungs contained the highest amounts of picolinafen metabolites labelled on the aniline ring.
-- Short-Term Studies. All mice fed picolinafen at dietary concentrations of 0, 100, 1000, 2000, 3500 or 7000 ppm for 28 days survived, but body weight gain was reduced in males at 7000 ppm... Spleen and liver weights were increased at ¥ 2000 ppm and the breakdown products of blood cells accumulated in the liver and spleen and the production of blood cells in the spleen were increased in males at ¥ 1000 ppm and females at ¥ 2000 ppm. The severity of these histopathological changes increased in a dose-related manner.
-- In mice fed picolinafen at dietary concentrations of 0, 50, 500, 1000 or 2000 ppm for 13 weeks, food consumption was decreased in males at 1000 and 2000 ppm... The spleens of some mice were enlarged and spleen weights were increased in females at ¥1000 ppm. Pigment deposition was increased in the spleen at ¥ 500 ppm and extramedullary haematopoiesis was increased in females at ¥ 500 ppm males at ¥1000 ppm. The NOEL in this study was 50 ppm, equal to 10 mg/kg bw/day in males and 13 mg/kg bw/day in females.
-- In mice fed picolinafen at dietary concentrations of 0, 50, 500, 1000 or 2000 ppm for 13 weeks, food consumption was decreased in males at 1000 and 2000 ppm... The spleens of some mice were enlarged and spleen weights were increased in females at ¥1000 ppm. Pigment deposition was increased in the spleen at ¥ 500 ppm and extramedullary haematopoiesis was increased in females at ¥ 500 ppm males at ¥1000 ppm. The NOEL in this study was 50 ppm, equal to 10 mg/kg bw/day in males and 13 mg/kg bw/day in females.
-- In rats fed picolinafen at dietary concentrations of 0, 80, 400 or 800 ppm for 13 weeks body weight gain was slightly reduced in females at 800 ppm... Spleen weights were increased at 400 and 800 ppm in males and 800 ppm in females. Liver to body weight ratios were increased in males at 800 ppm and females at 400 and 800 ppm. Pigment deposition was increased in the liver and spleen at 400 and 800 ppm. The NOEL in this study was 80 ppm, equal to 6.4 mg/kg bw/day in males and 6.8 mg/kg bw/day in females.
-- Long-Term Studies In mice fed picolinafen at dietary concentrations of 0, 40, 400 or 800 ppm for 18 months, there was no increase in the incidence of neoplasms... Splenic enlargement was slightly increased in incidence in females at 400 and 800 ppm. Extramedullary haematopoiesis was observed in the spleens of mice at 800 ppm with increased pigment deposition observed in males at 800 ppm and females at 400 and 800 ppm. The NOEL in this study was 40 ppm, equal to 6.9 mg/kg bw/day for males and 8.2 mg/kg bw/day for females.
-- In rats fed picolinafen at dietary concentrations of 0, 50, 250, or 500 ppm for 24 months there was no increase in the incidence of neoplasms. Haemoglobin, Hct and RBC were reduced at 3 and 6 months only at 250 and 500 ppm. Spleen weights were increased at 500 ppm and the amount of brown pigment observed in the spleen was increased at 250 and 500 ppm at both 12 and 24 months. The NOEL in this study was 50 ppm, equal to 2.4 mg/kg bw/day for males and 3.0 mg/kg bw/day for females.
-- Rats were fed picolinafen at dietary concentration of 0, 50, 250 or 500 ppm in a two-generation reproduction study... The spleen also showed congestion, increased amounts of brown pigment and extramedullary haematopoiesis at 250 and 500 ppm... The NOEL in this study is 50 ppm, equal to 3.7 mg/kg bw/day for males and 4.2 mg/kg bw/day for females.
-- Picolinafen was given to pregnant rats by oral gavage at 0, 100, 500 or 1000 mg/kg bw/day on days 6 to 19 of gestation. One dam at 1000 mg/kg bw/day appeared emaciated and body weight losses associated with reduced food consumption were observed on days 6-12 of gestation at ¥ 500 mg/kg bw/day. Spleen weights were increased in dams at ¥100 mg/kg bw/day and liver to body weight ratios were slightly increased at ¥ 500 mg/kg bw/day... The incidence and severity of extramedullary haematopoiesis and haemosiderosis in the spleen was increased in a dose dependent manner in all treated groups...
-- In a developmental study, picolinafen was given to rabbits by oral gavage at 0, 5, 20 or 50 mg/kg bw/day on days 6-28 of gestation... Congestion and haemosiderosis in the spleen were increased in incidence and severity at 20 and 50 mg/kg bw/day and increased extramedullary haematopoiesis was observed at 50 mg/kg bw/day.
Ref: Public Release Summary on Evaluation of the new active PICOLINAFEN in the products SNIPER HERBICIDE & PARAGON HERBICIDE. Australia. National Registration Authority for Agricultural and Veterinary Chemicals November 2000.
http://www.nra.gov.au/publications/prspic.pdf

Primisulfuron-methyl - Fungicide, Herbicide - CAS No. 86209-51-0

Organ toxicity: Target organs identified in animal studies include the liver, kidneys, spleen, and testes, as well as the skeleton.
Ref: E X T O X N E T Extension Toxicology Network Pesticide Information Profiles. Revised June 1996.
http://ace.ace.orst.edu/info/extoxnet/pips/primisul.htm

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

Chronic toxicity.
-- In a 104-week combined chronic/oncogenicity study in rats,
effects included decreased body weight gain, increased frequency of rearing (high dose females only), hematological alterations and histopathological alterations of the spleen. No oncogenicity was found. The NOAEL for this study is 100 ppm (3.4 mg/kg/day in males and 4.1 mg/kg/day in females).
Ref: Federal Register: December 5, 2003. Pyridalyl; Notice of Filing a Pesticide Petition.
http://www.fluorideaction.org/pesticides/pyridalyl.fr.dec.5.2003.htm

Sodium fluoride - Wood preservative, EPA List 4B Inert - CAS No. 7681-49-4

Objective: To examine qualitatively and quantitatively the histological changes in spleen of rats given sodium fluoride.
Material and Methods: Seventy-five female Wistar rats, each weighing approx. 200 g, were divided into three equal groups. Animals in groups 1 and 2 received intraperitoneally daily doses of 0.5 and 5 mg NaF, respectively, whereas group 3 (control) received physiological saline. The experiments were run for a period of 3 months.1 Afterwards, the spleen was removed for histological and histochemical examination and fixed in 1 0% formaldehyde solution. Histological sections were stained with haematoxylin and eosin, picrosirius red F3BA,2,3 and silver reagent according to Gomori. The ultrastructural changes in collagen fibres were investigated by optical polarisation methods.
Results: The lymphoid tissue mass of the spleen decreased and the relative proportion of reticulin and collagen structures increased. These changes correlated with the dose of fluoride.
Conclusions and Interpretation: The absolute and relative proportion of lymphoid tissue in spleen of rats given NaF decreased in a dose-related manner. Loss of lymphoid tissue may play an important role in the diminished reactivity of the organism and may be regarded as a consequence of fluoride toxicity.
Ref: Lymphoid depletion of spleen due to experimental fluorosis in rats; by M Bely. Fluoride 2000; 33(1):S1-S2. [XXIIIrd ISFR Conference abstracts, Szczecin, Poland, June 11-14 2000]. Full report available at:
http://www.fluoride-journal.com/00-33-1/331-s1.pdf

Sodium fluorosilicate (Sodium Hexafluorosilicate) - Insecticiide, Wood Preservative, EPA List 3 Inert - CAS No. 16893-85-9

-- Sheep, Awassi breed, 1- to 3- yr- old, 5F technical sodium hexafluorosilicate, 25, 50, 200, 1500, and 2000 mg/ kg (0.13, 0.27, 1.06, 7.976, and 10.63 mmol/ kg) suspended in water; duration and observation period n. p. With the 25- and 50- mg/ kg doses, animals exhibited grinding of teeth (an indication of pain), dullness, and mild diarrhea. At 200 mg/ kg, additional symptoms were experienced and included staggering and severe diarrhea. Animals died on day 6. With the two higher doses, licking of the lips, kicking of the belly, grinding of the teeth, falling down (after 1.5 h), frothing at the mouth, congested conjunctiva, protrudation of the tongue, forced and labored breathing, fever, and increased respiration and heart rates were observed. Animals died 3 h after administration of 1500 mg/ kg and 2.5 h after administration of 2000 mg/ kg. Post- mortem examination showed serous pericardial fluid (few milliliters), a slightly friable liver, mild edema in the lungs, and froth in the trachea. Hemorrhages occurred on the spleen and mucosal folds of the abomasum, and a gelatinous fluid was present in the colon. For the 1500 mg/ kg- dose group, the change in GOT went from 132% (of pretreatment activity) at 1.5 hours to 230% at 2.5 hours. For LDH, the change was 158% at death. The serum ICDH change increased from 168% after one hour to 984% at death. Egyed and Shlosberg (1975)
Ref: Review of Toxicological Literature. October 2001. Sodium Hexafluorosilicate [CASRN 16893-85-9] and Fluorosilicic Acid [CASRN 16961-83-4]. Prepared for Scott Masten, Ph.D. National Institute of Environmental Health Sciences P.O. Box 12233 Research Triangle Park, North Carolina 27709. Contract No. N01-ES-65402. Submitted by Karen E. Haneke, M.S. (Principal Investigator) Bonnie L. Carson, M.S. (Co-Principal Investigator) Integrated Laboratory Systems P.O. Box 13501 Research Triangle Park, North Carolina 27709.
http://www.fluoridealert.org/pesticides/fluorosilicates.nih.2001.pdf

Sulfentrazone - Herbicide - CAS No. 122836-35-5

A prenatal oral developmental toxicity study in the rat with dose levels at 25.0 or 50.0 mg/kg/day established a maternal NOEL of 25 mg/kg/day based on decreased body weight gain, increased spleen weight, and microscopic changes in the spleen, and a fetal NOEL of 10 mg/kg/day was based on fetal death, reduced body weights, and alterations in skeletal development at higher doses... Risk to infants and children was determined by use of developmental toxicity studies in rats and a two-generation reproduction study in rats. The oral developmental toxicity studies resulted in a maternal NOEL of 25 mg/kg/day based on decreased body weight gain, increased spleen weight, and microscopic changes in the spleen, and a fetal NOEL of 10 mg/kg/day based on fetal death, reduced body weights, and alterations in skeletal development at higher doses.
Ref: Federal Register: March 10, 1997. Sulfentrazone; Establishment of Tolerances. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/sulfentrazone.fr.mar10.1997.htm

-- 90-Day oral toxicity rodents (mice) - [870.3100] NOAEL = 60 mg/kg/day for males and 79.8 mg/kg/day for females LOAEL = 108.4 mg/ kg/day for males and 143.6 mg/kg/ day for females based on decreased body weights, body weight gains, red blood cells, hemoglobin, hematocrit, and severity of splenic micropathology (increased incidence and severity of extramedullary hematopoiesis)
-- 90-Day oral toxicity in nonrodents (dogs) - [870.3150] NOAEL = 28 mg/kg/day LOAEL = 57 mg/kg/ day for males and 73 mg/kg/day for females based on decreased body weights (7-10%) and body weight gains during first 5 weeks of study; decreased hemoglobin, hematocrit, mean cell volume, mean cell hemoglobin and mean cell hemoglobin concentration, and increased absolute liver weights and alkaline phosphatase levels, and microscopic changes in the liver and spleen (pigmented sinusoidal microphages in the liver, swollen centrilobular hepatocytes and pigmented reticuloendotheli al cells in the spleen)
-- Prenatal developmental in rodents (rats) - [870.3700] Maternal NOAEL = 25 mg/kg/day LOAEL = 50 mg/kg/ day based on increased relative splenic extramedullary hematopoiesis
-- Subchronic neurotoxicity screening battery - [870.6200] NOAEL = 30 mg/kg/day for males and 37 mg/kg/day for females LOAEL = 150 mg/kg/ day for males and 180 mg/kg/day for females based on increased incidence of clinical signs; decreased body weight, body weight gains, and food consumption in females; and increased motor activity in females. At 5,000 ppm, included increased mortality; decreased body weights, and body weight gains in males; decreased hindlimb grip strength and increased tail flick latency in males at week 8; distended bladders with red fluid and enlarged spleen. No evidence of neuropathology at 2,500 and 5,000 ppm.
Ref: Federal Register: September 24, 2003. Sulfentrazone; Pesticide Tolerances. Final Rule.
http://www.fluorideaction.org/pesticides/sulfentrazone.fr.sept24.03.htm

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

B6C3F1 mice (60/group/sex) received 0, 10, 100 or 1000 ppm mg kg transfluthrin (94.8-95%) pure in the diet for up to 104 weeks with 10/sex/dose killed after one yar. Two additional groups(10/sex) received 0 or 1000 ppm for 13 weeks... Serum cholesterol levels were significantly raised from 13 weeks at 1000 ppm (20% in males and 54% in females) and from 100 ppm from week 53 (approximately 11 - 30%) and at week 103 from 10 ppm in females (approximately 50 - 70%) and at 1000 ppm in males )~ 20%)... The incidences of hepatocellular carcinoma were within the historical control range for the laboratory (1 - 5 in females for studies using 50 animals), whereas the adenoma incidence of 13/50 exceeded the range (1 - 9). The low incidences of other tumours (haemangiosarcoma in the spleen, sarcoma of the subcutis and adenoma of the harderian gland) observed at the top dose in females were not statistically significant...
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.

Trifloxystrobin - Fungicide - CAS No. 141517-21-7

4. Subchronic toxicity. In subchronic studies, several mortality related changes were reported for the top dose in dogs (500 mg/kg) and rats (800 mg/kg). At these dose levels, excessive toxicity has resulted in body weight loss and mortality with the associated and non-specific changes in several organs (such as atrophy in the thymus, pancreas, bone marrow, lymph node, and spleen) which are not considered specific target organs for the test compound. In the dog, specific effects were limited to hepatocellular hypertrophy at 150 mg/kg and hyperplasia of the epithelium of the gall bladder at 500 mg/kg. Target organ effects in the rat were noted as hepatocellular hypertrophy (200 mg/kg) and the related liver weight increase (50 mg/kg). In the mouse, target organ effects included single cell necrosis (300 mg/kg) and hypertrophy (1,050 mg/ kg) in the liver and extramedullary hematopoiesis (300 mg/ kg) and hemosiderosis in the spleen (1,050 mg/kg). In general, definitive target organ toxicity, mostly in the liver, was seen at high feeding levels of over 100 mg/kg for an extended treatment period. At the lowest observed adverse effect level (LOAEL), no serious toxicity was observed other than mostly non-specific effects including a reduction in body weight and food consumption or liver hypertrophy. 5. Chronic toxicity. The liver appears to be the major primary target organ based on the chronic studies conducted in mice, rats, and dogs. It was identified as a target organ in both the mouse and the dog studies with trifloxystrobin. However, no liver effect was seen in the chronic rat study which produced the lowest NOAEL of 2.5 mg/kg based on reduced body weight gain and food consumption seen at higher dose levels.
Ref: Federal Register. November 14, 2001. [PF-1048; FRL-6806-6]
http://www.fluoridealert.org/pesticides/trifloxystrobin.fr.nov14.01.htm

Trifloxysulfuron-sodium - Herbicide - CAS No. 199119-58-9

-- Dogs were given trifloxysulfuron at doses of 0, 50, 200 or 500 mg/kg bw/day in gelatin capsules for 28 days. There were no mortalities, changes in food consumption, clinical signs of toxicity or effects on body weight gain. A white material in the faeces of animals at 500 mg/kg bw/day was confirmed by analysis to be the test material. Red blood cell count, haematocrit, haemoglobin, platelet counts and clotting times, plasma bilirubin, protein and albumin were lower and globulin and chloride were higher in both sexes at 500 mg/kg bw/day. Plasma bilirubin was also lower in females at 200 mg/kg bw/day and plasma potassium and calcium were lower in males at 500 mg/kg bw/day. Liver weights were higher in both sexes at 200 and 500 mg/kg bw/day. Thymus weights were marginally lower with one of two males and one of two females at 500 mg/kg bw/day having slight cortical atrophy in the thymus. Testes weight was lower in one of the two males at 500 mg/kg bw/day along with markedly reduced spermatogenesis and some single cell necrosis of tubular cells. This male also had slight follicular hypertrophy in the thyroid. Spleen weights were higher in females at 500 mg/kg bw/day with lymphoid hyperplasia observed in the spleen of males at 200 and 500 mg/kg bw/day and females at all doses. Pneumonia was observed in dogs at 500 mg/kg bw/day.
Ref: August 2002 - Evaluation of the new active Trifloxysulfuron-sodium in the product ENVOKE HERBICIDE. Public Release Summary. National Registration Authority for Agricultural and Veterinary Chemicals 2002 ISSN1443-1335.
http://www.fluoridealert.org/pesticides/trifloxysulfuron-s.eval.02.pdf