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

Ammonium fluosilicate- Insecticide, Miticide Wood Preservative, EPA List 3 Inert - CAS No. 16919-19-0

LD50 ranges of sodium, potassium, or ammonium fluorosilicates administered intragastrically in rats and mice were 89-128 and 45-64 mg fluoride ion/kg, respectively. Severe cornea damage was observed 3 hr after the administration of 50 mg of any of the salts into rabbits' eyes. Min toxic dose (intragastric) of fluorosilicic acid in rats was 8 mg/kg. Min toxic concn in 4 hr inhalation of the salt aerosols were 7.4-9.6 mg/cu m; nontoxic concn was 0.8 mg/cu m. Main toxic effects were decreased activities of cholinesterase and lactate dehydrogenase in blood serum. The intragastric effects of the fluorosilicates were similar to and additive with those of sodium fluoride. [Rumyantser GI et al; Oig Sanit (11): 80-2 (1988)]
Ref: TOXNET profile from Hazardous Substances Data Bank for AMMONIUM SILICOFLUORIDE.
http://www.fluoridealert.org/pesticides/ammonium.silicofluor.toxnet.htm

Chronic: Causes severe skin irritation and burns. Ingestion or inhalation may be harmful and possibly fatal depending on severity and length of over-exposure. Chronic over- exposure may cause fluorosis. Product may be absorbed through the skin and produce signs of fluorosis such as weight loss, brittleness of bones, anemia, weakness and stiffness of joints. Internal bleeding may develop. First aid procedures should be followed even in cases of suspected contact.
Ref: Ammonium fluorosilicate Material Safety Data Sheet from LCI, Ltd.
http://www.fluorideaction.org/pesticides/ammonium.fluosilicate.msds.htm

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

Increased relative liver weights, decreased red blood cell counts and decreased hematocrit and hemoglobin levels were observed in dogs orally administered benfluralin at a dose of 125 mg/kg/day for 2 years. The NOAEL was 25 mg/kg/day. Based on the NOAEL, EPA has established an oral RfD of 0.003 mg/kg/day. EPA believes that there is sufficient evidence for listing benfluralin on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available hematological toxicity data for this chemical.
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.

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

-- Target Organs: Lungs, blood, bones and teeth.
Ref: Material Safety Data Sheet for Boron Trifluoride (BF3). May 2001.
http://www.fluoridealert.org/pesticides/boron.trifluoride.msds.htm

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

The most susceptible species in long term studies was the mouse. A NOEL for butafenacil-allyl of 0.36 mg/kg bw/day was found for males in an 18 month study, essentially based on haematological effects mostly in males and liver toxicity in animals of both sexes. A rat 2-year study revealed a NOEL of 1.14 mg/kg bw/day for males, based on liver toxicity in animals of both sexes. A safety factor of 100 is considered appropriate for the ADI, due to the extensive toxicology database for butafenacil-allyl. This results in an ADI of 0.004 mg/kg bw/day (p 10).
Long-Term Studies. Mice received butafenacil in the diet at concentrations of 0, 1, 3, 10 and 60 ppm over 18 months. Haematological effects included lower mean values for erythrocyte count, haemoglobin concentration and haematocrit in males at 60 ppm at weeks 53 and 79, respectively, and for erythrocyte count, haemoglobin and haematocrit at week 79 in males at 10 ppm. Males also had slightly increased neutrophil and monocyte counts at 60 ppm, and a slight thrombocytosis. Mean absolute and relative liver weights were increased in both sexes at 60 ppm. The incidence of enlarged liver was increased in males at 60 ppm and in females at 10 and 60 ppm. Microscopic examination revealed an increased incidence of hepatocyte necrosis and hyperplasia of Kupffer cells in the liver of males at 10 and 60 ppm, and of females at 60 ppm. In addition, an increased incidence of lipofuscin deposition, and inflammatory cell infiltration was seen in males at 60 ppm. There was no treatment-related increase in the incidence of neoplasms at any dose. Butafenacil was not carcinogenic in mice. The NOEL was 3 ppm in males and 10 ppm in females, equivalent to 0.36 and 1.20 mg/kg bw/day for males and females, respectively (p7-8)....
Ref: Public Release Summary on Evaluation of the new active BUTAFENACIL in the products LOGRAN B-POWER HERBICIDE & TOUCHDOWN B-POWER HERBICIDE. National Registration Authority for Agricultural and Veterinary Chemicals. Australia. February 2002.
Also available at:
http://www.nra.gov.au/publications/prsbuta.pdf

Some excerpts from Table 3.--Toxicological Dose and Endpoints for Butafenacil - a summary of the toxicological endpoints used for human risk assessment Ref: Butafenacil; Pesticide Tolerance. Final Rule. Federal Register. September 19, 2003. http://www.fluorideaction.org/pesticides/butafenacil.fr.sept.19.2003.htm
-- Exposure Scenario -- Dose Used in Risk Assessment, UF -- Special FQPA SF* and Level of Concern for Risk Assessment	Study and Toxicological Effects
-- Chronic dietary (All populations) -- NOAEL= 1.2 mg/kg/day UF = 100 -- Chronic RfD = 0.012 mg/ kg/day. -- Special FQPA SF = 1 cPAD = chronic RfD -- Special FQPA SF = 0.012 mg/kg/day.	Mouse oncogenicity study. The LOAEL is 6.96 mg/kg/. day, based on enlarged livers with increased weights, and hepatic microscopic lesions including Kupffer cell hyperplasia, inflammatory cell infiltration, and single cell necrosis in both sexes and on deposits of lipofuscin in males
-- Short-term inhalation (1 to 30 days) -- Oral NOAEL = 18.8 mg/kg/ day -- Residential LOC for MOE = 100 -- Occupational = 100	90-day rat feeding study. The LOAEL for this study is 62.3 mg/kg/ day based on decreased hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular volume, increased red cell volume distribution width, and increased incidence of bone marrow hypercellularity
-- Short-term incidental oral (1 to 30 days) -- Intermediate-term incidental oral (1- 6 months) -- LOAEL = 18.8 mg/kg/day -- Residential LOC for MOE = 100 -- Occupational = NA	90-day rat feeding study. The LOAEL for this study is 62.3 mg/kg/ day, based on decreased hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular volume, increased red cell volume distribution width, and increased incidence of bone marrow hypercellularity
-- Short-term inhalation (1 to 30 days) -- Intermediate-term inhalation (1 to 6 months) -- Oral NOAEL = 18.8 mg/kg/day -- Residential LOC for MOE = 100 -- Occupational = 100	Same as above

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 (dietary) toxicity rodents (rat) - [870.3100]	NOAEL = 300 ppm (18.8/20.6 mg/kg/ day M/F). LOAEL = 1,000 ppm (62.3/69.3 mg/kg/ day M/F) based on decreased body weight gains, decreased hemoglobin, hematocrit, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), increased red cell volume, increased bone marrow hypercellularity; increased bilirubin and urobilinogen; increased alanine aminotransferase; hepatocyte necrosis; inflammatory liver cell infiltration
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
1-Year chronic oral (capsule) toxicity (dog) - [870.4100]	NOAEL = 500 mg/kg/day M/F LOAEL = 1,000 mg/kg/ day M/F, based on decreased body weight gain in males, decreased MCV, MCH, and mean corpuscular hemoglobin concentration (MCHC); increased thrombocytes and red cell volume distribution width; hepatic histopathology: glycogen disposition, inclusion bodies in cytoplasm, and pigment disposition in both sexes, and focal vaculolation in females
18-Month carcinogenicity dietary study (mouse) - [870.4200]	NOAEL = 10 ppm (1.17/1.20 mg/kg/day M/F) LOAEL = 60 ppm (6.96/ 6.59 mg/kg/day M/ F), based on enlarged livers with increased weights, and hepatic microscopic lesions including Kupffer cell hyperplasia, inflammatory cell infiltration, and single cell necrosis in both sexes and on deposits of lipofuscin in males No evidence of carcinogenicity
Mechanistic studies - [870.7485]	Effects on enzymes of cultured mouse, rat, and/or human hepatocytes involved with heme biosynthesis
Mechanistic studies - [870.7485]	Effects on liver microsomal and plasma protox activity and its metabolic conversion
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

-- Repeat-dose studies indicate that the primary targets for carfentrazone-ethyl toxicity are the liver, kidney, and the red blood cell forming system... Effects on the red blood cell forming system were seen in most studies. These effects included a reduction in the number of red cells in blood and an associated increase in the products of red blood cell degradation appearing in the urine and liver.
-- 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...
-- 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...
-- Short-Term Studies... In rats fed up to 20 000 ppm carfentrazone-ethyl in the diet for 90 days, abdominogenital staining and pink-brown discolouration of the cage-pan liner was observed at concentrations 4000 ppm. Body weight and food consumption were reduced in males at concentrations ¥ 8000 ppm and in females at concentrations ¥ 8000 and 4000 ppm respectively. Erythrocyte parameters (Hb, Hct, MCV, MCH) were reduced at concentrations ¥ 8000 ppm and platelets were increased in males at the same concentrations. Plasma ALT, AST, potassium, phosphorus and bilirubin were increased at concentrations ¥ 8000 ppm whereas glucose was reduced...
-- Short-Term Studies... Dogs given capsules containing carfentrazone-ethyl at doses up to 1000 mg/kg bw/day for 90 days exhibited subdued behaviour, salivation and vomiting at the highest dose. Mean corpuscular haemoglobin was reduced at doses ¥ 500 mg/kg bw/day and mean corpuscular volume was reduced in males at this dose. Red blood cell count was increased in males receiving the highest dose. Total urinary porphyrins were increased at doses ¥ 500 mg/kg bw/day and liver weight was increased in females at this dose....
-- Long-Term Studies. Mice fed carfentrazone-ethyl at concentrations of 0, 70, 700 or 7000 ppm for 80 weeks had increased mortality at concentrations ¥ 700 ppm. Body weights and body weight gains were reduced at 7000 ppm in females and in all treated males. Red blood cell count and haematocrit were reduced and mean corpuscular volume was increased in females at concentrations ¥ 70 ppm. Haemoglobin was reduced at concentrations ¥ 700 ppm and mean corpuscular volume and mean corpuscular haemoglobin concentration were increased in males at concentrations ¥ 70 ppm. Haemosiderosis, porphyrin deposits and treatment related histopathological changes were observed in males at concentrations ¥ 700 ppm and in females at the highest concentration. A NOEL was not established for this study, because reduced body weight gain was observed in males at the lowest concentration tested (70 ppm, equal to 10 mg/kg bw/day).
-- Long-Term Studies... In rats fed 0, 50, 200, 800 or 4000 ppm carfentrazone-ethyl for 52 or 104 weeks slight decreases in red blood cell counts in males and increases in mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration were observed at ¥ 200 ppm...
-- Long-Term Studies... In dogs given carfentrazone-ethyl in capsules at doses of 0, 50, 150, 500 or 10000 mg/kg bw/day for 52 weeks, increased urinary porphyrins were observed at doses ¥ 150 mg/kg bw/day. A slight reduction in mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration was observed in males at the same doses and an increase in liver to body weight ratio was observed in females at doses ¥ 500 mg/kg bw/day. The NOEL for this study was 50 mg/kg bw/day based on the slight increase in urinary porphyrins at 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

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

-- Carcinogenicity. In accordance with the EPA Proposed EPA Weight-of-the-Evidence Categories, August 1999, the Agency's Cancer Assessment Review Committee (CARC) classified clodinafop-propargyl as "likely to be carcinogenic to humans" by the oral route based on the occurrence of prostate tumors in male rats, ovarian tumors in female rats, and liver tumors in both sexes of mice, as well as blood vessel tumors in female mice. For the quantification of human cancer risk, the CARC recommended a linear low-dose extrapolation approach based on the most potent of these tumor types. This approach is supported by possible genotoxic potential and the lack of confirmation of the mode of action of clodinafop-propargyl. The most potent unit risk, Q1 * (mg/kg/day) -1 , of those calculated for clodinafop-propargyl is that for male mouse liver benign hepatoma and/or carcinoma combined tumor rates at 0.129 (mg/kg/day) -1 in human equivalents.
SUBCHRONIC AND CHRONIC TOXICITY
Ref: US EPA Pesticide Fact Sheet. Reason for Issuance: Conditional Registration. June 6, 2000. http://www.epa.gov/opprd001/factsheets/clodinafop.pdf

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

-- 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.
-- 21-day dermal (rabbit): Dermal Irritation NOEL 1000 mg/kg/day Systemic NOEL = 500 mg/kg/day Systemic LOEL = 1000 mg/kg/day based on decreased red cell count, hemoglobin and hematocrit, anisocytosis and macrocytosis of red cells for females.
-- 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.
Ref: USEPA. Pesticide Fact sheet. Cloransulam-methyl. Reason for Issuance: Conditional Registration Date Issued: October 29, 1997.
http://www.epa.gov/opprd001/factsheets/cloransulam.pdf

... 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.
http://www.fluoridealert.org/pesticides/gauntlet.herbicidemsds.2000.pdf.
Also available at http://www.cdms.net/ldat/mp48J001.pdf

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

-- Cyfluthrin. 28-Day oral toxicity NOAEL = 15.0 (males & females) based on minimal decrease in blood glucose. LOAEL = 50 based on, gait abnormalities, salivation, nervousness, decrease in body weight, food consumption, changes in hematological, clinical chem. & urinalysis parameters, increases in selected organ wts., cytoplasmic swelling of glandular epithelium of submaxillary gland, minimal degrees of fiber degeneration in sciatic nerve (# not reported) which disappeared after recovery period.
-- Cyfluthrin (93.8% a.i.). 4-Week inhalation toxicity study--rats. NOAEL = 0.00044 mg/L (0.12 mg/kg/day; males & females) LOAEL = 0.006 mg/L (1.6 mg/kg/day; males & females) based on decreases in body weight and body weight gain in males, hypothermia, reduction in leukocyte counts (F) and low serum protein.
Ref: Federal Register. September 27, 2002. Cyfluthrin; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/cyfluthrin.fr.sept.27.2002.htm

Groups of 18 rats (strain unspecified) of each sex received diets containing 0, 100, 300, or 1000 mg/kg cyfluthrin for one month, when 12 rats of each sex per group were sacrificed; the remainder were killed after one month of recovery on control diet... Total protein and blood glucose levels were significantly decreased in male rats given 300 mg/kg feed. No effects were seen on macroscopic examination... On the basis of the depressed blood glucose levels in male rats at 300 mg/kg feed, the NOEL was 100 mg/kg feed, equivalent to 5 mg/kg bw (Watanabe et al., 1982a)...
In separate studies, the NOEL in rats ranged from 5 mg/kg bw per day on the basis of depressed blood glucose levels to 20 mg/kg bw per day on the basis of mortality and decreased body-weight gain.
Ref: Toxicological evaluation of certain veterinary drug residues in food. 1997. WHO FOOD ADDITIVES SERIES 39.
http://www.fluoridealert.org/pesticides/cyfluthrin.who.tox.eval.97.htm

DFP: Diisopropyl fluorophosphate - Insecticide - CAS No. CAS No. 55-91-4

The study examined the relationship between inhibition of cholinesterase activity (CA) and thermoregulatory response in the rat following exposure to the organophosphate (OP), diisopropyl fluorophosphate (DFP). Male Long-Evans rats were injected with DFP dissolved in peanut oil in doses ranging from 0 to 1.5 mg/kg (s.c.). Colonic T(sub col) and tail skin temperature T(sub tail) were recorded at 0, 1, 2, and 3 hr post-injection. At 3 hr post-injection the rat was sacrificed and a blood sample was taken by cardiac puncture and analyzed for CA. There was a biphasic dose effect of DFP on T(sub col) with slight but significant elevation in T(sub col) in the dose range of 0.01 to 0.5 mg/kg and a significant depression in T(sub col) at doses of 1.0 and 1.5 mg/kg. There was a dose-dependent fall in CA with DFP administration in the erythrocyte, plasma, and whole blood fractions. Hypothermia was associated with 80 to 87% inhibition in CA, whereas the elevation in T(sub col) was associated with 20 to 70% [abstract truncated]
Ref: 1991 - Relationship between Cholinesterase Inhibition and Thermoregulation Following Exposure to Diisopropyl Fluorophosphate in the Rat; by Gordon CJ, Fogelson L, Richards J, Highfill J. Report No. NTIS/PB92-158658 from The National Technical Information Service.

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

-- One-year Study. A repeat-exposure study using Beagles (4/dose/sex) is available; it was GLP and OECD Annex V compliant. Animals were administered either vehicle or 2.5, 12.5 or 37.5/62.5 mg kg -1 d -1 of dichlofluanid (90 % purity) in capsule form for one year. The top dose was reduced at week 15 to 37.5 mg kg -1 d -1 because of excessive toxicity. As a NOEL could not be established with the initial dosing regime, a subsequent study was carried out in which 0 or 1.25 mg kg -1 d -1 dichlofluanid was used. Interim blood samples were taken at 13, 26, 39 and 52 week (terminal bleed); in addition samples were taken from some animals in the top-dose group at 14, 15 and 19 weeks... The haematology findings in males receiving 37.5 mg kg -1 d -1 from 6 months onwards were decreased numbers of erythrocytes (4 %), haemoglobin concentration (7.5 %) and haematocrit (7.4 %). Mild to moderate hepatic haemosiderin deposition was reported and was particularly extensive in two animals. None of these effects achieved statistical significance. However, as they were outside the range of supplied historical control data they were considered to be treatment related. The following data, in animals at the top dose, outside the range of supplied historical control data (¥¥¥¥¥2SD), except BUN, creatinine, and triglyceride levels in females. This clinical chemistry data refers to the first study and unless otherwise stated the data were collected at study termination. Increases in ALP (215 % and 18 % males and females respectively), AST (81 % males only*), ALT (595 % and 293 % males and females respectively) and gammaGT (360 % males only) levels were reported in animals 37.5 mg kg -1 d -1 . An increase in ALT levels (350 % males only) at 12.5 mg kg -1 d -1 was also reported. Serum concentrations of cholesterol were elevated in animals receiving 12.5 mg kg -1 d -1 (20 % and 23 % males and females respectively) and 37.5 mg kg -1 d -1 (132 %* and 89 % males and females respectively). The serum concentration of triglycerides were elevated in females only (63 % and 59 % at 12.5 mg kg -1 d -1 and 37.5 mg kg -1 d -1 respectively). Elevated BUN (males only 114 %) and creatanine levels were reported (77 %* and 22 %* males and females respectively) at 37.5 mg kg -1 d -1 . One male receiving 12.5 mg kg -1 d -1 was also reported to have elevated BUN and creatanine levels (*statistically significant)...
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:
http://www.pesticides.gov.uk/citizen/Evaluations/206_dichlofluanid.pdf

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).
There were no statistically significant exposure-related effects on survival or body weight gain. Clinical signs noted at a higher incidence, when summed across exposure periods, in both sexes exposed to 25,000 ppm HCFC- 152a included ocular/nasal discharges and wet/stained perinea. The 25,000-ppm females also exhibited significantly elevated incidences of stained body/face. These observations suggested chronic low-level irritation or stress in the animals exposed to HCFC-152a at the highest exposure level but were not observed consistently across exposure periods or exposure levels nor supported by histopathology. Although several statistically significant hematological changes were noted, none were considered to be toxicologically significant. For example, females exposed to 10,000 and 20,000 ppm HCFC-152a exhibited increased mean corpuscular volumes, and all exposed females exhibited increased serum bilirubin; increased hematocrits and mean corpuscular volumes were seen in males exposed to 10,000 and 25,000 ppm HCFC-152a. However, hematopoietic tissues and red blood cell counts were normal in these animals, which does not support the hemolytic effect that is suggested by the changes listed above. Statistically significant reductions in eosinophils and monocytes also were observed in some of the treated groups...
Ref: US EPA IRIS for 1,1-Difluoroethane.
http://www.fluorideaction.org/pesticides/1,1-difluoroethane.epa.iris.htm

Definitions:
• Eosinophil - A white blood cell that contains granules filled with chemicals damaging to parasites, and enzymes that damp down inflammatory reactions.

• MONOCYTE - a large white blood cell that plays a role in immune defense by acting as a scavenger that destroys invading microorganisms. Monocytes circulate in the bloodstream; when they migrate to the tissues, they mature into macrophages.

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 1000 ppm 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.

Abstract: The 18-year-old white male driver and 17-year-old white male passenger of an automobile were killed when their vehicle crossed the median of a 4-lane highway and collided with a minivan. A can of airbrush propellant was found in the automobile of the deceased. The only drug detected during initial toxicological analyses was 130 mg/L ethanol in the blood of the driver. When performing ethanol analysis by headspace gas chromatography, an unidentified peak was observed in the blood of both deceased. This peak was identified as difuoroethane (Freon 152), the propellant in the aerosol can found in the automobile. The concentrations of difluoroethane in the blood of the driver and passenger were 78 mg/L and 35 mg/L, respectively. Based on a literature search we believe that this is the first report of the quantitation of difluoroethane in biological samples.
Publication Types: • Case Reports
Ref: Two traffic fatalities related to the use of difluoroethane. Broussard LA, Brustowicz T, Pittman T, Atkins KD, Presley L. J Forensic Sci. 1997 Nov;42(6):1186-7.

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

-- TSCA Test Submissions: A subchronic inhalation toxicity study was conducted with groups of male (35) and female (35) albino rats (strain not reported) receiving whole body exposure to dichloromonofluoromethane at a nominal concentration of 0, 50, 150 or 500ppm in a dynamic air flow chamber for 6 hours per day, five days per week for approximately 90 days. On day 45 and day 90, 5 animals per sex and 20 animals per sex, respectively were sacrificed. The remaining animals were observed for an additional 30 days and then sacrificed. Four high dose males were found dead during the exposure period and one female and six males from the high dose group were found dead during the recovery period. High dose rats were observed to have statistically significant (p < 0.01) lower body weights than controls during the exposure period, but were comparable after the 30 day recovery period. Hematology, clinical chemistry and urine analysis values were similar between all dosed animals and control animals, with the exception of a slightly higher total blood leukocytes counts and elevated mean SAP and SGPT values for high dose animals at approximately 45, 90 and 120 days. A dose related increase in urine fluoride levels was also observed. Histopathology evaluation of treated animals revealed portal cirrhosis of the liver, interstitial edema of the pancreas and degeneration of the seminiferous epithelium. Three cases of leukemia were observed in high dose male rats. [Industrial Bio-Test Laboratories; Subacute Inhalation Toxicity Study with Genetron 21 in Albino Rats, (1979), EPA Document No. FYI-OTS-0779-0045, Fiche No. OTS0000045-0 ] **UNREVIEWED**
Ref: TOXNET profile from Hazardous Substances Data Base for DICHLOROFLUOROMETHANE
http://www.fluoridealert.org/pesticides/dichlorofluoromethan.toxnet.htm

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

-- 90-Day oral toxicity rodents. NOAEL < 8 mg/kg/day LOAEL = 8 mg/kg/day based on increased methemoglobinemia, and signs of hemolytic anemia, erythrocyte destruction in the spleen and liver and regeneration of erythrocytes in the bone marrow.
-- 90-Day oral toxicity in nonrodents. NOAEL = 2 mg/kg/day LOAEL = 6.24 mg/kg/day based on methemoglobinemia.
-- 21/28-Day dermal toxicity NOAEL = 500 mg/kg/day LOAEL = 1,000 mg/kg/day based on methemoglobinemia (limit dose).
-- Reproduction and fertility effects. Parental/Systemic NOAEL < 36 mg/kg/day (LDT) LOAEL = 36 mg/kg/day based on dose-related decreased hematocrit, hemoglobin concentration, red blood cell count and an increase in percent methemoglobin, changes in cell morphology and brown pigment in Kupffer cells. Reproductive NOAEL> 4254 mg/kg/day (HDT) LOAEL was not established. Offspring NOAEL = 427 mg/kg/day LOAEL = 4254 mg/kg/day based on Significant decrease in F-1 pup weights on day 4, 8 and 21 of lactation.
-- Chronic toxicity dogs NOAEL = 2 mg/kg/day LOAEL = 10 mg/kg/day based on methemoglobinemia and sulfhemoglobinemia.
-- Carcinogenicity mice NOAEL = 2.4 mg/kg/day LOAEL = 12 mg/kg/day based on increased methemoglobin and sulfhemoglobin levels. No evidence of carcinogenicity
-- Special studies. In acute oral toxicity study in rats CPA at 62 mg/kg caused significant increase in methemoglobinemia while CPU at 200 mg/kg did not cause methemoglobinemia.
Ref: Federal Register: September 19, 2002. Diflubenzuron; Pesticide Tolerances. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/diflubenzuron.fr.sept19.02.htm

In a 2-year study in which beagle dogs received diflubenzuron daily in gelatin capsules, the LOAEL for increases in sulfhemoglobin and methemoglobin was 10 mg/kg/day and the NOAEL was 2 mg/kg/day. EPA has derived an oral RfD of 0.02 mg/kg/day for this chemical from this study. Similar effects were noted in two separate 2-year rat feeding studies (the LOAEL was 7.8 to 8 mg/kg/day; the NOAEL was 2 mg/kg/day), and in a lifetime oral study in mice (the LOAEL was 12 mg/kg/day; the NOAEL was 2.4 mg/kg/day). EPA believes that there is sufficient evidence for listing diflubenzuron on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available hematological toxicity data. Measured aquatic acute toxicity data for diflubenzuron include a 48-hour LC 50 of 4.55 ppb for daphnids. EPA believes that there is sufficient evidence for listing diflubenzuron on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(C) based on the environmental toxicity data for this chemical.
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.

Chronic dietary (all populations) - Chronic toxicity study (dog): LOAEL = 10 mg/kg/day based on methemoglobinemia and sulfhemoglobinemia
Ref: Federal Register. February 15, 2002. Diflubenzuron; Pesticide Tolerance in or on Pear at 0.50 ppm. Final Rule.
http://www.fluoridealert.org/pesticides/diflubenzron.fr.feb.15.2002.htm

-- To assess subacute dermal toxicity, diflubenzuron was applied to the backs of male and female CD rats for 3 weeks at dose levels of 20, 500, and 1,000 mg/kg/day. Hematology evaluation showed reductions in red blood cell (RBC), hemoglobin (Hgb) and hematocrit values at 500 and 1,000 mg/kg/day. An increased incidence of polychromasia, hypochromasia, and anisocytosis was seen at 500 and 1,000 mg/kg/day. An increase in methemoglobin and sulfhemoglobin values was seen at 1,000 mg/kg/day. The NOAEL for systemic toxicity was 20 mg/kg/day. Also, a dermal absorption factor of 0.5%, for systemic absorption, was derived from a study where rats were dosed with either 0.005 or 0.05 mg/cm\2\ of (\14\C) diflubenzuron technical. This value can be used for converting dermal exposure to oral equivalents.
-- Chronic toxicity. Diflubenzuron was given by capsule to male and female Beagle dogs for 1 year at dose levels of 0, 2, 10, 50, and 250 mg/kg/day. Body weight (bwt) gain was slightly reduced in females at 250 mg/kg/day. Absolute liver and spleen weights were increased in males given 50 and 250 mg/kg/day. A reduction in hemoglobin and mean corpuscular hemoglobin concentration, with an elevation in reticulocyte count, was seen at 50 and 250 mg/kg/day. Methemoglobin and sulfhemoglobin values were increased at doses of 10 mg/kg/day and greater. Histopathological findings were limited to pigmented macrophages and Kupffer cells in the liver at doses of 50 and 250 mg/ kg/day. The NOAEL for chronic toxicity in dogs was 2 mg/kg/day.
-- Diflubenzuron was fed to male and female Sprague Dawley rats for 2 years at dose levels of 0, 156, 625, 2,500, and 10,000 ppm. Methemoglobin values were elevated in female rats at all dose levels and in male rats at the two highest dose levels. Sulfhemoglobin was elevated in females, only, at dose levels of 2,500 and 10,000 ppm. Mean corpuscular volume (MCV) and reticulocyte counts were increased in high dose females... In another study diflubenzuron was administered to male and female CD rats for 2 years at dose levels of 0, 10, 20, 40, and 160 ppm. Elevated methemoglobin levels were seen in high dose males and females. No additional effects, including carcinogenic findings, were observed. The NOAEL for chronic toxicity in rats was 40 ppm (2 mg/kg/ day).
-- 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).
-- Diflubenzuron was fed to male and female Sprague Dawley rats for 2 years at dose levels of 0, 156, 625, 2,500, and 10,000 ppm. Methemoglobin values were elevated in female rats at all dose levels and in male rats at the two highest dose levels. Blood sulfhemoglobin was elevated in females, only, at dose levels of 2,500, and 10,000 ppm. MCV and reticulocyte counts were increased in high dose females. Spleen and liver weights were elevated at the two highest doses. Histopathological examination demonstrated an increase in hemosiderosis of the liver and spleen, bone marrow and erythroid hyperplasia, and areas of cellular alteration in the liver. There was no increase in tumor formation. In another study, diflubenzuron was administered to male and female CD rats for 2 years at dose levels of 0, 10, 20, 40, and 160 ppm. Elevated methemoglobin levels were seen in high dose males and females. No additional effects, including carcinogenic findings, were observed.
-- In single dose treatments, after 7 days, 20% and 3% of the applied dose 5 and 100 mg/kg, respectively, were excreted in urine, while 79% and 98% of the applied dose 5 and 100 mg/ kg, respectively, were eliminated in the feces. Very little bioaccumulation in the tissues was observed. In the feces, only unchanged parent compound was detected. Several metabolites were observed in the urine which are, among others, 2,6-diflurobenzoic acid (DFBA), 2,6-difluorophippuric acid, 2,6-difluorobenzamide (DFBAM), and 2-hydroxydiflubenzuron (2-HDFB).
-- 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...
-- 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

Abstract: Five benzoylphenylurea insecticides were administered to male Wistar rats for 28 days at oral doses of 100 mg kg-1 each. Elevation of methaemoglobin was found only in the diflubenzuron- and triflumuron treated groups. The number of reticulocytes was increased in all of the treated groups.
Ref: J Appl Toxicol. 1993 Jan-Feb;13(1):67-8. Comparative study on the effects of five benzoylphenylurea insecticides on haematological parameters in rats. Tasheva M, Hristeva V. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8440876&dopt=Abstract

"Diflubenzuron causes methaemoglobinaemia and sulfhaemo- globinaemia. Dose-related methaemoglobinaemia has been demonstrated after oral, dermal or inhalatory exposure to diflubenzuron in various species. This effect is the most sensitive toxicological end-point in experimental animals. The NOEL based on methaemoglobin formation is 2 mg/kg body weight per day in rats and dogs and 2.4 mg/kg body weight per day in mice. In long-term toxicity studies with mice and rats, treatment-related changes were principally associated with oxidation of haemoglobin or with hepatocyte changes... It is attributable to the metabolite, 4-chloroaniline, which is known to induce methaemoglobin formation in several animal species and in humans."
Ref: ENVIRONMENTAL HEALTH CRITERIA 184: International Programme on Chemical Safety http://www.inchem.org/documents/ehc/ehc/ehc184.htm

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

1-year oral toxicity study in dogs. NOAEL = 4.0 mg/kg/day. LOAEL = 20 mg/kg/day based on altered red cell morphology and urinary bilirubin.
Ref: Federal Register: August 8, 2001. Ethalfluralin; Pesticide Tolerances for Emergency Exemptions. Final Rule.
http://www.fluoridealert.org/pesticides/ethalfluralin.fr.aug8.2001.htm