Eye - Adverse Effects
Fluorinated and Fluoride Pesticides
 
 

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

-- Food and Agricultural Organization of the United Nations


Three rare eye disorders are noted below. They are:

Microphthalmia
- small eye syndrome. Microphthalmia is a disorder in which one or both eyes are abnormally small;
Anophthalmia
is the absence of one or both eyes. These rare disorders develop during pregnancy and can be associated with other birth defects;
Coloboma - A defect of the iris caused by a failure of the eyeball to fuse properly during fetal development.

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

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

-- Acute Toxicity: Sodium acifluorfen has been placed in Acute Toxicity Category I for acute eye irritation and in Category II for acute dermal irritation.
Ref: April 4, 2002. Overview of Sodium Acifluorfen Risk Assessment. USEPA. http://www.fluorideaction.org/pesticides/acifluorfen.na.epa.apr.02.pdf

A developmental toxicity study in rats found qualitative evidence of increased susceptibility of offspring because developmental toxicity (increased resorptions, reduced fetal weights, slightly dilated lateral ventricles of the brain, hemorrhage in the eyeball, slight dilation of the renal pelvis, hemorrhage in peritoneal cavity and subcutaneous spaces, and changes in ossification)
Ref: January 15, 2002. MEMORANDUM. SUBJECT: SODIUM ACIFLUORFEN. HED Chapter for the Reregistration Eligibility Decision Document. http://www.fluorideaction.org/pesticides/acifluorfen.na.a.red.jan.02.pdf

Severe eye irritant; moderate skin irritant (rabbit). /Acifluorfen/ [Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994]
Ref: TOXNET profile from Hazardous Substances Data Base for ACIFLUORFEN-SODIUM..

http://www.fluoridealert.org/pesticides/acifluorfen.na.toxnet.hsdb.htm

Acifluorfen is very toxic and is labeled with a DANGER signal word due to its potential to cause serious eye injury.
Ref: Pesticide Information Profile. Extoxnet from Cornell Univeristy.
http://www.fluoridealert.org/pesticides/acifluorfen.extoxnet.htm

Benzotrifluoride - Insecticide - CAS No. 98-08-8

TARGET ORGANS: Central Nervous System, Eyes, Skin, Respiratory Tract.
Ref: BENZOTRIFLUORIDE Material Safety Data Sheet. OxyChem. Issue Date: 07-08-98

http://www.oxychem.com/products/msds/m7644.pdf

SYMPTOMS: This comound is extremely destructive to the mucous membranes, upper respiratory tract, skin and eyes. Inhalation may be fatal as a result of spasm, inflammation and edema of the larynx and bronchi; chemical pneumonitis and pulmonary edema. Other symptoms include a burning sensation, coughing, wheezing, laryngitis, shortness of breath; headache, nausea and vomiting.
Ref: 1987 Fact Sheet by National Toxicology Program.

http://www.fluoridealert.org/pesticides/benzotrifluoride.1987.ntp.htm

Beta-cyfluthrin - Insecticide - CAS No. 68359-37-5

-- Beta-cyfluthrin. 28-Day dog feeding study. NOAEL = 2.0 (both sexes) LOAEL = 8.0 based on impaired movement and conjunctival irritation.
Ref: Federal Register. September 27, 2002. Cyfluthrin; Pesticide Tolerance. Final Rule. http://www.fluoridealert.org/pesticides/cyfluthrin.fr.sept.27.2002.htm

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

-- Boron trifluoride is a colorless gas that is corrosive to tissues due to its rapid hydrolysis to hydrofluoric acid and boric acid. The principal acute effect in animals is irritation of the mucous membranes of the respiratory tract and eyes; post mortem examination also revealed pneumonia and degenerative changes in renal tubules.
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.

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

Chlorodifluoromethane causes malformations of the eyes of fetal rats, but has no reproductive effect in male rats and does not cause prenatal toxicity in rabbits following exposure by inhalation.
Ref: 5. Summary of Data Reported and Evaluation. International Agency for Research on Cancer IARC. 1986

http://www.fluorideaction.org/pesticides/chlorodifluoromethane.iarc.htm

Chlorodifluoromethane (FC-22) was evaluated for embyotoxicity and teratogenicity in groups of 40 pregnant Charles River rats exposed to the test substance by inhalation at concentrations of 0, 0.05, 0.10, and 2.00% on days 6-15 of gestation. No clinical signs of toxicity were observed in maternal animals. The number of implantations, early and late resorptions, and number of live fetuses per litter were unaffected. There was a sporadic appearance of major malformations of the eye in all test groups. The increased incidence of eye defects was not statistically significant. Authors believe that the test substance may have interacted with the genetic make-up of affected fetuses and caused the increased expressivity of a mutant gene. The authors considered the test substance to be a mutagen under the conditions of this study.
Ref: 1992 - INITIAL SUBMISSION: EMBRYOTOXIC AND TERATOGENIC STUDIES IN RATS WITH INHALED CHLORODIFLUOROMETHANE WITH COVER LETTER DATED 06-15-92 AND ATTACHMENTS. HASKELL LABORATORY. Report Nos. NTIS/OTS0540606 and EPA/OTS; Doc #88-920004258.

Palmer et al. (1978a) conducted a large developmental study in an attempt to elucidate the role of CFC-22 exposure in the eye lesion seen in the previous studies (see Culik et al., 1977, and Culik and Crowe, 1978, in the Additional Studies/Comments section). In this study, an experimental design was used in which 34 control pregnant rats were used, and 22/group were exposed to 100, 1000, or 50,000 ppm of CFC-22 (354, 3,540, or 176,800 mg/cu.m, respectively) for 6 hours/day on gestation days 6-15. This protocol was repeated 19 times so that more than 6000 control fetuses and 4000 fetuses from each exposed group were thoroughly examined for the eye defect... The eye abnormalities (small or missing eye) were noted again in all exposure groups, but statistical significance for these effects was achieved only in the 50,000-ppm group. The combined incidences of microphthalmia and anophthalmia were 3/607, 5/393, 3/390, and 10/383 in the control, 100, 1000, and 50,000-ppm groups, respectively. Additional data on the control incidence of the eye effects during 10 years after the Palmer et al. (1978a) study was conducted are presented in European Chemical Industry Ecology and Toxicology Center (ECETOC) (1989). The data were analyzed in blocks of 19 studies, and the control incidence in the first six blocks was similar to the controls in the Palmer study, while in later studies, the control incidence increased (0.4-2.4% in the last four blocks) and, in one experiment, was similar to the incidence found in the high-dose group in the Palmer study (2.6%). The incidence of the eye abnormality in the high-concentration group in the Palmer et al. (1978a) study is significantly increased compared with the overall controls in the studies conducted in the 10-year period after the study (ECETOC, 1989), adding strength to the interpretation that this is an adverse, treatment-related effect. This study identifies a LOAEL for maternal weight, fetal weight, and fetal abnormalities at 50,000 ppm. The LOAEL(HEC) is 176,800 mg/cu.m for the fetal effects (no duration adjustment is applied) and 44,200 mg/cu.m for the maternal toxicity (exposure is adjusted for duration).
Ref: US EPA IRIS for Chlorodifluoromethane.
http://www.fluoridealert.org/pesticides/chlorodifluoromethane.iris.htm

Teratogenicity was evaluated in 4 groups of 19 pregnant CD female rats receiving Arcton 22 via inhalation at concentration levels of 0, 100, 1,000 and 50,000 ppm for 6 hours per day on gestation days 6 through 15. There were no treatment-related effects in appearance, behavior, mortality, or pregnancy rate. At 50,000 ppm maternal weight gain was slightly lower than the control. There were no effects on body weight at 100 or 1,000 ppm. In all test groups litter size, post-implantation loss, litter wight, and mean fetal weight were similar to the control. At 50,000, there was an increased incidence of anophthalmic fetuses.
Ref: 1989 -  EFFECT OF ACRTON 22 ON PREGNANT RATS: RELATIONSHIP TO ANOPHTHALMIA AND MICROPHTHALMIA WITH ATTACHMENTS AND COVER LETTER DATED 07-05-89. Report Nos. NTIS/OTS0520413 and EPA/OTS; Doc #87-890000011

Anophthalmic definition: Absence of an eye(s).  It can be a congenital (born without) or an acquired condition (surgically removed).

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

Rat developmental studies via inhalation. In the first two studies, pregnant female rats at day 0 gestation were exposed head-only to cyfluthrin concentrations of 0, 1.1, 4.7 or 23.7 mg/m3/ day (milligrams/per cubic meter/day) for 6 hours/day on gestation days 6 through 15. In the second study, the dams were exposed to analytical concentrations of 0, 0.09, 0.25, 0.59 or 4.2 mg/m3 of the test material. The dams were sacrificed on day 20 and their pups removed by caesarian section. The maternal NOEL was 1.1 mg/ m3 and the maternal LOEL was 4.7 mg/m3 (reduced motility, dyspnea, piloerection, ungroomed coats and eye irritation. The developmental NOEL was 0.59 mg/m3 and the developmental LOEL was 1.1 mg/m3 (increases in the incidence of runts and skeletal anomalies in the sternum (1.1 mg/m3 and above); increases in post-implantation losses and decreases in pup weights (4.7 mg/m3 and above) and increased incidences of late embryonic deaths, in skeletal anomalies in the extremities, pelvis and skull and in microphthalmia [abnormal smallness of the eye] (23.7 mg/m3). The study was graded core minimum.
Ref: Federal Register: November 26, 1997. Cyfluthrin; Pesticide Tolerances. Final Rule.

http://www.fluoridealert.org/pesticides/cyfluthrin.fr.nov.26.1997.htm

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

Based on the findings of acute toxicology studies with two similar products, and by extrapolation from the characteristics of the individual constituents in the product, it is expected that Barnstorm Herbicide would be of low acute oral, dermal and inhalational toxicity. It is likely to be a slight skin irritant and a severe eye irritant, but not to be a skin sensitiser (page 5). ... Barnstorm Herbicide is expected to be of low oral, dermal and inhalational toxicity. It is expected to be a severe eye, and slight skin irritant, but not a skin sensitiser (page 9).
... Risks to workers during use. The main acute risks arising from exposure to Barnstorm Herbicide are slight skin irritation and severe eye irritation. Mixer/loaders may be exposed to the product by inhalation or by skin and ocular contact. The main risk during this activity is skin and eye and respiratory tract irritancy (page 17). ...Eye protection is indicated for handling undiluted product due to the potential for severe acute eye irritation (page 18). ... SAFETY DIRECTIONSWill damage the eyes (page 35).
Ref: July 2005 - Evaluation of the new active Cyhalofop-Butyl in the product Barnstorm Herbicide. Australian Pesticides and Veterinary Medicines Authority (APVMA). Canberra, Australia.
http://www.fluorideaction.org/pesticides/cyhalofop.butyl.aust.2005.pdf

Cyhalothrin - Acaricide, Insecticide - CAS No. 68085-85-8

The physical and behavioral effects of cyhalothrin were studied in rats. Pregnant Wistar rats were administered 0 or 0.018% cyhalothrin topically throughout pregnancy. After delivery the neonates were monitored for development of fur, testes descent, and ear, eye, and vaginal opening... The authors conclude that prenatal exposure to cyhalothrin delays development of fur, eye and ear opening, and testes descent and affects motivational behavior. The delays induced in fur development and eye and ear opening suggest that cyhalothrin interferes with maternal or neonatal epidermal growth factor activity. The delay in testes descent suggests that prenatal cyhalothrin exposure induces changes in male sexual development. [da Silva Gomes M et al; Vet Human Toxicol 33 (4): 315-7 (1991)]
Ref: TOXNET profile from Hazardous Substances Data Base for Cyhalothrin.
http://www.fluoridealert.org/pesticides/cyhalothrin.toxnet.hsdb.htm

Cyhalothrin, lambda - Insecticide - CAS No. 91465-08-6

21-Day inhalation toxicity - rat. 41387702. NOAEL: 0.08 mg/kg/day. LOAEL: 0.90 mg/kg/day. clinical signs of neurotoxicity, decreased body weight gains, increased incidence of punctuate foci in cornea, slight reductions in cholesterol in females, slight changes in selected urinalysis parameters
Ref: Federal Register: September 27, 2002. Lambda-cyhalothrin; Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/lambda.cyhalot.fr.sept27.02.htm

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

-- Combined Chronic/ carcinogenicity (rats). NOAEL is 200 ppm (equivalent to 7.32/8.92mg/ kg/day in males/females). LOAEL is 1,000 ppm (equivalent to 36.5/44.1mg/ kg/day in males/females) based on decreased body weights and body weight gains, and increased incidences of keratitis* in males and striated muscle fiber atrophy in females. At the high dose there was an incidence (12%)of nasolacrimal duct** squamous cell carcinomas slightly outside the historical control range (0-10%) in male rats. A correlation between the incidence of inflammation and the fluctuating incidence of nasal tumors was made across dose groups. EPA did not consider the nasolacrimal duct tumors to be treatment-related. Female rats had a significant increasing trend in nasolacrimal duct squamous cell carcinomas at < 0.05, and at the high dose was slightly above the historical control mean (0.8%) and range (0-4%). EPA considered the nasolacrimal duct squamous cell carcinomas to be possibly treatment related, but that a clear association with treatment could not be made.
Ref: August 31, 2005. Flonicamid; Pesticide Tolerance. Final Rule. Federal Register.
http://www.fluoridealert.org/pesticides/
flonicamid.fr.aug.31.2005.html

Definitions:
* Keratitis: A term used to define a wide variety of corneal infections, irritations, and inflammations
** The
nasolacrimal duct carries tears from the lacrimal sac into the nasal cavity.

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

-- Fluazifop-butyl (CAS # 69806-50-4) was evaluated for subchronic oral toxicity in beagle dogs (4/sex/group) administered doses of 0 (vehicle control, corn oil), 5, 25 and 250 mg/kg/day in gelatin capsules for 13 weeks. Severe corneal ulceration, requiring humane sacrifice of 2 males and 1 female of a 250 mg/kg/day dosage during Week 4, prompted adjustment of this regimen to 125 mg/kg/day for the remainder of study. Prior to sacrifice, these dogs also exhibited progressive conjunctivitis and photophobia, and all lost weight... Histopathological evaluation confirmed treatment-related lesions of the eyes, liver, testes and gastrointestinal tract. [ICI AMERS INC; Butyl 2-(4-(5-trifluoromethyl-2-pyridyloxy)phenoxy) propionate: 13-Week Oral Toxicity Study in Beagle Dogs; 04/24/80; EPA Doc No. 88-920006846; Fiche No. OTS0543851]
Ref: TOXNET profile from Hazardous Substances Data Bank for FLUAZIFOP-BUTYL.
http://www.fluoridealert.org/pesticides/fluazifop-butyl.toxnet.hsdb.htm

**411-083 069476 Virgo, D. M., "Fluazifop-butyl: 55 week oral toxicity study in beagle dogs," Life Science Research, Stock, Essex, England, 10/15/82. LSR Report No. 81/ILK019/620. Six dogs/sex/group were dosed for 55 weeks with Fluazifop-butyl, 99.6% purity, by gelatin capsules at dose levels of 0, 5, 25, and 125 mg/kg/day in a chronic study. Test article within capsules was dissolved in 0.4 ml/kg corn oil vehicle. NOEL = 5 mg/kg/day... All other noteworthy findings were limited to the high dose group, as follows... Eyes of eight high dose dogs had cataracts, usually accompanied by miliary ("seed-like" appearance) vacuolation of the lens... Possible adverse effects (many-faceted toxicity, including mortalities, at 125 mg/kg/day). Acceptable. Aldous, 5/20/02.
Ref: May 20, 2002. SUMMARY OF TOXICOLOGY DATA FLUAZIFOP-P-BUTYL. California EPA. Department of Pesticide Regulation. Medical Toxicology Branch.

http://www.fluoridealert.org/pesticides/fluazifop-p-butyl.caepa.02.pdf

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

-- 018 994244: Tesh, J. M., Ross, F. W. and Tesh, S. A. "PP009: Effects of Oral Administration upon Pregnancy in the Rabbit, Final report". Life Science Research report No. 80/ILK 027/498 [November 28, 1980]. PP009, purity 94.8%, administered via gavage at concentrations of 10, 30 or 90 mg/kg/day to 20-24 artificially inseminated female New Zealand rabbits during gestation days 6 through 28. Adverse effects: increased incidence of cloudy eyes (12.7%), small fetuses, delayed ossification and enlarged anterior and posterior fontanelle. Maternal NOEL = >90 mg/kg/day (no toxicity). UNACCEPTABLE (No MTD, too few pregnant dams at scheduled sacrifice). (C. Aldous, 8/27/85).
-- ONCOGENICITY, MOUSE [OR HAMSTER] 411-125 180756 Rattray, N. J., “Fluazifop-p-butyl: 80 week carcinogenicity study in hamsters,” Central Toxicology Laboratory (CTL), Alderley Park Macclesfield, 2/1/01. Lab Study ID: Syngenta No.1606-01. Golden Syrian hamsters, 51/sex/group, were dosed in diet with 0, 0, 200, 750, or 3000 ppm fluazifop-p-butyl (91.6%) for 81-83 weeks. The dual control groups were treated identically. An additional 12/sex/group (same doses) were allocated for 1-yr sacrifice (for hematology only). Estimated achieved doses were 12.5, 47, and 194 mg/kg/day (M) and 12.1, 46, and 181 mg/kg/day (F). No NOEL was established... Findings at the higher two dose levels only included decreased testes weights, reduced spermatozoa counts in epididymides and
increased cataract development in males...
Ref: May 20, 2002. SUMMARY OF TOXICOLOGY DATA FLUAZIFOP-P-BUTYL. California EPA. Department of Pesticide Regulation. Medical Toxicology Branch.

http://www.fluoridealert.org/pesticides/fluazifop-p-butyl.caepa.02.pdf

4.2.3.8 Fluazifop-P-butyl - Rabbit In a developmental toxicity study [MRID 46082904] [fluazifop-p-butyl (90.1% a.i., batch/lot # P12)] was administered to [(20 females) New Zealand White] rabbits/group by gavage in corn oil vehicle [1 ml/kg] at dose levels of 0, 2, 10 or 50 mg a.i./kg bw/day from days 8 through 20 of gestation. Day sperm was found was designated as day 1. On day 30 of gestation, dams were killed and the uterine contents examined for live and dead fetuses. Fetuses were weighed, examined for external and visceral abnormalities, sexed, eviscerated and stained for skeletal examination. ... Treatment related effects on development were seen in the 50 mg/kg/day group only. Statistically significant extra 13 th rib and delayed ossification was seen in sternebrae 2 and 5. An increase in partially ossified 5 sternebrae was seen at 10 mg/kg/day, but the litter incidence was not increased. A nominal increase in malformations were seen at 50 mg/kg/day, such as acephaly [1 fetus/1 litter], cebocephaly [1 fetus/1 litter], cleft palate [1 fetus/1 litter], microphthalmia [1 fetus/1 litter], gastroschisis [1 fetus/1 litter], and multiple anomalies in 1 fetus/1 litter. None were duplicated and all could have occurred 1 to 3 times in the same litter, with 0 in control. Since individual animal data was not submitted, this incidence in litters could not be verified. For developmental toxicity, the NOAEL is 10 mg/kg/day and the LOAEL is 50 mg/kg/day based on increased 13 th rib and increased incidence of delayed ossification of sternebrae 2 and 5. (page 39).
Ref: December 10, 2004. US EPA> Fluazifop-P-butyl: Revised HED Chapter of the Tolerance Reassessment Eligibility Decision (TRED) Document. EPA Docket number: OPP-2004-0347-0003
http://www.fluorideaction.org/pesticides/f-p-b.opp-2004-0347-0003.pdf

Definitions:

Acephaly: literally means absence of the head. The acephalic fetus is a parasitic twin attached to an otherwise intact fetus. The acephalic fetus has a body but lacks a head and a heart; the fetus’s neck is attached to the normal twin. The blood circulation of the acephalic fetus is provided by the heart of the twin. The acephalic fetus can not exist independently of the fetus to which it is attached.
Ref: http://www.icomm.ca/geneinfo/acep.htm

Cebocephaly: A facial anomaly, characterized by a small, flattened nose with a single nostril situated below incomplete or underdeveloped closely set eyes.
Ref: http://www.icomm.ca/geneinfo/cephaly.htm

Gastroschisis: is an abdominal wall defect located to the side of the umbilical cord (umbilicus). The infant is born with intestines protruding through this defect and no protective sac is present.
Ref: http://www.nlm.nih.gov/medlineplus/ency/article/002924.htm

Microphthalmia - small eye syndrome. Microphthalmia is a disorder in which one or both eyes are abnormally small.

Fluazinam - Fungicide - CAS No. 79622-59-6

In subchronic and chronic toxicity studies, fluazinam targeted the following organs: liver, lung, uterus, testes, pancreas, thymus, thyroid, stomach, eyes and brain...
Ref:
Canada: Regulatory Note REG2003-12. Fluazinam. Pest Management Regulatory Agency. Health Canada. Ottawa. October 27, 2003.
http://www.fluorideaction.org/pesticides/fluazinam.canada.report2003.pdf

Acute eye irritation rabbits. Technical grade fluazinam. Extremely irritating. Corneal opacity did NOT reverse in 21 days. Toxicity Category I.
Ref: US EPA Pesticide Fact Sheet. Fluazinam. August 10, 2001.

http://www.epa.gov/opprd001/factsheets/fluazinam.pdf

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

Results of a reproductive toxicity study in rats (exposure route not stated):
Increased incidence of eyeball enlargement and dark-colored liver 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

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

A 1-year dog chronic feeding study with a NOEL was 40 ppm (1.29 mg/kg/day in males and 1.14 mg/kg/day in females) and a LOEL of 800 ppm (27.75 mg/kg/day in males and 26.82 mg/kg/day in females) based on increased alkaline phosphatase, kidney, and liver weight in both sexes, increased cholesterol in males, decreased T2, T4 and ALT values in both sexes, and increased incidences of microscopic lesions in the brain, eye, kidney, spinal cord, sciatic nerve and liver.
Ref: Federal Register: September 23, 1998. Flufenacet; Time-Limited Pesticide Tolerance. Final Rule.
http://www.fluoridealert.org/pesticides/flufenacet.fr.sept.23.1998.htm

In a mouse carcinogenicity study the NOAEL was less than 50 ppm (7.4 mg/kg/day) for males and the NOAEL was 50 ppm (9.4 mg/kg/day) for females. The LOAEL was 50 ppm (7.4 mg/kg/day) for males and the LOAEL was 200 ppm (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: Federal Register. March 29, 2000. Notice of Filing a Pesticide Petition to Establish a Tolerance for Certain Pesticide Chemicals in or on Food.

http://www.fluoridealert.org/pesticides/flufenacet.fr.mar.29.2000.htm

Flumequine - Microbiocide - CAS No. 42835-25-6

--PubMed Abstract: Flumequine (1 200 mg/day) was prescribed as treatment for infection of the urinary tract to three patients with chronic renal failure, who reported positive scotoma three days later. Ophthalmologic examination evinced bilateral symmetrical macular bullae. A characteristic yellow papule was present at foveal level. In all three cases, visual acuity was impaired (down to 4/10), without any angiographic alteration. Foveolas showed a moderate persistent hyperfluorescence. All patients recovered a normal visual acuity, within two days after treatment cessation, and bullae disappeared without sequelae within 5 days. The chronology and kinetics of clinical manifestations were clearly and reproducibly correlated with flumequine therapy in all patients, and suggest that this drug may be considered responsible for the ocular symptom reported. Chronic renal failure (creatinine clearance lower than 25 ml/mn) most certainly favoured the appearance of visual troubles, but other factors may possibly play a similar role: hepatic failure, individual hypersensitivity... Quinolones used as urinary antiseptics (nalidixic acid, oxolinic acid, pipemidic acid...), and other flumequine analogues may possibly be involved in such side-effects. This was reported by Bouissou et al. in an experimental model with nalidixic acid, where transient bullae appeared on young animals' articular cartilage. Such lesions are related to focal alterations of the C2 intermediary layer of cartilage, with marked edema of the interstitial material. The volume of synovial fluid increases concomitantly. These alterations suggest a direct cytotoxic effect at the intercellular level of target organs, a mechanism possibly also occurring in the retina.
• FAN Note: Scotoma definition: An island-like blind gap in the visual field. Taber's Medical Dictionary
Ref: J Fr Ophtalmol 1983;6(10):829-36.
[Serous macular detachment of the neuro-epithelium and flumequine]. [Article in French]. Sirbat D et al.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6672059&dopt=Abstract

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

Primary eye irritation: Induces corneal opacity, Toxicity Category I. Fluometuron (Cotoran, Lanex) Herbicide Profile 12/85.
Ref: Chemical Fact Sheet for Fluometuron. Fact Sheet Number 88. December 1985.

http://pmep.cce.cornell.edu/profiles/herb-growthreg/fatty-alcohol-monuron/fluometuron/herb-prof-fluometuron.html

• Fluometuron is of low to moderate toxicity with toxicity categories of III and IV, except for dermal and eye irritation (II). (page 2)
• Primary eye irritation studies indicate fluometuron produces corneal opacity, iris irritation, redness, chemosis, and discharge, all of which cleared from day 4 to day 10 (Tox Category II) (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

Fluometuron is a mild skin and eye irritant. It has caused skin sensitization in guinea pigs and in humans. It affects the cornea of the eye in such a way that light cannot pass through it. This condition is referred to as corneal opacity. Skin or eye contact with it may cause burning... Prolonged or repeated exposure to fluometuron may cause conjunctivitis.
Ref: Pesticide Informationnn Profile. Fluometuron. March 1994. EXTOXNET.

http://www.fluoridealert.org/pesticides/fluometuron.extoxnet.1994.htm

Fluosilicic acid - Wood Preservative - CAS No. 16961-83-4

-- Rabbits, New Zealand, fluorosilicic acid (~ 23%, neat), purity n. p. instillation; 0.1 mL (0.8 mol) into the left eye. Eyes were observed at 24, 48, and 72 h following treatment. Severe and permanent corneal opacity with scar tissue occurred. Rhone- Poulenc Inc. (1971)
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

Fluridone - Aquatic Herbicide - CAS No. 59756-60-4

Fluridone was shown to cause slight to moderate corneal dullness, iritis, and conjunctivitis, and it was toxicity category II for primary eye irritation.
Ref: US EPA.
August 30, 2004. FLURIDONE: Toxicology Chapter for RED and Updating Executive Summaries for 11 Studies

-- Three studies were conducted concurrently, using Fischer rats fed the same dietary levels of Fluridone [0, 200, 650, 2000 ppm (0, 8, 25, 81 mg/kg/day)]. The first study was a 1-year feeding study (R-1126) in which 120 animals were divided into four groups of 15 animals/sex/dietary level. The other two studies were reported to be replicate 2-year oncogenic assays (Nos. R-1136 and R-1146), in which 240 animals per assay were divided into four groups of 30 animals/sex/dietary level. These three studies constitute a 2-year study with 75 animals/sex/dietary level of which 15 animals/sex/dietary level were sacrificed at 12 months. Effects observed at 650 ppm included glomerulonephritis [kidney], atrophic testes, eye keratitis, decreased body weight and organ weights. [Elanco Products Company, Division of Eli Lilly and Company. 1980a. MRID No. 00103251, 00103305. Available from EPA. Write to FOI, EPA, Washington, DC 20460.]
Ref: US EPA IRIS for Fluridone. 1990.
http://www.fluoridealert.org/pesticides/fluridone.epa.iris.1990.htm

Note: Eye keratitis = inflammation of the cornea.

Flusilazol / Flusilazole - Fungicide - CAS No. 85509-19-9

Parents believe that exposure to Flusilazol during pregnacy resulted in severe eye deformities such as microphthalmia (small eyes) and coloboma, a defect in the structure of the eyes.
Ref: Scottish Daily Record & Sunday Mail Ltd. - Sunday Mail. October 15, 2000
http://www.fluoridealert.org/pesticides/flusilazole.scot.eye.2000.htm

Definitions:
Coloboma - A defect of the iris caused by a failure of the eyeball to fuse properly during fetal development. These are developmental anomalies and do not worsen as the child grows older.
Microphthalmia - An unnatural smallness of the eyes, occurring as the result of disease or of imperfect development.

Abstract: This report describes the first part of a study which was undertaken to examine the teratogenic potential of triazole compounds used as fungicides in agriculture. Pregnant Wistar rats were given single oral dosages of flusilazole or bitertanol on days 9, 10, 11 or 13th of gestation (positive vaginal smear=day 1) at levels of 1/5, 1/10 and 1/50 LD50. The dosages were calculated from the reported LD50 values of 1272 mg/kg for flusilazole and 5000 mg/kg for bitertanol. The results of the study demonstrated that both compounds induce congenital anomalies when given on days 9, 10 or 11th at levels corresponding to 1/5 and 1/10 LD50. The types of the registered malformations after flusilazole treatment were exophthalmus, hypognathia, macroglossia and cleft palate and after bitertanol treatment micro- and acaudia and in rare cases exophthalmus, hypognathia and cleft palate. A clear dose effect relationship was established for both compounds.
Ref: Vergieva T (1990). Vergieva T. eratology 1990 Aug;42(2):27A-28A. Abstract from Toxnet.

Definitions:
Exophthalmia (n.) The protrusion of the eyeball so that the eyelids will not cover it, in consequence of disease.
Hypognathus - Unequal conjoined twins in which the rudimentary parasite is attached to the mandible of the autosite.
Macroglossia - Excessively large tongue.

Much of what is known about the possible dangers of flusilazole is considered a trade secret -- unavailable even to state agents investigating health complaints. What is known about the fungicide -- which is not approved for use in the United States -- offers little comfort to those who applied it to Florida farmland as an undisclosed ingredient in some lots of Benlate 50 DF. According to a study conducted in Bulgaria, oral doses of flusilazole given to pregnant rats produced congenital defects such as protruding eyes, twins of unequal size joined at the jaw and grossly enlarged tongues...
Ref: Jan Hollingsworth. Fungicide studies offer little comfort. Memo: BURIED SECRETS PURSUING A MEDICAL MYSTERY. December 18, 1995. Tampa Tribune (Florida). page 4

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

Chronic toxicity. A 1-year dog chronic feeding study with a NOEL was 40 ppm [1.29 mg/kg/day in males and 1.14 mg/kg/day in females] and a LOEL of 800 ppm [27.75 mg/kg/day in males and 26.82 mg/kg/day in females] based on increased alkaline phosphatase, kidney, and liver weight in both sexes, increased cholesterol in males, decreased T2, T4 and ALT values in both sexes, and increased incidences of microscopic lesions in the brain, eye, kidney, spinal cord, sciatic nerve and liver.
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

Flutriafol - Fungicide - CAS No. 76674-21-0

Ophthalmoscopic examinations, performed on 20 males and 20 femals from the control and top dosage groups after 52 and 104 weeks of the study, found a variety of ocular changes. Apart from retinal pallor, changes were regarded as age-related (or the incidence of the changes was within the historical data). At 52 weeks, very pale to pale retinal pallor was found in 3/20 male and 2/20 female animals in the hgh dosage group compared to nil in the control animals. On termination, slightly pale to pale retinal pallor was seen in 6/19 male and 5/18 female rats from the high dosage group compared to 1/18 males in the control group. No opthalmoscopic examinations were carried out on the low and intermediate dosage groups. In the absence of abnormalities in the retinal vessels and hyper-reflection of the retina, the study authros concluded that the retinal pallor was not toxicologically significant. No treatment-related histopathological abnormalities were detected in eyes at termination in any dosage group... Data requirements: To be submitted within 6 months of the date of issue of approval: The applicant must address the increased retinal pallor seen in the two chronic two year feeding study in rats or provide a reasoned argument as to why it is not of toxicological significance.
Evaluation on: Flutriafol. October 1996. Issue No. 158, UK Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Mallard House, Kings Pool, 3 Peasholme Green, York YO1 7PX.
http://www.pesticides.gov.uk/citizen/evaluations/158_confirm-box.htm

Hexaflumuron - Insecticide, Plant Growth Regulator - CAS No. 86479-06-3

Recruit (hexaflumuron) Health Effects: eye irritant, liver and kidney damage
Ref: Physical Properties And Health Effects of Pesticides Used On National Park Service Collections. Conserve O Gram. U.S. National Park Service. September 2001. Number 2/17.

http://www.fluoridealert.org/pesticides/Natl.Park.Serv.Pesticides01.pdf

Isoxaflutole - Herbicide - CAS No. 141112-29-0

-- In a combined chronic toxicity/carcinogenicity study in rats, evidence of systemic toxicity was observed at 500 mg/kg/day and included: abnormal gait, limited use of limbs, lower body weight gains and food consumption, decreased food efficiency during the first 14 weeks of the study, elevated cholesterol levels throughout the 104-week study, increased absolute and relative liver weights, and thyroid hyperplasia. Increased incidence of periacinar hepatocytic hypertrophy, portal tract (senile) bile duct changes, focal cystic degeneration of the liver was observed in males at 20 mg/kg/day and greater, females at 500 mg/kg/day. Eye opacity, gross necropsy changes in eyes, corneal lesions, degeneration of sciatic nerve and thigh muscles was observed in males at 20 mg/kg/day and higher doses and in females at 500 mg/kg/day. The chronic LOAEL is 20 mg/kg/day based on liver, thyroid, ocular, and nervous system toxicity in males and liver toxicity in females. The chronic NOEL is 2.0 mg/kg/day.
-- Reproductive Toxicity. In a 2-generation reproduction study in rats, evidence of toxicity was observed in the male and female parental rats of both generations: at 20 and 500 mg/kg/day, increased absolute and relative liver weights associated with liver hypertrophy was observed; at 500 mg/kg/day (HDT), decreased body weight, body weight gain and food consumption during premating and gestation, and increased incidence of subacute inflammation of the cornea of the eye in F0 adults as well as keratitis in F1 adults were reported. There were no other systemic effects that were attributed to treatment, nor was there any indication, at any treatment level, of an effect on reproductive performance of the adults. Treatment-related effects were observed in F1 and F2 offspring: at 20 and 500 mg/kg/day, reduction in pup survival was noted; at 500 mg/kg/day, decrease in body weights of F1 and F2 pups throughout lactation, increased incidence of chronic keratitis, low incidence of inflammation of the iris, as well as retinal and vitreous bleeding in F2 pups and weanlings were observed. Necropsy of F1 and F2 pups culled on Day 4 revealed an increased number of pups with no milk in the stomach and underdeveloped renal papillae. The Systemic LOAEL is 17.4 mg/kg/day for males and females, based upon increased liver weights and hypertrophy and the Systemic NOEL is 1.76 mg/kg/day for males and females. The Reproductive LOAEL is greater than 437 mg/kg/day, based on lack of reproductive effects and the Reproductive NOEL is greater than or equal to 437 mg/kg/day.
Ref: US EPA. Pesticide Fact Sheet. Isoxaflutole Reason for Issuance: Conditional Registration Date Issued: September 15, 1998.

http://www.epa.gov/opprd001/factsheets/isoxaflutole.pdf

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

At 37.5 mg/kg/day, there was also an increased incidence of cataracts and renal pigmentation. Based on the LOEL, an oral RfD of 0.002 mg/kg/day was derived.
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.

Mefluidide, diethanolamine salt - Herbicide - CAS No. 53780-36-2

The studies reviewed below were conducted with either the free acid or the diethanolamine salt of mefluidide. The diethanolamine salt is the registered active ingredient in California. Possible toxicological differences between the free acid and diethanolamine salt were not considered in the following reviews. The free acid and diethanolamine salt have been grouped by the US EPA (Morris, 10/5/93)...
-- 386-004 987263, "Two Year Feeding study in Rats", (International Research and Development Corporation, Mattawan, MI, study no. 102-208, report no. 225, 6/14/79). Mefluidide (MBR 12325) technical, purity 93%, fed in the diet to 50/sex/group at 0, 600, 1800 or 6000 ppm over two (2) years starting at in utero from a reproductive study. ADVERSE EFFECT: retinal degeneration. Eye effect NOEL = 600 ppm.
Ref: Summary of Toxicology Data. 1986. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch.
http://www.fluoridealert.org/pesticides/mefluidide.ca.epa.1986.pdf

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

-- “XDE-007: Two-year Dietary Chronic Toxicity/Oncogenicity and Chronic Neurotoxicity Study in Fischer 344 Rats,” (Yano, B.L., Dryzga, M.D., Thomas, J.; Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, MI; Laboratory Project Study ID: 011168; 4.22.05). Noviflumuron ((N-[3,5-dichloro-2-fluoro-4(1,1,2,3,3,3-hexafluoropropoxy)phenyl]-N’-(2,6-difluorobenzoyl)urea; XDE-007, 97.9% pure) was fed in diet to Fischer 344 rats (75/sex/dose) for 90 days, 1 or 2 years at 0, 0.1, 1.0, 75 or 300 mg/kg/day. Subchronic toxicity was assessed after 90 days of treatment on 10/sex/dose at 0 and 1.0 mg/kg/day doses only. At 1 year,10/sex/dose (chronic toxicity group), and 5/sex/dose (chronic neurotoxicity group) were necropsied. The remaining 50/sex/dose were necropsied after 2 years (oncogenicity group). Chronic NOEL = 1.0 mg/kg/day (At > 75 mg/kg/day there were decreased body weights and body weight gains along with increases or decreases in absolute and/or relative organ weights (liver, kidney, brain, heart, adrenal, testes, spleen, epididymides were affected) at 12 and/or 24 months. Skin/tail papules and pustules were observed in males (300 mg/kg/day) and females (> 75 mg/kg/day) in the second year. Females showed an increase in phthisis bulbi* at 300 mg/kg/day...
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

* Definition: Phthisis bulbi is an end-stage ocular response to severe ocular disease, inflammation, or insult.  Clinically, the globe will be soft and hypotonus with minimal or no vision and loss of much of the normal architecture of the eye.  Histopathologically, the globe is small and shrunken with marked thickening of the sclera, as well as disorganization and atrophy of much of the intraocular contents.  The intraocular contents are markedly dirupted and difficult to recognize.  Commonly, the retinal pigment epithelium may undergo a metaplasia leading to intraocular ossification or bone formation in the end-stage of phthisis bulbi.
Ref: University of Utah. John A. Moran Eye Center.
http://insight.med.utah.edu/opatharch/uvea/phthisis_bubli.htm

PFOS - PFOA - Insecticide, US EPA List 3 Inert

" DuPont tested for and found PFOA in the blood of female plant workers in Parkersburg. The company followed and documented pregnancy outcomes in exposed workers. Two of seven children born to female plant workers between 1979 and 1981 had birth defects, one an “unconfirmed” eye and tear duct defect, and one a nostril and eye defect. [Dupont Document] In 1981 fifty women were reassigned in the plant."
Ref: Environmental Working Group.
2003 report: PFCs: a family of chemicals that contaminate the planet. Part 4: PFC Health Concerns

3.6 Developmental Toxicity. Three prenatal developmental toxicity studies of PFOS have been conducted, two studies in rats and one study in rabbits. In addition, preliminary results are available for developmental toxicity studies in rats and mice. The first study administered four groups of 22 time-mated Sprague-Dawley rats 0, 1, 5, and 10 mg/kg/day PFOS in corn oil by gavage on gestation days (GD) 6-15 (Gortner, 1980). Doses were adjusted according to body weight. Dams were monitored on GD 3-20 for clinical signs of toxicity. Individual body weights were recorded on GD 3, 6, 9, 12, 15, and 20. Animals were sacrificed on GD 20 by cervical dislocation and the ovaries, uteri and contents were examined for the number of corpora lutea, number of viable and non-viable fetuses, number of resorption sites, and number of implantation sites... The most notable sign of developmental toxicity observed in all dose groups consisted of abnormalities of the lens of the eye, which was not seen in controls. The proportion of fetuses with the lens abnormality in one or both lenses was significantly higher in the high dose group. All eye abnormalities appeared to be localized to the area of the embryonal lens nucleus, although a variety of morphological appearances were present within that location. According to the authors, this abnormality appeared to be an arrest in development of the primary lens fibers forming the embryonal lens nucleus. Secondary lens fiber development progressed normally except immediately surrounding the abnormal embryonal nucleus. Under the conditions of the study, a LOAEL for developmental toxicity of 1 mg/kg/day was indicated; a developmental NOAEL could not be established.
Ref: November 21, 2002 report:
Hazard Assessment of Perfluorooctane sulfonate (PFOS) and its salts. Organisation for Economic Co-operation and Development. ENV/JM/RD(2002)17/FINAL.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf

Pyraflufen-ethyl - Herbicide - CAS No. 129630-19-9

Human Health Effects. The U.S. Environmental Protection Agency (EPA) classifies Edict [which contains pyraflufe-ethyl] as category I (High Toxicity) with a signal word of DANGER because of irreversible damage to the eyes and harm if swallowed or absorbed through the skin.
Ref: Pyraflufen. Roadside Vegetation Management Herbicide Fact Sheet. Washington State Department of Transportation.
http://www.fluorideaction.org/pesticides/pyraflufen.fact.sheet.washington.pdf

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

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

tau-Fluvalinate - Acaricide, Insecticide - CAS No. 102851-06-9

Acute & Chronic Dietary (general population). LOAEL = 1 mg/kg/day. Clinical signs in the rat chronic feeding study coupled with a LOAEL of 2 mg/kg/day based on excessive grooming and bulging eyes in the subchronic neurotoxicity study.
Ref: October 28, 2005. Reregistration Eligibility Decision (RED) for Tau-fluvalinate. List A. Case No. 2295. US EPA. Federal Register Docket No. OPP-2005-0230-0002. (Page 1).

http://www.fluorideaction.org/pesticides/tau-fluvalinate.red.2005.pdf  

Tembotrione - Herbicide - CAS No. 335104-84-2

Long-term dietary administration of tembotrione resulted in an increased incidence of thyroid adenomas and squamous cell carcinomas of the cornea in male rats. Since the incidence of thyroid adenomas was not statistically significant, they were considered unrelated to treatment. The levels of the doses tested were adequate. No tumors were noted in female rats or in male and female mice after long-term dietary administration of tembotrione. The HED CARC (April 11, 2007) classified tembotrione as "Suggestive Evidence of Carcinogenic Potential" by the oral route based on the occurrence of eye tumors in male rats; therefore, the quantification of cancer risk is not required.
Reference: Tembotrione. Human-Health Risk Assessment for Proposed Uses on Field Corn, Sweet Corn and Popcorn. USEPA. September 7, 2007.
The eye, liver and kidney are the primary target organs of tembotrione. In the subchronic, chronic and reproduction rat studies, and the subchronic dog study, corneal opacity, edema of the cornea, neovascularization, and keratitis were seen at various doses indicating ocular toxicity. Males appear to be more susceptible to ocular toxicity than females. Also, corneal opacity was completely reversible following subchronic and chronic exposures in rats and some neovascularizations were reversible following subchronic exposure in rats; but these effects were not reversible following chronic exposure (page 15).
• In a combined chronic/carcinogenicity study (MRID 46695708) AE 0172747 was administered to 60 Rj: WI (IOPS HAN) Wistar male rats/dose in the diet at dose levels of 0, 1, 20, 200 or 800 ppm (equivalent to 0, 0.04, 0.79, 8.3 or 31.7 mg/kg bw/day) in the diet for 104 weeks. Gross necropsy revealed a higher incidence of ocular opacity at 20, 200, and 800 ppm. The incidence of minimal to marked keratitis of the eye(s) was significantly increased (p≤0.01) in males in the 20, 200, and 800 ppm groups (97-98%) when compared to controls (3%). Keratitis included one or more of the following changes in the cornea: acute inflammation, epithelial hyperplasia, keratinization, epithelial vacuolization, erosion and/or ulceration. Generally, the keratitis observed in this study was a multifocal to diffuse chronic active superficial keratitis, involving the corneal epithelium and superficial aspects of the corneal stroma, which did not penetrate the cornea. A slight non-statistically significant elevation (3-5%) of hyperplastic lesions was noted on the cornea of the eye at 200 and 800 ppm, when compared to controls (0 %). In addition, a minimal to moderate retinal degeneration, mostly located in the ora serrata area of the retina, was significantly increased (p≤0.05) in the 800 ppm group (15%) when compared to controls (3%) (page 79-80).
Dose and Endpoint for Establishing RfD: (page 22)
-- Study Selected: Chronic Toxicity/Carcinogenicity (Feeding)/Rat MRID No.: 46695708
-- The NOAEL of 0.04 mg/kg/day was based on neovascularization and edema of the cornea and snow flake-like corneal opacity, unilateral or bilateral keratitis of the eye, decreased mean body weight and mean body-weight gain, increased total cholesterol, higher ketone levels and lower pH values, higher protein levels, increased kidney weight, kidney to body weight and kidney to brain weight ratios, chronic nephropathy and atrophy of the sciatic nerve observed in the male at 0.79 mg/kg/day (LOAEL).
-- UF(s): An UF of 100 was applied to account for interspecies extrapolation (10
-- Comments about Study/Endpoint/UF: This study provided the lowest NOAEL in the database (most sensitive endpoint) and will also provide the most protective limits for human effects.
Reference: Tembotrione. Human-Health Risk Assessment for Proposed Uses on Field Corn, Sweet Corn and Popcorn. USEPA. September 7, 2007.

1,1,1,2-Tetrafluoroethane (HFC-134a) - Propellant, US EPA List 4B Inert - CAS No. 811-97-2

-- In the perinatal and postnatal part of the study, groups of 41 female rats were administered concentrations of 1,800, 9,900, or 64,400 ppm of HFC-134a (99.3% pure) for 1 h daily during days 17 to 20 of pregnancy and days 1 to 21 postpartum (Alexander et al. 1996). Females were allowed to deliver and rear their young. Selected F1 animals were mated; these animals were sacrified on day 20 of pregnancy, and the uterine contents were examed... There was a statistically significant delay in the occurrence of pinnae detatchment, eye-opening, and startle response in the F1 generation, whose dams inhaled 64,400 ppm....
-- Alexander DJ, Libretto SE, Adams MJ, Hughes EW, Bannerman M. 1996. HFA-134a (1,1,1,2-tetrafluoroethane): effects of inhalation exposure upon reproductive performance, development and maturation of rats. Human Exp Toxicol 15:508-517.
Ref: National Research Council. 2002. Acute Exposure Guideline Levels for Selected Airborne Chemicals. Volume 2. Subcommittee on Acute Exposure Guideline Levels, Committee on Toxicology, Board of Environmental Studies and Toxicology, Division of Earth and Life Studies. Available from: National Academy Press, 2101 Constitution Ave, NW, Box 285, Washington DC 20055. ISBN 0-309-08511-X. Online at: http://books.nap.edu/books/030908511X/html/index.html

Thiazopyr - Herbicide - CAS No. 117718-60-2

-- It is considered to be moderately irritating to the skin and substantially irritating to the eye.
-- A two year rat carcinogenicity study at doses of 0, 0.04, 4.4, 44.2 or 136.4 mg/kg/day (Males) 0, 0.06, 0.6, 5.6, 56.3 or 177.1 mg/kg/day (female) with a NOEL of 4.4 mg/kg/day. The effects were protruding eyes, evidence of mild anemia, increased GGT and cholesterol, increased absolute and relative liver, kidney and thyroid weights and significant increase in microscopic lesions in the liver (hypertrophy and vacuolar changes), kidney (nephropathy) and thyroid (hypertrophy and hyperplasia); decreased mean body weight and body weight gain and food consumption. A statistically significant increase in thyroid follicular cell adenomas/cystadenomas were observed in males at 44.2 and 136.4 mg/kg/day. A nonsignificant increase in renal tubular adenomas in high-dose females was considered to be equivocal.
Ref: US EPA Pesticide Fact Sheet. February 20, 1997.

http://www.epa.gov/opprd001/factsheets/thiazopyr.pdf

Tolylfluanid - Fungicide - CAS No. 731-27-1

-- Prenatal developmental toxicity/rabbit LOAEL = 70 mg/kg/day based on increased malformations (arthrogryposis of front extremities and small orbital cavity/folded retina) and variations (floating ribs and accelerated ossification).
Ref: Federal Register: September 25, 2002. Tolylfluanid; Pesticide Tolerance. Final Rule. Federal Register.

http://www.fluoridealert.org/pesticides/tolylfluanid.fr.sept25.2002.htm

Tributyltin fluoride - Antifoulant, Fungicide, Microbiocide - CAS No. 1983-10-4

Abstract: The acute and chronic toxicities of anti fouling coatings were studied in animals. The acute oral median lethal dose (LD50) was determined for bis(tri-n-butyltin)oxide (56-35-9), tributyltin-fluoride (1983-10-4) and triphenyltin-fluoride (379-52-2) for rats and rabbits... All were severe or extreme eye irritants and most were moderate to severe skin irritants.
Ref:
1975 Journal of Paint Technology, Vol. 47, No. 600, pages 54-58. Effects Of Organotin Anti-Fouling Coatings On Man And His Environment by Sheldon AW. http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~AAAjCaaO4:1

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

-- Reproductive toxicity. Target / critical effect - Reproduction: Decreased bodyweight gain of pups and delayed eye opening at parental toxic doses. Lowest relevant reproductive NOAEL / NOEL: 50 ppm(2.3 mg/kg bw/day)...
-- Medical data New active substance. Limited data. Some evidence of skin and eye irritation in 3 people during field trials (but 120 people without effects).

Ref: Review report for the active substance trifloxystrobin. Trifloxystrobin. SANCO/4339/2000-Final. 7 April 2003. Finalised in the [European Commission] Standing Committee on the Food Chain and Animal Health at its meeting on 15 April 2003 in view of the inclusion of trifloxystrobin in Annex I of Directive 91/414/EEC.

http://www.fluorideaction.org/pesticides/trifloxystrobin.eu.april.03.pdf

Triphenyltin fluoride - Antifoulant, Algaecide, Herbicide - CAS No. 379-52-2

Abstract: The acute and chronic toxicities of anti fouling coatings were studied in animals. The acute oral median lethal dose (LD50) was determined for bis(tri-n-butyltin)oxide (56-35-9), tributyltin-fluoride (1983-10-4) and triphenyltin-fluoride (379-52-2) for rats and rabbits... All were severe or extreme eye irritants and most were moderate to severe skin irritants.
Ref:
1975 Journal of Paint Technology, Vol. 47, No. 600, pages 54-58. Effects Of Organotin Anti-Fouling Coatings On Man And His Environment by Sheldon AW.
http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~AAAjCaaO4:1

Abstract. An acute dust inhalation toxicity study using albino rats as experimental animals was performed for the compound triphenyltin-fluoride. The acute dust inhalation median lethal concentration of the test compound is 0.29 milligrams per liter of air based on a four hour exposure period. Untoward behavioral reactions exhibited by the animals included gasping, bloody nasal discharge, bloody ocular discharge, and weakness. Body weight gains of the survivors of the 14 day observation period were less than normal. Gross pathologic observation revealed mild to severe focal discoloration of the lungs in all test animals.
Ref: Acute Dust Inhalation Toxicity Study with Triphenyltin Fluoride in Albino Rats; by Elliott CB. Source: M and T Chemicals, Inc. (Unpublished report submitted to NIOSH), Rahway, N. J., IBT No. N1632, 14 pages, 1 reference, 1972. [Toxline abstract at Toxnet]

 
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