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Activity: Fumigant, Insecticide (Fluorine Inorganic)
Structure:

• Due to its length, we present this section in 2 Parts:

Adverse Effects Part 1
Amyloidosis - Kidney
Blood
Body Weight Decrease
Bone
Brain
CNS
Deaths from Vikane fumigation
Endocrine: Adrenal
Endocrine: Hypothalmus
Endocrine: Thyroid

Adverse Effects Part 2
Eye
Heart
Kidney
Liver
Lung
Tremors/Convulsions

Amyloidosis (click on for all fluorinated pesticides)

ONCOGENICITY, MOUSE **50223-028 125636 "Sulfuryl Fluoride: 18-Month Inhalation Oncogenicity Study in CD-1 Mice", (J. F. Quast, G. J. Bradley and K. D. Nitschke, Dow Chemical Co., Toxicology Research Laboratory, Lab Project Study ID K-016399-039, 8/19/93). Sulfuryl fluoride, 99.8% purity, was administered via inhalation at concentrations of 0, 5, 20, or 80 ppm to 50 CD-1 mice/sex/group for 6 hours/day, 5 days/week for 18 months. Ten additional mice/sex per dose level were included for sacrifice at 12 months. NOEL = 20 ppm. Primary concern was increased mortality in females (mainly due to increased incidence of severe degree of bilateral amyloidosis in glomeruli). Possibly treatment-related findings in males were food impaction in esophagus and inflammation and/or abscesses in the head and/or oral cavity at 80 ppm. Lesser changes at 80 ppm included very slight vacuolation of brain, particularly of cerebral external capsule (M and F), and very slight hypertrophy of thyroid epithelial cells (especially in males). This study is considered to indicate a "possible adverse effect", based on the exacerbation of geriatric renal disease in high dose females. Considering how high the NOEL and LEL of this study are to levels which cannot be tolerated in acute and subacute toxicity exposure, this flagging of a "possible adverse effect" should not be taken to indicate unusual concern. No oncogenicity effects. Acceptable. Kishiyama and Aldous, Sept. 14, 1994.
Ref: SUMMARY OF TOXICOLOGY DATA SULFURYL FLUORIDE. Revised 11/17/98. California EPA, Department of Pesticide Regulation, Medical Toxicology Branch.
http://www.fluorideaction.org/pesticides/sulfuryl.fluoride.tox.data.pdf

• Definition of Glomeruli - Network of microscopic blood vessel structures in the kidney, responsible for filtering waste from the blood.

Blood (click on for all fluorinated pesticides)

Poisonings and fatalities have been reported in humans following inhalation exposure to sulfuryl fluoride... A second person died of cardiac arrest after sleeping in the house overnight following fumigation. A plasma fluoride level of 0.5 mg/L (10 times normal) was found in this person following exposure. Prolonged chronic inhalation exposure to concentrations of sulfuryl fluoride gas significantly above the TLV of 5 ppm have caused fluorosis in humans because sulfuryl fluoride is converted to fluoride anion in the body. Fluorosis is characterized by binding of fluoride anion to teeth (causing mottling of the teeth) and to bone.
Ref: Federal Register: September 5, 2001 (Volume 66, Number 172). Sulfuryl Fluoride; Proposed Pesticide Temporary Tolerances.
http://www.fluorideaction.org/pesticides/sulfuryl.flu.fr.sept.5.2001.htm

-- 2-Week inhalation study--dog NOAEL = 26/27 (M/F) mg/kg/day
LOAEL = 79/80 (M/F) mg/kg/day based on intermittant tremors and tetany during exposure, minimal inflammatory changes in upper respiratory tract, decreased body weight (F only).
Note: Increased serum fluoride at >= 26/27 mg/kg/day
-- 90-Day inhalation toxicity--mouse NOAEL = 38/36 (M/F) mg/kg/day
LOAEL = 125/121 (M/F) mg/kg/day based on miscroscopic lesions in caudate-putamen nucleus and external capsule of the brain, decreased body weight, decreased body weight gain, follicular cell hypertrophy in thyroid.
Note: Increased serum fluoride at >= 26/27 mg/kg/day
Ref: January 23, 2004. Sulfuryl Fluoride; Pesticide Tolerance.
40 CFR Part 180 [OPP-2003-0373; FRL-7342-1]. Final Rule. Federal Register

Body Weight Decrease (click on for all fluorinated pesticides)

-- In subchronic (90-day) inhalation studies in rats, dogs, rabbits and mice, the brain was the major target organ. Malacia and/or vacuolation were observed in the white matter of the brain in all four species. The portions of the brain most often affected were the caudate-putamen nucleus in the basal ganglia, the white fiber tracts in the internal and external capsules, and the globus pallidus of the cerebrum. In dogs and rabbits, clinical signs of neurotoxicity (including tremors, tetany, incoordination, convulsions and/or hind limb paralysis) were also observed. Inflammation of the nasal passages and histiocytosis of the lungs were observed in rats and rabbits; but not in dogs, in which species inflammation of the upper respiratory tract was more prominent in the 2-week study. In rats, kidney damage was also observed. In mice, follicular cell hypertrophy was noted in the thyroid gland. Decreased body weights and body weight gains were also observed in rats, dogs and mice.
-- In chronic (1-2 year) inhalation studies in rats, dogs and mice, target organs were the same as in the 90-day studies. In rats, severe kidney damage caused renal failure and mortalities in many animals. Additional gross and histopathological lesions in numerous organs and tissues were considered to be secondary to the primary effect on the kidneys. Other treatment-related effects in rats included effects in the brain (vacuolation of the cerebrum and thalamus/hypothalamus) and respiratory tract (reactive hyperplasia and inflammation of the respiratory epithelium of the nasal turbinates, lung congestion, aggregates of alveolar macrophages). In dogs and mice, increased mortalities, malacia and/or vacuolation in the white matter in the brain, histopathology in the lungs, and follicular cell hypertrophy in the thyroid gland were observed. Decreased body weights and body weight gains were also noted in all three species.
-- In a developmental toxicity inhalation study in rats, no developmental toxicity was observed in the pups. Although no maternal toxicity was observed in this study at the highest dose tested (225 ppm), significant maternal toxicity (decreased body weight, body weight gain and food consumption; increased water consumption and kidney weights; and gross pathological changes in the kidneys and liver) was observed in a previously conducted range-finding study at a slightly higher dose level (300 ppm). In a developmental toxicity inhalation study in rabbits, decreased fetal body weights were observed in the pups. At the same dose level, decreased body weight and body weight gain were observed in the dams. In a 2-generation reproduction inhalation study in rats, vacuolation of the white matter in the brain, pathology in the lungs (pale, gray foci; increased alveolar macrophages) and decreased body weights were observed in the parental animals. Decreased pup body weights in the F1 and F2 generations were observed in the offspring. No effects on reproductive parameters were noted in this study. No quantitative or qualitative evidence of increased susceptibility of fetuses or pups was observed in the developmental toxicity or reproduction studies on sulfuryl fluoride.
Ref: Federal Register: September 5, 2001 (Volume 66, Number 172). Sulfuryl Fluoride; Proposed Pesticide Temporary Tolerances.
http://www.fluorideaction.org/pesticides/sulfuryl.flu.fr.sept.5.2001.htm

-- Two fatalities occurred when the owners of a home re-entered after the dwelling had been fumigated with 250 pounds of sulfuryl fluoride. The concentration to which the occupants were exposed was not determined. The man died within 24 hr, and the woman expired 6 days after exposure. Signs of intoxication included severe dyspnea [abnormal breathing], cough, generalized seizure, cardiopulmonary arrest (in the male), and weakness, anorexia, nausea, repeated vomiting, and hypoxemia [subnormal oxygenation of arterial blood, short of anoxia]; ventricular fibrillation and diffuse pulmonary infiltration were also reported in the female. [American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991.1471]
-- Groups of 35 to 36 pregnant Fischer 344 rats and 28 to 29 pregnant New Zealand White rabbits were exposed to 0, 25, 75, or 225 ppm of sulfuryl fluoride vapor via inhalation for 6 hr/day on days 6 to 15 and 6 to 18 of gestation, respectively. Among rats, maternal water consumption was increased in the 225 ppm exposure group (p < 0.05), but there were no indications of embryotoxicity, fetotoxicity, or teratogenicity in any of the exposed groups. Among rabbits, maternal weight loss during the exposure period (days 6 to 18) was observed in the 225 ppm group. Decr fetal body wt, considered secondary to maternal weight loss, were also observed at 225 ppm. However, no evidence of embryotoxicity or teratogenicity was observed among rabbits in any exposure group. For both species a low incidence of malformations were seen scattered among all exposure groups, with no indication of any treatment related effects. In preliminary studies, exposure of pregnant rats and rabbits to 30, 100, or 300 ppm sulfuryl fluoride produced significantly decr maternal wt gain in both rats and rabbits exposed to 300 ppm. Increased absolute kidney wt (rats) and decr liver wt (rabbits) were also observed at this exposure level. No adverse effects were observed at either 30 or 100 ppm in either species.
Ref: Hazardous Substances Data Bank for SULFURYL FLUORIDE CASRN: 2699-79-8.
http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB

Bone (click on for all fluorinated pesticides)

Prenatal developmental--rabbit (870.3700) Developmental NOAEL = 75 ppm or 29/29 (M/F) mg/kg/ day LOAEL = 225 ppm or 86 (F) mg/kg/day based on decreased fetal body weight, decreased crown-rump length, possible increased fetal liver pathology (pale liver) Ref: January 23, 2004. Sulfuryl Fluoride; Pesticide Tolerance. 40 CFR Part 180 [OPP-2003-0373; FRL-7342-1]. Final Rule. Federal Register

From FAN Note the similarity of effect with the following: - EC.

Abstract: Fluoride was first associated with fetal malformation shortly after water fluoridation was initiated in the 1940s. Since many chemicals can interact directly with the embryo to cause malformation, the effects of fluoride on embryonic and fetal development were investigated. The effects of sodium fluoride on the development of frog embryos were studied under conditions described by the Frog Embryo Teratogenesis Assay —Xenopus (FETAX), a screening assay for teratogens. The most prominent malformations caused by sodium fluoride are reduction in the head-tail lengths and dysfunction of the neuromuscular system of the tadpoles. The values for LC50, EC50, and minimal concentration to inhibit growth (MCIG) of sodium fluoride met the limits established for a teratogen in frog embryos, showing that sodium fluoride is a direct acting teratogen on developing embryos. Since FETAX has a high degree of success in identifying mammalian teratogens, the observed teratogenic action of sodiu fluoride on frog embryos would indicate a strong possibility that sodiun fluoride may also act directly on developing mammalian fetuses to cause malformation. Ref: Effects of fluoride on Xenopus embryo development EH Goh, AW Neff Food and Chemical Toxicology 41 (2003)1501 –1508 • Note: The fluoride anion is the toxicological endpoint of concern for Sulfuryl fluoride.

... Rats exposed by inhalation to 100 to 600 ppm (0.4 to 0.25 mg/L) sulfuryl fluoride for 13 weeks developed mottled teeth (indicative of fluoride toxicity), renal and respiratory effects, and cerebral vacuolation. EPA believes that there is sufficient evidence for listing sulfuryl fluoride on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available neurological, renal, and respiratory 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.

-- 90-Day inhalation toxicity--rat. NOAEL = 24/25 (M/F) mg/kg/day. LOAEL = 80/83 (M/F) mg/kg/day based on dental fluorosis*.
-- 90-Day inhalation toxicity--rabbit. NOAEL = 8.6/8.5 (M/F) mg/kg/day. LOAEL = 29/28 (M/F) mg/kg/day based on decreased body weight, decreased liver weight, dental fluorosis*, vacuolation of white matter of the brain (F only).
-- 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...
-- 1-Year chronic inhalation toxicity--dog. NOAEL = 5.0/5.1 (M/F) mg/kg/day. LOAEL = 20/20 (M/F) mg/kg/day based on decreased body weight gain, increased alveolar macrophages in lungs, dental fluorosis*.
-- 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...
* = dental fluorosis is not considered an adverse health effect, and the identification of that effect in any of these toxicological studies has not served to define a safe level of exposure to sulfuryl fluoride under the FFDCA.
Ref: January 23, 2004. Sulfuryl Fluoride; Pesticide Tolerance.
40 CFR Part 180 [OPP-2003-0373; FRL-7342-1]. Final Rule. Federal Register

-- Poisonings and fatalities have been reported in humans following inhalation exposure to sulfuryl fluoride. The severity of these effects has depended on the concentration of sulfuryl fluoride and the duration of exposure. Short-term inhalation exposure to high concentrations has caused respiratory irritation, pulmonary edema, nausea, abdominal pain, central nervous system depression, and numbness in the extremities. In addition, there have been two reports of deaths of persons entering houses treated with sulfuryl fluoride. One person entered the house illegally and was found dead the next morning. A second person died of cardiac arrest after sleeping in the house overnight following fumigation. A plasma fluoride level of 0.5 mg/L (10 times normal) was found in this person following exposure. Prolonged chronic inhalation exposure to concentrations of sulfuryl fluoride gas significantly above the TLV of 5 ppm have caused fluorosis in humans because sulfuryl fluoride is converted to fluoride anion in the body. Fluorosis is characterized by binding of fluoride anion to teeth (causing mottling of the teeth) and to bone.
-- In many subchronic and chronic inhalation studies in rats, dogs, and rabbits, dental fluorosis was the most sensitive toxic effect observed in the study. In two 90-day studies in rats and rabbits, in which serum fluoride levels were determined, an increased serum level of fluoride anions was observed at even lower dose levels. The increased serum fluoride levels were due to the conversion of sulfuryl fluoride to fluoride anions in the body.
Ref: Federal Register: September 5, 2001 (Volume 66, Number 172). Sulfuryl Fluoride; Proposed Pesticide Temporary Tolerances.
http://www.fluorideaction.org/pesticides/sulfuryl.flu.fr.sept.5.2001.htm

Chronic exposure to either too low or too high a concentration of fluoride may have deleterious effects on the skeletal system. An increased in the incidence of severe osteoporosis was correlated with use of drinking water containing 0.4 mg/l fluoride. Severe skeletal fluorosis has been reported in persons living in areas of naturally high fluoride concentrations (up to 14 mg/l). Radiologically detectable osteosclerosos has been observed in about 10 percent of long term residents using water supplies containing 8 mg/l fluoride. Retardation of skeletal maturity has been observed in children using a water supply containing 3.6 mg/l fluoride. In other situations, skeletal fluorosis has not been described in populations whose water supplies contained less than 4 mg/l fluoride.
Ref: [USEPA, Office of Drinking Water; Criteria Document (Draft): Fluoride p.vi-48 (1985)] as cited in Hazardous Substances Data Bank for Ammonium fluoride
http://www.fluoridealert.org/pesticides/Ammonium.fluoride.TOXNET.htm

• Note: Inorganic fluoride is the toxicological endpoint of concern for Sulfuryl fluoride

Brain (click on for all fluorinated pesticides)

Ref: January 23, 2004. Sulfuryl Fluoride; Pesticide Tolerance. 40 CFR Part 180 [OPP-2003-0373; FRL-7342-1]. Final Rule. Federal Register
Excerpts from: Table 1.--Subchronic, Chronic, and Other Toxicity
Study Guideline	Type of Study	NOAEL mg/kg/day	LOAEL mg/kg/day	Based on:
None cited	2-Week inhalation study--rabbit	30/30 (M/F)	90/90 (M/F)	malacia (necrosis) in cerebrum, vacuolation of cerebrum
None cited	2-Week inhalation study--rabbit	-	180/180 (M/F)	malacia (necrosis) in cerebrum, vacuolation of cerebrum
(870.3100)	90-Day inhalation toxicity--rat	24/25 (M/F)	90/90 (M/F)	malacia (necrosis) in cerebrum, vacuolation of cerebrum
(870.3100)	90-Day inhalation toxicity--rat	-	180/180 (M/F)	malacia (necrosis) in cerebrum, vacuolation of cerebrum
(870.3100)	90-Day inhalation toxicity--rat	-	240/250 (M/F)	vacuolation of caudate-putamen nucleus and white fiber tracts of the internal capsule of the brain
(870.3100)	90-Day inhalation toxicity--mouse	38/36 (M/F)	125/121 (M/F)	miscroscopic lesions in caudate-putamen nucleus and external capsule of the brain
(870.3150)	90-Day inhalation toxicity--dog	25/26 (M/F)	50/51 (M/F)	slight histopathology of the caudate nucleus of the basal ganglia
(870.3150)	90-Day inhalation toxicity-- rabbit	8.6/8.5 (M/F)	29/28 (M/F)	vacuolation of white matter of the brain (F only)
(870.3150)	90-Day inhalation toxicity-- rabbit	-	86/85 (M/F)	malacia (necrosis) and vacuolation of putamen, globus pallidus and internal and external capsules in the brain
(870.4100)	Chronic toxicity--rodents	3.5 for M 16 for F	14 for M 62 for F	histopathology in brain (vacuolation in cerebrum and thalmus/hypothalmus)
(870.4100)	1-Year chronic inhalation toxicity--dog	5.0/5.1 (M/F)	50/51 (M/F)	malacia (necrosis) in caudate nucleus of brain
(870.4200)	18-Month carcinogenicity inhalation study--mouse	25/25 (M/F)	101/101 (M/F)	cerebral vacuolation in brain
(870.4300)	2-Year combined chronic/ carcinogenicity--rat	3.5 for M 16 for F	14 for M 62 for F	histopathology in brain (vacuolation in cerebrum and thalmus/hypothalmus)

Ref: January 23, 2004. Sulfuryl Fluoride; Pesticide Tolerance. 40 CFR Part 180 [OPP-2003-0373; FRL-7342-1]. Final Rule. Federal Register
Excerpts: Table 2.--Summary of Toxicological Dose and Endpoints for sulfuryl fluoride for Use in Human Risk
Exposure Scenario	Dose Used in Risk Assessment, Interspecies and Intraspecies and any Traditional UF	Special FQPA SF and Level of Concern for Risk Assessment	Study and Toxicological Effects
Chronic dietary (all populations)	NOAEL = 8.5 mg/kg/day UF = 3,000... Chronic RfD = 0.003 mg/kg/day.	Special FQPA SF = 1X cPAD = chronic RfD/ Special FQPA SF = 0.003 mg/kg/day	Rabbit - 90-Day inhalation LOAEL = 28 mg/kg/day based on vacuolation of white matter in the brain of females.
Short-term inhalation (1 to 30 days)	Inhalation study NOAEL = 30 mg/kg/day (100 ppm; 0.42 mg/L).	Residential LOC for MOE = 1,000 Occupational LOC = 100	Rabbit - 2-Week inhalation LOAEL = 90 mg/kg/day (300 ppm; 1.25 mg/L) based on malacia (necrosis) and vacuolation in brain, inflammation of nasal tissue and trachea
Intermediate-term inhalation (1 to 6 months)	Inhalation study NOAEL = 8.5 mg/kg/day (100 ppm; 0.42mg/L).	Residential LOC for MOE = 1,000 Occupational LOC for MOE = 100.	Rabbit - 90-Day inhalation LOAEL = 28 mg/kg/day (100 ppm; 0.42 mg/L) based on vacuolation of white matter in the brain of females.
Long-term inhalation (>6 months)	Inhalation study NOAEL = 8.5 mg/kg/day (30 ppm; 0.13 mg/L).	Residential LOC for MOE = 3,000 Occupational LOC for MOE = 300.	Rabbit - 90-Day inhalation LOAEL = 28 mg/kg/day based on vacuolation of white matter in the brain of females

Federal Register: September 5, 2001. Sulfuryl Fluoride; Proposed Pesticide Temporary Tolerances. Volume 66, Number 172. Proposed Rules. Page 46415-46425. Excerpt from Table 1. Summary of Toxicological Doses and Endpoints for sulfuryl fluoride for Use in Human Risk Assessment
Exposure Scenario \1\	Dose (mg/kg/day)	Endpoint	Study
Chronic Dietary (General Population including Infants and Children)	NOAEL = 8.5; UF = 300; FQPA Factor = 3	Vacuolation of white matter in the brain of females. Chronic RfD = 0.028 mg/ kg/day Chronic Population- Adjusted Dose (cPAD) = 0.0093 mg/kg/day	90-Day inhalation- rabbits
Inhalation Short-Term (Occupational)	NOAEL = 30; MOE = 100; FQPA Factor = N/A	Malacia (necrosis) and vacuolation in the cerebrum, inflammation of nasal tissues and trachea.	2-Week inhalation- rabbits
Inhalation Short-Term (Residential)	NOAEL = 30; MOE = 300; FQPA Factor = 3	Malacia (necrosis) and vacuolation in the cerebrum, inflammation of nasal tissues and trachea.	2-Week inhalation- rabbits
Inhalation Intermediate-Term (Occupational)	NOAEL = 8.5; MOE = 100; FQPA Factor = N/A	Vacuolation of white matter in the brain of females.	90-Day inhalation- rabbits
Inhalation Intermediate-Term (Residential)	NOAEL = 8.5; MOE = 300; FQPA Factor = 3	Vacuolation of white matter in the brain of females.	90-Day inhalation- rabbits
\*\ The reference to the FQPA Safety Factor refers to any additional safety factor retained due to concerns unique to the FQPA.
\1\ The only significant route of exposure for inorganic fluoride is dietary exposure, which includes residues in drinking water. This risk assessment uses the maximum concentration limit goal (MCLG) of 4.0 ppm for fluoride as the basis for a maximum allowable exposure to inorganic fluoride (see the Cryolite Reregistration Eligibility Decision, 8/96, EPA- 738-R-96-016). Using the Agency default values of body weight (70 kg) and water consumption (2 liters/day), the MCLG converts to an exposure limit of 0.114 mg/kg/day. This exposure is used as the cPAD for inorganic fluoride in this risk assessment.

-- In 2-week inhalation studies in rats, dogs and rabbits, different target organs were affected... In rabbits, the primary target organ was the brain, in which malacia (necrosis) and vacuolation were observed in the cerebrum...
-- In subchronic (90-day) inhalation studies in rats, dogs, rabbits and mice, the brain was the major target organ. Malacia and/or vacuolation were observed in the white matter of the brain in all four species. The portions of the brain most often affected were the caudate-putamen nucleus in the basal ganglia, the white fiber tracts in the internal and external capsules, and the globus pallidus of the cerebrum. In dogs and rabbits, clinical signs of neurotoxicity (including tremors, tetany, incoordination, convulsions and/or hind limb paralysis) were also observed...
-- In chronic (1-2 year) inhalation studies in rats, dogs and mice, target organs were the same as in the 90-day studies. In rats, severe kidney damage caused renal failure and mortalities in many animals. Additional gross and histopathological lesions in numerous organs and tissues were considered to be secondary to the primary effect on the kidneys. Other treatment-related effects in rats included effects in the brain (vacuolation of the cerebrum and thalamus/hypothalamus) and respiratory tract (reactive hyperplasia and inflammation of the respiratory epithelium of the nasal turbinates, lung congestion, aggregates of alveolar macrophages). In dogs and mice, increased mortalities, malacia and/or vacuolation in the white matter in the brain, histopathology in the lungs, and follicular cell hypertrophy in the thyroid gland were observed. Decreased body weights and body weight gains were also noted in all three species. No evidence of carcinogenicity was observed in either the combined chronic toxicity/ carcinogenicity study in rats or in the 18-month carcinogenicity study in mice.
-- In specially designed acute and subchronic inhalation neurotoxicity studies in rats, several electrophysiological parameters (EEGs) were recorded in addition to observations for clinical signs of neurotoxicity, functional observational battery (FOB) and motor activity testing, and/or neurohistopathologic examination. Following two exposures on consecutive days for 6 hours/day at 300 ppm of sulfuryl fluoride (354 mg/kg/day), no treatment-related neurotoxic effects were noted. In a 90-day study, changes in some EEG patterns were observed at 100 ppm (80 mg/kg/day) and in several additional patterns at 300 ppm (240 mg/kg/day). Vacuolation of the white matter in the cerebrum was also observed at 300 ppm in this study. In a specially designed 1-year chronic inhalation neurotoxicity study in rats, no treatment-related neurotoxic effects were observed at 80 ppm (56 mg/kg/ day). EEGs were not recorded in this study.
Ref: Federal Register: September 5, 2001 (Volume 66, Number 172). Sulfuryl Fluoride; Proposed Pesticide Temporary Tolerances.
http://www.fluorideaction.org/pesticides/sulfuryl.flu.fr.sept.5.2001.htm

Vikane, sulfuryl fluoride, Lot No. TWP 830919-408, 99.8%, was administered to New Zealand White rabbits via inhalation for 6 hours/day, 5 days/week for 13 weeks at 0, 30, 100 or 300 ppm. Seven animals per sex per group. NOEL = 30 ppm; [cerebral vacuolation in regions of internal and external capsules, putamen, and globus pallidus of one female: and nasal tissue inflammation in one male]. At 300 ppm, common brain findings were vacuolation to severe malacia of cerebrum (both sexes, in the above regions), and gliosis and/or hypertrophy of vascular endothelial cells in some females in the same regions.
Ref: CA EPA, Summary of Toxicolgy Data, August 1, 1986. http://www.cdpr.ca.gov/docs/toxsums/pdfs/618.pdf

The primary effects of sulfuryl fluoride in humans are respiratory irritation and central nervous system depression, followed by excitation and possibly convulsions. Rabbits exposed via inhalation (6 hours/day, 5 days/week, for 2 weeks) to sulfuryl fluoride showed hyperactivity, convulsions and vacuolation of the cerebrum at 600 ppm (2.5 mg/L). Renal lesions were present in all rats exposed by inhalation (6 hours/day, 5 days/week, for 2 weeks) to 600 ppm (2.5 mg/ L) sulfuryl fluoride. Minimal renal changes were noted in rats exposed to 300 ppm (1252 mg/L), whereas no effects occurred at 100 ppm (4.2 mg/ L). Convulsions at near lethal concentrations were reported in rabbits, mice, and rats. In a 30-day inhalation study, loss of control, tremors of the hind quarters, and histopathological changes in the lung, liver, and kidney were reported in rabbits exposed to 400 ppm (1.6 mg/L) for 7 hours/day, 5 days/week for 5 weeks. The NOEL was 200 ppm (0.83 mg/L). Cerebral vacuolation and/or malacia and inflammation of nasal tissues were observed in rabbits exposed by inhalation to 100 or 300 ppm (0.4 or 1.25 mg/L) for 13 weeks. The NOEL was 30 ppm (0.125 mg/L). Rats exposed by inhalation to 100 to 600 ppm (0.4 to 0.25 mg/L) sulfuryl fluoride for 13 weeks developed mottled teeth (indicative of fluoride toxicity), renal and respiratory effects, and cerebral vacuolation. EPA believes that there is sufficient evidence for listing sulfuryl fluoride on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available neurological, renal, and respiratory 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.

CNS (click on for all fluorinated pesticides)

PubMed abstract: This study assessed the health effects associated with occupational exposure to methyl bromide and sulfuryl fluoride among structural fumigation workers... Sulfuryl fluoride exposure over the year preceding examination was associated with significantly reduced performance on the Pattern Memory Test and on olfactory testing... Occupational sulfuryl fluoride exposures may be associated with subclinical effects on the central nervous system, including effects on olfactory and some cognitive functions.
Ref: Am J Public Health 1998 Dec;88(12):1774-80. Health effects associated with sulfuryl fluoride and methyl bromide exposure among structural fumigation workers by Calvert GM et al.

"Sulphuryl fluoride induces CNS depression."
Ref: Pesticide Policies in Zimbabwe. Status and Implications for Change. Godfrey D. Mudimu Hermann Waibel Gerd Fleischer (eds). A Publication of the Pesticide Policy Project Hannover, September 1999 Special Issue Publication Series, No. 1.
http://www.ifgb.uni-hannover.de/ppp/ppp_s01.pdf

A review of unpublished reports of animal experiments apparently ... /indicated/ that dosages sufficient to produce illness from a single exposure produce respiratory irritation, CNS depression, and possible liver and kidney injury. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991. 564]
Ref: Hazardous Substances Data Bank for SULFURYL FLUORIDE CASRN: 2699-79-8.
http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB

The primary effects of sulfuryl fluoride in humans are respiratory irritation and central nervous system depression, followed by excitation and possibly convulsions. Rabbits exposed via inhalation (6 hours/day, 5 days/week, for 2 weeks) to sulfuryl fluoride showed hyperactivity, convulsions and vacuolation of the cerebrum at 600 ppm (2.5 mg/L). Renal lesions were present in all rats exposed by inhalation (6 hours/day, 5 days/week, for 2 weeks) to 600 ppm (2.5 mg/ L) sulfuryl fluoride. Minimal renal changes were noted in rats exposed to 300 ppm (1252 mg/L), whereas no effects occurred at 100 ppm (4.2 mg/ L). Convulsions at near lethal concentrations were reported in rabbits, mice, and rats. In a 30-day inhalation study, loss of control, tremors of the hind quarters, and histopathological changes in the lung, liver, and kidney were reported in rabbits exposed to 400 ppm (1.6 mg/L) for 7 hours/day, 5 days/week for 5 weeks. The NOEL was 200 ppm (0.83 mg/L). Cerebral vacuolation and/or malacia and inflammation of nasal tissues were observed in rabbits exposed by inhalation to 100 or 300 ppm (0.4 or 1.25 mg/L) for 13 weeks. The NOEL was 30 ppm (0.125 mg/L). Rats exposed by inhalation to 100 to 600 ppm (0.4 to 0.25 mg/L) sulfuryl fluoride for 13 weeks developed mottled teeth (indicative of fluoride toxicity), renal and respiratory effects, and cerebral vacuolation. EPA believes that there is sufficient evidence for listing sulfuryl fluoride on EPCRA section 313 pursuant to EPCRA section 313(d)(2)(B) based on the available neurological, renal, and respiratory 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.
http://www.epa.gov/tri/frnotices/59fr1788.htm

Endocrine: Adrenal (click on for all fluorinated pesticides)

- (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

Endocrine: Hypothalmus (click on for all fluorinated pesticides)

Ref: January 23, 2004. Sulfuryl Fluoride; Pesticide Tolerance. 40 CFR Part 180 [OPP-2003-0373; FRL-7342-1]. Final Rule. Federal Register
Excerpts from: Table 1.--Subchronic, Chronic, and Other Toxicity
Study Guideline	Type of Study	NOAEL mg/kg/day	LOAEL mg/kg/day	Based on:
(870.4100)	Chronic toxicity--rodents	3.5 for M 16 for F	14 for M 62 for F	histopathology in brain (vacuolation in cerebrum and thalmus/hypothalmus)
(870.4300)	2-Year combined chronic/ carcinogenicity--rat	3.5 for M 16 for F	14 for M 62 for F	histopathology in brain (vacuolation in cerebrum and thalmus/hypothalmus)

Endocrine: Thyroid (click on for all fluorinated pesticides)

-- In subchronic (90-day) inhalation studies - In mice, follicular cell hypertrophy was noted in the thyroid gland. Decreased body weights and body weight gains were also observed in rats, dogs and mice.
-- In chronic (1-2 year) inhalation studies - . In dogs and mice, increased mortalities, malacia and/or vacuolation in the white matter in the brain, histopathology in the lungs, and follicular cell hypertrophy in the thyroid gland were observed. Decreased body weights and body weight gains were also noted in all three species. No evidence of carcinogenicity was observed in either the combined chronic toxicity/ carcinogenicity study in rats or in the 18-month carcinogenicity study in mice.
Ref: Federal Register: September 5, 2001 (Volume 66, Number 172). Sulfuryl Fluoride; Proposed Pesticide Temporary Tolerances.
http://www.fluorideaction.org/pesticides/sulfuryl.flu.fr.sept.5.2001.htm

18-Month carcinogenicity NOAEL = 25/25 (M/F) mg/kg/day inhalation study--mouse LOAEL = 101/101 (M/F) mg/kg/day based (870.4200) on for both M/F cerebral vacuolation in brain, decreased body weight gain, follicular hypertrophy in thyroid (M only), increased mortality (F only), heart thrombus (F only), and lung congestion (F only). No evidence of carcinogenicity in M or F.
Ref: January 23, 2004. Sulfuryl Fluoride; Pesticide Tolerance.
40 CFR Part 180 [OPP-2003-0373; FRL-7342-1]. Final Rule. Federal Register

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