Sulfuryl fluoride – Fumigant insecticide – CAS No. 2699-79-8
Molecular formula for Sulfuryl Fluoride:

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.
— 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.
https://www.gpo.gov/fdsys/pkg/FR-2001-09-05/pdf/01-22283.pdf

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.

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.

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