Ether, 1-chloro-2,2,2-trifluoroethyl difluoromethyl

RTECS #
KN6799000
CAS #
26675-46-7
See: NMAM or OSHA Methods
Updated
March 2019
Molecular Weight
184.50
Molecular Formula
C3H2ClF5O
Synonyms
(+-)-Isoflurane
2-Chloro-2-(difluoromethoxy)-1,1,1-trifluoroethane
Ethane, 2-chloro-2-(difluoromethoxy)-1,1,1-trifluoro- (9CI)
Forane
ISF
Isoflurane
Pentafluoran
R-E 235dal

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
DNA Damageinhalation/human1 pph/2HMUREAV 492,99,2001
DNA Damageinhalation/rat1 pph/30MTXCYAC 220,169,2006
micronucleus testoral/rat4 mmol/kgMUREAV 413,1,1998

Reproductive Effects Data and References

Route/OrganismDoseEffectReference
inhalation/rat 10500 ppm/6H (14-16D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)ANESAV 64,339,1986
inhalation/rat 4000 ppm/3H (7-17D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)KSRNAM 21,3091,1987
inhalation/rat 12000 ppm/3H (17-20D preg/21D after birth)Reproductive: Effects on newborn: PhysicalKSRNAM 21,3109,1987
inhalation/mouse 6000 ppm/4H (6-15D pregnant)Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Musculoskeletal system

Reproductive: Specific developmental abnormalities: Urogenital system
TJADAB 29(2),54A,1984
inhalation/rat 1.3 pph (21D pregnant)Reproductive: Other effects to embryo or fetusNEPHBW 53,942,2007

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
In Vitro/Human, lymphocyte Inhibitor Concentration Low: 0.5 pph/4HImmunological Including Allergic: Decrease in cellular immune responseTOLED5 266,23,2017
In Vitro/Human, neuroblastoma Inhibitor Concentration Low: 0.56 mmol/l/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.NETEEC 65,19,2018
In Vitro/maaInhibitor Concentration Low: 0.8 mmol/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.

In Vitro Toxicity Studies: Other assays
TXAPA9 250,291,2011
In Vitro/maaInhibitor Concentration Low: 0.8 mmol/L/12.5MNutritional and Gross Metabolic: Changes in: CaTXAPA9 250,291,2011
In Vitro/maaInhibitor Concentration Low: 0.8 mmol/L/4.2MNutritional and Gross Metabolic: Changes in: CaTXAPA9 250,291,2011
In Vitro/maaInhibitor Concentration Low: 0.8 mmol/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TXAPA9 250,291,2011
In Vitro/paxInhibitor Concentration Low: 1.5 pph/6HIn Vitro Toxicity Studies: Apoptosis in vitro

In Vitro Toxicity Studies: Other assays
TOLED5 233,102,2015
inhalation/human lowest published toxic concentration: 1.8 pphCardiac: Change in rate

Vascular: BP lowering not characterized in autonomic section

Vascular: Other changes
AANEAB 45,971,2001
inhalation/monkey lowest published toxic concentration: 1.9 pph/5HBrain and Coverings: Other degenerative changesNETEEC 60,63,2017
inhalation/mouse lowest published toxic concentration: 1.30 pph/80MBehavioral: General anestheticNETEEC 60,69,2017
inhalation/mouse lowest published toxic concentration: 0.73 pph/80MBehavioral: Altered sleep time (including change in righting reflex)NETEEC 60,69,2017
inhalation/mouse lowest published toxic concentration: 2 pph/1HBehavioral: Alteration of classical conditioningNETEEC 61,92,2017
inhalation/mouse lowest published toxic concentration: 1.5 pph/12MBehavioral: General anestheticJPETAB 323,924,2007
inhalation/mouse lethal concentration (50 percent kill): 16800 ppm/3HBehavioral: Somnolence (general depressed activity)

Behavioral: Excitement

Lung, Thorax, or Respiration: Respiratory depression
KSRNAM 21,3031,1987
inhalation/mouse lethal concentration (16 percent kill): 35.3 gm/m3/2HBehavioral: General anesthetic

Behavioral: Ataxia

Lung, Thorax, or Respiration: Respiratory depression
TOVEFN (5),12,1998
inhalation/mouse lethal concentration (50 percent kill): 50.5 gm/m3/2HBehavioral: General anesthetic

Behavioral: Ataxia

Lung, Thorax, or Respiration: Respiratory depression
TOVEFN (5),12,1998
inhalation/mouse lowest published toxic concentration: 1.27 pph/6MBehavioral: AnalgesiaJPETAB 317,615,2006
inhalation/rat lowest published toxic concentration: 1.5 pph/5HVascular: BP lowering not characterized in autonomic section

Kidney, Ureter, and Bladder: Hematuria

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects
FCTOD7 46,3550,2008
inhalation/rat Lowest published lethal concentration: 1.5 pph/2HLung, Thorax, or Respiration: Acute pulmonary edema

Lung, Thorax, or Respiration: Pleural effusion
FCTOD7 46,3550,2008
inhalation/rat lowest published toxic concentration: 1.5 pph/1HVascular: BP lowering not characterized in autonomic sectionFCTOD7 46,3550,2008
inhalation/rat lowest published toxic concentration: 1 pph/30MBrain and Coverings: Other degenerative changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other enzymes

Biochemical: Metabolism (intermediary): Other
AANEAB 46,378,2002
inhalation/rat lowest published toxic concentration: 1.2 pph/30MBehavioral: AnalgesiaAANEAB 46,451,2002
inhalation/rat lowest published toxic concentration: 1 pph/90MBrain and Coverings: Other degenerative changesEJPHAZ 503,49,2004
inhalation/rat lethal concentration (50 percent kill): 15300 ppm/3HBehavioral: Somnolence (general depressed activity)

Behavioral: Excitement

Lung, Thorax, or Respiration: Respiratory depression
KSRNAM 21,3031,1987
inhalation/rat lethal concentration (16 percent kill): 35.2 gm/m3/4HBehavioral: General anesthetic

Behavioral: Ataxia

Lung, Thorax, or Respiration: Respiratory depression
TOVEFN (5),12,1998
inhalation/rat lethal concentration (50 percent kill): 58.5 gm/m3/4HBehavioral: General anesthetic

Behavioral: Ataxia

Lung, Thorax, or Respiration: Respiratory depression
TOVEFN (5),12,1998
inhalation/rat lowest published toxic concentration: 1.5 pph/6HBrain and Coverings: Other degenerative changes

Behavioral: Alteration of classical conditioning
TOLED5 233,102,2015
intraperitoneal/mouse lowest published lethal dose: 60000 mg/kgTOVEFN (5),12,1998
intraperitoneal/mouse lethal dose (50 percent kill): 3030 µL/kgBehavioral: Ataxia

Lung, Thorax, or Respiration: Respiratory depression

Nutritional and Gross Metabolic: Body temperature decrease
KSRNAM 21,3031,1987
intraperitoneal/mouse lowest published toxic dose: 5.5 gm/kgBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: TransaminasesTOLED5 228,13,2014
intraperitoneal/mouse lowest published toxic dose: 0.729 mL/kgBehavioral: Altered sleep time (including change in righting reflex)BCLPT* 103,31,2008
intraperitoneal/mouse lowest published toxic dose: 0.4 mL/kgBehavioral: AnalgesiaBCLPT* 105,120,2009
intraperitoneal/rat lethal dose (50 percent kill): 4280 µL/kgBehavioral: Ataxia

Lung, Thorax, or Respiration: Respiratory depression

Nutritional and Gross Metabolic: Body temperature decrease
KSRNAM 21,3031,1987
intraperitoneal/rat lethal dose (16 percent kill): 10250 mg/kgTOVEFN (5),12,1998
intraperitoneal/rat lethal dose (50 percent kill): 14400 mg/kgTOVEFN (5),12,1998
intraperitoneal/rat lowest published lethal dose: 20200 mg/kgTOVEFN (5),12,1998
oral/man lowest published lethal dose: 1143 µL/kgBrain and Coverings: Changes in surface EEG

Behavioral: Muscle weakness

Blood: Changes in leukocyte (WBC) count
NLJMAV 33,74,1988
oral/man lowest published lethal dose: 1071 µL/kgJFSCAS 38,968,1993
oral/mouse lethal dose (50 percent kill): 5080 µL/kgBehavioral: Ataxia

Lung, Thorax, or Respiration: Respiratory depression

Nutritional and Gross Metabolic: Body temperature decrease
KSRNAM 21,3031,1987
oral/rat lethal dose (50 percent kill): 4770 µL/kgBehavioral: Ataxia

Lung, Thorax, or Respiration: Respiratory depression

Nutritional and Gross Metabolic: Body temperature decrease
KSRNAM 21,3031,1987

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
inhalation/guinea pig lowest published toxic concentration: 1500 ppm/24H/5W- continuousNutritional and Gross Metabolic: Weight loss or decreased weight gainANESAV 42,408,1975
inhalation/mouse lowest published toxic concentration: 150 ppm/24H/5W- continuousNutritional and Gross Metabolic: Weight loss or decreased weight gainANESAV 42,408,1975
inhalation/rat lowest published toxic concentration: 12000 ppm/3H/10W- intermittentEndocrine: Changes in adrenal weight

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
KSRNAM 21,3037,1987
inhalation/rat lowest published toxic concentration: 24 gm/m3/3D- intermittentBiochemical: Metabolism (intermediary): OtherTOVEFN (5),12,1998

Reviews

OrganizationStandardReference
International Agency for Research on Cancer (IARC)Cancer Review:Animal Inadequate EvidenceIMSUDL 7,93,1987
TOXICOLOGY REVIEWTPHSDY 23,519,2002
TOXICOLOGY REVIEWTPHSDY 24,648,2003
TOXICOLOGY REVIEWMUREAV 566,209,2004
TOXICOLOGY REVIEWDIMON* 39,678,1993
TOXICOLOGY REVIEWENTOX* -,125,2005
TOXICOLOGY REVIEWHUTOX* -,577,1996
TOXICOLOGY REVIEWNCLNA* 16,503,1998
TOXICOLOGY REVIEWMUREAV 721,27,2011
TOXICOLOGY REVIEWMUTAEX 30,459,2015
TOXICOLOGY REVIEWMUREAV 770,26,2016
TOXICOLOGY REVIEWNETEEC 60,102,2017
TOXICOLOGY REVIEWNETEEC 60,117,2017
TOXICOLOGY REVIEWNETEEC 60,2,2017
TOXICOLOGY REVIEWNETEEC 60,24,2017
TOXICOLOGY REVIEWNETEEC 60,33,2017
TOXICOLOGY REVIEWNETEEC 60,50,2017
TOXICOLOGY REVIEWNETEEC 60,59,2017
TOXICOLOGY REVIEWNETEEC 60,95,2017
TOXICOLOGY REVIEWRTOPDW 59,364,2011

Standards and Regulations

OrganizationStandardReference
Occupational Exposure Limit-AUSTRIAMAK-TMW 10 ppm (80 mg/m3);KZW 20 ppm (160 mg/m3), 2007
Occupational Exposure Limit-FINLANDtime-weighted average 10 ppm (77 mg/m3), short term exposure limit 20 ppm (150 mg/m3), NOV2011
Occupational Exposure Limit-NORWAYtime-weighted average 2 ppm (15 mg/m3), JAN1999
Occupational Exposure Limit-PERUtime-weighted average 50 ppm (377 mg/m3), JUL2005
Occupational Exposure Limit-SWEDENtime-weighted average 10 ppm (80 mg/m3);short term exposure limit 20 ppm (150 mg/m3), JUN2005
Occupational Exposure Limit-SWITZERLANDMAK-week 10 ppm (77 mg/m3), KZG-week 80 ppm (616 mg/m3), JAN2011
Occupational Exposure Limit-THE NETHERLANDSMAC-TGG 153 mg/m3, 2003
Occupational Exposure Limit-UNITED KINGDOMtime-weighted average 50 ppm (383 mg/m3), OCT2007

NIOSH Documentation and Surveillance

OrganizationStandardReference
National Occupational Exposure Survey 1983Hazard Code X3787; Number of Industries 2; Total Number of Facilities 1009; Number of Occupations 7; Total Number of Employees Exposed 33152; Total Number of Female Employees Exposed 27151

Status in Federal Agencies

OrganizationReference
EPA GENETOX PROGRAM 1988, Inconclusive: Histidine reversion-Ames test
EPA GENETOX PROGRAM 1988, Negative: Sperm morphology-mouse
OSHA ANALYTICAL METHOD #103
Page last reviewed: November 16, 2018