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Registry of Toxic Effects of Chemical Substances (RTECS)

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

RTECS #

KN6799000

CAS #

26675-46-7

Updated

December 2013

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/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
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/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/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 lowest published toxic concentration: 1.5 pph/12MBehavioral: General anestheticJPETAB 323,924,2007
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/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
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/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 lethal dose: 60000 mg/kgTOVEFN (5),12,1998
intraperitoneal/rat lowest published lethal dose: 20200 mg/kgTOVEFN (5),12,1998
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
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

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
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