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 Test	Route/Organism/Tissue	Dose	Reference
DNA Damage	inhalation/human	1 pph/2H	MUREAV 492,99,2001
DNA Damage	inhalation/rat	1 pph/30M	TXCYAC 220,169,2006
micronucleus test	oral/rat	4 mmol/kg	MUREAV 413,1,1998

Reproductive Effects Data and References

Route/Organism	Dose	Effect	Reference
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: Physical	KSRNAM 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 fetus	NEPHBW 53,942,2007

Acute Toxicity Data and References

Route/Organism	Dose	Effect	Reference
In Vitro/Human, lymphocyte	Inhibitor Concentration Low: 0.5 pph/4H	Immunological Including Allergic: Decrease in cellular immune response	TOLED5 266,23,2017
In Vitro/Human, neuroblastoma	Inhibitor Concentration Low: 0.56 mmol/l/24H	In Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.	NETEEC 65,19,2018
In Vitro/maa	Inhibitor Concentration Low: 0.8 mmol/L/24H	In 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/maa	Inhibitor Concentration Low: 0.8 mmol/L/12.5M	Nutritional and Gross Metabolic: Changes in: Ca	TXAPA9 250,291,2011
In Vitro/maa	Inhibitor Concentration Low: 0.8 mmol/L/4.2M	Nutritional and Gross Metabolic: Changes in: Ca	TXAPA9 250,291,2011
In Vitro/maa	Inhibitor Concentration Low: 0.8 mmol/L/24H	In Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.	TXAPA9 250,291,2011
In Vitro/pax	Inhibitor Concentration Low: 1.5 pph/6H	In Vitro Toxicity Studies: Apoptosis in vitro In Vitro Toxicity Studies: Other assays	TOLED5 233,102,2015
inhalation/human	lowest published toxic concentration: 1.8 pph	Cardiac: 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/5H	Brain and Coverings: Other degenerative changes	NETEEC 60,63,2017
inhalation/mouse	lowest published toxic concentration: 1.30 pph/80M	Behavioral: General anesthetic	NETEEC 60,69,2017
inhalation/mouse	lowest published toxic concentration: 0.73 pph/80M	Behavioral: Altered sleep time (including change in righting reflex)	NETEEC 60,69,2017
inhalation/mouse	lowest published toxic concentration: 2 pph/1H	Behavioral: Alteration of classical conditioning	NETEEC 61,92,2017
inhalation/mouse	lowest published toxic concentration: 1.5 pph/12M	Behavioral: General anesthetic	JPETAB 323,924,2007
inhalation/mouse	lethal concentration (50 percent kill): 16800 ppm/3H	Behavioral: 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/m³/2H	Behavioral: General anesthetic Behavioral: Ataxia Lung, Thorax, or Respiration: Respiratory depression	TOVEFN (5),12,1998
inhalation/mouse	lethal concentration (50 percent kill): 50.5 gm/m³/2H	Behavioral: General anesthetic Behavioral: Ataxia Lung, Thorax, or Respiration: Respiratory depression	TOVEFN (5),12,1998
inhalation/mouse	lowest published toxic concentration: 1.27 pph/6M	Behavioral: Analgesia	JPETAB 317,615,2006
inhalation/rat	lowest published toxic concentration: 1.5 pph/5H	Vascular: 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/2H	Lung, 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/1H	Vascular: BP lowering not characterized in autonomic section	FCTOD7 46,3550,2008
inhalation/rat	lowest published toxic concentration: 1 pph/30M	Brain 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/30M	Behavioral: Analgesia	AANEAB 46,451,2002
inhalation/rat	lowest published toxic concentration: 1 pph/90M	Brain and Coverings: Other degenerative changes	EJPHAZ 503,49,2004
inhalation/rat	lethal concentration (50 percent kill): 15300 ppm/3H	Behavioral: 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/m³/4H	Behavioral: General anesthetic Behavioral: Ataxia Lung, Thorax, or Respiration: Respiratory depression	TOVEFN (5),12,1998
inhalation/rat	lethal concentration (50 percent kill): 58.5 gm/m³/4H	Behavioral: General anesthetic Behavioral: Ataxia Lung, Thorax, or Respiration: Respiratory depression	TOVEFN (5),12,1998
inhalation/rat	lowest published toxic concentration: 1.5 pph/6H	Brain and Coverings: Other degenerative changes Behavioral: Alteration of classical conditioning	TOLED5 233,102,2015
intraperitoneal/mouse	lowest published lethal dose: 60000 mg/kg		TOVEFN (5),12,1998
intraperitoneal/mouse	lethal dose (50 percent kill): 3030 µL/kg	Behavioral: 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/kg	Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases	TOLED5 228,13,2014
intraperitoneal/mouse	lowest published toxic dose: 0.729 mL/kg	Behavioral: Altered sleep time (including change in righting reflex)	BCLPT* 103,31,2008
intraperitoneal/mouse	lowest published toxic dose: 0.4 mL/kg	Behavioral: Analgesia	BCLPT* 105,120,2009
intraperitoneal/rat	lethal dose (50 percent kill): 4280 µL/kg	Behavioral: 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/kg		TOVEFN (5),12,1998
intraperitoneal/rat	lethal dose (50 percent kill): 14400 mg/kg		TOVEFN (5),12,1998
intraperitoneal/rat	lowest published lethal dose: 20200 mg/kg		TOVEFN (5),12,1998
oral/man	lowest published lethal dose: 1143 µL/kg	Brain 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/kg		JFSCAS 38,968,1993
oral/mouse	lethal dose (50 percent kill): 5080 µL/kg	Behavioral: 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/kg	Behavioral: 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/Organism	Dose	Effect	Reference
inhalation/guinea pig	lowest published toxic concentration: 1500 ppm/24H/5W- continuous	Nutritional and Gross Metabolic: Weight loss or decreased weight gain	ANESAV 42,408,1975
inhalation/mouse	lowest published toxic concentration: 150 ppm/24H/5W- continuous	Nutritional and Gross Metabolic: Weight loss or decreased weight gain	ANESAV 42,408,1975
inhalation/rat	lowest published toxic concentration: 12000 ppm/3H/10W- intermittent	Endocrine: 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- intermittent	Biochemical: Metabolism (intermediary): Other	TOVEFN (5),12,1998

Reviews

Organization	Standard	Reference
International Agency for Research on Cancer (IARC)	Cancer Review:Animal Inadequate Evidence	IMSUDL 7,93,1987
TOXICOLOGY REVIEW		TPHSDY 23,519,2002
TOXICOLOGY REVIEW		TPHSDY 24,648,2003
TOXICOLOGY REVIEW		MUREAV 566,209,2004
TOXICOLOGY REVIEW		DIMON* 39,678,1993
TOXICOLOGY REVIEW		ENTOX* -,125,2005
TOXICOLOGY REVIEW		HUTOX* -,577,1996
TOXICOLOGY REVIEW		NCLNA* 16,503,1998
TOXICOLOGY REVIEW		MUREAV 721,27,2011
TOXICOLOGY REVIEW		MUTAEX 30,459,2015
TOXICOLOGY REVIEW		MUREAV 770,26,2016
TOXICOLOGY REVIEW		NETEEC 60,102,2017
TOXICOLOGY REVIEW		NETEEC 60,117,2017
TOXICOLOGY REVIEW		NETEEC 60,2,2017
TOXICOLOGY REVIEW		NETEEC 60,24,2017
TOXICOLOGY REVIEW		NETEEC 60,33,2017
TOXICOLOGY REVIEW		NETEEC 60,50,2017
TOXICOLOGY REVIEW		NETEEC 60,59,2017
TOXICOLOGY REVIEW		NETEEC 60,95,2017
TOXICOLOGY REVIEW		RTOPDW 59,364,2011

Standards and Regulations

Organization	Standard	Reference
Occupational Exposure Limit-AUSTRIA	MAK-TMW 10 ppm (80 mg/m³);KZW 20 ppm (160 mg/m³), 2007
Occupational Exposure Limit-FINLAND	time-weighted average 10 ppm (77 mg/m³), short term exposure limit 20 ppm (150 mg/m³), NOV2011
Occupational Exposure Limit-NORWAY	time-weighted average 2 ppm (15 mg/m³), JAN1999
Occupational Exposure Limit-PERU	time-weighted average 50 ppm (377 mg/m³), JUL2005
Occupational Exposure Limit-SWEDEN	time-weighted average 10 ppm (80 mg/m³);short term exposure limit 20 ppm (150 mg/m³), JUN2005
Occupational Exposure Limit-SWITZERLAND	MAK-week 10 ppm (77 mg/m³), KZG-week 80 ppm (616 mg/m³), JAN2011
Occupational Exposure Limit-THE NETHERLANDS	MAC-TGG 153 mg/m³, 2003
Occupational Exposure Limit-UNITED KINGDOM	time-weighted average 50 ppm (383 mg/m³), OCT2007

NIOSH Documentation and Surveillance

Organization	Standard	Reference
National Occupational Exposure Survey 1983	Hazard 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

Organization	Reference
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

Content source: National Institute for Occupational Safety and Health