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 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/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
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/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/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	lowest published toxic concentration: 1.5 pph/12M	Behavioral: General anesthetic	JPETAB 323,924,2007
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/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
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/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 lethal dose: 60000 mg/kg		TOVEFN (5),12,1998
intraperitoneal/rat	lowest published lethal dose: 20200 mg/kg		TOVEFN (5),12,1998
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
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

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

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Page last reviewed:March 7, 2014
Page last updated:February 6, 2017
Content source:
- National Institute for Occupational Safety and Health (NIOSH) Education and Information Division

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