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Phthalic anhydride

RTECS #
TI3150000
CAS #
85-44-9
See: NMAM or OSHA Methods
Updated
December 2018
Molecular Weight
148.12
Molecular Formula
C8H4O3
Synonyms
1,2-Benzenedicarboxylic acid anhydride
1,3-Dioxophthalan
1,3-Isobenzofurandione
1,3-Phthalandione
Anhydrid kyseliny ftalove (Czech)
Anhydride phtalique (French)
Anidride ftalica (Italian)
ESEN
Ftaalzuuranhydride (Dutch)
Ftalanhydrid (Czech)
Ftalowy bezwodnik (Polish)
Isobenzofuran, 1,3-dihydro-1,3-dioxo-
NCI-C03601
Phthalandione
Phthalic acid anhydride
Phthalic anhydride (ACGIH:OSHA)
Phthalsaeureanhydrid (German)
RCRA waste number U190
Retarder AK
Retarder PD
Vulkalent B

Skin and Eye Irritation and References

Route/OrganismDoseEffectReference
eye /rabbit 50 mg/24H moderateATDAEI 15(Suppl 1),S68,1996

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
DNA Damageliver/rat3 mmol/LEMMUEG 24,181,1994
DNA Damageother cell types/human1000 µmol/L/24HMUTAEX 31,83,2016
micronucleus testlymphocyte/mouse140 mg/L/3HMUREAV 789,7,2015
micronucleus testother cell types/human150 mg/L/3HMUREAV 789,7,2015
micronucleus testlung/hamster1380 mg/L/3H (-enzymatic activation step)MUREAV 742,11,2012
micronucleus testother cell types/human575 mg/L/3H (-enzymatic activation step)MUREAV 742,11,2012
micronucleus testliver/human1481 mg/L/3H (-enzymatic activation step)MUREAV 742,11,2012
specific locus testother cell types/human1000 µmol/L/24HEMMUEG 54,737,2013

Reproductive Effects Data and References

Route/OrganismDoseEffectReference
inhalation/rat 1 mg/m3 (45D male)Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Reproductive: Paternal effects: Testes, epididymis, sperm duct
GISAAA 35(1),105,1970
intraperitoneal/mouse 203 mg/kg (8-10D pregnant)Reproductive: Other developmental abnormalitiesTCMUD8 2,61,1982

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
In Vitro/Human, leukemia cells Inhibitor Concentration (5 percent kill): 475 mg/L/30MIn Vitro Toxicity Studies: Cell countingTIVIEQ 27,857,2013
In Vitro/Human, lung Inhibitor Concentration (20 percent kill): 1.33 mmol/LIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 30,274,2015
In Vitro/Human, lymphocyte Inhibitor Concentration (30 percent kill): >200 mg/L/45HIn Vitro Toxicity Studies: Cell viability (dye exclusion): trypan blue assay etc.TIVIEQ 29,901,2015
In Vitro/Human, lymphocyte Inhibitor Concentration (50 percent kill): >200 mg/L/45HIn Vitro Toxicity Studies: Other assaysTIVIEQ 29,901,2015
In Vitro/Human, melanoma Inhibitor Concentration (50 percent kill): 755.4 mg/L/48HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.FCTOD7 50,2084,2012
In Vitro/Human, monocyte Inhibitor Concentration Low: 2500 mg/L/2HIn Vitro Toxicity Studies: Other assaysTIVIEQ 27,1233,2013
In Vitro/Human, skin Inhibitor Concentration (50 percent kill): >2000 µmol/L/48HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 29,688,2015
In Vitro/Human, skin Inhibitor Concentration (50 percent kill): >2000 µmol/L/48HIn Vitro Toxicity Studies: Cell metabolic activity: Alamar Blue assay etc.TIVIEQ 29,688,2015
In Vitro/Human, skin Inhibitor Concentration (30 percent kill): 1994.9 µmol/L/48HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 29,688,2015
In Vitro/Human, skin Inhibitor Concentration (30 percent kill): >2000 µmol/L/48HIn Vitro Toxicity Studies: Cell metabolic activity: Alamar Blue assay etc.TIVIEQ 29,688,2015
In Vitro/jrdInhibitor Concentration (50 percent kill): >3200 mg/L/24HIn Vitro Toxicity Studies: Other assaysTIVIEQ 28,626,2014
intraperitoneal/guinea pig lethal dose (50 percent kill): 100 mg/kg29ZWAE -,410,1968
intratracheal/rat Lethal dose: >30 mg/kgGastrointestinal: Hypermotility, diarrhea

Gastrointestinal: Necrotic changes

Liver: Fatty liver degeneration
TPKVAL 2,59,1961
ocular/rabbit lowest published toxic dose: 100 pphEye: Conjunctiva irritationTPKVAL 4,35,1962
oral/cat lethal dose (50 percent kill): 800 mg/kg85JCAE -,322,1986
oral/mouse lowest published lethal dose: 1000 mg/kgLung, Thorax, or Respiration: Structural or functional change in trachea or bronchi

Lung, Thorax, or Respiration: Changes in pulmonary vascular resistance

Gastrointestinal: Ulceration or bleeding from stomach
TPKVAL 2,59,1961
oral/mouse lethal dose (50 percent kill): 1500 mg/kgTPKVAL 2,59,1961
oral/rat lowest published lethal dose: 1500 mg/kgTPKVAL 2,59,1961
oral/rat lethal dose (50 percent kill): 1530 mg/kgBehavioral: Somnolence (general depressed activity)ATDAEI 15(Suppl 1),S68,1996
rectal/mouse lethal dose (50 percent kill): 400 mg/kgFCTOD7 41,405,2003

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
inhalation/mouse lowest published toxic concentration: 15 mg/m3/3D- intermittentImmunological Including Allergic: Increased immune response

Biochemical: Metabolism (intermediary): Other proteins

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TXCYAC 261,103,2009
inhalation/rat lowest published toxic concentration: 0.1 gm/m3/14D- intermittentLung, Thorax, or Respiration: Structural or functional change in trachea or bronchi

Lung, Thorax, or Respiration: Other changes

Liver: Other changes
TPKVAL 2,59,1961
inhalation/rat lowest published toxic concentration: 500 µg/m3/5D- intermittentLung, Thorax, or Respiration: Other changes

Immunological Including Allergic: Increase in humoral response
TOXID9 60,173,2001
inhalation/rat lowest published toxic concentration: 0.008 gm/m3/30D- intermittentPeripheral Nerve and Sensation: Recording from peripheral motor nerve

Blood: Eosinophilia

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
TPKVAL 4,35,1962
inhalation/rat lowest published toxic concentration: 0.008 gm/m3/0.5Y- intermittentLung, Thorax, or Respiration: Structural or functional change in trachea or bronchi

Liver: Other changes

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)
TPKVAL 4,35,1962
oral/guinea pig lowest published toxic dose: 6 gm/kg/42D- intermittentLung, Thorax, or Respiration: Other changes

Gastrointestinal: Gastritis

Gastrointestinal: Other changes
TPKVAL 2,59,1961
oral/guinea pig lowest published toxic dose: 10500 mg/kg/42D- intermittentNutritional and Gross Metabolic: Weight loss or decreased weight gain

Biochemical: Metabolism (intermediary): Other proteins
TPKVAL 2,59,1961
oral/guinea pig lowest published toxic dose: 7000 mg/kg/28D- intermittentLung, Thorax, or Respiration: Changes in pulmonary vascular resistance

Gastrointestinal: Gastritis

Gastrointestinal: Necrotic changes
TPKVAL 2,59,1961
oral/rat lowest published toxic dose: 7000 mg/kg/4W- intermittentReproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
TERP2* -,310,2004
skin/mouse lowest published toxic dose: 25 pph/3D- intermittentImmunological Including Allergic: Increased immune response

Biochemical: Metabolism (intermediary): Other proteins

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TXCYAC 261,103,2009
skin/mouse lowest published toxic dose: 1036 mg/kg/13D- intermittentImmunological Including Allergic: Increase in cellular immune response

Immunological Including Allergic: Hypersensitivity delayed (multiple organ involvement)
JJATDK 20,221,2000
skin/mouse lowest published toxic dose: 3 mg/kg/3D- intermittentImmunological Including Allergic: Increase in cellular immune responseJJATDK 20,221,2000
skin/mouse lowest published toxic dose: 60 mg/kg/3D- intermittentSkin: After topical application: Cutaneous sensitization (experimental)

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TXAPA9 184,46,2002
skin/mouse lowest published toxic dose: 90 mg/kg/3D- intermittentSkin: After topical application: Cutaneous sensitization (experimental)TXCYAC 193,191,2003
unreported route/guinea pig lowest published toxic dose: 5000 mg/kg/50D- intermittentCardiac: Other changes

Liver: Other changes

Kidney, Ureter, and Bladder: Other changes
TPKVAL 2,59,1961

Reviews

OrganizationStandardReference
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-time-weighted average 1 ppm (sen)DTLVS* TLV/BEI,2013
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-Not classifiable as a human carcinogenDTLVS* TLV/BEI,2013
TOXICOLOGY REVIEWBPCT** -,183,1974
TOXICOLOGY REVIEWEVHPAZ 4,3,1973
TOXICOLOGY REVIEWCMTVAS 10(3),49,1973
TOXICOLOGY REVIEWTOLED5 140-141,213,2003
TOXICOLOGY REVIEWEMMUEG 43,36,2004
TOXICOLOGY REVIEWMUREAV 584,1,2005
TOXICOLOGY REVIEWMUREAV 653,99,2008
TOXICOLOGY REVIEWFCTOD7 49,1877,2011
TOXICOLOGY REVIEWFCTOD7 55,596,2013
TOXICOLOGY REVIEWMUREAV 802,1,2016
TOXICOLOGY REVIEWRTOPDW 55,43,2009
TOXICOLOGY REVIEWRTOPDW 56,54,2010

Standards and Regulations

OrganizationStandardReference
Mine Safety and Health Administration (MSHA) STANDARD-airtime-weighted average 2 ppm (12 mg/m3)DTLVS* 3,212,1971
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN check ACGIH TLV;
Occupational Exposure Limit IN SINGAPORE, VIETNAM check ACGIH TLV
Occupational Exposure Limit-AUSTRALIAtime-weighted average 1 ppm (6.1 mg/m3), JUL2008
Occupational Exposure Limit-AUSTRIAMAK-TMW 1 mg/m3;KZW 2 mg/m3, inhal, sen, 2007
Occupational Exposure Limit-BELGIUMtime-weighted average 1 ppm (6.2 mg/m3), MAR2002
Occupational Exposure Limit-DENMARKtime-weighted average 1 mg/m3, MAY2011
Occupational Exposure Limit-FINLANDtime-weighted average 0.2 mg/m3, NOV2011
Occupational Exposure Limit-FRANCEVLE 6 mg/m3, FEB2006
Occupational Exposure Limit-HUNGARYtime-weighted average 1 mg/m3, short term exposure limit 1 mg/m3, SEP2000
Occupational Exposure Limit-ICELANDtime-weighted average 1 ppm (6 mg/m3), sen, NOV2011
Occupational Exposure Limit-JAPANceiling concentration 0.33 ppm (0.2 mg/m3), a1 sen, MAY2012
Occupational Exposure Limit-KOREAtime-weighted average 1 ppm (6 mg/m3), 2006
Occupational Exposure Limit-MEXICOtime-weighted average 1 ppm (6 mg/m3);short term exposure limit 4 ppm (24 mg/m3), 2004
Occupational Exposure Limit-NEW ZEALANDtime-weighted average 1 ppm (6.1 mg/m3), sen, JAN2002
Occupational Exposure Limit-NORWAYtime-weighted average 2 mg/m3, JAN1999
Occupational Exposure Limit-PERUtime-weighted average 1 ppm (6 mg/m3), JUL2005
Occupational Exposure Limit-POLANDMAC(time-weighted average) 1 mg/m3, short term exposure limit 2 mg/m3 (vapors and aerosols), JAN1999
Occupational Exposure Limit-RUSSIAshort term exposure limit 1 mg/m3, Skin, JUN2003
Occupational Exposure Limit-SWEDENtime-weighted average 2 mg/m3, ceiling concentration 3 mg/m3, Sen, JUN2005
Occupational Exposure Limit-SWITZERLANDceiling concentration 1 mg/m3, inhal, sen, JAN2011
Occupational Exposure Limit-THE NETHERLANDSMAC-TGG 1 mg/m3, 2003
Occupational Exposure Limit-THE PHILIPPINEStime-weighted average 2 ppm (12 mg/m3), JAN1993
Occupational Exposure Limit-UNITED KINGDOMtime-weighted average 4 mg/m3;short term exposure limit 12 mg/m3, sen, OCT2007
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Construction)8H time-weighted average 2 ppm (12 mg/m3)CFRGBR 29,1926.55,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Federal Contractors)8H time-weighted average 2 ppm (12 mg/m3)CFRGBR 41,50-204.50,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (General Industry)8H time-weighted average 2 ppm (12 mg/m3)CFRGBR 29,1910.1000,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Shipyards)8H time-weighted average 2 ppm (12 mg/m3)CFRGBR 29,1915.1000,1993

NIOSH Documentation and Surveillance

OrganizationStandardReference
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO PHTHALIC ANHYDRIDE-air10H time-weighted average 1 ppmNIOSH* DHHS #92-100,1992
National Occupational Exposure Survey 1983Hazard Code 59230; Number of Industries 72; Total Number of Facilities 5265; Number of Occupations 67; Total Number of Employees Exposed 81312; Total Number of Female Employees Exposed 14675
National Occupational Hazard Survey 1974Hazard Code 59230; Number of Industries 128; Total Number of Facilities 10056; Number of Occupations 90; Total Number of Employees Exposed 134716

Status in Federal Agencies

OrganizationReference
EPA GENETOX PROGRAM 1988, Negative: Carcinogenicity-mouse/rat
EPA TSCA Section 8(b) CHEMICAL INVENTORY
EPA TSCA Section 8(d) unpublished health/safety studies
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001
NCI Carcinogenesis Bioassay (feed);no evidence:mouse,ratNCITR* NCI-TR-159,1979
On EPA IRIS database
OSHA ANALYTICAL METHOD #90
Page last reviewed: November 16, 2018