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Phthalic acid, diethyl ester

RTECS #
TI1050000
CAS #
84-66-2
See: NMAM or OSHA Methods
Updated
March 2019
Molecular Weight
222.26
Molecular Formula
C12H14O4
Synonyms
1,2-Benzenedicarboxylic acid, diethyl ester
Anozol
DEP
Diethyl 1,2-benzenedicarboxylate
Diethyl o-phthalate
Diethyl phthalate
Diethyl phthalate (ACGIH)
Diethylester kyseliny ftalove (Czech)
DPX-F5384
Ethyl phthalate
NCI-C60048
Neantine
o-Benzenedicarboxylic acid diethyl ester
Palatinol A
Phthalol
Phthalsaeurediaethylester (German)
Placidol E
RCRA waste number U088
Solvanol
Unimoll DA

Skin and Eye Irritation and References

Route/OrganismDoseEffectReference
eye /rabbit 112 mgJPETAB 82,377,1944
skin /human 2%/3W- intermittent mildFCTOD7 41,589,2003

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
mutation in microorganisms/Salmonella typhimurium200 µg/plate (+enzymatic activation step)JTEHD6 16,61,1985

Reproductive Effects Data and References

Route/OrganismDoseEffectReference
intraperitoneal/rat 506 mg/kg (5-15D pregnant)Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Musculoskeletal system
JPMSAE 61,51,1972
oral/mouse 171 gm/kg (7D male/7D pre-21D after birth)Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Reproductive: Paternal effects: Prostate, seminal vesicle, Cowper's gland, accessory glands

Reproductive: Effects on newborn: Live birth index (Litter size (e.g., # fetuses per litter; measured after birth)
TXAPA9 88,255,1987
oral/mouse 171 gm/kg (7D male/7D pre-21D after birth)Reproductive: Effects on newborn: PhysicalTXAPA9 88,255,1987
oral/mouse 3.64 gm/kg (multigenerations)Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)NTIS** #PB85118636
oral/mouse 3.64 gm/kg (multigenerations)Reproductive: Specific developmental abnormalities: Hepatobiliary system

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)
NTIS** #PB85118636
oral/mouse 3.64 gm/kg (multigenerations)Reproductive: Specific developmental abnormalities: Hepatobiliary system

Reproductive: Specific developmental abnormalities: Urogenital system

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)
NTIS** #PB85118636
oral/mouse 3.64 gm/kg (multigenerations)Reproductive: Specific developmental abnormalities: Urogenital systemNTIS** #PB85118636
oral/mouse 11.9 gm/kg (7D male/7D prior to copulation/21D pregnant)Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)NTIS** #PB85118636
oral/rat 32100 mg/kg (6-15D pregnant)Reproductive: Other effects on femaleHPV349 -,-,2001
oral/rat 25 gm/kg (6-15D pregnant)Reproductive: Specific developmental abnormalities: Musculoskeletal systemTJADAB 48,33,1993
skin/mouse 101 gm/kg (1-17D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Musculoskeletal system
OYYAA2 33,387,1987
skin/rabbit 26 mL/kg (6-18D pregnant)Reproductive: Specific developmental abnormalities: Musculoskeletal systemNTIS** OTS0572465

Tumorigenic Data and References

Route/OrganismDoseEffectReference
skin/mouse lowest published toxic dose: 618 mL/kg/2Y- intermittentTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Liver: Tumors
NTPTR* NTP-TR-429,1995

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
In Vitro/Human, endocrine tumor Inhibitor Concentration Low: 10 mg/L/48HEndocrine: EstrogenicTOLED5 217,50,2013
In Vitro/Human, fibroblast Inhibitor Concentration Low: 5 mmol/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.FCTOD7 65,105,2014
In Vitro/Human, leukemia cells Inhibitor Concentration (5 percent kill): 13300 mg/L/30MIn Vitro Toxicity Studies: Cell countingTIVIEQ 27,857,2013
In Vitro/Human, leukemia cells Inhibitor Concentration Low: 1420 mg/L/30MIn Vitro Toxicity Studies: Other assaysTIVIEQ 27,857,2013
In Vitro/Human, leukemia cells Inhibitor Concentration (25 percent kill): 600.0 mg/L/24HIn Vitro Toxicity Studies: Cell viability (dye exclusion): trypan blue assay etc.TIVIEQ 26,1150,2012
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): 167 mg/L/45HIn Vitro Toxicity Studies: Other assaysTIVIEQ 29,901,2015
In Vitro/Human, monocyte Inhibitor Concentration Low: 512 mg/L/2HIn Vitro Toxicity Studies: Other assaysTIVIEQ 27,1233,2013
In Vitro/Human, skin Inhibitor Concentration Low: 5 mmol/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.FCTOD7 65,105,2014
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.TXAPA9 245,281,2010
In Vitro/jrdInhibitor Concentration Low: 100 mg/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.

In Vitro Toxicity Studies: Apoptosis in vitro
TOLED5 217,50,2013
In Vitro/ntaInhibitor Concentration Low: 10 mg/L/96HBiochemical: Metabolism (intermediary): Lipids including transport

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
TOLED5 217,50,2013
In Vitro/ntaInhibitor Concentration Low: 5 µmol/L/4HIn Vitro Toxicity Studies: Cell Viability (cell death), unspecified assayTIVIEQ 30,383,2015
In Vitro/ntaInhibitor Concentration Low: 5 µmol/L/48HIn Vitro Toxicity Studies: Cell morphology: overgrowth of cell appendixes etc.

In Vitro Toxicity Studies: Other assays
TIVIEQ 30,383,2015
In Vitro/ntaInhibitor Concentration Low: 11 mg/L/8HIn Vitro Toxicity Studies: Cell Viability (cell death), unspecified assayTIVIEQ 30,383,2015
In Vitro/ntaInhibitor Concentration Low: 11 mg/L/48HIn Vitro Toxicity Studies: Cell morphology: overgrowth of cell appendixes etc.

In Vitro Toxicity Studies: Other assays
TIVIEQ 30,383,2015
In Vitro/Rat, testis Inhibitor Concentration Low: 100 µmol/L/24HBiochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammationTIVIEQ 36,210,2016
inhalation/human lowest published toxic concentration: 1000 mg/m3Eye: Lacrimation

Lung, Thorax, or Respiration: Cough

Lung, Thorax, or Respiration: Other changes
AGGHAR 5,1,1933
inhalation/rat lethal concentration (50 percent kill): >4640 mg/m3/6HHPV349 -,-,2001
intraperitoneal/mouse lethal dose (50 percent kill): 2749 mg/kgLung, Thorax, or Respiration: Acute pulmonary edema

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Blood: Changes in spleen
FEPRA7 6,342,1947
intraperitoneal/rat lethal dose (50 percent kill): 5058 µL/kgJPMSAE 61,51,1972
intravenous/rabbit lowest published lethal dose: 100 mg/kgAGGHAR 5,1,1933
oral/guinea pig lethal dose (50 percent kill): 8600 mg/kgBehavioral: Somnolence (general depressed activity)

Behavioral: Withdrawal

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
GTPZAB 24(3),25,1980
oral/man lowest published toxic dose: 357 µL/kgEye: Miosis (pupilliary constriction)

Behavioral: General anesthetic

Lung, Thorax, or Respiration: Dyspnea
YAKUD5 32,1456,1990
oral/mouse lethal dose (50 percent kill): 6172 mg/kgGTPZAB 17(11),51,1973
oral/non-mammalian species lowest published toxic dose: 5 mg/kgBlood: Granulocytopenia

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
AQUTO* 74,160,2005
oral/rabbit lethal dose (50 percent kill): 1 gm/kg14CYAT 2,1904,1963
oral/rat lethal dose (50 percent kill): 8600 mg/kgBehavioral: Somnolence (general depressed activity)

Behavioral: Withdrawal

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
GTPZAB 24(3),25,1980
skin/guinea pig lethal dose (50 percent kill): >20 mL/kgHPV349 -,-,2001
subcutaneous/guinea pig lethal dose (50 percent kill): 3 gm/kg14CYAT 2,1904,1963
Tank with water/Zebrafish lowest published toxic concentration: 11 mg/L/4WLiver: Fatty liver degeneration

Endocrine: Hypoglycemia
TIVIEQ 30,383,2015
Tank with water/Zebrafish lowest published toxic concentration: 22 mg/L/4WAquatic organism effects: Growth retardation

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TIVIEQ 30,383,2015
unreported route/guinea pig lethal dose (50 percent kill): 3 gm/kgGISAAA 55(9),26,1990
unreported route/mouse lethal dose (50 percent kill): 8600 mg/kgGTPZAB 32(7),52,1988
unreported route/rat lethal dose (50 percent kill): 9500 mg/kgGTPZAB 32(7),52,1988

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
oral/non-mammalian species lowest published toxic dose: 20 mg/kg/4D- intermittentBlood: Granulocytopenia

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

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
AQUTO* 74,160,2005
oral/rat lowest published toxic dose: 1120 mg/kg/28D- intermittentKidney, Ureter, and Bladder: Changes in kidney weightARTODN 80,10,2006
oral/rat lowest published toxic dose: 28000 mg/kg/28D- intermittentEndocrine: Changes in adrenal weightARTODN 80,10,2006
oral/rat lowest published toxic dose: 1120 mg/kg/28D- intermittentBlood: Change in clotting factors

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects
ARTODN 80,10,2006
oral/rat lowest published toxic dose: 28000 mg/kg/28D- intermittentKidney, Ureter, and Bladder: Other changes

Endocrine: Other changes
ARTODN 80,10,2006
oral/rat lowest published toxic dose: 14000 mg/kg/4W- intermittentReproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)TERP2* -,310,2004
oral/rat lowest published toxic dose: 85.5 mg/kg/150D- continuousReproductive: Paternal effects: Testes, epididymis, sperm duct

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Changes in testicular weight
PCBPBS 90,52,2008
oral/rat lowest published toxic dose: 84000 mg/kg/16W- continuousBehavioral: Food intake (animal)

Liver: Changes in liver weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
HPV349 -,,2001
oral/rat lowest published toxic dose: 44240 mg/kg/14D- continuousLiver: Changes in liver weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Changes in testicular weight
FCTXAV 16,415,1978
oral/rat lowest published toxic dose: 133 gm/kg/6W- continuousLiver: Changes in liver weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Changes in testicular weight
FCTXAV 16,415,1978
oral/rat lowest published toxic dose: 354 gm/kg/16W- continuousGastrointestinal: Other changes

Liver: Changes in liver weight

Related to Chronic Data: Changes in testicular weight
FCTXAV 16,415,1978
oral/rat lowest published toxic dose: 25200 mg/kg/3W- continuousBlood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)TOLED5 10,379,1982
oral/rat lowest published toxic dose: 7636 mg/kg/4D- continuousBehavioral: Food intake (animal)

Behavioral: Fluid intake

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
NTIS** #PB89-140081/AS
skin/mouse lowest published toxic dose: 25 mL/kg/4W- intermittentLiver: Changes in liver weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
NTPTR* NTP-TR-429,1995
skin/rat lowest published toxic dose: 24 mL/kg/4W- intermittentLiver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in bladder weight
NTPTR* NTP-TR-429,1995

Reviews

OrganizationStandardReference
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-time-weighted average 5 mg/m3DTLVS* TLV/BEI,2013
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-Not classifiable as a human carcinogenDTLVS* TLV/BEI,2013
TOXICOLOGY REVIEWEVHPAZ 3,73,1973
TOXICOLOGY REVIEWRREVAH 54,1,1975
TOXICOLOGY REVIEWEVHPAZ 4,3,1973
TOXICOLOGY REVIEWESKHA5 (93),1,1975
TOXICOLOGY REVIEWJACTDZ 4(3),267,1985
TOXICOLOGY REVIEWFAATDF 13,747,1989
TOXICOLOGY REVIEWFCTOD7 39,97,2001
TOXICOLOGY REVIEWMUREAV 543,201,2003
TOXICOLOGY REVIEWEMCPT* 2,137,2005
TOXICOLOGY REVIEWIJTOFN 24,1,2005
TOXICOLOGY REVIEWCRTXB2 36,695,2006
TOXICOLOGY REVIEWREPTED 25,192,2008
TOXICOLOGY REVIEWREPTED 22,291,2006
TOXICOLOGY REVIEWHUTOX* -,649,1996
TOXICOLOGY REVIEWREPTED 34,298,2012
TOXICOLOGY REVIEWTOLED5 202,36,2011
TOXICOLOGY REVIEWNRTXDN 41,112,2014
TOXICOLOGY REVIEWTXAPA9 261,227,2012
TOXICOLOGY REVIEWNETEEC 36,17,2013
TOXICOLOGY REVIEWNRTXDN 55,92,2016
TOXICOLOGY REVIEWFCTOD7 109,1,2017
TOXICOLOGY REVIEWENVIN* 94,758,2016
TOXICOLOGY REVIEWRTOPDW 60,120,2011

Standards and Regulations

OrganizationStandardReference
Environmental Protection Agency (EPA) Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) 1988 PESTICIDE SUBJECT TO REGISTRATION OR RE-REGISTRATIONFEREAC 54,7740,1989
Environmental Protection Agency (EPA) Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) 1998 STATUS OF PESTICIDESCancelledRBREV* -,270,1998
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 5 mg/m3, JUL2008
Occupational Exposure Limit-AUSTRIAMAK-TMW 3 mg/m3;KZW 5 mg/m3, 2007
Occupational Exposure Limit-BELGIUMtime-weighted average 5 mg/m3, MAR2002
Occupational Exposure Limit-DENMARKtime-weighted average 3 mg/m3, MAY2011
Occupational Exposure Limit-FINLANDtime-weighted average 5 mg/m3, short term exposure limit 10 mg/m3, NOV2011
Occupational Exposure Limit-FRANCEVME 5 mg/m3, FEB2006
Occupational Exposure Limit-ICELANDtime-weighted average 3 mg/m3, NOV2011
Occupational Exposure Limit-JAPANOccupational Exposure Limit 5 mg/m3, MAY2012
Occupational Exposure Limit-KOREAtime-weighted average 5 mg/m3, 2006
Occupational Exposure Limit-MEXICOtime-weighted average 5 mg/m3;short term exposure limit 10 mg/m3, 2004
Occupational Exposure Limit-NEW ZEALANDtime-weighted average 5 mg/m3, JAN2002
Occupational Exposure Limit-NORWAYtime-weighted average 3 mg/m3, JAN1999
Occupational Exposure Limit-PERUtime-weighted average 5 mg/m3, JUL2005
Occupational Exposure Limit-POLANDMAC(time-weighted average) 5 mg/m3, MAC(short term exposure limit) 15 mg/m3, JAN1999
Occupational Exposure Limit-RUSSIAtime-weighted average 0.5 mg/m3, short term exposure limit 1.5 mg/m3, JUN2003
Occupational Exposure Limit-SWEDENtime-weighted average 3 mg/m3;short term exposure limit 5 mg/m3, JUN2005
Occupational Exposure Limit-SWITZERLANDMAK-week 5 mg/m3, inhal, JAN2011
Occupational Exposure Limit-UNITED KINGDOMtime-weighted average 5 mg/m3;short term exposure limit 10 mg/m3, OCT2007

NIOSH Documentation and Surveillance

OrganizationStandardReference
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO DIETHYL PHTHALATE-air10H time-weighted average 5 mg/m3NIOSH* DHHS #95-121,1995
National Occupational Exposure Survey 1983Hazard Code 81806; Number of Industries 120; Total Number of Facilities 16408; Number of Occupations 98; Total Number of Employees Exposed 239149; Total Number of Female Employees Exposed 108580
National Occupational Hazard Survey 1974Hazard Code 81806; Number of Industries 30; Total Number of Facilities 1334; Number of Occupations 49; Total Number of Employees Exposed 109691

Status in Federal Agencies

OrganizationReference
ATSDR TOXICOLOGY PROFILE (NTIS** PB/95/264214/AS)
EPA TSCA 8(a) PRELIMINARY ASSESSMENT INFORMATION, FINAL RULEFEREAC 47,26992,82
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 Studies (derm);equivocal evidence:mouse
NCI Carcinogenesis Studies (derm);no evidence:mouse,rat
On EPA IRIS database
OSHA ANALYTICAL METHOD #104
Page last reviewed: November 16, 2018