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Registry of Toxic Effects of Chemical Substances (RTECS)

Phthalic acid, diethyl ester

RTECS #

TI1050000

CAS #

84-66-2

Updated

October 2017

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, 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
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
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

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
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