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Registry of Toxic Effects of Chemical Substances (RTECS)

Phosphoric triamide, hexamethyl-

RTECS #

TD0875000

CAS #

680-31-9

Updated

September 2013

Molecular Weight

179.24

Molecular Formula

C6H18N3OP

Synonyms

Eastman Inhibitor HPT
ENT 50882
Hempa
Hexametapol
Hexamethyl phosphoramide
Hexamethyl phosphoramide (ACGIH)
Hexamethylfosforamid (Czech)
Hexamethylphosphoric acid triamide
Hexamethylphosphoric triamide
Hexamethylphosphorotriamide
Hexamethylphosphotriamide
Hexmethylphosphoramide
HMPA
HMPT
HPT
N,N,N,N,N,N-Hexamethylphosphoric triamide
Phosphoric acid hexamethyltriamide
Phosphoric tris(dimethylamide)
Phosphoryl hexamethyltriamide
Tri(dimethylamino)phosphineoxide
Tris-(dimethylamid) kyseliny fosforecne (Czech)
Tris(dimethylamino)phosphine oxide
Tris(dimethylamino)phosphorus oxide

Skin and Eye Irritation and References

Route/OrganismDoseEffectReference
skin /guinea pig 50 µL/24H severeNTIS** OTS0571620

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
body fluid assayovary/rat1 gm/kgMUREAV 143,263,1985
Cytogenetic Analysisintraperitoneal/rat1800 mg/kgMUREAV 182,309,1987
Cytogenetic Analysislymphocyte/human500 mg/LMUREAV 156,19,1985
Cytogenetic Analysisleukocyte/human5 mmol/LCHROAU 24,314,1968
Cytogenetic Analysisskin/other insects250 ppmCYTOAN 38,21,1973
Cytogenetic Analysisparenteral/other insects159 mmol/LCNJGA8 11,648,1969
Cytogenetic Analysisliver/hamster2 mg/LPMRSDJ 5,397,1985
Cytogenetic Analysislung/hamster2 gm/LPMRSDJ 5,427,1985
DNA Damage/Bacillus subtilis20 µL/discPMRSDJ 1,175,1981
DNA Damageother cell types/human15 µmol/LMUREAV 468,213,2000
DNA repair/Saccharomyes cerevisiae100 mg/LPMRSDJ 1,502,1981
Dominant Lethal Testparenteral/other insects159 mmol/LCNJGA8 11,648,1969
Dominant Lethal Testunreported route/other insects100 ppmBWHOA6 47,305,1972
Dominant Lethal Testparenteral/Drosophila melanogaster5 mmol/LFOBLAN 18,139,1972
Dominant Lethal Testintraperitoneal/mouse250 mg/kg/12HFOBLAN 16,407,1970
gene conversion and mitotic recombination/Saccharomyes cerevisiae2 gm/LPMRSDJ 1,481,1981
heritable translocation testparenteral/Drosophila melanogaster10 mmol/LFOBLAN 18,139,1972
heritable translocation testoral/Drosophila melanogaster100 ppmEMMUEG 23,51,1994
micronucleus testoral/mouse600 mg/kgCHYCDW 22,60,1988
micronucleus testintraperitoneal/mouse1280 mg/kgMUREAV 122,143,1983
micronucleus testmultiple/non-mammalian species30 ppmMUTAEX 4,17,1989
micronucleus testintraperitoneal/rat1800 mg/kgMUREAV 182,309,1987
morphological transformliver/human80 µg/LBJCAAI 37,873,1978
morphological transformembryo/mouse1 gm/LPMRSDJ 5,659,1985
morphological transformembryo/hamster400 mg/LPMRSDJ 5,665,1985
morphological transformkidney/hamster2500 µg/LBJCAAI 36,564,1977
morphological transformfibroblast/mouse0.1 pph/21D (-enzymatic activation step)EMMUEG 35,300,2000
mutation in mammalian somatic cellslymphocyte/mouse3 gm/LPMRSDJ 1,580,1981
mutation in microorganismslymphocyte/mouse3 mL/L (+enzymatic activation step)PMRSDJ 5,531,1985
mutation in microorganisms/Saccharomyes cerevisiae100 mg/L (-enzymatic activation step)PMRSDJ 1,414,1981
mutation in microorganisms/Saccharomyes cerevisiae3490 mg/L (+enzymatic activation step)PMRSDJ 5,257,1985
mutation in microorganisms/Salmonella typhimurium4 µg/plate (-enzymatic activation step)BJCAAI 36,564,1977
mutation in microorganisms/Escherichia coli50 µg/plate (+enzymatic activation step)PMRSDJ 1,351,1981
sex chromosome loss and nondisjunction/Saccharomyes cerevisiae25 mg/LPMRSDJ 1,468,1981
sex chromosome loss and nondisjunctionmultiple/Drosophila melanogaster250 ppmPMRSDJ 1,651,1981
sex chromosome loss and nondisjunctionparenteral/Drosophila melanogaster1000 ppmIMSUAI 38,442,1969
sex chromosome loss and nondisjunctionoral/Drosophila melanogaster100 ppmPMRSDJ 1,666,1981
sex chromosome loss and nondisjunctionliver/hamster10 mg/LPMRSDJ 5,397,1985
sister chromatid exchangeovary/hamster5 gm/LPMRSDJ 5,413,1985
sister chromatid exchangelung/hamster5 mmol/LPMRSDJ 5,469,1985
sister chromatid exchangeliver/rat2 gm/LPMRSDJ 5,387,1985
sister chromatid exchangeintraperitoneal/mouse1700 µg/kgPMRSDJ 1,673,1981
specific locus testoral/Drosophila melanogaster560 µmol/LPMRSDJ 5,313,1985
specific locus testoral/Drosophila melanogaster0.2 mmol/L/72HMUREAV 545,59,2004
sperm morphologyparenteral/other insects200 µgABABAC 17,661,1977
Unscheduled DNA SynthesisHeLa cell/human125 mg/LPMRSDJ 5,375,1985
Unscheduled DNA Synthesisfibroblast/human156 mg/LPMRSDJ 1,517,1981
Unscheduled DNA Synthesisliver/rat100 mg/LPMRSDJ 5,341,1985

Reproductive Effects Data and References

Route/OrganismDoseEffectReference
intraperitoneal/rat 43750 mg/kg (5W male)Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)NTIS** OTS0555525
oral/rat 2430 mg/kg (multigenerations)Reproductive: Effects on fertility: Female fertility index (e.g., # females pregnant per # sperm positive females; # females pregnant per # females mated)TXAPA9 18,499,1971
oral/rat 2 gm/kg (1D male)Reproductive: Paternal effects: Testes, epididymis, sperm ductNATUAS 211,146,1966

Tumorigenic Data and References

Route/OrganismDoseEffectReference
inhalation/rat lowest published toxic concentration: 50 ppb/52W- continuousTumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors
AJPAA4 106,8,1982
inhalation/rat toxic concentration: 400 ppb/35W- intermittentTumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors
SCIEAS 190,422,1975
inhalation/rat toxic concentration: 100 ppb/26W- continuousTumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors
AJPAA4 106,8,1982
inhalation/rat toxic concentration: 50 ppb/6H/1Y- continuousTumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors
JJIND8 68,157,1982
inhalation/rat toxic concentration: 4000 ppb/39W- continuousTumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors
AJPAA4 106,8,1982
inhalation/rat toxic concentration: 100 ppb/6H/26W- intermittentTumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors
JJIND8 68,157,1982
inhalation/rat toxic concentration: 400 ppb/6H/43W- intermittentTumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors
JJIND8 68,157,1982
inhalation/rat toxic concentration: 50 ppb/6H/52W- intermittentTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Olfaction: Tumors
TXAPA9 62,90,1982
inhalation/rat toxic concentration: 100 ppb/6H/26W- intermittentTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Olfaction: Tumors
TXAPA9 62,90,1982
inhalation/rat toxic concentration: 50 ppb/6H/52W- intermittentTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Olfaction: Tumors
ENVRAL 33,106,1984

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
inhalation/rat Lowest published lethal concentration: 2920 mg/m3/4HLung, Thorax, or Respiration: Dyspnea

Blood: Other changes
NTIS** OTS0571242
intraperitoneal/mouse lethal dose (50 percent kill): 1600 mg/kgPMRSDJ 1,682,1981
intravenous/mouse lethal dose (50 percent kill): 800 mg/kgCHINAG (36),1529,1966
oral/chicken lethal dose (50 percent kill): 835 mg/kgPeripheral Nerve and Sensation: Flaccid paralysis without anesthesia (usually neuromuscular blockage)

Behavioral: Ataxia
TXAPA9 16,100,1970
oral/guinea pig lethal dose (50 percent kill): 1600 mg/kg85DZAJ -,315,1968
oral/mouse lethal dose (50 percent kill): 2400 mg/kgNYKZAU 70,114P,1974
oral/quail lethal dose (50 percent kill): 1 gm/kgJRPFA4 48,371,1976
oral/rabbit lowest published lethal dose: 1500 mg/kgJEENAI 48,139,1955
oral/rat lethal dose (50 percent kill): 2650 mg/kgBehavioral: Convulsions or effect on seizure threshold

Kidney, Ureter, and Bladder: Hematuria

Kidney, Ureter, and Bladder: Incontinence
NATUAS 211,146,1966
skin/guinea pig lethal dose (50 percent kill): 1175 mg/kg85DZAJ -,315,1968
skin/rabbit lethal dose (50 percent kill): 2600 mg/kgBehavioral: Altered sleep time (including change in righting reflex)

Behavioral: Somnolence (general depressed activity)

Lung, Thorax, or Respiration: Dyspnea
TXAPA9 18,499,1971
skin/rat lowest published lethal dose: 3500 mg/kgPeripheral Nerve and Sensation: Fasciculations

Behavioral: Convulsions or effect on seizure threshold

Kidney, Ureter, and Bladder: Hematuria
NATUAS 211,146,1966

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
inhalation/rat lowest published toxic concentration: 400 ppb/6H/32W- intermittentRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldAIHAAP 36,916,1975
oral/rat lowest published toxic dose: 4600 mg/kg/92D- intermittentLung, Thorax, or Respiration: Fibrosis, focal (pneumoconiosis)

Endocrine: Changes in thymus weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
TXAPA9 18,499,1971
oral/rat lowest published toxic dose: 6 gm/kg/60D- continuousRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldNATUAS 211,146,1966
oral/rat lowest published toxic dose: 8640 mg/kg/72D- continuousLung, Thorax, or Respiration: Bronchiectasis

Lung, Thorax, or Respiration: Fibrosis, focal (pneumoconiosis)
TXAPA9 10,411,1967
skin/rabbit lowest published toxic dose: 1500 mg/kg/21D- intermittentGastrointestinal: Hypermotility, diarrhea

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Changes in ovarian weight
TXAPA9 18,499,1971

Reviews

OrganizationStandardReference
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-skinDTLVS* TLV/BEI,2013
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-Confirmed animal carcinogenDTLVS* TLV/BEI,2013
International Agency for Research on Cancer (IARC)Cancer Review:Animal Sufficient EvidenceIMEMDT 15,211,1977
International Agency for Research on Cancer (IARC)Cancer Review:Animal Sufficient EvidenceIMEMDT 71,1465,1999
International Agency for Research on Cancer (IARC)Cancer Review:Human No Adequate DataIMEMDT 15,211,1977
International Agency for Research on Cancer (IARC)Cancer Review:Human No Adequate DataIMEMDT 71,1465,1999
International Agency for Research on Cancer (IARC)Cancer Review:Group 2BIMEMDT 71,1465,1999
TOXICOLOGY REVIEWMUTAEX 14,5,1999
TOXICOLOGY REVIEWMUTAEX 14,271,1999
TOXICOLOGY REVIEWMUREAV 721,27,2011

Standards and Regulations

OrganizationStandardReference
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN check ACGIH TLV;
Occupational Exposure Limit IN SINGAPORE, VIETNAM check ACGIH TLV
Occupational Exposure Limit-AUSTRALIACarcinogen, JUL2008
Occupational Exposure Limit-BELGIUMSkin, MAR2002
Occupational Exposure Limit-JAPAN2B carc, MAY2012
Occupational Exposure Limit-KOREAskin, 2006
Occupational Exposure Limit-NEW ZEALANDskin, JAN2002
Occupational Exposure Limit-SWEDENGroup A Carcinogen, JUN2005
Occupational Exposure Limit-SWITZERLANDcarc 2, JAN2011

NIOSH Documentation and Surveillance

OrganizationStandardReference
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO THE CHEMICAL-airCarcinogen lowest feasible concentrationNIOSH* DHHS #92-100,1992
National Occupational Exposure Survey 1983Hazard Code X4066; Number of Industries 1; Total Number of Facilities 92; Number of Occupations 2; Total Number of Employees Exposed 700; Total Number of Female Employees Exposed 51

Status in Federal Agencies

OrganizationReference
EPA GENETOX PROGRAM 1988, Positive: Carcinogenicity-mouse/rat
EPA GENETOX PROGRAM 1988, Positive: D melanogaster Sex-linked lethal
EPA GENETOX PROGRAM 1988, Positive: D melanogaster-reciprocal translocation
EPA GENETOX PROGRAM 1988, Positive: Rodent dominant lethal; Mammalian micronucleus
EPA GENETOX PROGRAM 1988, Positive: Sperm morphology-mouse; Sperm morphology-rabbit
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
NIOSH CURRENT INTELLIGENCE BULLETIN 6, 1975
NTP 11th Report on Carcinogens,2004:Reasonably anticipated to be a human carcinogen
On EPA IRIS database
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