Phosphoric triamide, hexamethyl-

RTECS #

TD0875000

CAS #

680-31-9
See: NMAM or OSHA Methods

Updated

March 2019

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/Organism	Dose	Effect	Reference
skin /guinea pig	50 µL/24H	severe	NTIS** OTS0571620

Mutation Data and Reference

System Test	Route/Organism/Tissue	Dose	Reference
body fluid assay	ovary/rat	1 gm/kg	MUREAV 143,263,1985
Cytogenetic Analysis	intraperitoneal/rat	1800 mg/kg	MUREAV 182,309,1987
Cytogenetic Analysis	lymphocyte/human	500 mg/L	MUREAV 156,19,1985
Cytogenetic Analysis	leukocyte/human	5 mmol/L	CHROAU 24,314,1968
Cytogenetic Analysis	skin/other insects	250 ppm	CYTOAN 38,21,1973
Cytogenetic Analysis	parenteral/other insects	159 mmol/L	CNJGA8 11,648,1969
Cytogenetic Analysis	liver/hamster	2 mg/L	PMRSDJ 5,397,1985
Cytogenetic Analysis	lung/hamster	2 gm/L	PMRSDJ 5,427,1985
DNA Damage	other cell types/human	1000 µmol/L/4H (+enzymatic activation step)	EMMUEG 57,546,2016
DNA Damage	/Bacillus subtilis	20 µL/disc	PMRSDJ 1,175,1981
DNA Damage	other cell types/human	15 µmol/L	MUREAV 468,213,2000
DNA repair	/Saccharomyes cerevisiae	100 mg/L	PMRSDJ 1,502,1981
Dominant Lethal Test	parenteral/other insects	159 mmol/L	CNJGA8 11,648,1969
Dominant Lethal Test	unreported route/other insects	100 ppm	BWHOA6 47,305,1972
Dominant Lethal Test	parenteral/Drosophila melanogaster	5 mmol/L	FOBLAN 18,139,1972
Dominant Lethal Test	intraperitoneal/mouse	250 mg/kg/12H	FOBLAN 16,407,1970
gene conversion and mitotic recombination	/Saccharomyes cerevisiae	2 gm/L	PMRSDJ 1,481,1981
heritable translocation test	parenteral/Drosophila melanogaster	10 mmol/L	FOBLAN 18,139,1972
heritable translocation test	oral/Drosophila melanogaster	100 ppm	EMMUEG 23,51,1994
micronucleus test	oral/mouse	600 mg/kg	CHYCDW 22,60,1988
micronucleus test	intraperitoneal/mouse	1280 mg/kg	MUREAV 122,143,1983
micronucleus test	multiple/non-mammalian species	30 ppm	MUTAEX 4,17,1989
micronucleus test	intraperitoneal/rat	1800 mg/kg	MUREAV 182,309,1987
morphological transform	liver/human	80 µg/L	BJCAAI 37,873,1978
morphological transform	embryo/mouse	1 gm/L	PMRSDJ 5,659,1985
morphological transform	embryo/hamster	400 mg/L	PMRSDJ 5,665,1985
morphological transform	kidney/hamster	2500 µg/L	BJCAAI 36,564,1977
morphological transform	fibroblast/mouse	0.1 pph/21D (-enzymatic activation step)	EMMUEG 35,300,2000
mutation in mammalian somatic cells	lymphocyte/mouse	3 gm/L	PMRSDJ 1,580,1981
mutation in microorganisms	lymphocyte/mouse	3 mL/L (+enzymatic activation step)	PMRSDJ 5,531,1985
mutation in microorganisms	/Saccharomyes cerevisiae	100 mg/L (-enzymatic activation step)	PMRSDJ 1,414,1981
mutation in microorganisms	/Saccharomyes cerevisiae	3490 mg/L (+enzymatic activation step)	PMRSDJ 5,257,1985
mutation in microorganisms	/Salmonella typhimurium	4 µg/plate (-enzymatic activation step)	BJCAAI 36,564,1977
mutation in microorganisms	/Escherichia coli	50 µg/plate (+enzymatic activation step)	PMRSDJ 1,351,1981
sex chromosome loss and nondisjunction	/Saccharomyes cerevisiae	25 mg/L	PMRSDJ 1,468,1981
sex chromosome loss and nondisjunction	multiple/Drosophila melanogaster	250 ppm	PMRSDJ 1,651,1981
sex chromosome loss and nondisjunction	parenteral/Drosophila melanogaster	1000 ppm	IMSUAI 38,442,1969
sex chromosome loss and nondisjunction	oral/Drosophila melanogaster	100 ppm	PMRSDJ 1,666,1981
sex chromosome loss and nondisjunction	liver/hamster	10 mg/L	PMRSDJ 5,397,1985
sister chromatid exchange	ovary/hamster	5 gm/L	PMRSDJ 5,413,1985
sister chromatid exchange	lung/hamster	5 mmol/L	PMRSDJ 5,469,1985
sister chromatid exchange	liver/rat	2 gm/L	PMRSDJ 5,387,1985
sister chromatid exchange	intraperitoneal/mouse	1700 µg/kg	PMRSDJ 1,673,1981
specific locus test	oral/Drosophila melanogaster	560 µmol/L	PMRSDJ 5,313,1985
specific locus test	oral/Drosophila melanogaster	0.2 mmol/L/72H	MUREAV 545,59,2004
sperm morphology	parenteral/other insects	200 µg	ABABAC 17,661,1977
Unscheduled DNA Synthesis	HeLa cell/human	125 mg/L	PMRSDJ 5,375,1985
Unscheduled DNA Synthesis	fibroblast/human	156 mg/L	PMRSDJ 1,517,1981
Unscheduled DNA Synthesis	liver/rat	100 mg/L	PMRSDJ 5,341,1985

Reproductive Effects Data and References

Route/Organism	Dose	Effect	Reference
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 duct	NATUAS 211,146,1966

Tumorigenic Data and References

Route/Organism	Dose	Effect	Reference
inhalation/rat	lowest published toxic concentration: 50 ppb/52W- continuous	Tumorigenic: Carcinogenic by RTECS criteria Olfaction: Tumors	AJPAA4 106,8,1982
inhalation/rat	toxic concentration: 400 ppb/35W- intermittent	Tumorigenic: Carcinogenic by RTECS criteria Olfaction: Tumors	SCIEAS 190,422,1975
inhalation/rat	toxic concentration: 100 ppb/26W- continuous	Tumorigenic: Carcinogenic by RTECS criteria Olfaction: Tumors	AJPAA4 106,8,1982
inhalation/rat	toxic concentration: 50 ppb/6H/1Y- continuous	Tumorigenic: Carcinogenic by RTECS criteria Olfaction: Tumors	JJIND8 68,157,1982
inhalation/rat	toxic concentration: 4000 ppb/39W- continuous	Tumorigenic: Carcinogenic by RTECS criteria Olfaction: Tumors	AJPAA4 106,8,1982
inhalation/rat	toxic concentration: 100 ppb/6H/26W- intermittent	Tumorigenic: Carcinogenic by RTECS criteria Olfaction: Tumors	JJIND8 68,157,1982
inhalation/rat	toxic concentration: 400 ppb/6H/43W- intermittent	Tumorigenic: Carcinogenic by RTECS criteria Olfaction: Tumors	JJIND8 68,157,1982
inhalation/rat	toxic concentration: 50 ppb/6H/52W- intermittent	Tumorigenic: Equivocal tumorigenic agent by RTECS criteria Olfaction: Tumors	TXAPA9 62,90,1982
inhalation/rat	toxic concentration: 100 ppb/6H/26W- intermittent	Tumorigenic: Equivocal tumorigenic agent by RTECS criteria Olfaction: Tumors	TXAPA9 62,90,1982
inhalation/rat	toxic concentration: 50 ppb/6H/52W- intermittent	Tumorigenic: Equivocal tumorigenic agent by RTECS criteria Olfaction: Tumors	ENVRAL 33,106,1984

Acute Toxicity Data and References

Route/Organism	Dose	Effect	Reference
inhalation/rat	Lowest published lethal concentration: 2920 mg/m³/4H	Lung, Thorax, or Respiration: Dyspnea Blood: Other changes	NTIS** OTS0571242
intraperitoneal/mouse	lethal dose (50 percent kill): 1600 mg/kg		PMRSDJ 1,682,1981
intravenous/mouse	lethal dose (50 percent kill): 800 mg/kg		CHINAG (36),1529,1966
oral/chicken	lethal dose (50 percent kill): 835 mg/kg	Peripheral 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/kg		85DZAJ -,315,1968
oral/mouse	lethal dose (50 percent kill): 2400 mg/kg		NYKZAU 70,114P,1974
oral/quail	lethal dose (50 percent kill): 1 gm/kg		JRPFA4 48,371,1976
oral/rabbit	lowest published lethal dose: 1500 mg/kg		JEENAI 48,139,1955
oral/rat	lethal dose (50 percent kill): 2650 mg/kg	Behavioral: 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/kg		85DZAJ -,315,1968
skin/rabbit	lethal dose (50 percent kill): 2600 mg/kg	Behavioral: 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/kg	Peripheral 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/Organism	Dose	Effect	Reference
inhalation/rat	lowest published toxic concentration: 400 ppb/6H/32W- intermittent	Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field	AIHAAP 36,916,1975
oral/rat	lowest published toxic dose: 4600 mg/kg/92D- intermittent	Lung, 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- continuous	Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field	NATUAS 211,146,1966
oral/rat	lowest published toxic dose: 8640 mg/kg/72D- continuous	Lung, 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- intermittent	Gastrointestinal: 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

Organization	Standard	Reference
American Conference of Governmental Industrial Hygienists (ACGIH)	Threshold Limit Value-skin	DTLVS* TLV/BEI,2013
American Conference of Governmental Industrial Hygienists (ACGIH)	Threshold Limit Value-Confirmed animal carcinogen	DTLVS* TLV/BEI,2013
International Agency for Research on Cancer (IARC)	Cancer Review:Animal Sufficient Evidence	IMEMDT 15,211,1977
International Agency for Research on Cancer (IARC)	Cancer Review:Animal Sufficient Evidence	IMEMDT 71,1465,1999
International Agency for Research on Cancer (IARC)	Cancer Review:Human No Adequate Data	IMEMDT 15,211,1977
International Agency for Research on Cancer (IARC)	Cancer Review:Human No Adequate Data	IMEMDT 71,1465,1999
International Agency for Research on Cancer (IARC)	Cancer Review:Group 2B	IMEMDT 71,1465,1999
TOXICOLOGY REVIEW		MUTAEX 14,5,1999
TOXICOLOGY REVIEW		MUTAEX 14,271,1999
TOXICOLOGY REVIEW		MUREAV 721,27,2011

Standards and Regulations

Organization	Standard	Reference
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN check ACGIH TLV;
Occupational Exposure Limit IN SINGAPORE, VIETNAM check ACGIH TLV
Occupational Exposure Limit-AUSTRALIA	Carcinogen, JUL2008
Occupational Exposure Limit-BELGIUM	Skin, MAR2002
Occupational Exposure Limit-JAPAN	2B carc, MAY2012
Occupational Exposure Limit-KOREA	skin, 2006
Occupational Exposure Limit-NEW ZEALAND	skin, JAN2002
Occupational Exposure Limit-SWEDEN	Group A Carcinogen, JUN2005
Occupational Exposure Limit-SWITZERLAND	carc 2, JAN2011

NIOSH Documentation and Surveillance

Organization	Standard	Reference
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO THE CHEMICAL-air	Carcinogen lowest feasible concentration	NIOSH* DHHS #92-100,1992
National Occupational Exposure Survey 1983	Hazard 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

Organization	Reference
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 14th Report on Carcinogens,2016:Reasonably anticipated to be human carcinogen
On EPA IRIS database

Page last reviewed: November 16, 2018

Content source: National Institute for Occupational Safety and Health