The Registry of Toxic Effects of Chemical Substances

Phosphoric triamide, hexamethyl -

RTECS #: TD0875000

CAS #: 680-31-9

UPDATE: May 2005 MW: 179.24 MF: C6H18N3OP


NOTE:

TABLE OF CONTENTS:
  1. SYNONYMS:
  2. SKIN AND EYE IRRITATION DATA:
  3. MUTATION DATA:
  4. REPRODUCTIVE EFFECTS DATA:
  5. TUMORIGENIC DATA:
  6. ACUTE TOXICITY DATA:
  7. OTHER MULTIPLE DOSE DATA:
  8. REVIEWS:
  9. STANDARDS AND REGULATIONS:
  10. NIOSH DOCUMENTATION AND SURVEILLANCE:
  11. STATUS IN FEDERAL AGENCIES:
  12. REFERENCES:

SYNONYMS:

  1. ENT 50882
  2. Eastman Inhibitor HPT
  3. HMPA
  4. HMPT
  5. HPT
  6. Hempa
  7. Hexametapol
  8. Hexamethyl phosphoramide
  9. Hexamethyl phosphoramide (ACGIH)
  10. Hexamethylfosforamid (Czech)
  11. Hexamethylphosphoric acid triamide
  12. Hexamethylphosphoric triamide
  1. Hexamethylphosphorotriamide
  2. Hexamethylphosphotriamide
  3. Hexmethylphosphoramide
  4. N,N,N,N,N,N - Hexamethylphosphoric triamide
  5. Phosphoric acid hexamethyltriamide
  6. Phosphoric tris (dimethylamide)
  7. Phosphoryl hexamethyltriamide
  8. Tri (dimethylamino) phosphineoxide
  9. Tris (dimethylamino) phosphine oxide
  10. Tris (dimethylamino) phosphorus oxide
  11. Tris - (dimethylamid) kyseliny fosforecne (Czech)


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
skin
guinea pig 		50 µL/24 hour severe NTIS** OTS0571620


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE 		DOSE REFERENCE
body fluid assay rat
ovary 		1 gm/kg MUREAV 143,263,1985
cytogenetic analysis hamster liver 2 mg/L PMRSDJ 5,397,1985
cytogenetic analysis hamster lung 2 gm/L PMRSDJ 5,427,1985
cytogenetic analysis human lymphocyte 500 mg/L MUREAV 156,19,1985
cytogenetic analysis human leukocyte 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 intraperitoneal
rat 		1,800 mg/kg MUREAV 182,309,1987
dominant lethal test parenteral
Drosophila melanogaster 		5 mmol/L FOBLAN 18,139,1972
dominant lethal test intraperitoneal
mouse 		250 mg/kg/12 hour FOBLAN 16,407,1970
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
DNA damage Bacillus subtilis 20 µL/disc PMRSDJ 1,175,1981
DNA damage human other cell types 15 µmol/L MUREAV 468,213,2000
DNA repair Saccharomyes cerevisiae 100 mg/L PMRSDJ 1,502,1981
unscheduled DNA synthesis human HeLa cell 125 mg/L PMRSDJ 5,375,1985
unscheduled DNA synthesis human fibroblast 156 mg/L PMRSDJ 1,517,1981
unscheduled DNA synthesis rat liver 100 mg/L PMRSDJ 5,341,1985
mutation in microorganisms Escherichia coli 50 µg/plate (+enzymatic activation step) PMRSDJ 1,351,1981
mutation in microorganisms mouse lymphocyte 3 mL/L (+enzymatic activation step) PMRSDJ 5,531,1985
mutation in microorganisms Salmonella typhimurium 4 µg/plate (-enzymatic activation step) BJCAAI 36,564,1977
mutation in microorganisms Saccharomyes cerevisiae 100 mg/L (-enzymatic activation step) PMRSDJ 1,414,1981
mutation in microorganisms Saccharomyes cerevisiae 3,490 mg/L (+enzymatic activation step) PMRSDJ 5,257,1985
micronucleus test oral
mouse 		600 mg/kg CHYCDW 22,60,1988
micronucleus test intraperitoneal
mouse 		1,280 mg/kg MUREAV 122,143,1983
micronucleus test multiple
non-mammalian species 		30 ppm MUTAEX 4,17,1989
micronucleus test intraperitoneal
rat 		1,800 mg/kg MUREAV 182,309,1987
gene conversion and mitotic recombination Saccharomyes cerevisiae 2 gm/L PMRSDJ 1,481,1981
mutation in mammalian somatic cells mouse lymphocyte 3 gm/L PMRSDJ 1,580,1981
morphological transform hamster embryo 400 mg/L PMRSDJ 5,665,1985
morphological transform hamster kidney 2,500 µg/L BJCAAI 36,564,1977
morphological transform human liver 80 µg/L BJCAAI 37,873,1978
morphological transform mouse embryo 1 gm/L PMRSDJ 5,659,1985
morphological transform mouse fibroblast 0.1 pph/21 day (-enzymatic activation step) EMMUEG 35,300,2000
sister chromatid exchange hamster ovary 5 gm/L PMRSDJ 5,413,1985
sister chromatid exchange hamster lung 5 mmol/L PMRSDJ 5,469,1985
sister chromatid exchange intraperitoneal
mouse 		1,700 µg/kg PMRSDJ 1,673,1981
sister chromatid exchange rat liver 2 gm/L PMRSDJ 5,387,1985
sex chromosome loss and nondisjunction multiple
Drosophila melanogaster 		250 ppm PMRSDJ 1,651,1981
sex chromosome loss and nondisjunction parenteral
Drosophila melanogaster 		1,000 ppm IMSUAI 38,442,1969
sex chromosome loss and nondisjunction oral
Drosophila melanogaster 		100 ppm PMRSDJ 1,666,1981
sex chromosome loss and nondisjunction hamster liver 10 mg/L PMRSDJ 5,397,1985
sex chromosome loss and nondisjunction Saccharomyes cerevisiae 25 mg/L PMRSDJ 1,468,1981
specific locus test oral
Drosophila melanogaster 		560 µmol/L PMRSDJ 5,313,1985
sperm morphology parenteral
other insects 		200 µg ABABAC 17,661,1977
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


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraperitoneal
rat 		lowest published toxic dose: 43,750 mg/kg (5 week male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) NTIS** OTS0555525
oral
rat 		lowest published toxic dose: 2,430 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 		lowest published toxic dose: 2 gm/kg (1 day 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/52 week- continuous Tumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors 		AJPAA4 106,8,1982
inhalation
rat 		toxic concentration (other than lowest) : 400 ppb/35 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors 		SCIEAS 190,422,1975
inhalation
rat 		toxic concentration (other than lowest) : 100 ppb/26 week- continuous Tumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors 		AJPAA4 106,8,1982
inhalation
rat 		toxic concentration (other than lowest) : 50 ppb/6 hour/1 year- continuous Tumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors 		JJIND8 68,157,1982
inhalation
rat 		toxic concentration (other than lowest) : 4,000 ppb/39 week- continuous Tumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors 		AJPAA4 106,8,1982
inhalation
rat 		toxic concentration (other than lowest) : 100 ppb/6 hour/26 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors 		JJIND8 68,157,1982
inhalation
rat 		toxic concentration (other than lowest) : 400 ppb/6 hour/43 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Olfaction: Tumors 		JJIND8 68,157,1982
inhalation
rat 		toxic concentration (other than lowest) : 50 ppb/6 hour/52 week- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Olfaction: Tumors 		TXAPA9 62,90,1982
inhalation
rat 		toxic concentration (other than lowest) : 100 ppb/6 hour/26 week- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Olfaction: Tumors 		TXAPA9 62,90,1982
inhalation
rat 		toxic concentration (other than lowest) : 50 ppb/6 hour/52 week- 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: 2,920 mg/m3/4 hour Lung, Thorax, or Respiration: Dyspnea

Blood: Other changes 		NTIS** OTS0571242
intraperitoneal
mouse 		lethal dose (50 percent kill): 1,600 mg/kg N/R PMRSDJ 1,682,1981
intravenous
mouse 		lethal dose (50 percent kill): 800 mg/kg N/R 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): 1,600 mg/kg N/R 85DZAJ -,315,1968
oral
mouse 		lethal dose (50 percent kill): 2,400 mg/kg N/R NYKZAU 70,114P,1974
oral
quail 		lethal dose (50 percent kill): 1 gm/kg N/R JRPFA4 48,371,1976
oral
rat 		lethal dose (50 percent kill): 2,650 mg/kg Behavioral: Convulsions or effect on seizure threshold

Kidney, Ureter, and Bladder: Hematuria

Kidney, Ureter, and Bladder: Incontinence 		NATUAS 211,146,1966
oral
rabbit 		lowest published lethal dose: 1,500 mg/kg N/R JEENAI 48,139,1955
skin
guinea pig 		lethal dose (50 percent kill): 1,175 mg/kg N/R 85DZAJ -,315,1968
skin
rat 		lowest published lethal dose: 3,500 mg/kg Peripheral Nerve and Sensation: Fasciculations

Behavioral: Convulsions or effect on seizure threshold

Kidney, Ureter, and Bladder: Hematuria 		NATUAS 211,146,1966
skin
rabbit 		lethal dose (50 percent kill): 2,600 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


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
rat 		lowest published toxic concentration: 400 ppb/6 hour/32 week- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field AIHAAP 36,916,1975
oral
rat 		lowest published toxic dose: 6 gm/kg/60 day- continuous Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field NATUAS 211,146,1966
oral
rat 		lowest published toxic dose: 8,640 mg/kg/72 day- continuous Lung, Thorax, or Respiration: Bronchiectasis

Lung, Thorax, or Respiration: Fibrosis, focal (pneumoconiosis) 		TXAPA9 10,411,1967
oral
rat 		lowest published toxic dose: 4,600 mg/kg/92 day- 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
skin
rabbit 		lowest published toxic dose: 1,500 mg/kg/21 day- 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 Confirmed Animal Carcinogen with Unknown DTLVS* TLV/BEI,2003
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


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
Occupational Exposure Limit - AUSTRALIA Skin, Carcinogen, JAN1993
Occupational Exposure Limit - AUSTRIA Carcinogen, JAN1999
Occupational Exposure Limit - BELGIUM Skin, Carcinogen, JAN1993
Occupational Exposure Limit - FINLAND Carcinogen, JAN1999
Occupational Exposure Limit - FRANCE Carcinogen, JAN1993
Occupational Exposure Limit - GERMANY Carcinogen, JAN1999
Occupational Exposure Limit - SWEDEN Carcinogen, JAN1999
Occupational Exposure Limit - SWITZERLAND Skin, Carcinogen, JAN1999
Occupational Exposure Limit - SWITZERLAND Skin, Carcinogen JAN1993
Occupational Exposure Limit - UNITED KINGDOM Carcinogen, SEP2000
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN, KOREA American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value;

Confirmed Animal Carcinogen with Unknown
Occupational Exposure Limit IN NEW ZEALAND, SINGAPORE, VIETNAM American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value
Confirmed Animal Carcinogen with Unknown


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
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 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-reciprocal translocation
EPA GENETOX PROGRAM 1988, Positive: Rodent dominant lethal; Mammalian micronucleus
EPA GENETOX PROGRAM 1988, Positive: Sperm morphology-mouse; Sperm morphology-rabbit
EPA GENETOX PROGRAM 1988, Positive: D melanogaster Sex-linked lethal
EPA TSCA Section 8(b) CHEMICAL INVENTORY
Used as an ultra-violet light absorber and stabilizer for polymeric materials
EPA TSCA Section 8(d) unpublished health/safety studies
On EPA IRIS database
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


REFERENCES:

CODEN
REFERENCE
85DZAJ "Principles of Insect Chemosterilization," Labrecque, G.C., and C.N. Smith, eds., New York, Appleton-Century-Crofts, 1968
ABABAC Annales de Biologie Animale, Biochimie, Biophysique. (Versailles, France) V.1-19, 1961-79.
AIHAAP American Industrial Hygiene Association Journal. (AIHA, 475 Wolf Ledges Pkwy., Akron, OH 44311) V.19- 1958-
AJPAA4 American Journal of Pathology. (Lippincott/Harper, Journal Fulfillment Dept., 2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1925-
BJCAAI British Journal of Cancer. (Macmillan Press Ltd., Houndmills, Basingstoke, Hants. RG21 2XS, UK) V.1- 1947-
BWHOA6 Bulletin of the World Health Organization. (WHO, Pub. Center USA, 49 Sheridan Ave., Albany, NY 12210)
CHINAG Chemistry and Industry (London). (Royal Soc. of Chemistry, Distribution Centre, Blackhorse Rd., Letchworth, Herts SG6 1HN, UK) V.1- 1923-
CHROAU Chromosoma. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.1- 1939-
CHYCDW Zhonghua Yufangyixue Zazhi. Chinese Journal of Preventive Medicine. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) Beginning history not known.
CNJGA8 Canadian Journal of Genetics and Cytology. (National Research Council of Canada, Publication Sales and Distribution, Ottawa ON K1A OR6, Canada) V.1- 1959-
CYTOAN Cytologia. (Japan Pub. Trading Co. (USA), 1255 Howard St., San Francisco, CA 94103) V.1- 1929-
DTLVS* The Threshold Limit Values (TLVs) and Biological Exposure Indices (BEIs) booklet issues by American Conference of Governmental Industrial Hygienists (ACGIH), Cincinnati, OH, 1996
EMMUEG Environmental and Molecular Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.10- 1987-
ENVRAL Environmental Research. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1967-
FOBLAN Folia Biologica (Prague). (Academic Press Inc. Ltd., 24-28 Oval Rd., London NW1 7DX, UK) V.1- 1955-
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972-
IMSUAI Industrial Medicine and Surgery. (Northbrook, IL) V.18-42, 1949-73. For publisher information, see IOHSA5.
JEENAI Journal of Economic Entomology. (Entomological Soc. of America, 4603 Calvert Rd., College Park, MD 20740) V.1- 1908-
JJIND8 JNCI, Journal of the National Cancer Institute. (Washington, DC) V.61-79, 1978-87. For publisher information, see JNCIEQ.
JRPFA4 Journal of Reproduction and Fertility. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1960-
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964-
MUTAEX Mutagenesis. (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1986-
NATUAS Nature. (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736) V.1- 1869-
NIOSH* National Institute of Occupational Safety and Health, U.S. Dept. of Health, Education, and Welfare, Reports and Memoranda.
NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information.
NYKZAU Nippon Yakurigaku Zasshi. Japanese Journal of Pharmacology. (Nippon Yakuri Gakkai, c/o Kyoto Daigaku Igakubu Yakurigaku Kyoshitsu, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606, Japan) V.40- 1944-
PMRSDJ Progress in Mutation Research. (Elsevier Science Pub. Co., Inc., 52 Vanderbilt Ave., New York, NY 10017) V.1- 1981-
SCIEAS Science. (American Assoc. for the Advancement of Science, 1333 H St., NW, Washington, DC 20005) V.1- 1895-
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959-

Used as an ultra-violet light absorber and stabilizer for polymeric materials

NIOSH PROFILE (HEXAMETHYLPHOSPHORAMIDE), SRC, 12/79

RTECS Compound Description:
   Agricultural Chemical
   Tumorigen
   Mutagen
   Reproductive Effector
   Primary Irritant

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