The Registry of Toxic Effects of Chemical Substances

Phosphoric acid, trimethyl ester

RTECS #: TC8225000

CAS #: 512-56-1

UPDATE: February 2003 MW: 140.09 MF: C3H9O4P


NOTE:

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

SYNONYMS:

  1. Methyl phosphate
  2. NCI - C03781
  3. O,O,O - Trimethyl phosphate
  4. Trimethoxyphosphine oxide
  1. Trimethyl orthophosphate
  2. Trimethyl phosphate
  3. Trimethylfosfat (Czech)
  4. Trimethylphosphate


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
N/R
 N/R N/R N/R


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE 		DOSE REFERENCE
body fluid assay mouse
Salmonella typhimurium 		1,750 mg/kg MUREAV 65,121,1979
cytogenetic analysis oral
hamster 		1 gm/kg/5 day- intermittent ARZNAD 25,1889,1975
cytogenetic analysis human lymphocyte 100 mmol/L/5 hour MUREAV 65,121,1979
cytogenetic analysis unreported route
mouse 		1,250 mg/kg MUREAV 65,121,1979
cytogenetic analysis intraperitoneal
mouse 		1 gm/kg JTCEEM 6,5,1986
cytogenetic analysis intraperitoneal
rat 		500 mg/kg/24 hour MUREAV 65,121,1979
dominant lethal test oral
mouse 		2,500 mg/kg/5 day- intermittent SCIEAS 168,584,1970
dominant lethal test parenteral
mouse 		200 mg/kg MUREAV 65,121,1979
dominant lethal test intraperitoneal
mouse 		1 mg/kg MUREAV 65,121,1979
DNA damage rat liver 300 µmol/L SinJF# 26OCT1982
DNA repair Escherichia coli 1,500 µg/well MUREAV 133,161,1984
host-mediated assay mouse
Escherichia coli 		1,500 mg/kg MUREAV 272,161,1992
mutation in microorganisms Escherichia coli 5 mg/plate (-enzymatic activation step) MUREAV 28,405,1975
mutation in microorganisms Klebsiella pneumoniae 2 pph (-enzymatic activation step) MUREAV 16,413,1972
mutation in microorganisms other microorganisms 320 mmol/L (-enzymatic activation step) MUREAV 21,175,1973
mutation in microorganisms Salmonella typhimurium 320 mmol/L (+enzymatic activation step) MUREAV 21,175,1973
mutation in microorganisms Salmonella typhimurium 125 µg/plate (-enzymatic activation step) MUREAV 65,121,1979
mutation in microorganisms Serratia marcescens 125 µg/disc (-enzymatic activation step) MUREAV 65,121,1979
micronucleus test intraperitoneal
mouse 		2,500 mg/kg/5 day- continuous MUREAV 28,101,1975
morphological transform mouse fibroblast 0.1 mg/L/21 day (-enzymatic activation step) EMMUEG 37,231,2001
sister chromatid exchange parenteral
chicken 		25,424 µg/kg 47JMAE -,137,1982
sex chromosome loss and nondisjunction unreported route
Drosophila melanogaster 		10 mmol/L MUREAV 65,121,1979
sex chromosome loss and nondisjunction oral
Drosophila melanogaster 		1 mmol/L MUREAV 28,465,1975
specific locus test oral
Drosophila melanogaster 		5 mmol/L/48 hour MUREAV 222,359,1989
sperm morphology intraperitoneal
mouse 		3,500 mg/kg/5 day PNASA6 72,4425,1975
heritable translocation test oral
Drosophila melanogaster 		3 mmol/L MUREAV 28,465,1975
heritable translocation test oral
mouse 		21,728 mg/kg/8 week- continuous ENMUDM 7(Suppl 3),65,1985
heritable translocation test intraperitoneal
mouse 		1 gm/kg MUREAV 157,205,1985


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraperitoneal
mouse 		lowest published toxic dose: 700 mg/kg (1 day male) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants) TXAPA9 23,288,1972
intraperitoneal
mouse 		lowest published toxic dose: 1 gm/kg (1 day male) Reproductive: Effects on embryo or fetus: Fetal death SCIEAS 168,584,1970
intraperitoneal
mouse 		lowest published toxic dose: 1 gm/kg (1 day male) Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea)

Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)

Reproductive: Effects on newborn: Viability index (e.g., # alive at day 4 per # born alive) 		MUREAV 157,205,1985
oral
hamster 		lowest published toxic dose: 1 gm/kg (2 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) ARZNAD 25,1889,1975
oral
mouse 		lowest published toxic dose: 2,500 mg/kg (5 day male) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants) TXAPA9 23,288,1972
oral
mouse 		lowest published toxic dose: 2,500 mg/kg (5 day male) Reproductive: Effects on embryo or fetus: Fetal death SCIEAS 168,584,1970
oral
mouse 		lowest published toxic dose: 5 gm/kg (5 day male) Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea) SCIEAS 168,584,1970
oral
rat 		lowest published toxic dose: 1 gm/kg (5 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) JTSCDR 24,347,1999
oral
rat 		lowest published toxic dose: 500 mg/kg (5 day male) Reproductive: Effects on fertility: Male fertility index (e.g., # males impregnating females per # males exposed to fertile nonpregnant females) BCSTB5 1,523,1973
oral
rat 		lowest published toxic dose: 600 mg/kg (1 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) CGANE7 39,191,1999
oral
rat 		lowest published toxic dose: 5,500 mg/kg (22 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Reproductive: Effects on fertility: Male fertility index (e.g., # males impregnating females per # males exposed to fertile nonpregnant females) 		EXPEAM 37,999,1981


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
mouse 		lowest published toxic dose: 154 gm/kg/2 year- continuous Tumorigenic: Carcinogenic by RTECS criteria

Reproductive: Tumorigenic effects: Uterine tumors 		NCITR* NCI-TR-81,1978
oral
rat 		lowest published toxic dose: 31 gm/kg/2 year- continuous Tumorigenic: Neoplastic by RTECS criteria

Skin and Appendages: Tumors 		NCITR* NCI-TR-81,1978
oral
rat 		toxic dose : 16 gm/kg/2 year- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Skin and Appendages: Tumors 		NCITR* NCI-TR-81,1978
oral
rat 		toxic dose : 77 gm/kg/2 year- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Skin and Appendages: Tumors 		NCITR* NCI-TR-81,1978


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraperitoneal
mouse 		lethal dose (50 percent kill): 2,250 mg/kg N/R THERAP 15,237,1960
intraperitoneal
rat 		lowest published lethal dose: 800 mg/kg Behavioral: General anesthetic

Gastrointestinal: Other changes 		JPPMAB 11,150,1959
intravenous
rat 		lowest published lethal dose: 2,400 mg/kg Behavioral: General anesthetic

Behavioral: Muscle weakness

Lung, Thorax, or Respiration: Dyspnea 		NATUAS 179,154,1957
oral
guinea pig 		lethal dose (50 percent kill): 1,676 mg/kg N/R 85JCAE -,1129,1986
oral
mouse 		lethal dose (50 percent kill): 1,470 mg/kg N/R NCILB* NCI-E-C-72-3252,1973
oral
quail 		lethal dose (50 percent kill): 750 mg/kg N/R JRPFA4 48,371,1976
oral
rat 		lethal dose (50 percent kill): 840 mg/kg N/R NCILB* NCI-E-C-72-3252,1973
oral
rabbit 		lethal dose (50 percent kill): 1,275 mg/kg Behavioral: Tremor

Behavioral: Muscle weakness

Lung, Thorax, or Respiration: Dyspnea 		JPETAB 88,338,1946
skin
rabbit 		lethal dose (50 percent kill): 2,830 µL/kg N/R AIHAAP 30,470,1969
unreported route
mouse 		lethal dose (50 percent kill): 540 mg/kg Behavioral: Somnolence (general depressed activity)

Behavioral: Convulsions or effect on seizure threshold

Behavioral: Change in motor activity (specific assay) 		GNAMAP 17,37,1978
unreported route
rat 		lethal dose (50 percent kill): 500 mg/kg Behavioral: Somnolence (general depressed activity)

Behavioral: Convulsions or effect on seizure threshold

Behavioral: Change in motor activity (specific assay) 		GNAMAP 17,37,1978


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
dog 		lowest published toxic dose: 170 mL/kg/17 week- intermittent Spinal Cord: Other degenerative changes

Peripheral Nerve and Sensation: Structural change in nerve or sheath

Behavioral: Muscle weakness 		NTOTDY 6,39,1984
oral
rat 		lowest published toxic dose: 18,900 mg/kg/9 week- continuous Kidney, Ureter, and Bladder: Changes in bladder weight

Blood: Changes in erythrocyte (RBC) count

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		TOLED5 13,29,1982
oral
rat 		lowest published toxic dose: 64,050 mg/kg/2.5 year- continuous Peripheral Nerve and Sensation: Sensory syndrome diagnostic of central lesion

Behavioral: Muscle weakness

Blood: Pigmented or nucleated red blood cells 		FAATDF 40,75,1997
oral
rat 		lowest published toxic dose: 500 mg/kg/5 day- intermittent Endocrine: Androgenic

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

Related to Chronic Data: Changes in prostate weight 		LIFSAK 10,917,1971
oral
rabbit 		lowest published toxic dose: 2,160 mg/kg/6 day- intermittent Peripheral Nerve and Sensation: Flaccid paralysis without anesthesia (usually neuromuscular blockage)

Behavioral: Tremor

Behavioral: Muscle weakness 		JPETAB 88,338,1946
subcutaneous
cat 		lowest published toxic dose: 9,037 mg/kg/18 week- intermittent Behavioral: Muscle weakness JPETAB 88,338,1946
skin
rabbit 		lowest published toxic dose: 34,020 mg/kg/14 day- intermittent Behavioral: Tremor

Behavioral: Muscle weakness

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		JPETAB 88,338,1946


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
N/R N/R N/R


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
Occupational Exposure Limit - AUSTRIA Skin, Suspected Carcinogen, JAN1999
Occupational Exposure Limit - FINLAND time-weighted average 0.05 ppm (2.6 mg/m3), short term exposure limit 10 ppm, Skin, Carcinogen,JAN1999
Occupational Exposure Limit - GERMANY Skin, Carcinogen, JAN1999


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Occupational Hazard Survey 1974 National Occupational Hazard Survey 1974: Hazard Code: A1121;
Number of Industries 1;
Total Number of Facilities 21;
Number of Occupations 2;
Total Number of Employees Exposed 104


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
EPA GENETOX PROGRAM 1988, Positive: Carcinogenicity-mouse/rat; Mammalian micronucleus
EPA GENETOX PROGRAM 1988, Positive: Sperm morphology-mouse; D melanogaster Sex-linked lethal
EPA GENETOX PROGRAM 1988, Positive/dose response: In vitro cytogenetics-human lymphocyte
EPA GENETOX PROGRAM 1988, Positive/dose response: Rodent dominant lethal
EPA GENETOX PROGRAM 1988, Inconclusive: E coli polA without S9
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 Bioassay (gavage);clear evidence:mouse,rat NCITR* NCI-TR-81,1978


REFERENCES:

CODEN
REFERENCE
47JMAE "Cytogenetic Assays of Environmental Mutagens," Hsu, T.C., ed., Totowa, NJ, Allanheld, Osmun & Co., 1982
85JCAE "Prehled Prumyslove Toxikologie; Organicke Latky," Marhold, J., Prague, Czechoslovakia, Avicenum, 1986
AIHAAP American Industrial Hygiene Association Journal. (AIHA, 475 Wolf Ledges Pkwy., Akron, OH 44311) V.19- 1958-
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
BCSTB5 Biochemical Society Transactions. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1973-
CGANE7 Congenital Anomalies. (Nippon Senten Ijo Gakkai, 377-2 Ono-higashi, Osakasayama, Osaka-Fu 589 Japan) V.27- 1987-
EMMUEG Environmental and Molecular Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.10- 1987-
ENMUDM Environmental Mutagenesis. (New York, NY) V.1-9, 1979-87. For publisher information, see EMMUEG.
EXPEAM Experientia. (Birkhaeuser Verlag, POB 133, CH-4010 Basel, Switzerland) V.1- 1945-
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1-40, 1981-97. For publisher information, see TOSCF2
GNAMAP Gigiena Naselennykh Mest. Hygiene in Populated Places. (Izdatel'stvo Zdorov'ya, Kiev, USSR) V.7- 1967-
JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10-
JPPMAB Journal of Pharmacy and Pharmacology. (Pharmaceutical Soc. of Great Britain, 1 Lambeth High St., London SEI 7JN, UK) V.1- 1949-
JRPFA4 Journal of Reproduction and Fertility. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1960-
JTCEEM Journal de Toxicologie Clinique et Experimentale. (SPPIF, B.P.22, F-41353 Vineuil, France) V.5- 1985-
JTSCDR Journal of Toxicological Sciences. (Japanese Soc. of Toxicological Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku, Tokyo 113, Japan) V.1- 1976-
LIFSAK Life Sciences. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1-8, 1962-69; V.14- 1974-
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964-
NATUAS Nature. (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736) V.1- 1869-
NCILB* Progress Report for Contract No. NIH-NCI-E-C-72-3252, Submitted to the National Cancer Institute by Litton Bionetics, Inc. (Bethesda, MD)
NCITR* National Cancer Institute Carcinogenesis Technical Report Series. (Bethesda, MD) No.0-205. For publisher information, see NTPTR*.
NTOTDY Neurobehavioral Toxicology and Teratology. (Fayetteville, NY) V.3-8, 1981-86. For publisher information, see NETEEC.
PNASA6 Proceedings of the National Academy of Sciences of the United States of America. (National Academy of Sciences, Printing & Pub. Office, 2101 Constitution Ave., Washington, DC 20418) V.1- 1915-
SCIEAS Science. (American Assoc. for the Advancement of Science, 1333 H St., NW, Washington, DC 20005) V.1- 1895-
SinJF# Personal Communication from J.F. Sina, Merck Institute for Therapeutic Research, West Point, PA 19486, Oct. 26, 1982
THERAP Therapie. (Doin, Editeurs, 8, Place de l'Odeon, F-75006 Paris, France) V.1- 1946-
TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1977-
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959-

RTECS Compound Description:
   Agricultural Chemical
   Tumorigen
   Mutagen
   Reproductive Effector

ALT CAS #: 91316-44-8
Click Here for Additional Information about RTECS