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Registry of Toxic Effects of Chemical Substances (RTECS)

Phosphoric acid, trimethyl ester

RTECS #

TC8225000

CAS #

512-56-1; 91316-44-8

Updated

December 2010

Molecular Weight

140.09

Molecular Formula

C3H9O4P

Synonyms

Methyl phosphate
NCI-C03781
O,O,O-Trimethyl phosphate
Trimethoxyphosphine oxide
Trimethyl orthophosphate
Trimethyl phosphate
Trimethylfosfat (Czech)
Trimethylphosphate

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
body fluid assaySalmonella typhimurium/mouse1750 mg/kgMUREAV 65,121,1979
Cytogenetic Analysisunreported route/mouse1250 mg/kgMUREAV 65,121,1979
Cytogenetic Analysisintraperitoneal/mouse1 gm/kgJTCEEM 6,5,1986
Cytogenetic Analysislymphocyte/human100 mmol/L/5HMUREAV 65,121,1979
Cytogenetic Analysisintraperitoneal/rat500 mg/kg/24HMUREAV 65,121,1979
Cytogenetic Analysisoral/hamster1 gm/kg/5D- intermittentARZNAD 25,1889,1975
DNA Damageliver/rat300 µmol/LSinJF# 26OCT1982
DNA Damageliver/rat7000 µmol/L/3HMUREAV 629,49,2007
DNA repair/Escherichia coli1500 µg/wellMUREAV 133,161,1984
Dominant Lethal Testoral/mouse2500 mg/kg/5D- intermittentSCIEAS 168,584,1970
Dominant Lethal Testparenteral/mouse200 mg/kgMUREAV 65,121,1979
Dominant Lethal Testintraperitoneal/mouse1 mg/kgMUREAV 65,121,1979
heritable translocation testoral/Drosophila melanogaster3 mmol/LMUREAV 28,465,1975
heritable translocation testoral/mouse21728 mg/kg/8W-continuousENMUDM 7(Suppl 3),65,1985
heritable translocation testintraperitoneal/mouse1 gm/kgMUREAV 157,205,1985
host-mediated assayEscherichia coli/mouse1500 mg/kgMUREAV 272,161,1992
micronucleus testintraperitoneal/mouse2500 mg/kg/5D-continuousMUREAV 28,101,1975
morphological transformfibroblast/mouse0.1 mg/L/21D (-enzymatic activation step)EMMUEG 37,231,2001
mutation in microorganisms/Serratia marcescens125 µg/disc (-enzymatic activation step)MUREAV 65,121,1979
mutation in microorganisms/Klebsiella pneumoniae2 pph (-enzymatic activation step)MUREAV 16,413,1972
mutation in microorganisms/Other microorganisms320 mmol/L (-enzymatic activation step)MUREAV 21,175,1973
mutation in microorganisms/Salmonella typhimurium320 mmol/L (+enzymatic activation step)MUREAV 21,175,1973
mutation in microorganisms/Salmonella typhimurium125 µg/plate (-enzymatic activation step)MUREAV 65,121,1979
mutation in microorganisms/Escherichia coli5 mg/plate (-enzymatic activation step)MUREAV 28,405,1975
sex chromosome loss and nondisjunctionunreported route/Drosophila melanogaster10 mmol/LMUREAV 65,121,1979
sex chromosome loss and nondisjunctionoral/Drosophila melanogaster1 mmol/LMUREAV 28,465,1975
sister chromatid exchangeparenteral/chicken25424 µg/kg47JMAE -,137,1982
specific locus testoral/Drosophila melanogaster5 mmol/L/48HMUREAV 222,359,1989
sperm morphologyintraperitoneal/mouse3500 mg/kg/5DPNASA6 72,4425,1975

Reproductive Effects Data and References

Route/OrganismDoseEffectReference
intraperitoneal/mouse 700 mg/kg (1D 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 1 gm/kg (1D male)Reproductive: Effects on embryo or fetus: Fetal deathSCIEAS 168,584,1970
intraperitoneal/mouse 1 gm/kg (1D 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
intraperitoneal/rat 30 mg/kg (3W male)Reproductive: Effects on fertility: Male fertility index (e.g., # males impregnating females per # males exposed to fertile nonpregnant females)TOVEFN (4),9,2007
intraperitoneal/rat 150 mg/kg (2W male)Reproductive: Effects on fertility: Male fertility index (e.g., # males impregnating females per # males exposed to fertile nonpregnant females)TOVEFN (4),9,2007
oral/hamster 1 gm/kg (2D male)Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)ARZNAD 25,1889,1975
oral/rat 1 gm/kg (5D male)Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)JTSCDR 24,347,1999
oral/rat 500 mg/kg (5D 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 600 mg/kg (1D male)Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)CGANE7 39,191,1999
oral/rat 5500 mg/kg (22D 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
oral/mouse 2500 mg/kg (5D 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 2500 mg/kg (5D male)Reproductive: Effects on embryo or fetus: Fetal deathSCIEAS 168,584,1970
oral/mouse 5 gm/kg (5D 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

Tumorigenic Data and References

Route/OrganismDoseEffectReference
oral/mouse lowest published toxic dose: 154 gm/kg/2Y- continuousTumorigenic: Carcinogenic by RTECS criteria

Reproductive: Tumorigenic effects: Uterine tumors
NCITR* NCI-TR-81,1978
oral/rat toxic dose: 16 gm/kg/2Y- intermittentTumorigenic: Equivocal tumorigenic agent by RTECS criteria

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

Skin and Appendages: Tumors
NCITR* NCI-TR-81,1978
oral/rat lowest published toxic dose: 31 gm/kg/2Y- continuousTumorigenic: Neoplastic by RTECS criteria

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

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
intraperitoneal/mouse lethal dose (50 percent kill): 2250 mg/kgTHERAP 15,237,1960
intraperitoneal/rat lowest published lethal dose: 800 mg/kgBehavioral: General anesthetic

Gastrointestinal: Other changes
JPPMAB 11,150,1959
intraperitoneal/rat lethal dose (50 percent kill): 1500 mg/kgTOVEFN (4),9,2007
intravenous/rat lowest published lethal dose: 2400 mg/kgBehavioral: General anesthetic

Behavioral: Muscle weakness

Lung, Thorax, or Respiration: Dyspnea
NATUAS 179,154,1957
oral/guinea pig lethal dose (50 percent kill): 1676 mg/kg85JCAE -,1129,1986
oral/mouse lethal dose (50 percent kill): 1470 mg/kgNCILB* NCI-E-C-72-3252,1973
oral/quail lethal dose (50 percent kill): 750 mg/kgJRPFA4 48,371,1976
oral/rabbit lethal dose (50 percent kill): 1275 mg/kgBehavioral: Tremor

Behavioral: Muscle weakness

Lung, Thorax, or Respiration: Dyspnea
JPETAB 88,338,1946
oral/rat lethal dose (50 percent kill): 840 mg/kgNCILB* NCI-E-C-72-3252,1973
skin/rabbit lethal dose (50 percent kill): 2830 µL/kgAIHAAP 30,470,1969
unreported route/mouse lethal dose (50 percent kill): 540 mg/kgBehavioral: 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/kgBehavioral: 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/OrganismDoseEffectReference
intraperitoneal/rat lowest published toxic dose: 3150 mg/kg/3W- intermittentReproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)TOVEFN (4),9,2007
oral/Dog lowest published toxic dose: 170 mL/kg/17W- intermittentSpinal Cord: Other degenerative changes

Peripheral Nerve and Sensation: Structural change in nerve or sheath

Behavioral: Muscle weakness
NTOTDY 6,39,1984
oral/rabbit lowest published toxic dose: 2160 mg/kg/6D- intermittentPeripheral Nerve and Sensation: Flaccid paralysis without anesthesia (usually neuromuscular blockage)

Behavioral: Tremor

Behavioral: Muscle weakness
JPETAB 88,338,1946
oral/rat lowest published toxic dose: 500 mg/kg/5D- intermittentEndocrine: 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/rat lowest published toxic dose: 18900 mg/kg/9W- continuousKidney, 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: 64050 mg/kg/2.5Y- continuousPeripheral Nerve and Sensation: Sensory syndrome diagnostic of central lesion

Behavioral: Muscle weakness

Blood: Pigmented or nucleated red blood cells
FAATDF 40,75,1997
skin/rabbit lowest published toxic dose: 34020 mg/kg/14D- intermittentBehavioral: Tremor

Behavioral: Muscle weakness

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
JPETAB 88,338,1946
subcutaneous/cat lowest published toxic dose: 9037 mg/kg/18W- intermittentBehavioral: Muscle weaknessJPETAB 88,338,1946

Reviews

OrganizationStandardReference
TOXICOLOGY REVIEWMUREAV 584,1,2005

NIOSH Documentation and Surveillance

OrganizationStandardReference
National Occupational Hazard Survey 1974Hazard 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

OrganizationReference
EPA GENETOX PROGRAM 1988, Inconclusive: E coli polA without S9
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, Positive: Carcinogenicity-mouse/rat; Mammalian micronucleus
EPA GENETOX PROGRAM 1988, Positive: Sperm morphology-mouse; D melanogaster Sex-linked lethal
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,ratNCITR* NCI-TR-81,1978
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