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Phenothiazine, 2 - chloro - 10 - (3 - (dimethylamino) propyl) - , monohydrochloride

RTECS #: SO1750000

CAS #: 69-09-0

UPDATE: February 2009 MW: 355.35 MF: C17H19ClN2S•ClH


NOTE:

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

SYNONYMS:

  1. 10 - (3 - Dimethylaminopropyl) - 2 - chlorophenothiazine monohydrochloride
  2. 10H - Phenothiazine - 10 - propanamine, 2 - chloro - N,N - dimethyl - , monohydrochloride
  3. 2 - Chloro - 10 - (3 - dimethylaminopropyl) phenothiazine monohydrochloride
  4. 4560 RP hydrochloride
  5. Aminazin monohydrochloride
  6. Ampliactil monohydrochloride
  7. CPZ
  8. Chlorazin
  9. Chlorpromazine hydrochloride
  10. Chlorpromazine monohydrochloride
  11. Chlorpromazinium chloride
  12. Hebanil
  13. Hibernal
  14. Klorproman
  1. Klorpromex
  2. Largactil monohydrochloride
  3. NCI - C05210
  4. Neurazine
  5. Norcozine
  6. Phenothiazine hydrochloride
  7. Plegomazin
  8. Promacid
  9. Promapar
  10. Propaphen
  11. Propaphenin hydrochloride
  12. Sonazine
  13. Taroctyl
  14. Thorazine hydrochloride


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
DNA damage mouse other cell types 1.25 mg/L/20 minute MUREAV 632,44,2007
DNA inhibition Escherichia coli 48 mg/L BCPCA6 26,1205,1977
mutation in microorganisms Escherichia coli 5 mg/L (+enzymatic activation step) GENRA8 30,13,1977
mutation in microorganisms Salmonella typhimurium 5 mg/L (-enzymatic activation step) MUREAV 208,33,1988
other mutation test systems Escherichia coli 48 mg/L BCPCA6 26,1205,1977
other mutation test systems intraperitoneal
rat 		25 mg/kg DCTODJ 9,41,1986


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraperitoneal
rat 		lowest published toxic dose: 2,500 µg/kg (1 day male) Reproductive: Effects on fertility: Mating performance (e.g., # sperm positive females per # females mated; # copulations per # estrus cycles) PSEBAA 103,392,1960
intraperitoneal
rat 		lowest published toxic dose: 25 mg/kg (8 day pregnant) Reproductive: Effects on embryo or fetus: Extra embryonic structures (e.g., placenta, umbilical cord)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) 		IJEBA6 18,344,1980
intraperitoneal
rat 		lowest published toxic dose: 100 mg/kg (14 day pregnant) Reproductive: Effects on newborn: Stillbirth

Reproductive: Effects on newborn: Live birth index (Litter size (e.g., # fetuses per litter; measured after birth)

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain) 		IJEBA6 16,542,1978
intraperitoneal
rat 		lowest published toxic dose: 100 mg/kg (14 day pregnant) Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Musculoskeletal system

Reproductive: Specific developmental abnormalities: Gastrointestinal system 		IJMRAQ 67,300,1978
intraperitoneal
rat 		lowest published toxic dose: 50 mg/kg (12 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system TJADAB 18,167,1978
oral
mouse 		lowest published toxic dose: 300 mg/kg (6-15 day pregnant) Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Musculoskeletal system

Reproductive: Specific developmental abnormalities: Urogenital system 		NTIS** PB83-179846
oral
mouse 		lowest published toxic dose: 300 mg/kg (6-15 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetal death

Reproductive: Specific developmental abnormalities: Eye, ear 		NTIS** PB83-179846
oral
mouse 		lowest published toxic dose: 300 mg/kg (6-15 day pregnant) Reproductive: Specific developmental abnormalities: Eye, ear

Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Effects on embryo or fetus: Fetal death 		NTIS** #PB83-179846
oral
mouse 		lowest published toxic dose: 300 mg/kg (6-15 day pregnant) Reproductive: Specific developmental abnormalities: Musculoskeletal system

Reproductive: Specific developmental abnormalities: Urogenital system 		NTIS** #PB83-179846
oral
mouse 		lowest published toxic dose: 150 mg/kg (6-15 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) NTIS** #PB83-179846
oral
rat 		lowest published toxic dose: 300 mg/kg (6-20 day pregnant) Reproductive: Effects on newborn: Behavioral TJADAB 37,185,1988
oral
rat 		lowest published toxic dose: 50 mg/kg (7-16 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) TXAPA9 21,230,1972
oral
rat 		lowest published toxic dose: 250 mg/kg (7-16 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants) TXAPA9 21,230,1972
oral
rat 		lowest published toxic dose: 350 mg/kg (7-16 day pregnant) Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth) TXAPA9 21,230,1972
oral
rat 		lowest published toxic dose: 1,980 mg/kg (4 week male/4 week prior to copulation-3 week after birth) Reproductive: Effects on newborn: Biochemical and metabolic JONRA9 20,625,1973
oral
rat 		lowest published toxic dose: 300 mg/kg (6-15 day pregnant) Reproductive: Other developmental abnormalities NTIS** #PB83-191080
oral
rat 		lowest published toxic dose: 150 mg/kg (6-15 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death NTIS** #PB83-191080
oral
rat 		lowest published toxic dose: 50 mg/kg (6-15 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) NTIS** #PB83-191080
subcutaneous
mouse 		lowest published toxic dose: 21 mg/kg (9 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death

Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue) 		DGDFA5 22,61,1980
subcutaneous
mouse 		lowest published toxic dose: 10 mg/kg (3 day pregnant) Reproductive: Effects on embryo or fetus: Cytological changes (including somatic cell genetic material)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Other effects to embryo or fetus 		JRPFA4 76,527,1986
subcutaneous
rat 		lowest published toxic dose: 12 mg/kg (12-15 day pregnant) Reproductive: Effects on newborn: Biochemical and metabolic BRREAP 21,460,1970
subcutaneous
rat 		lowest published toxic dose: 24 mg/kg (17-20 day pregnant) Reproductive: Maternal effects: Postpartum

Reproductive: Effects on newborn: Stillbirth

Reproductive: Effects on newborn: Weaning or lactation index (e.g., # alive at weaning per # alive at day 4) 		JNEUAY 4,87,1962
subcutaneous
rat 		lowest published toxic dose: 12 mg/kg (12-15 day pregnant) Reproductive: Effects on newborn: Behavioral DEPBA5 3,225,1970
subcutaneous
rat 		lowest published toxic dose: 24 mg/kg (17-20 day pregnant) Reproductive: Effects on newborn: Stillbirth

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain) 		JNEUAY 4,87,1962
subcutaneous
rat 		lowest published toxic dose: 125 mg/kg (5 day male) Reproductive: Paternal effects: Testes, epididymis, sperm duct JRPFA4 28,177,1972


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

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


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
inhalation
mouse 		lethal concentration (50 percent kill): 40 mg/m3/2 hour N/R 85JCAE -,1106,1986
inhalation
rat 		lethal concentration (50 percent kill): 40 mg/m3/2 hour N/R 85JCAE -,1106,1986
intramuscular
mouse 		lowest published toxic dose: 4 mg/kg Behavioral: Altered sleep time (including change in righting reflex)

Behavioral: Change in motor activity (specific assay) 		FTRPAE 76,187,2005
intraperitoneal
chicken 		lethal dose (50 percent kill): 160 mg/kg N/R TXAPA9 2,558,1960
intraperitoneal
guinea pig 		lethal dose (50 percent kill): 109 mg/kg N/R PHARAT 38,749,1983
intraperitoneal
mouse 		lethal dose (50 percent kill): 92,200 µg/kg N/R TXAPA9 2,558,1960
intraperitoneal
mouse 		lowest published toxic dose: 0.2 mg/kg Behavioral: Rigidity (includes catalepsy) PBBHAU 21,17,1984
intraperitoneal
mouse 		lowest published toxic dose: 0.5 mg/kg Behavioral: Rigidity (includes catalepsy)

Behavioral: Alteration of classical conditioning 		PBBHAU 21,17,1984
intraperitoneal
rat 		lethal dose (50 percent kill): 62 mg/kg N/R PSYPAG 12,142,1968
intraperitoneal
rat 		lowest published toxic dose: 1 mg/kg Behavioral: Alteration of classical conditioning NEROEW 28,284,2003
intravenous
chicken 		lethal dose (50 percent kill): 28 mg/kg N/R TXAPA9 2,558,1960
intravenous
man 		lowest published toxic dose: 1,786 µg/kg/2 day- intermittent Behavioral: Irritability

Lung, Thorax, or Respiration: Respiratory stimulation

Skin and Appendages: Other: Sweating 		BIPCBF 18,1441,1983
intravenous
mouse 		lethal dose (50 percent kill): 20 mg/kg N/R ARZNAD 21,808,1971
intravenous
rat 		lethal dose (50 percent kill): 25 mg/kg N/R FAZMAE 5,269,1963
intravenous
rabbit 		lethal dose (50 percent kill): 5 mg/kg N/R 27ZQAG -,15,1972
intravenous
woman 		lowest published toxic dose: 822 µg/kg Behavioral: Somnolence (general depressed activity)

Behavioral: Excitement

Cardiac: Pulse rate increased without fall in BP 		AEMED3 17,380,1988
oral
man 		lowest published toxic dose: 6,071 µg/kg Reproductive: Other effects on male IJMDAI 5,1254,1969
oral
man 		lowest published toxic dose: 18 mg/kg/5 day- intermittent Reproductive: Other effects on male IJMDAI 5,1254,1969
oral
monkey 		lowest published lethal dose: >30 mg/kg Behavioral: Somnolence (general depressed activity)

Behavioral: Muscle weakness

Behavioral: Rigidity (includes catalepsy) 		AIPTAK 122,129,1959
oral
mouse 		lethal dose (50 percent kill): 135 mg/kg Behavioral: Somnolence (general depressed activity)

Behavioral: Rigidity (includes catalepsy)

Behavioral: Alteration of classical conditioning 		CPBTAL 24,1179,1976
oral
mouse 		lowest published toxic dose: 30 mg/kg Behavioral: Change in motor activity (specific assay) NEROEW 23,375,2000
oral
mouse 		lowest published toxic dose: 5 mg/kg Behavioral: Change in motor activity (specific assay)

Nutritional and Gross Metabolic: Body temperature decrease 		JOETD7 97,541,2005
oral
mouse 		lowest published toxic dose: 6 mg/kg Behavioral: Altered sleep time (including change in righting reflex) BPBLEO 27,641,2004
oral
rat 		lethal dose (50 percent kill): 145 mg/kg N/R JPETAB 148,151,1965
oral
woman 		lowest published toxic dose: 6 mg/kg Behavioral: Anorexia (human)

Gastrointestinal: Other changes 		PGMJAO 60,564,1984
oral
woman 		lowest published toxic dose: 35 gm/kg/16 year- intermittent Behavioral: Rigidity (includes catalepsy)

Cardiac: Pulse rate increased without fall in BP

Lung, Thorax, or Respiration: Respiratory stimulation 		BIPCBF 18,1441,1983
subcutaneous
guinea pig 		lethal dose (50 percent kill): 420 mg/kg N/R AIPTAK 137,375,1962
subcutaneous
mouse 		lethal dose (50 percent kill): 420 mg/kg N/R BJPCAL 22,301,1964
unreported route
rat 		lethal dose (50 percent kill): 90 mg/kg N/R 27ZQAG -,15,1972


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
mouse 		lowest published toxic dose: 300 mg/kg/10 day- continuous Behavioral: Antianxiety

Skin and Appendages: Other: Hair 		NTIS** #PB83-179846
oral
mouse 		lowest published toxic dose: 300 mg/kg/10 day- continuous Nutritional and Gross Metabolic: Body temperature decrease

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		NTIS** #PB83-179846
oral
mouse 		lowest published toxic dose: 30 mg/kg/6 day- continuous Nutritional and Gross Metabolic: Weight loss or decreased weight gain NTIS** #PB83-179846
oral
mouse 		lowest published toxic dose: 150 mg/kg/10 day- continuous Liver: Changes in liver weight NTIS** #PB83-179846
oral
rat 		lowest published toxic dose: 900 mg/kg/30 day- intermittent Related to Chronic Data: Changes in ovarian weight

Related to Chronic Data: Changes in uterine weight 		KSRNAM 8,3446,1974
oral
rat 		lowest published toxic dose: 450 mg/kg/10 day- continuous Behavioral: Antianxiety

Skin and Appendages: Other: Hair

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		NTIS** #PB83-191080
oral
rat 		lowest published toxic dose: 450 mg/kg/10 day- continuous Eye: Lacrimation

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		NTIS** #PB83-191080
oral
rat 		lowest published toxic dose: 50 mg/kg/10 day- continuous Nutritional and Gross Metabolic: Weight loss or decreased weight gain NTIS** #PB83-191080
oral
rat 		lowest published toxic dose: 300 mg/kg/10 day- continuous Liver: Changes in liver weight NTIS** #PB83-191080
subcutaneous
rat 		lowest published toxic dose: 50 mg/kg/5 day- intermittent Related to Chronic Data: Changes in ovarian weight

Related to Chronic Data: Changes in uterine weight 		KSRNAM 8,3446,1974


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
TOXICOLOGY REVIEW
JMSCA9 106,755,1960
TOXICOLOGY REVIEW
MUREAV 584,1,2005
TOXICOLOGY REVIEW
REPTED 25,192,2008
TOXICOLOGY REVIEW
REPTED 25,192,2008


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
Occupational Exposure Limit - RUSSIA short term exposure limit 0.3 mg/m3, Skin, JUN2003


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Occupational Hazard Survey 1974 National Occupational Hazard Survey 1974: Hazard Code: M1050;
Number of Industries 2;
Total Number of Facilities 830;
Number of Occupations 3;
Total Number of Employees Exposed 905
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: M1050;
Number of Industries 1;
Total Number of Facilities 188;
Number of Occupations 3;
Total Number of Employees Exposed 3,661;
Total Number of Female Employees Exposed 1,936


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
EPA TSCA Section 8(b) CHEMICAL INVENTORY
Used as an antipsychotic agent and in the prevention and treatment of nausea
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001


REFERENCES:

CODEN
REFERENCE
27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972
85JCAE "Prehled Prumyslove Toxikologie; Organicke Latky," Marhold, J., Prague, Czechoslovakia, Avicenum, 1986
AEMED3 Annals of Emergency Medicine. (American College of Emergency Physicians, 1125 Executive Circle, Irving, TX 75038)
AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898-
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
BCPCA6 Biochemical Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1958-
BIPCBF Biological Psychiatry. (Plenum Pub. Corp., 233 Spring St., New York, NY 10013) V.1- 1969-
BJPCAL British Journal of Pharmacology and Chemotherapy. (London, UK) V.1-33, 1946-68. For publisher information, see BJPCBM.
BPBLEO Biological and Pharmaceutical Bulletin. (Pharmaceutical Society of Japan, 2-12-15-201 Shibuya Shibuya-ku, Tokyo 150, Japan) V.16- 1993-
BRREAP Brain Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1966-
CPBTAL Chemical and Pharmaceutical Bulletin. (Japan Pub. Trading Co., USA, 1255 Howard St., San Francisco, CA 94103) V.6- 1958-
DCTODJ Drug and Chemical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.1- 1977/78-
DEPBA5 Developmental Psychobiology. (John Wiley & Sons, Inc., 605 Third Ave., New York, NY 10158) V.1- 1968-
DGDFA5 Development, Growth & Differentiation. (Japan Pub. Trading Co. (USA), 1255 Howard St., San Francisco, CA 94103) V.11- 1969-
FAZMAE Fortschritte der Arzneimittelforschung. Progress in Drug Research. (Birkhauser Boston, Inc., c/o Springer-Verlag New York, 44 Hartz Way, Secaucus, NJ 07094) V.1- 1959-
FTRPAE Fitoterapia. (Inverni della Beffa SpA, via Ripamonti, 99, 20141 Milan, Italy) V.18- 1947-
GENRA8 Genetical Research. (Cambridge Univ. Press, 32 E. 57th St., New York, NY 10022) V.1- 1960-
IJEBA6 Indian Journal of Experimental Biology. (Publications & Information Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963-
IJMDAI Israel Journal of Medical Sciences. (POB 1435, Jerusalem 91013, Israel) V.1- 1965-
IJMRAQ Indian Journal of Medical Research. (Indian Council of Medical Research, Ansari Nagar, New Delhi 110 029, India) V.1- 1913-
JMSCA9 Journal of Mental Science. (London, UK) V.4-108, 1857-1962. For publisher information, see BJPYAJ.
JNEUAY Journal of Neuropsychiatry. (Chicago, IL) V.1-5, 1959-64. For publisher information, see BENPBG.
JOETD7 Journal of Ethnopharmacology. (Elsevier Scientific Pub. Ireland Ltd., POB 85, Limerick, Ireland) V.1- 1979-
JONRA9 Journal of Neurochemistry. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) V.1- 1956-
JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10-
JRPFA4 Journal of Reproduction and Fertility. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1960-
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964-
NEROEW Neuropsychopharmacology. (Elsevier Science, 655 Avenue of the Americas, New York, NY 10010) V.1- 1987-
NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information.
PBBHAU Pharmacology, Biochemistry and Behavior. (ANKHO International Inc., P.O. Box 426, Fayetteville, NY 13066) V.1- 1973-
PGMJAO Postgraduate Medical Journal. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1925-
PHARAT Pharmazie. (VEB Verlag Volk und Gesundheit, Neue Gruenstr. 18, Berlin DDR-1020, Ger. Dem. Rep.) V.1- 1946-
PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04-
PSYPAG Psychopharmacologia (Berlin). (Berlin, Ger.) V.1-46, 1959-76. For publisher information, see PSCHDL.
REPTED Reproductive Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1987-
TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968-
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959-

Used as an antipsychotic agent and in the prevention and treatment of nausea

FDA-proprietary drug

RTECS Compound Description:
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   Reproductive Effector
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