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3 - Heptanone, 6 - (dimethylamino) - 4,4 - diphenyl - , hydrochloride

RTECS #: MJ6300000

CAS #: 1095-90-5

UPDATE: November 2008 MW: 345.95 MF: C21H27NO•ClH


NOTE:

TABLE OF CONTENTS:
  1. SYNONYMS:
  2. MUTATION DATA:
  3. REPRODUCTIVE EFFECTS DATA:
  4. ACUTE TOXICITY DATA:
  5. OTHER MULTIPLE DOSE DATA:
  6. NIOSH DOCUMENTATION AND SURVEILLANCE:
  7. REFERENCES:

SYNONYMS:

  1. (+ - ) - Methadone hydrochloride
  2. 1,1 - Diphenyl - 1 - (beta - dimethylaminopropyl) butanone - 2 hydrochloride
  3. 4,4 - Diphenyl - 6 - dimethylamino - heptanone - 3 hydrochloride
  4. 6 - Dimethylamino - 4,4 - diphenyl - 3 - heptanone hydrochloride
  5. AN 148
  6. Adanon hydrochloride
  7. Adolan
  8. Algidon
  9. Algolysin
  10. Althose hydrochloride
  11. Butalgin
  1. DL - Methadone hydrochloride
  2. Depridol
  3. Diaminon hydrochloride
  4. Dolofin hydrochloride
  5. Dolophin hydrochloride
  6. Fenadone
  7. Hoechst 10820
  8. Mecodin
  9. Methadone hydrochloride
  10. Polamidon
  11. dl - 6 - Dimethylamino - 4,4 - diphenyl - 3 - heptanone 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
cytogenetic analysis intraperitoneal
mouse 		3 mg/kg/3 day- continuous MUREAV 68,235,1979
dominant lethal test intraperitoneal
mouse 		3 mg/kg/3 day MUREAV 68,235,1979
DNA repair Escherichia coli 800 ppm DCTODJ 4,1,1981
mutation in microorganisms Neurospora crassa 300 mg/L (-enzymatic activation step) DCTODJ 4,1,1981


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
implant
rat 		lowest published toxic dose: 210 mg/kg (8-21 day pregnant) Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)

Reproductive: Effects on newborn: Behavioral 		NETEEC 14,65,1992
implant
rat 		lowest published toxic dose: 126 mg/kg (16-22 day pregnant/7 day after birth) Reproductive: Other effects on female

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)

Reproductive: Effects on newborn: Behavioral 		PBBHAU 60,97,1998
implant
rat 		lowest published toxic dose: 88 mg/kg (7-20 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system NETEEC 14,265,1992
implant
rat 		lowest published toxic dose: 150 mg/kg (8-22 day pregnant) Reproductive: Effects on newborn: Live birth index (Litter size (e.g., # fetuses per litter; measured after birth)

Reproductive: Effects on newborn: Behavioral 		NETEEC 15,157,1993
implant
rat 		lowest published toxic dose: 108 mg/kg (12 day after birth) Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain) JPETAB 298,797,2001
implant
rat 		lowest published toxic dose: 135 mg/kg (7-21 day pregnant) Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain) JPETAB 298,797,2001
implant
rat 		lowest published toxic dose: 180 mg/kg (7-21 day pregnant/5 day after birth) Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain) JPETAB 298,797,2001
intraperitoneal
mouse 		lowest published toxic dose: 22 mg/kg (9 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death TJADAB 31,235,1985
intraperitoneal
mouse 		lowest published toxic dose: 19 mg/kg (9 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system TJADAB 31,235,1985
intraperitoneal
rat 		lowest published toxic dose: 135 mg/kg (5 day prior to copulation/1-22 day pregnant) Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain) BNEOBV 34,48,1978
oral
rat 		lowest published toxic dose: 130 mg/kg (8-22 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)

Reproductive: Effects on newborn: Behavioral 		JPETAB 208,106,1979
oral
rat 		lowest published toxic dose: 308 mg/kg (1-22 day pregnant) Reproductive: Effects on newborn: Stillbirth

Reproductive: Effects on newborn: Live birth index (Litter size (e.g., # fetuses per litter; measured after birth) 		NETOD7 1,87,1979
oral
rat 		lowest published toxic dose: 2,445 mg/kg (8 week male/8 week prior to copulation-3 week after birth) Reproductive: Effects on newborn: Weaning or lactation index (e.g., # alive at weaning per # alive at day 4)

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)

Reproductive: Effects on newborn: Delayed effects 		DPTHDL 6,125,1983
oral
rat 		lowest published toxic dose: 70 mg/kg (9-22 day pregnant) Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain) NETOD7 2,331,1980
oral
rat 		lowest published toxic dose: 75 mg/kg (8-22 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants) JPETAB 197,171,1976
subcutaneous
hamster 		lowest published toxic dose: 35 mg/kg (8 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system AJOGAH 123,705,1975
subcutaneous
hamster 		lowest published toxic dose: 83 mg/kg (8 day pregnant) Reproductive: Other developmental abnormalities AJOGAH 123,705,1975
subcutaneous
hamster 		lowest published toxic dose: 201 mg/kg (8 day pregnant) Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth) AJOGAH 123,705,1975
subcutaneous
mouse 		lowest published toxic dose: 100 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 		DCTODJ 6,41,1983
subcutaneous
mouse 		lowest published toxic dose: 50 mg/kg (6-15 day pregnant) Reproductive: Effects on newborn: Viability index (e.g., # alive at day 4 per # born alive)

Reproductive: Effects on newborn: Weaning or lactation index (e.g., # alive at weaning per # alive at day 4)

Reproductive: Effects on newborn: Physical 		DCTODJ 6,41,1983
subcutaneous
mouse 		lowest published toxic dose: 24 mg/kg (9 day pregnant) Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Musculoskeletal system 		JEEMAF 30,449,1973
subcutaneous
mouse 		lowest published toxic dose: 30 mg/kg (16-21 day pregnant) Reproductive: Effects on newborn: Behavioral NETOD7 2,307,1980
subcutaneous
mouse 		lowest published toxic dose: 50 mg/kg (10 day male) Reproductive: Paternal effects: Testes, epididymis, sperm duct

Reproductive: Paternal effects: Prostate, seminal vesicle, Cowper's gland, accessory glands 		AIPTAK 215,215,1975
subcutaneous
rat 		lowest published toxic dose: 66 mg/kg (10-22 day pregnant/1 day after birth) Reproductive: Effects on newborn: Biochemical and metabolic TOLED5 14,131,1982
subcutaneous
rat 		lowest published toxic dose: 120 mg/kg (12 day male) Reproductive: Paternal effects: Prostate, seminal vesicle, Cowper's gland, accessory glands

Reproductive: Effects on fertility: Mating performance (e.g., # sperm positive females per # females mated; # copulations per # estrus cycles)

Reproductive: Effects on fertility: Other measures of fertility 		TXAPA9 45,797,1978
subcutaneous
rat 		lowest published toxic dose: 120 mg/kg (12 day male) Reproductive: Effects on newborn: Weaning or lactation index (e.g., # alive at weaning per # alive at day 4)

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain) 		TXAPA9 45,797,1978
subcutaneous
rat 		lowest published toxic dose: 161 mg/kg (10-22 day pregnant/21 day after birth) Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Effects on newborn: Biochemical and metabolic 		LIFSAK 24,1223,1979
subcutaneous
rat 		lowest published toxic dose: 20 mg/kg (4 day male) Reproductive: Effects on newborn: Behavioral

Reproductive: Effects on newborn: Physical 		MUREAV 229,201,1990
subcutaneous
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) PSEBAA 173,398,1983


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
intraperitoneal
mouse 		lethal dose (50 percent kill): 8,300 µg/kg Behavioral: Altered sleep time (including change in righting reflex)

Behavioral: Excitement

Lung, Thorax, or Respiration: Dyspnea 		NYKZAU 57,585,1961
intraperitoneal
rat 		lethal dose (50 percent kill): 11 mg/kg Behavioral: Analgesia AIPTAK 123,48,1959
intraperitoneal
rat 		lowest published toxic dose: 5 mg/kg Brain and Coverings: Other degenerative changes PHREP* 58,120,2006
intraperitoneal
rat 		lowest published lethal dose: 25 mg/kg N/R PHREP* 58,120,2006
intravenous
chicken 		lowest published lethal dose: 12,500 µg/kg Behavioral: Convulsions or effect on seizure threshold

Lung, Thorax, or Respiration: Cyanosis 		AIPTAK 79,282,1949
intravenous
duck 		lethal dose (50 percent kill): 12 mg/kg Behavioral: Altered sleep time (including change in righting reflex)

Behavioral: Convulsions or effect on seizure threshold 		AIPTAK 79,282,1949
intravenous
mouse 		lethal dose (50 percent kill): 16 mg/kg N/R TXAPA9 6,334,1964
intravenous
pigeon 		lethal dose (50 percent kill): 51 mg/kg Behavioral: Ataxia

Behavioral: Convulsions or effect on seizure threshold 		AIPTAK 79,282,1949
intravenous
rat 		lethal dose (50 percent kill): 9,200 µg/kg N/R JPETAB 92,269,1948
oral
child 		lowest published lethal dose: 5 mg/kg Brain and Coverings: Other degenerative changes

Lung, Thorax, or Respiration: Acute pulmonary edema 		JAMAAP 238,2516,1977
oral
mouse 		lethal dose (50 percent kill): 124 mg/kg N/R APSXAS 6,207,1969
oral
rat 		lethal dose (50 percent kill): 30 mg/kg Behavioral: Analgesia AIPTAK 123,48,1959
parenteral
frog 		lethal dose (50 percent kill): 55,500 mg/kg Behavioral: Change in motor activity (specific assay) AIPTAK 79,282,1949
subcutaneous
frog 		lethal dose (50 percent kill): 56 mg/kg N/R ANYAA9 51,83,1948
subcutaneous
guinea pig 		lethal dose (50 percent kill): 54 mg/kg N/R ANYAA9 51,83,1948
subcutaneous
monkey 		lowest published lethal dose: 10 mg/kg Lung, Thorax, or Respiration: Other changes PSEBAA 65,113,1947
subcutaneous
mouse 		lethal dose (50 percent kill): 34 mg/kg N/R ANYAA9 51,83,1948
subcutaneous
rat 		lethal dose (50 percent kill): 12 mg/kg N/R ANYAA9 51,83,1948
subcutaneous
rat 		lowest published toxic dose: 3 mg/kg Behavioral: Alteration of operant conditioning PSCHDL 164,108,2002
subcutaneous
rat 		lowest published toxic dose: 30 mg/kg/24 hour Cardiac: Pulse rate decreased with fall in BP

Lung, Thorax, or Respiration: Respiratory depression 		EJPHAZ 484,303,2004


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
implant
rat 		lowest published toxic dose: 126 mg/kg/14 day- continuous Behavioral: Food intake (animal)

Behavioral: Fluid intake

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		JPETAB 298,797,2001
intraspinal
dog 		lowest published toxic dose: 8.4 mg/kg/28 day- continuous Peripheral Nerve and Sensation: Sensory change involving peripheral nerve

Behavioral: Change in motor activity (specific assay)

Behavioral: Stiffness 		TOXID9 72,386,2003
oral
monkey 		lowest published toxic dose: 105 mg/kg/3 week- intermittent Behavioral: Ataxia

Behavioral: Change in psychophysiological tests

Lung, Thorax, or Respiration: Respiratory depression 		PBBHAU 6,87,1977
oral
monkey 		lowest published toxic dose: 420 mg/kg/4 week- intermittent Behavioral: Ataxia

Lung, Thorax, or Respiration: Respiratory depression

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		PBBHAU 6,87,1977
oral
rat 		lowest published toxic dose: 25 gm/kg/14 week- continuous Lung, Thorax, or Respiration: Fibrosis, focal (pneumoconiosis)

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		JPETAB 92,269,1948
subcutaneous
dog 		lowest published toxic dose: 430 mg/kg/14 week- intermittent Blood: Hemorrhage

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		JPETAB 92,269,1948
subcutaneous
mouse 		lowest published toxic dose: 100 mg/kg/5 day- intermittent Lung, Thorax, or Respiration: Changes in lung weight

Immunological Including Allergic: Decreased immune response

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		NTPTR* IMM-9400
subcutaneous
mouse 		lowest published toxic dose: 200 mg/kg/5 day- intermittent Endocrine: Changes in spleen weight

Endocrine: Changes in thymus weight 		NTPTR* IMM-9400
subcutaneous
mouse 		lowest published toxic dose: 400 mg/kg/5 day- intermittent Liver: Changes in liver weight NTPTR* IMM-9400
subcutaneous
mouse 		lowest published toxic dose: 600 mg/kg/5 day- intermittent Brain and Coverings: Changes in brain weight

Lung, Thorax, or Respiration: Changes in lung weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		NTPTR* IMM-94008
subcutaneous
mouse 		lowest published toxic dose: 600 mg/kg/5 day- intermittent Blood: Changes in erythrocyte (RBC) count

Immunological Including Allergic: Increase in cellular immune response

Immunological Including Allergic: Decrease in cellular immune response 		NTPTR* IMM-94008
subcutaneous
mouse 		lowest published toxic dose: 200 mg/kg/5 day- intermittent Blood: Other changes

Blood: Changes in leukocyte (WBC) count

Immunological Including Allergic: Decrease in cellular immune response 		NTPTR* IMM-94008
subcutaneous
mouse 		lowest published toxic dose: 400 mg/kg/5 day- intermittent Immunological Including Allergic: Increase in cellular immune response NTPTR* IMM-94008
subcutaneous
rat 		lowest published toxic dose: 120 mg/kg/4 day- continuous Behavioral: Tolerance

Cardiac: Pulse rate decreased with fall in BP

Lung, Thorax, or Respiration: Respiratory depression 		EJPHAZ 484,303,2004
subcutaneous
rat 		lowest published toxic dose: 60 mg/kg/6 day- continuous Behavioral: Change in motor activity (specific assay) NEROEW 29,1312,2004
subcutaneous
rat 		lowest published toxic dose: 1,210 mg/kg/136 day- intermittent Nutritional and Gross Metabolic: Weight loss or decreased weight gain PBBHAU 9,405,1978
unreported route
mouse 		lowest published toxic dose: 720 mg/kg/24 day- intermittent Blood: Normocytic anemia

Blood: Luekopenia 		NTPTR* RACB-92023


REVIEWS:

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


STANDARDS AND REGULATIONS:

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


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Occupational Hazard Survey 1974 National Occupational Hazard Survey 1974: Hazard Code: 84485;
Number of Industries 2;
Total Number of Facilities 61;
Number of Occupations 4;
Total Number of Employees Exposed 1,624
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: 84485;
Number of Industries 3;
Total Number of Facilities 128;
Number of Occupations 6;
Total Number of Employees Exposed 5,244;
Total Number of Female Employees Exposed 3,282


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
N/R


REFERENCES:

CODEN
REFERENCE
AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898-
AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920-
ANYAA9 Annals of the New York Academy of Sciences. (New York Academy of Sciences, 2 E. 63rd St., New York, NY 10021) V.1- 1877-
APSXAS Acta Pharmaceutica Suecica. (Apotekarsocieteten-Farmacevtiska Foereningen, Box 1136, S-111, 81 Stockholm, Sweden) V.1- 1964-
BNEOBV Biology of the Neonate. (S. Karger Pub., Inc., 79 Fifth Ave., New York, NY 10003) V.15- 1970-
DCTODJ Drug and Chemical Toxicology. (Marcel Dekker, 270 Madison Ave., New York, NY 10016) V.1- 1977/78-
DPTHDL Developmental Pharmacology and Therapeutics. (S. Karger Pub., Inc., 79 Fifth Ave., New York, NY 10003) V.1- 1980-
EJPHAZ European Journal of Pharmacology. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1967-
JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883-
JEEMAF Journal of Embryology and Experimental Morphology. (Essex, UK) V.1-98, 1953-86. For Publisher information, see DEVPED
JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10-
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-
NEROEW Neuropsychopharmacology. (Elsevier Science, 655 Avenue of the Americas, New York, NY 10010) V.1- 1987-
NETEEC Neurotoxicology and Teratology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.9- 1987-
NETOD7 Neurobehavioral Toxicology. (Fayetteville, NY) V.1-2, 1979-80. For publisher information, see NTOTDY.
NTPTR* National Toxicology Program Technical Report Series. (Research Triangle Park, NC 27709) No.206-
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-
PBBHAU Pharmacology, Biochemistry and Behavior. (ANKHO International Inc., P.O. Box 426, Fayetteville, NY 13066) V.1- 1973-
PHREP*
PSCHDL Psychopharmacology (Berlin). (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.47- 1976-
PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04-
TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968-
TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1977-
TOXID9 Toxicologist. (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway, Akron, OH 44311) V.1- 1981-
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959-

Used as an analgesic

FDA-proprietary drug

RTECS Compound Description:
   Drug
   Mutagen
   Reproductive Effector
   Human Data

ALT CAS #: 125-56-4
ALT CAS #: 70172-45-1
ALT CAS #: 70181-39-4
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