(-)-N,N-DIMETHYLEPHEDRINIUMBROMIDE

MOLECULAR FORMULA :

C21-H28-O2

MOLECULAR WEIGHT :

312.49

WISWESSER LINE NOTATION :

L E5 B666 OV MUTJ E2 FQ F1UU1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>5 gm/kg

TOXIC EFFECTS :

Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 41,295,1991

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1470 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - effect, not otherwise specified Behavioral - altered sleep time (including change in righting reflex) Behavioral - ataxia

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 41,295,1991

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>5 gm/kg

TOXIC EFFECTS :

Skin and Appendages - dermatitis, other (after systemic exposure) Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 41,295,1991

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>5 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 41,295,1991

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2990 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - ataxia Skin and Appendages - hair

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 41,295,1991

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>5 gm/kg

TOXIC EFFECTS :

Skin and Appendages - dermatitis, other (after systemic exposure)

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 41,295,1991 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

9100 mg/kg/52W-C

TOXIC EFFECTS :

Liver - changes in liver weight Endocrine - changes in adrenal weight Nutritional and Gross Metabolic - other changes

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 42,291,1991

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

910 mg/kg/1Y-C

TOXIC EFFECTS :

Nutritional and Gross Metabolic - other changes

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 42,301,1991 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

2607 ug/kg

SEX/DURATION :

male 52 week(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - other effects on male Endocrine - androgenic

REFERENCE :

CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 21,631,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

219 ug/kg

SEX/DURATION :

female 52 week(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

REFERENCE :

CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 25,243,1982

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Implant

DOSE :

875 ug/kg

SEX/DURATION :

female 35 week(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

REFERENCE :

CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 22,71,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Implant

DOSE :

3171 ug/kg

SEX/DURATION :

male 60 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - impotence

REFERENCE :

CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 25,591,1982

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Implant

DOSE :

110 ug/kg

SEX/DURATION :

female 52 week(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - menstrual cycle changes or disorders Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

REFERENCE :

CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 18,151,1978

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Implant

DOSE :

4080 ug/kg

SEX/DURATION :

female 52 week(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

REFERENCE :

CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 27,473,1983

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravaginal

DOSE :

102 ug/kg

SEX/DURATION :

female 17 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - uterus, cervix, vagina

REFERENCE :

CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 22,71,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intracervical

DOSE :

12 ug/kg

SEX/DURATION :

female 30 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - menstrual cycle changes or disorders

REFERENCE :

CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 23,473,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intracervical

DOSE :

36 ug/kg

SEX/DURATION :

female 90 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

REFERENCE :

CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 23,473,1981

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

250 mg/kg

SEX/DURATION :

female 1-4 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

REFERENCE :

CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 21,537,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

2800 ug/kg

SEX/DURATION :

male 14 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct

REFERENCE :

ENDKAC Endokrinologie. (Leipzig, Ger. Dem. Rep.) V.1-80, 1928-82. For publisher information, see EXCEDS. Volume(issue)/page/year: 76,13,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

500 mg/kg

SEX/DURATION :

female 8-12 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

EXCEDS Experimental and Clinical Edocrinology. (Johann Ambrosius Barth Verlag, Postfach 109, Leipzig DDR-7010, Ger. Dem. Rep.) V.81- 1983- Volume(issue)/page/year: 81,197,1983

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

50 mg/kg

SEX/DURATION :

female 3-7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - parturition Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

EXCEDS Experimental and Clinical Edocrinology. (Johann Ambrosius Barth Verlag, Postfach 109, Leipzig DDR-7010, Ger. Dem. Rep.) V.81- 1983- Volume(issue)/page/year: 81,197,1983

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

5 mg/kg

SEX/DURATION :

female 8-12 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - stillbirth

REFERENCE :

EXCEDS Experimental and Clinical Edocrinology. (Johann Ambrosius Barth Verlag, Postfach 109, Leipzig DDR-7010, Ger. Dem. Rep.) V.81- 1983- Volume(issue)/page/year: 81,197,1983

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

5 gm/kg

SEX/DURATION :

female 3-7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :

EXCEDS Experimental and Clinical Edocrinology. (Johann Ambrosius Barth Verlag, Postfach 109, Leipzig DDR-7010, Ger. Dem. Rep.) V.81- 1983- Volume(issue)/page/year: 81,197,1983

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

200 mg/kg

SEX/DURATION :

female 1-4 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

REFERENCE :

CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 21,537,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

80 ug/kg

SEX/DURATION :

female 1 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

REFERENCE :

CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 21,537,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

80 mg/kg

SEX/DURATION :

male 56 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - mating performance (e.g. # sperm positive females per # females mated; # copulations per # estrus cycles)

REFERENCE :

CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 21,641,1980

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

500 ug/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 33,231,1983