Reserpine

Reserpine is an inhibitor of the vesicular monoamine transporter 2 (VMAT2).

Signaling Pathways >> Membrane Transporter/Ion Channel >> Monoamine Transporter

Natural Products >> Alkaloid

Research Areas >> Neurological Disease

VMAT2[1]

Reserpine is an inhibitor of the vesicular monoamine transporter 2 (VMAT2). Reserpine displays a significant effect on the density of dopamine D1 receptors (F2,12=8.81, p<0.01) in the rat striatum. The affinity (Kd) for the dopamine D1 and D2 receptors during withdrawal from acute and chronic administration of reserpine is not change[1]. IC50 values of 43.9 and 54.9 μM are obtained after 1 day of treatment with Reserpine in JB6 P+ and HepG2-C8 cells, respectively. Reserpine induces luciferase activity in a dose-dependent manner at concentrations ranging from 5 to 50 μM, and no significant induction is observed at concentrations lower than 5 μM. Results demonstrate that Reserpine (2.5 to 10 μM) also increases the protein expression of Nrf2, HO-1, and NQO1. Reserpine at concentrations of 2.5 to 10 μM decreases the mRNA expression of DNMT1, DNMT3a, and DNMT3b in a concentration-dependent manner in JB6 P+ cells after 7 days of treatment. Reserpine at 10 μM generates a significant difference for DNMT3a expression (p<0.05)[2].

Withdrawal (48 h) from chronic (14-day) but not acute Reserpine administration in a dose of 0.2 mg/kg i.p. produces a significant reduction of the immobility time (F2,18=3.68, p<0.05), but increases the climbing time (F2,18=4.48, p<0.02), and does not change the swimming time (F2,18=1.78; NS) in the forced swim test (FST) in rats[1]. Reserpine at a dose of 5 mg/kg body weight produces significant increase in the urinary excretion profile of vanillylmandelic acid (VMA) compare to control animals. The amount of 5-hydroxyindoleacetic acid (5-HIAA) excreted in animals treated with Reserpine is found to be more than in the control. Dose dependent hypotension is observed with Reserpine. Reserpine at doses of 0.5, 1, 5, 10 and 15 μg/kg produce significant (p<0.01) reduction in blood pressure compare to control[3].

After incubation for 24 h, JB6 P+ cells (1×105 cells/10-cm dish) are treated with various concentrations of Reserpine. Whole cell lysates are prepared from the treated cells using radioimmunoprecipitation assay buffer supplemented with a protease inhibitor cocktail, and a BCA kit is used to determine protein concentrations[2].

JB6 P+ cells are seeded in 96-well plates containing Minimum essential media (MEM) at a density of 1×104 cells/mL (100 μL/well) for 1, 3, and 5 days, and HepG2-C8 cells are seeded in plates containing DMEM. After incubation for 24 h, the cells are treated with either DMSO or various concentrations of Reserpine. For JB6 P+ cells, the medium is changed every 2 days for the 3-day and 5-day treatments. Cell viability is assessed using a MTS assay kit according to the manufacturer’s instructions. The absorbance of the formazan product is read at 490 nm, and the cell viability is calculated and compared with the DMSO control group[2].

Albino rats of either sex weighing between 100 to 150 g are used in the study. They are acclimatized to the laboratory conditions for at least 10 days prior to the experiment and provided with standard diet and water ad libitum with 12 h light and dark cycle. Animals are divided into different groups of six each and are housed individually in metabolic cages. Group 1: Control animals treated with DMSO intraperitoneally at a dose of 0.1 mL/100 g body weight. Group 2: Animals administered intraperitoneally with Reserpine at a dose of 5 mg/kg body weight. The 24 h urine samples from the point of drug administration are collected for each animal[3].

[1]. Antkiewicz-Michaluk L, et al. Withdrawal from repeated administration of a low dose of reserpine induced opposing adaptive changes in the noradrenaline and serotonin system function: a behavioral and neurochemical ex vivo and in vivo studies in the rat. Prog Neuropsychopharmacol Biol Psychiatry. 2015 Mar 3;57:146-54.

[2]. Hong B, et al. Reserpine Inhibit the JB6 P+ Cell Transformation Through Epigenetic Reactivation of Nrf2-Mediated Anti-oxidative Stress Pathway. AAPS J. 2016 May;18(3):659-69.

[3]. Sreemantula S, et al. Reserpine methonitrate, a novel quaternary analogue of reserpine augments urinary excretion of VMA and 5-HIAA without affecting HVA in rats. BMC Pharmacol. 2004 Nov 16;4:30.

NBI-98782 | (±)-Tetrabenazine | Reserpine hydrochloride | Radafaxine (hydrochloride) | Vanilpyruvic acid

DATA ITEMS CITED :

82

MOLECULAR FORMULA :

C33-H40-N2-O9

MOLECULAR WEIGHT :

608.75

WISWESSER LINE NOTATION :

T F6 D5 C666 EM ON&&TTTJ HO1 SOVR CO1 DO1 EO1& TO1 UVO1

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 :

420 mg/kg

TOXIC EFFECTS :

Behavioral - antipsychotic

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

44 mg/kg

TOXIC EFFECTS :

Brain and Coverings - recordings from specific areas of CNS

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

25 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

15 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>50 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

5 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

5610 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

21 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - changes in motor activity (specific assay) Gastrointestinal - hypermotility, diarrhea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

500 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

7 mg/kg

TOXIC EFFECTS :

Nutritional and Gross Metabolic - body temperature decrease

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

15 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

65 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

16 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Bird - wild bird species

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

945 mg/kg/75W-C

TOXIC EFFECTS :

Blood - changes in erythrocyte (RBC) count Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

54 mg/kg/9W-I

TOXIC EFFECTS :

Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

456 ug/kg/Y-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Skin and Appendages - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

54 mg/kg/77W-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors Blood - lymphoma, including Hodgkin's disease

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

132 mg/kg/2.5Y-I

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Gastrointestinal - tumors Skin and Appendages - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

433 mg/kg/2Y-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Skin and Appendages - tumors Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

200 mg/kg/2Y-I

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Lungs, Thorax, or Respiration - tumors Skin and Appendages - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

216 mg/kg/2Y-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Endocrine - adrenal cortex tumors Skin and Appendages - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

73 mg/kg/2Y-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Skin and Appendages - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

24 mg/kg/13Y-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Brain and Coverings - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

16 mg/kg/3Y-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Skin and Appendages - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

340 mg/kg/3Y-I

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Gastrointestinal - tumors Endocrine - thyroid tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1120 mg/kg/2Y-I

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Blood - tumors Skin and Appendages - tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

200 ug/kg

SEX/DURATION :

female 39 week(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - other neonatal measures or effects

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

DOSE :

4800 ug/kg

SEX/DURATION :

female 32-39 week(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - stillbirth

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

11130 ug/kg

SEX/DURATION :

male 21 day(s) pre-mating

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

17500 mg/kg

SEX/DURATION :

female 3-9 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)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

6 mg/kg

SEX/DURATION :

female 60 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - menstrual cycle changes or disorders

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

21217 ug/kg

SEX/DURATION :

female 30 week(s) pre-mating

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

2 mg/kg

SEX/DURATION :

female 2 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - ovaries, fallopian tubes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

700 ug/kg

SEX/DURATION :

female 8-14 day(s) after conception

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

2500 ug/kg

SEX/DURATION :

female 19 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1 mg/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - menstrual cycle changes or disorders

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1250 ug/kg

SEX/DURATION :

male 5 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

400 ug/kg

SEX/DURATION :

female 11-14 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - behavioral

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

3 mg/kg

SEX/DURATION :

female 12-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Effects on Newborn - physical

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1500 ug/kg

SEX/DURATION :

female 12-15 day(s) after conception

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

2 mg/kg

SEX/DURATION :

female 12-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - ovaries, fallopian tubes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

400 ug/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

4 mg/kg

SEX/DURATION :

female 16-19 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system Reproductive - Effects on Newborn - biochemical and metabolic

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

800 ug/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - eye/ear Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

800 ug/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Maternal Effects - other effects Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

1 mg/kg

SEX/DURATION :

female 9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

1500 ug/kg

SEX/DURATION :

female 10 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

9 mg/kg

SEX/DURATION :

female 1-9 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)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

DOSE :

3750 ug/kg

SEX/DURATION :

male 15 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Fertility - mating performance (e.g. # sperm positive females per # females mated; # copulations per # estrus cycles)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

DOSE :

50 mg/kg

SEX/DURATION :

female 8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

600 ug/kg

SEX/DURATION :

female 7-12 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

10 mg/kg

SEX/DURATION :

female 1 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

120 ug/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

400 ug/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

3200 ug/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - uterus, cervix, vagina

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

DOSE :

1600 ug/kg

SEX/DURATION :

female 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - other measures of fertility

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

32 ug/kg

SEX/DURATION :

male 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - other effects on male

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

100 mg/kg

SEX/DURATION :

female 14 week(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - menstrual cycle changes or disorders

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

170 ug/kg

SEX/DURATION :

female 35-68 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

340 ug/kg

SEX/DURATION :

female 35-68 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - other neonatal measures or effects Reproductive - Effects on Newborn - biochemical and metabolic

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

Cytogenetic analysis

TYPE OF TEST :

Dominant lethal test

MUTATION DATA

TEST SYSTEM :

Rodent - hamster

DOSE/DURATION :

4 ng/kg

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 327,237,1995 *** REVIEWS *** IARC Cancer Review:Animal Limited Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 24,211,1980 IARC Cancer Review:Human Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 24,211,1980 IARC Cancer Review:Group 3 IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979- Volume(issue)/page/year: 7,330,1987 TOXICOLOGY REVIEW CLPTAT Clinical Pharmacology and Therapeutics (St. Louis). (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1960- Volume(issue)/page/year: 5,480,1964 TOXICOLOGY REVIEW ADVPA3 Advances in Pharmacology. (New York, NY) V.1-6, 1962-68. For publisher information, see AVPCAQ. Volume(issue)/page/year: 4,263,1966 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 84711 No. of Facilities: 68 (estimated) No. of Industries: 1 No. of Occupations: 6 No. of Employees: 2770 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 84711 No. of Facilities: 142 (estimated) No. of Industries: 2 No. of Occupations: 10 No. of Employees: 5611 (estimated) No. of Female Employees: 2414 (estimated)