Dexamethasone

Dexamethasone is a glucocorticoid receptor agonist.

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> GPCR/G Protein >> Glucocorticoid Receptor

Signaling Pathways >> Autophagy >> Mitophagy

Research Areas >> Inflammation/Immunology

Glucocorticoid receptor[1]

Dexamethasone regulates several transcription factors, including activator protein-1, nuclear factor-AT, and nuclear factor-kB, leading to the activation and repression of key genes involved in the inflammatory response[1]. Dexamethasone potently inhibits granulocyte-macrophage colony stimulating factor (GM-CSF) release from A549 cells with EC50 of 2.2 nM. Dexamethasone (EC50=36 nM) induces transcription of the β2-receptor is found to correlate with glucocorticoid receptor (GR) DNA binding and occurred at 10-100 fold higher concentrations than the inhibition of GM-CSF release. Dexamethasone (IC50=0.5 nM) inhibits a 3×κB (NF-κB, IκBα, and I-κBβ), which is associated with inhibition of GM-CSF release[2].

It has previously been reported that treatment with Dexamethasone at a dose of 2×5 mg/kg efficiently inhibits lipopolysaccharide (LPS)-induced inflammation. In our experimental system, treatment with a single dose of Dexamethasone 10 mg/kg (i.p.) significantly decreases recruitment of granulocytes as well as spontaneous production of oxygen radicals compared with animals expose to LPS and injected with solvent alone (saline). The effects are statistically significant when administered both 1 h before and 1 h after inhalation of LPS. The number of granulocytes in BALF decreased to levels comparable to healthy animals (given an aerosol of water)[3]. Rats treated with Dexamethasone consume less food and weighed less than control rats. Treated rats also weigh less than pair-fed animals though their food intake is similar. Five days of Dexamethasone injection result in a significant increase in both the liver mass (+42%) and the liver to body weight ratio (+65%). The wet weight of gastrocnemius muscle decreases 20% after 5 days of treatment, but it remains unaffected relative to body weight (g/100 g body weight), indicating that muscle weight loss paralleled body weight loss[4].

Mice[3] Female C57Bl/6JBom mice (age 10-12 weeks) are used in all experiments. Dexamethasone is administered as a single injection of 1 or 10 mg/kg. Dexamethasone is dissolved in saline and 400 μL are injected intraperitoneally, either 1 h before or 1 h after LPS exposure. In one experiment, N-acetylcysteine (NAC) (100 and 500 mg/kg) is injected successively every 4•5 h, starting 1 h before challenge (five injections in total). A control group of LPS-exposed animals are injected intraperitoneally with solvent alone (saline). Intratracheal administration is performed by instillation of 100 μL NAC (50, 100 or 500 mg/kg) or Dexamethasone (10 mg/kg) into the lungs of mice anaesthetized with 15 mg/kg Rapinovet (i.v.). Rats[4] Male Sprague-Dawley rats are used.Dexamethasone-treated rats are injected intraperitoneally once daily with Dexamethasone (1.5 mg/kg body weight) for 5 days and are allowed to feed ad libitum. The Dexamethasone dose (1.5 mg/kg/day) and the duration of treatment (5 days) are specifically chosen as this treatment induced a reproducible and marked catabolic state. Control rats received no treatment and are fed ad libitum. In order to take into account the decrease in food intake induced by Dexamethasone treatment, a third group of pair-fed rats are used. These rats are provided with the same amount of food as Dexamethasone-injected rats and are treated with a daily isovolumic intraperitoneal injection of NaCl (0.9%) for 5 days. After the final injection of Dexamethasone or NaCl, the animals are fasted overnight prior to being killed by decapitation.

[1]. LaLone CA, et al. Effects of a glucocorticoid receptor agonist, Dexamethasone, on fathead minnow reproduction, growth, and development. Environ Toxicol Chem. 2012 Mar;31(3):611-22.

[2]. Adcock IM, et al. Ligand-induced differentiation of glucocorticoid receptor (GR) trans-repression and transactivation: preferential targetting of NF-kappaB and lack of I-kappaB involvement. Br J Pharmacol. 1999 Jun;127(4):1003-11

[3]. Rocksén D, et al. Differential anti-inflammatory and anti-oxidative effects of Dexamethasone and N-acetylcysteine in endotoxin-induced lung inflammation. Clin Exp Immunol. 2000 Nov;122(2):249-56

[4]. Roussel D, et al. Dexamethasone treatment specifically increases the basal proton conductance of rat liver mitochondria. FEBS Lett. 2003 Apr 24;541(1-3):75-9.

[5]. Maher HM, et al. Simultaneous determination of selected tyrosine kinase inhibitors with corticosteroids and antiemetics in rat plasma by solid phase extraction and ultra-performance liquid chromatography-tandem mass spectrometry: Application to pharmacokinetic interaction studies. J Pharm Biomed Anal. 2016 May 30;124:216-27.

3-Methyladenine | SB203580 | U0126-EtOH | Acadesine (AICAR) | Brefeldin A | Hydrocortisone | 17-AAG | Resveratrol | Melatonine | Curcumin | Salinomycin | ABT-737 | Quercetin | Mifepristone | Celastrol

MOLECULAR FORMULA :

C22-H29-F-O5

MOLECULAR WEIGHT :

392.51

WISWESSER LINE NOTATION :

L E5 B666 OV KU MUTJ A1 BF CQ E1 FV1Q FQ G1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Multiple routes

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

4759 ug/kg/18D-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - urine volume increased

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>3 gm/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 - rat

DOSE/DURATION :

54 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Gastrointestinal - hypermotility, diarrhea Skin and Appendages - hair

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

14 mg/kg

TOXIC EFFECTS :

Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

410 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 :

4400 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 - rabbit

DOSE/DURATION :

7200 ug/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Gastrointestinal - hypermotility, diarrhea

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

70 mg/kg/14D-I

TOXIC EFFECTS :

Endocrine - changes in spleen weight Endocrine - changes in thymus weight Immunological Including Allergic - decrease in cellular immune response

TYPE OF TEST :

TCLo - Lowest published toxic concentration

ROUTE OF EXPOSURE :

Inhalation

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

26700 ug/m3/30M/21D-I

TOXIC EFFECTS :

Endocrine - other changes Endocrine - changes in thymus weight Blood - changes in erythrocyte (RBC) count

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Administration onto the skin

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

7500 ug/kg/30D-I

TOXIC EFFECTS :

Endocrine - changes in thymus weight 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 :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3 mg/kg/14D-I

TOXIC EFFECTS :

Endocrine - changes in thymus weight Blood - changes in leukocyte (WBC) count Immunological Including Allergic - hypersensitivity delayed

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

250 ug/kg/26W-I

TOXIC EFFECTS :

Endocrine - other changes Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Related to Chronic Data - changes in testicular weight

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

280 ug/kg/28D-I

TOXIC EFFECTS :

Endocrine - changes in adrenal weight Endocrine - changes in spleen weight Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

3821 ug/kg/14D-C

TOXIC EFFECTS :

Endocrine - changes in spleen weight Endocrine - changes in thymus weight Blood - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

6 mg/kg

SEX/DURATION :

female 8-13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

2 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

880 ug/kg

SEX/DURATION :

female 7-17 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 - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

8800 ug/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Effects on Embryo or Fetus - other effects to embryo

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

7500 ug/kg

SEX/DURATION :

female 15-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - body wall

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

8800 ug/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - parturition Reproductive - Effects on Newborn - live birth index (measured after birth)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Administration onto the skin

DOSE :

4200 ug/kg

SEX/DURATION :

male 9 week(s) pre-mating female 2 week(s) pre-mating - 7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Administration onto the skin

DOSE :

1802 ug/kg

SEX/DURATION :

male 26 week(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 :

Intraperitoneal

DOSE :

1500 ug/kg

SEX/DURATION :

female 17-19 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - respiratory system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

5 mg/kg

SEX/DURATION :

female 14-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - biochemical and metabolic

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

3 mg/kg

SEX/DURATION :

female 14-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - biochemical and metabolic

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

2 mg/kg

SEX/DURATION :

female 20 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - respiratory system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

1500 ug/kg

SEX/DURATION :

female 16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - other effects to embryo

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

3 mg/kg

SEX/DURATION :

male 3 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 :

700 ug/kg

SEX/DURATION :

female 12-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - endocrine system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

900 ug/kg

SEX/DURATION :

female 8-16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1100 ug/kg

SEX/DURATION :

female 7-17 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 - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

3600 ug/kg

SEX/DURATION :

female 8-16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

11 mg/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - body wall Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1500 ug/kg

SEX/DURATION :

female 16-20 day(s) after conception

TOXIC EFFECTS :

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 - Specific Developmental Abnormalities - endocrine system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

1500 ug/kg

SEX/DURATION :

female 16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - other effects to embryo Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) Reproductive - Effects on Newborn - physical

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

5 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

3600 ug/kg

SEX/DURATION :

female 7-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

28800 ug/kg

SEX/DURATION :

female 7-15 day(s) after conception

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

10 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

400 ug/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

50 mg/kg

SEX/DURATION :

female 13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - skin and skin appendages

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Ocular

DOSE :

1200 ug/kg

SEX/DURATION :

female 10-13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Ocular

DOSE :

6 mg/kg

SEX/DURATION :

female 10-13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

6 mg/kg

SEX/DURATION :

female 16 day(s) after conception

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

400 ug/kg

SEX/DURATION :

female 16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - respiratory system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intratesticular

DOSE :

18 mg/kg

SEX/DURATION :

male 1 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

3700 mg/kg

SEX/DURATION :

female 18-23 week(s) after conception

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

400 ug/kg

SEX/DURATION :

female 13-16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

2 mg/kg

SEX/DURATION :

female 13-16 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 :

Subcutaneous

DOSE :

130 ug/kg

SEX/DURATION :

female 6-18 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 - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

390 ug/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

1600 ug/kg

SEX/DURATION :

female 25-26 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - parturition

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Ocular

DOSE :

554 ug/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - gastrointestinal system Reproductive - Specific Developmental Abnormalities - urogenital system Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

2 mg/kg

SEX/DURATION :

female 25-26 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - parturition

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

360 ug/kg

SEX/DURATION :

female 25-27 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - endocrine system Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

6667 ug/kg

SEX/DURATION :

female 14 week(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - parturition Reproductive - Specific Developmental Abnormalities - blood and lymphatic systems (including spleen and marrow) Reproductive - Specific Developmental Abnormalities - urogenital system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

6670 ug/kg

SEX/DURATION :

female 14 week(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - parturition

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

3750 ug/kg

SEX/DURATION :

female 14 week(s) after conception

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

4 mg/kg

SEX/DURATION :

female 11 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

1905 ug/kg

SEX/DURATION :

female 45 week(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - parturition

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

800 ug/kg

SEX/DURATION :

female 45-46 week(s) after conception

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

120 ug/kg

SEX/DURATION :

female 40 week(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - parturition Reproductive - Effects on Newborn - other postnatal measures or effects

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

60 ug/kg

SEX/DURATION :

female 39 week(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - immune and reticuloendothelial system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Parenteral

DOSE :

889 ug/kg

SEX/DURATION :

female 45-46 week(s) after conception

TOXIC EFFECTS :

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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

877 mg/kg

SEX/DURATION :

male 20 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :

Micronucleus test

TYPE OF TEST :

DNA inhibition

TYPE OF TEST :

Mutation test systems - not otherwise specified

TYPE OF TEST :

Sister chromatid exchange

MUTATION DATA

TYPE OF TEST :

DNA inhibition

TEST SYSTEM :

Bird - chicken Embryo

DOSE/DURATION :

150 pmol/L

REFERENCE :

NATUAS Nature. (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736) V.1- 1869- Volume(issue)/page/year: 257,804,1975 *** REVIEWS *** TOXICOLOGY REVIEW AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920- Volume(issue)/page/year: 96,985,1966 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 81600 No. of Facilities: 862 (estimated) No. of Industries: 2 No. of Occupations: 2 No. of Employees: 1035 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X1854 No. of Facilities: 403 (estimated) No. of Industries: 1 No. of Occupations: 5 No. of Employees: 4029 (estimated) No. of Female Employees: 2015 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 81600 No. of Facilities: 728 (estimated) No. of Industries: 4 No. of Occupations: 20 No. of Employees: 30657 (estimated) No. of Female Employees: 17738 (estimated)