Succimer

Succimer is a widely used chelating agent for the treatment of Pb poisoning.

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Succimer is a widely used chelating agent for the treatment of Pb poisoning. Red blood cells (RBCs) from lead exposed animals treated with NAC or Succimer are shown to have significantly higher glutathione (GSH) levels and diminished malondialdehyde (MDA) levels when compare to the lead group. Succimer administration also results in decreased glucose 6-phosphate dehydrogenase (G6PD) activity in RBCs from lead exposed animals[1]. Succimer treatment produces a significant reduction in blood lead levels for both lead exposure conditions: the High Pb-succ group has blood lead levels that are 27% of the blood lead levels of the High Pb group at the end of treatment. Succimer is effective in substantially reducing brain lead, as brain lead levels in the High Pb-succ group are 37% of levels in the High Pb group[2].

All experiments are performed with Fisher 344 male rats weighing 75 to 100 g. The animals are randomized into four groups. Group I (n=11) serves as the control and is given only standard rat chow and water for 6 weeks. Group II (n=11) receives 2000 ppm lead acetate in its drinking water for 5 weeks and, during the 6th week, this group receives water. Group III (n=6) receives 2000 ppm lead acetate in its drinking water for 5 weeks and, during the 6th week, these animals receive 800 mg/kg/day NAC dissolved in water. Group IV (n=6) is treated like group III, except that it receives 90 mg/kg/day Succimer during the last week. At the end of the 6th week, after overnight fasting, the animals are anesthetized with metofane and blood samples are collected via intracardiac puncture using heparin as an anticoagulant. Plasma and the buffy coat are removed by centrifugation for 10 min at 3000 rpm. The RBCs are washed three times with an equal volume of cold saline[1].

[1]. Gürer H, et al. Antioxidant effects of N-acetylcysteine and succimer in red blood cells from lead-exposed rats. Toxicology. 1998 Jul 17;128(3):181-9.

[2]. Beaudin SA, et al. Succimer chelation normalizes reactivity to reward omission and errors in lead-exposed rats. Neurotoxicol Teratol. 2007 Mar-Apr;29(2):188-202.

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DATA ITEMS CITED :

12

MOLECULAR FORMULA :

C4-H6-O4-S2

MOLECULAR WEIGHT :

182.22

WISWESSER LINE NOTATION :

SHYVQYVQSH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>5011 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CRTXB2 CRC Critical Reviews in Toxicology. (CRC Press, Inc., 2000 Corporate Blvd., NW, Boca Raton, FL 33431) V.1- 1971- Volume(issue)/page/year: 20,83,1989

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

500 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: AD691-490

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1725 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Skin and Appendages - hair

REFERENCE :

AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 131,283,1961

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

2700 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Skin and Appendages - hair

REFERENCE :

AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 131,283,1961 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1 gm/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

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) Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

JTEHD6 Journal of Toxicology and Environmental Health. (Hemisphere Pub., 1025 Vermont Ave., NW, Washington, DC 20005) V.1- 1975/76- Volume(issue)/page/year: 30,181,1990

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

10 gm/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

JTEHD6 Journal of Toxicology and Environmental Health. (Hemisphere Pub., 1025 Vermont Ave., NW, Washington, DC 20005) V.1- 1975/76- Volume(issue)/page/year: 30,181,1990

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1 gm/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - biochemical and metabolic

REFERENCE :

JTEHD6 Journal of Toxicology and Environmental Health. (Hemisphere Pub., 1025 Vermont Ave., NW, Washington, DC 20005) V.1- 1975/76- Volume(issue)/page/year: 30,191,1990

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

17600 mg/kg

SEX/DURATION :

female 14-21 day(s) after conception lactating female 14 day(s) post-birth

TOXIC EFFECTS :

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

REFERENCE :

LIFSAK Life Sciences. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1-8, 1962-69; V.14- 1974- Volume(issue)/page/year: 47,1745,1990

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

8200 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)

REFERENCE :

FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 11,715,1988

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

16400 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - 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 - craniofacial (including nose and tongue)

REFERENCE :

FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 11,715,1988

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

4100 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 11,715,1988