Record Information
Version 1.0
Creation Date 2009-03-06 11:58:01 -0700
Update Date 2013-04-25 02:32:40 -0600
Accession Number T3D0064
Identification
Common Name trans-Chlordane
Description Trans-chlordane, also known as gamma-chlordane, is one of two isomers of chlordane. Chlordane is a manufactured chemical that was used as a pesticide in the United States from 1948 to 1988. (R158)
Compound Type
  • Organic Compound
  • Organochloride
  • Pesticide
Chemical Structure
Thumb
Synonyms
  1. Beta-chlordane
  2. trans-Chlordan
  3. Chlordane gamma
  4. Chlordane trans
  5. Trans-(gamma)-chlordane
  6. Trans-chlordan
  7. Trans-gamma-chlordane
  8. b-Chlordan
  9. b-Chlordane
Chemical Formula Not Available
Average Molecular Weight Not Available
Monoisotopic Molecular Weight Not Available
Chemical IUPAC Name
Not Available
CAS Registry Number 5103-74-2
SMILES
Not Available
InChI Identifier
Not Available
InChI Key Not Available
Chemical Taxonomy
Kingdom Not Available
Super Class Not Available
Class Not Available
Sub Class Not Available
Direct Parent Not Available
Alternative Parents Not Available
Molecular Framework Not Available
Substituents Not Available
External Descriptors Not Available
DrugBank ID Not Available
PubChem Compound ID 12303036
KEGG ID Not Available
UniProt ID Not Available
OMIM ID Not Available
ChEBI ID 39069
BioCyc ID Not Available
CTD ID Not Available
Stitch ID Chlordane, trans-
PDB ID Not Available
ACToR ID Not Available
Wikipedia Link Not Available
Physical Properties
Appearance Colorless to amber liquid.
Melting Point Not Available
Solubility 5.6e-05 mg/mL at 25 °C [MABEY,WR et al. (1981)]
Predicted LogP Not Available
Toxicity Profile
Route of Exposure Oral (R259) ; inhalation (R259)
Mechanism of Action Chlordane is believed to bind irreversibly to DNA, leading to cell death or altered cellular function. It also affects transcription by antagonizing estrogen-related receptors. Chlordane induces hepatic cytochrome P-450, causing a large increase in the volume of the smooth endoplasmic reticulum, which results in hepatocellular enlargement and hypertrophy. Chlordane has also been shown to bind and activate retinoic acid receptor, causing various developmental defects, and inhibit alkaline phosphatases in hepatic and renal tissues. (R159, R162, R163, R205, R206)
Metabolism Chlordane is highly lipophilic and is thus easily absorbed by ingestion, inhalation, and dermal exposure, then stored mainly in the fat. Chlordane is metabolized mainly in the liver and kidney. Metabolism is slow, and is believed to occur by multiple pathways involving cytochrome P-450 enzymes, glutathione-S-transferase type enzymes, and microsomal mixed-function oxidase systems. The metabolites are generally less toxic and include chlordene chlorohydrin, monohydroxylated dihydrochlordene, and oxychlordane. They are excreted in the urine and faeces. (R159)
Toxicity Values LD50: 200 mg/kg (Oral, Rat) (R261) LD50: 343 mg/kg (Intraperitoneal, Rat) (R261) LD50: 10 mg/kg (Intravenous, Mouse) (R263) LD50: 780 mg/kg (Dermal, Rat) (R263) LC50: 100 mg/m3 over 4 hours (Inhalation, Cat) (R263)
Lethal Dose 100 mg/kg for an adult human. (R265)
Carcinogenicity (IARC Classification) 2B, possibly carcinogenic to humans. (R264)
Uses/Sources Chlordane was used as a pesticide. (R158)
Minimum Risk Level Intermediate Inhalation: 0.0002 mg/m3 (R260) Chronic Inhalation: 0.00002 mg/m3 (R260) Acute Oral: 0.001 mg/kg/day (R260) Intermediate Oral: 0.0006 mg/kg/day (R260) Chronic Oral: 0.0006 mg/kg/day (R260)
Health Effects Chlordane is a central nervous system stimulant, and can also damage the digestive system and the liver. Large doses have been shown to cause convulsions, respiratory failure, and death. Chlordane is also known to have adverse reproductive and developmental effects. (R159)
Symptoms Ingestion and inhalation of chlordane cause headaches, irritability, confusion, weakness, vision problems, vomiting, stomach cramps, diarrhea, and jaundice. (R159)
Treatment Treatment is symptomatic. It is aimed at controlling convulsions, coma, and respiratory depression. Gastric lavage, followed by the administration of activated charcoal, may be performed following ingestion. (R282)
References
General References
  • R158 — Wikipedia. Chlordane. Last Updated 2 April 2009. [Link]
  • R259 — Melnick RL, Schiller CM: Mitochondrial toxicity of phthalate esters. Environ Health Perspect. 1982 Nov;45:51-6. [7140696 ]
  • R159 — ATSDR - Agency for Toxic Substances and Disease Registry (1994). Toxicological profile for chlordane. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  • R162 — Ariazi EA, Jordan VC: Estrogen-related receptors as emerging targets in cancer and metabolic disorders. Curr Top Med Chem. 2006;6(3):203-15. [16515477 ]
  • R163 — Lemaire G, Balaguer P, Michel S, Rahmani R: Activation of retinoic acid receptor-dependent transcription by organochlorine pesticides. Toxicol Appl Pharmacol. 2005 Jan 1;202(1):38-49. [15589975 ]
  • R205 — Nims RW, Lubet RA: Induction of cytochrome P-450 in the Norway rat, Rattus norvegicus, following exposure to potential environmental contaminants. J Toxicol Environ Health. 1995 Nov;46(3):271-92. [7473857 ]
  • R206 — Chatterjee K, Banerjee SK, Tiwari R, Mazumdar K, Bhattacharyya A, Chatterjee GC: Studies on the protective effects of L-ascorbic acid in chronic chlordane toxicity. Int J Vitam Nutr Res. 1981;51(3):254-65. [7319725 ]
  • R261 — Lewis RJ Sr. (ed) (2004). Sax's Dangerous Properties of Industrial Materials. 11th Edition. Hoboken, NJ: Wiley-Interscience, Wiley & Sons, Inc.
  • R263 — Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.
  • R265 — US Environmental Protection Agency (2001). OHM/TADS: Oil and Hazardous Materials/Technical Assistance Data System. Washington, DC (Internet Version). Edition expires 2001. Greenwood Village, CO: Thomson Healthcare Inc.
  • R264 — International Agency for Research on Cancer (2009). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  • R260 — ATSDR - Agency for Toxic Substances and Disease Registry (2001). Minimal Risk Levels (MRLs) for Hazardous Substances. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  • R282 — International Programme on Chemical Safety (IPCS) INCHEM (2000). Poison Information Monograph for Chlordane. [Link]

Targets

1. Alkaline phosphatase, tissue-nonspecific isozyme

This isozyme may play a role in skeletal mineralization.

Chlordane inhibit alkaline phosphatases in hepatic and renal tissues. (R206)
UniProt ID: P05186
Gene: ALPL
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:

2. Cytochrome P450 2B6

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.

Chlordane induces hepatic cytochrome P-450, causing a large increase in the volume of the smooth endoplasmic reticulum, which results in hepatocellular enlargement and hypertrophy. (R159, R205)
UniProt ID: P20813
Gene: CYP2B6
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:

3. Cytochrome P450 3A4

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.

Chlordane induces hepatic cytochrome P-450, causing a large increase in the volume of the smooth endoplasmic reticulum, which results in hepatocellular enlargement and hypertrophy. (R159, R205)
UniProt ID: P08684
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:

4. Cytochrome P450 3A43

Exhibits low testosterone 6-beta-hydroxylase activity.

Chlordane induces hepatic cytochrome P-450, causing a large increase in the volume of the smooth endoplasmic reticulum, which results in hepatocellular enlargement and hypertrophy. (R159, R205)
UniProt ID: Q9HB55
Gene: CYP3A43
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:

5. Cytochrome P450 3A5

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.

Chlordane induces hepatic cytochrome P-450, causing a large increase in the volume of the smooth endoplasmic reticulum, which results in hepatocellular enlargement and hypertrophy. (R159, R205)
UniProt ID: P20815
Gene: CYP3A5
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:

6. Cytochrome P450 3A7

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.

Chlordane induces hepatic cytochrome P-450, causing a large increase in the volume of the smooth endoplasmic reticulum, which results in hepatocellular enlargement and hypertrophy. (R159, R205)
UniProt ID: P24462
Gene: CYP3A7
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:

7. Estrogen-related receptor gamma

Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity).

Chlordane affects transcription by antagonizing estrogen-related receptors. (R162)
UniProt ID: P62508
Gene: ESRRG
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:

8. Retinoic acid receptor beta

Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence or presence of hormone ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function.

Chlordane has been shown to bind and activate retinoic acid receptor, causing various developmental defects. (R163)
UniProt ID: P10826
Gene: RARB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:

9. Retinoic acid receptor gamma

Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. Required for limb bud development. In concert with RARA or RARB, required for skeletal growth, matrix homeostasis and growth plate function (By similarity).

Chlordane has been shown to bind and activate retinoic acid receptor, causing various developmental defects. (R163)
UniProt ID: P13631
Gene: RARG
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:

10. Steroid hormone receptor ERR1

Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism.

Chlordane affects transcription by antagonizing estrogen-related receptors. (R162)
UniProt ID: P11474
Gene: ESRRA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:

11. Steroid hormone receptor ERR2

Nuclear receptor, may regulate ESR1 transcriptional activity.

Chlordane affects transcription by antagonizing estrogen-related receptors. (R162)
UniProt ID: O95718
Gene: ESRRB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:

12. Cytokine receptor common subunit beta

High affinity receptor for interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor.

Chlordane is believed to bind irreversibly to DNA, leading to cell death or altered cellular function. (R159)
UniProt ID: P32927
Gene: CSF2RB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:

13. Estrogen receptor

Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.

Causes endocrine disruption in humans by binding to and inhibiting the estrogen receptor. (S301)
UniProt ID: P03372
Gene: ESR1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:

14. Estrogen receptor beta

Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.

Causes endocrine disruption in humans by binding to and inhibiting the estrogen receptor. (S301)
UniProt ID: Q92731
Gene: ESR2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References: