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EC number: 202-486-1 | CAS number: 96-18-4
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- Endpoint summary
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- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
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- Toxicological Summary
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- Carcinogenicity
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Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian germ cell study: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- abstract
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 996
Materials and methods
Test guideline
- Qualifier:
- no guideline available
- Principles of method if other than guideline:
- DNA was isolated from paraffin-embedded tumor sections (obtained from the forestomach of mice of the NTP bioassay on 1,2,3-trichloropropane, see chapter 7.7), amplified by polymerase chain reaction, and analyzed by direct sequencing for mutations in the ras-genes
- GLP compliance:
- no
- Type of assay:
- other: PCR analysis of nature of H-ras and K-ras mutations in tumors
Test material
- Reference substance name:
- 1,2,3-trichloropropane
- EC Number:
- 202-486-1
- EC Name:
- 1,2,3-trichloropropane
- Cas Number:
- 96-18-4
- Molecular formula:
- C3H5Cl3
- IUPAC Name:
- 1,2,3-trichloropropane
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- see chapter 7.7 "National Toxicology Program (1993) / Mouse"
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - corn oil
- see chapter 7.7 "National Toxicology Program (1993) / Mouse" - Details on exposure:
- see chapter 7.7 "National Toxicology Program (1993) / Mouse"
- Duration of treatment / exposure:
- 2 years, see chapter 7.7 "National Toxicology Program (1993) / Mouse"
- Frequency of treatment:
- daily 5 d/wk
- Post exposure period:
- non
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 6, 20 and 60 mg/kg
Basis:
actual ingested
gavage
- No. of animals per sex per dose:
- 60
- Control animals:
- yes, concurrent vehicle
Examinations
- Tissues and cell types examined:
- paraffin-embedded tumor sections from the forestomach
- Details of tissue and slide preparation:
- DNA was isolated from paraffin-embedded tumor sections (obtained from the forestomach of mice of the NTP bioassay on 1,2,3-trichloropropane, see chapter 7.7), amplified by polymerase chain reaction, and analyzed by direct sequencing for mutations in the ras-genes
Results and discussion
- Additional information on results:
- - 10 of 16 analysed tumors had a highly specific H-ras or K-ras mutation.
- 6 of the 10 had a H-ras mutation at codon 61 with 5 of the 6 showing a AT to TA transversion in base 1.
- 4 of the 10 had a K-ras mutation at codon 13 all of which showed a GC to CG transversion in base 1.
- These transversions aremost probably not caused by S-[1-(hydroxymethyl)-2-(N7- guanypethyl]glutathione which is the major DNA adduct that was found after 1,2,3-trichloropropane treatment.
- Based on preliminary results that are not further specified in the abstract, the authors propose that the found mutations are rather caused through etheno DNA adducts (1,N6-ethenodeoxyadenosine and 3,N4-ethenodeoxycytidine) which stem from lipid peroxidation.
- Their explanation is that the depletion of glutathion in cells that are exposed to 1,2,3-trichloropropane cause an increase in lipid peroxidation and thereby lead to the detrimental transversion mutations that were found in the ras-genes.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results: positive
DNA was isolated from paraffin-embedded tumor sections (obtained from the forestomach of mice of the NTP bioassay on 1,2,3-trichloropropane, see chapter 7.7), amplified by polymerase chain reaction, and analyzed by direct sequencing for mutations in the ras-genes.
Based on these results it is confirmed that 1,2,3-trichloropropane induces mutations, but a alternative mode of action is proposed: 1,2,3-trichloropropane exposure leads to glutathion depletion in cells, lipid peroxidation increases and etheno DNA adducts are formed that lead to transversion mutations. - Executive summary:
The present abstract to a poster presentation (Ito, 1996) reports the analysis of mouse forestomach tumor tissues via PCR. DNA was isolated from paraffin-embedded tumor sections (obtained from the forestomach of mice of the NTP bioassay on 1,2,3-trichloropropane, see chapter 7.7), amplified by polymerase chain reaction, and analyzed by direct sequencing for mutations in the ras-genes.
10 of 16 analysed tumors had a highly specific H-ras or K-ras mutation. 6 of the 10 had a H-ras mutation at codon 61 with 5 of the 6 showing a AT to TA transversion in base 1. 4 of the 10 had a K-ras mutation at codon 13 all of which showed a GC to CG transversion in base 1. These transversions are most probably not caused by S-[1-(hydroxymethyl)-2-(N7- guanypethyl]glutathione which is the major DNA adduct that was found after 1,2,3-trichloropropane treatment.
Based on preliminary results that are not further specified in the abstract, the authors propose that the found mutations are rather caused through etheno DNA adducts (1,N6-ethenodeoxyadenosine and 3,N4-ethenodeoxycytidine) which stem from lipid peroxidation. The proposed explanation is that the depletion of glutathion in cells that are exposed to 1,2,3-trichloropropane causes an increase in lipid peroxidation and thereby lead to the detrimental transversion mutations that were found in the ras-genes.
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