Registration Dossier

Administrative data

Endpoint:
biochemical or cellular interactions
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets scientific standards with acceptable restrictions (e.g. partly limited documentation, e.g. no details about the test substance).

Data source

Reference
Reference Type:
publication
Title:
An investigation of the role of microsomal oxidative metabolism in the in vivo genotoxicity of 1,2-dichloroethane
Author:
Storer RD & Conolly RB
Year:
1985
Bibliographic source:
Tox Appl Pharmacol 77: 36-46

Materials and methods

Principles of method if other than guideline:
Biochemical effects in the liver of mice after i.p. injection
GLP compliance:
no
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no details

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
physiological saline
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
single injection
Post exposure period:
see results
Doses / concentrations
Remarks:
Doses / Concentrations:
24; 48; 72.5 mg/kg bw in the 1st trial or 24; 48; 72.5; 96.6 mg/kg bw in the 2nd
Basis:

No. of animals per sex per dose:
see below
Control animals:
other: untreated controls in trial 1 and concurrent vehicle control in trial 2

Results and discussion

Details on results:
1st trial: depletion to 30% of untreated control level at the high dose level 1.5 h after injection, slight amelioration after 3 h. Similar but less severe effects at lower doses.
2nd trial: rel. liver weight significantly increased at the high dose level; serum IDH and AAT significantly increased at the high dose level.

Applicant's summary and conclusion

Conclusions:
Toxic dose levels resulted in depletion of liver glutathione and in liver toxicity in mice.
Executive summary:

The study meets scientific standards with acceptable restrictions (e.g. partly limited documentation, e.g. no details about the test substance).

In trial 1 4 male B6C3F1 mice were i.p. injected once with 24, 48, or 72.5 mg/kg bw (untreated control) and liver glutathione levels measured 1.5 and 3 h after application. A depletion to 30% of untreated control level at the high dose level 1.5 h after injection was measured and a slight amelioration was found after 3 h. Similar but less severe effects were found at lower doses.

In the 2nd trial 3 -6 male B6C3F1 mice per groupp received single i.p. injections of 0, 24, 48, 72.5, or 97 mg/kg bw and sacrificed 24 h later. Liver weight was significantly increased at the high dose level as well as serum iditol dehydrogenase and serum alanine aminotransferase.

Conclusion: Toxic dose levels resulted in depletion of liver glutathione and in liver toxicity in mice.