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Toxicological information

Specific investigations: other studies

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Administrative data

Endpoint:
specific investigations: hepatotoxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No data on GLP, sufficient data is available for interpretation of results.

Data source

Reference
Reference Type:
publication
Title:
Comparison of the Hepatotoxicity in Mice and the Mutagenicity of Three Nitroalkanes
Author:
Dayal, R., Gescher, A., Harpur, E.S., Pratt, I., Chipman, J.K.
Year:
1989
Bibliographic source:
Fundamental and Applied Toxicology, 13:341-348

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
not specified
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
Balb/c
Sex:
male/female

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
other: DMSO in phosphate buffer solution
Details on exposure:
Mice were injected with the test cimpounds via the IP route in a volume of 0.2 mL.
Duration of treatment / exposure:
single injection
Frequency of treatment:
once
Post exposure period:
96 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 4.5, 6.7, 9.0 mmol/kg
Basis:
nominal conc.
No. of animals per sex per dose:
3-5/sex/dose
Control animals:
yes, concurrent no treatment
Details on study design:
Nitroalkanes were dissolved in DMSO and then diluted with phosphate buffer to a pH~7.8. BALB/c mice were obtained from a commercial supplier and fed a commercial breeding diet. They were treated in dose groups of 3-5.

Mice were injected with the test cimpounds via the IP route in a volume of 0.2 mL. Mice were sacrificed at 24, 48, or 96 hours post-dosing, and plasma was assayed for measurements of sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). For histopathological investigation, livers were fixed, hydrated, and embedded. Sections from at least 3 lobes were cut and stained, and sections were evaluated blindly.

Examinations

Examinations:
Mice were sacrificed at 24, 48, or 96 hours post-dosing, and plasma was assayed for measurements of sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). For histopathological investigation, livers were fixed, hydrated, and embedded. Sections from at least 3 lobes were cut and stained, and sections were evaluated blindly.

Results and discussion

Details on results:
A consistent finding was the absence of any effect in male mice 24 hours after dosing up to 9 mmol. Mean enzyme levels in plasma were elevated at 48 and 96 hours. Individual mice showed a striking variability in their succeptibility to the hepatotoxic effect of 2-NP, and there was a sex-dependent difference (females with larger increases in enzyme activity). The most severely affected livers showed an extensive hemorrhagic necrosis with apoptosis and disruption of the normal parenchyma. Mild proliferation of ductal-type cells in periportal areas was also noted. Less affected livers had single-cell necrosis, predominantly in a periportal location.

Applicant's summary and conclusion

Conclusions:
Mean enzyme levels in plasma were elevated at 48 and 96 hours. Individual mice showed a striking variability in their succeptibility to the hepatotoxic effect of 2-NP, and there was a sex-dependent difference (females with larger increases in enzyme activity).