Registration Dossier

Administrative data

Endpoint:
hepatotoxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was not conducted according to guideline/s and GLP but the report contains sufficient data for interpretation of study 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

Principles of method if other than guideline:
Mice were injected with the test compounds 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.
GLP compliance:
not specified
Type of method:
in vivo
Endpoint addressed:
not applicable

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purchased from Fluka Chemical Company (UK).

Test animals

Species:
mouse
Strain:
Balb/c
Sex:
male/female
Details on test animals and environmental conditions:
Male or female BALB/c mice (19-25 g) were purchased from Bantin and Kingman Ltd. (UK) and fed on Heygate 41B breeding diet.

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
physiological saline
Details on exposure:
Mice were injected with the test material via the ip route in a volume of 0.2 ml. Nitromethane was injected at doses of 4.5, 6.7 or 9.0 mmol/kg; control mice were injected with NaCl (0.9% w/v).
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data.
Duration of treatment / exposure:
Single ip injection
Frequency of treatment:
Single ip injection
Post exposure period:
24, 48, 72 or 96 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
4.5, 6.7, or 9.0 mmol/kg
Basis:
nominal conc.
No. of animals per sex per dose:
each group consisted of 3-5 mice.
Control animals:
yes, concurrent vehicle
Details on study design:
Mice were injected with the test compounds 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.
Positive control:
No data

Results and discussion

Details on results:
The clinical chemistry measurements (SDH, ALT and AST activities) and histopathologic examination of livers of mice injected with NM did not show any significant abnormalities.

Any other information on results incl. tables

The clinical chemistry measurements (SDH, ALT and AST activities) and histopathologic examination of livers of mice injected with NM did not show any significant abnormalities.

Applicant's summary and conclusion

Conclusions:
The clinical chemistry measurements (SDH, ALT and AST activities) and histopathologic examination of livers of mice injected with NM did not show any significant abnormalities.
Executive summary:

The effects of nitromethane on liver clinical chemistry measurements and liver histopathology were examined in mice. The clinical chemistry measurements (SDH, ALT and AST activities) and histopathologic examination of livers of mice injected with NM did not show any significant abnormalities.