Registration Dossier

Administrative data

Endpoint:
hepatotoxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
circa 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was not conducted according to guidelines or GLPs but the report contains sufficient data for interpretation of study results

Data source

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

Materials and methods

Principles of method if other than guideline:
Hepatotoxicity was assessed biochemically and histopathologically in BALB/c mice.
GLP compliance:
not specified
Type of method:
in vivo

Test material

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

Test animals

Species:
mouse
Strain:
Balb/c
Sex:
male/female
Details on test animals and environmental conditions:
The animals used in the hepatotoxicity study were male or female BALB/c mice (19-25 g) purchased from Bantin and Kingman Ltd. (UK) and fed on Heygate 41B breeding diet. Mice were treated in groups of three to five.

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
physiological saline
Details on exposure:
Mice were injected with the test compounds between 9 and 11 AM via the ip route in a volume of 0.2 ml. Nitroethane was injected at doses of 4.5, 6.7 or 9.0 mmol/kg; control mice were injected with NaCl (0.9% w/v). They were killed by cervical dislocation 24, 48, 72 or 96 hours after dosing.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No additional information available.
Duration of treatment / exposure:
Single ip dose administered and mice were sacrificed 24 - 96 hours after.
Frequency of treatment:
Single ip dose
Post exposure period:
Mice were sacrificed 24 - 96 hours after.
Doses / concentrations
Remarks:
Doses / Concentrations:4.5, 6.7 or 9.0 mmol/kgBasis:other: nominal dose in saline
No. of animals per sex per dose:
3-5 mice
Control animals:
yes, concurrent vehicle

Examinations

Examinations:
Blood was obtained by cardiac puncture and the activities in the plasma of the following three enzymes were assayed: sorbitol dehydrogenase (SDH), as described by Rose and Henderson (1975), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as described by Kachmar and Moss (1976). For histopathological investigation, livers were fixed in formol-saline (10% v/v), dehydrated, and embedded in paraffin wax. Sections (5 um), from at least three different lobes, were cut and stained with hematoxylin and eosin. All sections were evaluated without prior knowledge of the treatment group.References:Kachmar, J.F. and Moss, D.W. (1976). Enzymes: The transaminases. In Fundamentals of Clinical Chemistry. (N.W.Tietz, Ed), pp 672-681. Sanders, PhiladelphiaRose, C.I. and Henderson, A.R. (1975). Reaction-rate assay of serum sorbitol dehydrogenase activity at 37C. Clin Chem 21:1619-1626.
Positive control:
No data

Results and discussion

Details on results:
There was no significant increase in SDH, ALT or AST activity noted in mice dosed with nitroethane. The livers of mice which had received nitroethane (9 mmol/kg) did not show significant abnormalities.

Any other information on results incl. tables

No additional information available.

Applicant's summary and conclusion

Conclusions:
There was no biochemical or histopathologic effect observed in mice dosed with 9 mmol/kg nitroethane.
Executive summary:

The hepatoxicity of nitroethane was examined following ip administration. There was no biochemical or histopathologic effect observed in mice dosed with 9 mmol/kg nitroethane.