2-nitropropane

Specific investigations: other studies

Administrative data

Endpoint:

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

Test material information

Constituent 1

Reference substance name:

2-nitropropane

EC Number:

201-209-1

EC Name:

2-nitropropane

Cas Number:

79-46-9

Molecular formula:

C3H7NO2

IUPAC Name:

2-nitropropane

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).