Heptane

Repeated dose toxicity: other routes

Administrative data

Endpoint:

sub-chronic toxicity: other route

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Basic data given (comparable to guidelines/standards) Only female rats were used without explanation as to suitability. No discussion of similarity of responses seen at 7 days with those from 45 days biweekly treament. Data from 45 day treatment not presented for all endpoints.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Toxicity of n-hexane and n-heptane: Some biochemical changes in liver and serum.

Author:

Goel, S. et al.

Year:

1982

Bibliographic source:

Toxicol. Letters 14, 169-174

Reference 2

Reference Type:

publication

Title:

Hepatotoxic effects elicited by n-hexane and n-heptane.

Author:

Goel, S. et al.

Year:

1988

Bibliographic source:

Journal of Applied Toxicology 8, 81-84

Materials and methods

Principles of method if other than guideline:

No method specified.
Purpose of the study was to evaluate biochemical changes and potential for hepatotoxicity. Animals were treated with heptane or normal saline daily for 1, 2, 7 days or twice a week for 45 days by a single intraperitoneal injection. Food and water were available ad libitum. Effect on pentabarbitone (50mg/kg)-induced sleeping time [time elapsed between loss and regaining of righting reflex] was measured in rats treated with heptane for 2 or 7 days.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Heptane

EC Number:

205-563-8

EC Name:

Heptane

Cas Number:

142-82-5

Molecular formula:

C7H16

IUPAC Name:

heptane

Details on test material:

- Name of test material (as cited in study report): n-heptane
- Analytical purity: no data

Test animals

Species:

rat

Strain:

other: Industrial Toxicology Research Center breeding colony, Lucknow India

Sex:

female

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

physiological saline

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

1, 2, 7 or 45 days

Frequency of treatment:

daily or twice a week for 45 day exposure

Doses / concentrations

Remarks:

Doses / Concentrations:
approx. 684 mg/kg bw

No. of animals per sex per dose:

6 per exposure interval

Control animals:

yes

Results and discussion

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Toxic response/effects by dose level: Animals did not show any overt signs of toxicity. Rats administered heptane had decreased hepatic protein content [16.6 mg protein/100mg liver compared to control 19.7 mg/protein/100 g liver in whole homogenate, p <0.001) and decreased total sulphydryl content (19% below controls for 7 day and 45 day animals, p<0.001). Glucose-6-phosphatase activity was also decreased from 2 days of treatment onward.

Lipid peroxidation activity increased significantly after 24 and 48 hr treatment (85% to 150% above controls at 24 and 48 hr, respectively). Marked inhibition of biotransforming activity was demonstrated by prolonged elapsed sleeping time (100% longer than controls) after 2 and 7 days and decreased activity of marker metabolizing enzymes which reached levels 50-65% lower than controls by 7 days and were also seen at those levels with 45 days of biweekly treatment.

The peroxidative decomposition of lipid demonstrated in this study stimulates a series of reactions that can disrupt the equilibrium between synthesis and degradation of hepatic protein. These results correlate with excessive levels of alkaline phosphatase in the liver reported by Goel et al., 1982 and the depressed biotransforming activity of the liver and consequent increase in pentabarbitone induced sleeping time. Mechanisms of cytotoxicity may be attributed to reactive aldehydes produced by peroxidation of membrane lipids in the liver endoplasmic reticulum. Similar biochemical changes have been reported for n-Octane and nonane by the same authors [Robust summaries included].

Applicant's summary and conclusion

Conclusions:

Treatment with n-heptane intraperitoneally for 1-7 days daily or for 45 days biweekly demonstrated decreases in levels of hepatic biotransformation activity and increases in liver lipid peroxidation.

Executive summary:

Treatment with n-heptane intraperitoneally for 1-7 days daily or for 45 days biweekly demonstrated decreases in levels of hepatic biotransformation activity and increases in liver lipid peroxidation.