Heptane

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets generally accepted scientific principles, acceptable for assessment. Only one dose employed; statistical methods not identified.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

A comparative study of the toxicity of n-pentane, n-hexane, and n-heptane to the peripheral nerve of the rat.

Author:

Takeuchi, Y. et al.

Year:

1981

Bibliographic source:

Clinical Toxicology 18(12): 1395-1402

Reference 2

Reference Type:

publication

Title:

A comparative study on the neurotoxicity of n-pentane, n-hexane, and n-heptane in the rat

Author:

Takeuchi, Y. et al.

Year:

1980

Bibliographic source:

British Journal of Industrial Medicine 37: 241-247

Reference 3

Reference Type:

publication

Title:

Studies on the method of measuring nerve conduction velocity in rat's tail and the comparative toxicity of n-hexane, methyl n-butyl ketone and 2,5-hexanedione.

Author:

Ono, Y. et al.

Year:

1979

Bibliographic source:

Japanese Journal of Industrial Health 21(6): 528-538

Materials and methods

Principles of method if other than guideline:

Single concentration repeated dose study for peripheral nerve toxicity.

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: > 99 %

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: not specified
- Weight at study initiation: 308 ± 18 g

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: room air

Remarks on MMAD:

MMAD / GSD: not applicable, vapour

Details on inhalation exposure:

TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography and Kitagawa gas detection

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Animals were actually exposed to 2960 ± 200 ppm of Normal-Heptane.

Duration of treatment / exposure:

16 weeks

Frequency of treatment:

12 hours/day, 7 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
12.47 mg/L (re-calculated; corresponding to 3000 ppm)
Basis:
nominal conc.

No. of animals per sex per dose:

7 males

Control animals:

yes, sham-exposed

Details on study design:

- Post-exposure recovery period: none

Positive control:

none

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: no data
- Cage side observations included: behaviour


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: before and after 4, 5, 12, 16 weeks of exposure


BODY WEIGHT: Yes
- Time schedule for examinations: not further specified, very likely weekly


OTHER:
Neurophysiology: motor nerve conductivity velocity (MCV), distal latency (DL), mixed nerve conduction velocity (MNCV)
- Time schedule: before and at 4, 5, 12, 16 weeks of exposure

Sacrifice and pathology:

GROSS PATHOLOGY: No data
HISTOPATHOLOGY: Yes (one rat): gastrocnemeius and soleus muscles, the dorsal trunk of the tail nerve and the tibial nerve were examined by light and electron microscopy

Statistics:

Employed but not identified by test name.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Details on results:

CLINICAL SIGNS AND MORTALITY
No abnormal behavioural changes were observed.

BODY WEIGHT AND WEIGHT GAIN
Body weight gain was statistically significantly depressed (p<0.01) after 8 weeks of exposure compared to controls but gradually increased throughout the experiment, albeit to body weight levels below control values, but not statistically significantly lower.


HISTOPATHOLOGY: NON-NEOPLASTIC
Peripheral nerves, muscles and neuromass junctions, examined microscopically, were normal.

OTHER FINDINGS
Neurophysiology: There were no statistically significant differences in motor nerve conduction velocity, distal latency or mixed nerve conduction velocity in any region of the tail.

Effect levels

1

Key result

Dose descriptor:

NOAEC

Remarks:

neurotoxicity

Effect level:

12 470 mg/m³ air (nominal)

Sex:

male

Basis for effect level:

other: no effects except reversible body weight changes

2

Key result

Dose descriptor:

NOAEC

Remarks:

systemic

Effect level:

12 470 mg/m³ air (nominal)

Sex:

male

Basis for effect level:

other: no effects except reversible body weight changes

Target system / organ toxicity

Key result

Critical effects observed:

not specified

Any other information on results incl. tables

Normal-Heptane is not a neurotoxicant in this assay system.

Applicant's summary and conclusion

Conclusions:

Normal-heptane is not a neurotoxicant in this assay system.

Executive summary:

Normal-heptane is not a neurotoxicant in this assay system.