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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
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

Referenceopen allclose all

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 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
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

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

Reference
Name:
Unnamed
Type:
Constituent
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 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

open allclose all
Dose descriptor:
NOAEC
Remarks:
neurotoxicity
Effect level:
12 470 mg/m³ air (nominal)
Sex:
male
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

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.