3-methylpentane

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

30 male Wistar rats were feeded with the test substance in olive oil for 8 weeks. The conduction velocity of the peripheral nerve was obtained in the rats tail.
Therefore the rat kept immobilized by wrapping into a towel, turned on his back and got electrodes inserted in his tail. Then the tail was immersed in a warm parrafin bath and the tail nerve was stimulated by a square pulse of 0.2 ms and supramaximal strenght. Biopotentials were observed with an adscope between two different distances.Then the conduction velocity was calculated.

GLP compliance:

not specified

Test material

Test material information

1

Reference substance name:

3-methylpentane

EC Number:

202-481-4

EC Name:

3-methylpentane

Cas Number:

96-14-0

Molecular formula:

C6H14

IUPAC Name:

3-methylpentane

Test material form:

liquid

Specific details on test material used for the study:

The four chemicals (2-methylpentane, 3-methylpentane, methylcyclopentane and n-hexane) used were more than 99 % pure.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

thirty Wistar male rats: mean body weight 343 g, SD 27 g

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

olive oil

Details on oral exposure:

The solvents were diluted with olive oil and orally administered for 8 weeks. Weeks 1-4: 0.4 ml test substance + 0.6 ml olive oil, weeks 5-6: 0.6 ml test substance + 0.4 ml olive oil, weeks 7-8: 1.2 ml test substance + 0.8 ml olive oil

Duration of treatment / exposure:

8 weeks

Frequency of treatment:

once daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.4 other: ml

Remarks:

wks. 1-4

Doses / concentrations 2

Dose / conc.:

0.6 other: ml

Remarks:

wks. 5+6

Doses / concentrations 3

Dose / conc.:

0.8 other: ml

Remarks:

wks. 7+8

No. of animals per sex per dose:

5-7 (males only)

Control animals:

yes, concurrent vehicle

Positive control:

5 different test substances tested

Examinations

Observations and examinations performed and frequency:

before administration and after 2, 4, 6 and 8 weeks; Body weight, conduction velocity, motor distal latency, mixed nerve conduction velocity
3 points at the rat´s tail were inserted with electrodes: A (3 cm down from the anus), B (7-10 cm down from A) and C (3-4 cm up from the tail`s end). Stimulating at A or B by a single stimulation and measuring the resulting EMGs at C were used to obtain the motor nerve conduction velocity (MCV) and the distal latency (DL). Stimulating the nerve at C by 100 times by 2 c/s and measuring the nerve impulses at A and B obtained the mixed nerve conduction velocity (MNCV).

Results and discussion

Results of examinations

Clinical signs:

not examined

Mortality:

not examined

Body weight and weight changes:

no effects observed

Description (incidence and severity):

The changes in body weight are shown in Fig. 2. There were no statistically significant differences between the solvent-administered groups and the control.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

no effects observed

Description (incidence and severity):

No abnormal changes in the behavior of rats were found in every group throughout the experiment.

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Neuropathological findings:

effects observed, treatment-related

Description (incidence and severity):

The changes in MCV are shown in Fig. 3 MCV in the n-hexane group was significantly less than the control after four and eight weeks of administration. MCV in methylcyclopentane group was significantly less than the control after eight weeks' administration. But there was no significant difference between MCVs in 2-methylpentane or 3-methylpentane group and the control.
DLs in every groups had a tendency to decrease as the rats grew. There were no statistically significant differences between the solvent-administered groups and the control.

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Any other information on results incl. tables

The changes in MNCV (distal) are shown in Fig. 4. MNCV (distal) in n-hexane group was significantly less than the control after four weeks' administration. But there was no significant difference between MNCVs (distal) in 2-methylpentane, 3-methylpentane or methylcyclopentane group and the control.

The changes in MNCV (proximal) are shown in Fig. 5. MNCV (proximal) in n-hexane group was significantly less than the control after six weeks' administration. MNCVs (proximal) in the 2-methylpentane and methylcyclopentane groups

were significantly less than the control after eight weeks' administration.

The summary of the results is shown in Fig. 6. The results demonstrated that the n-hexane group showed a distinct impairment of the functional states of the peripheral nerve, the methylcyclopentane and 2-methylpentane groups showed

only slight impairment of them, and 3-methylpentane group barely showed any impairment.

The ratios of the conduction velocities and distal latencies to the predosing ones were calculated and compared between each solvent-administered group and the control group (Fig. 7). MNCV (distal) significantly differed from that of the

control even in 3-methylpentane group after eight weeks' administration. There were no significant differences in distal latency.

Applicant's summary and conclusion

Conclusions:

The n-hexane group showed a distinct impairment of the functional states of the peripheral nerve Methylcyclopentane, 2-methylpentane and 3-methylpentane group had some significant differences in comparison with the control in the experiment, although these differences were not so distinct as those in n-hexane group. The results revealed that the neurotoxicity of the three chemicals was not so severe as that of n-hexane and were in the order of
n-hexane > methylcyclopentane > 2-methylpentane = 3-methylpentane.

Executive summary:

Commercial hexane which caused polyneuropathy in many workers contained 10-40 % of 2-methylpentane, 3-methylpentane and methylcyclopentane in addition to n-hexane. The hexacarbon compounds methyl n-butyl ketone, 2,5-hexanedione and etc were shown to be neurotoxic like n-hexane. Therefore, 2-methylpentane, 3-methylpentane and methylcyclopentane which are also hexacarbon compounds were suspected to be neurotoxic, but their neurotoxicity had not been sufficiently investigated.

The present experiment was performed to clarify their neurotoxicity by measuring the nerve conduction velocity in the rat's tail Thirty rats were divided into five groups of 5-7 rats. n-Hexane, 2 -methylpentane, 3-methylpentane and methylcyclopentane were diluted with olive oil and orally administered daily for eight weeks. The body weight, motor nerve conduction velocity, motor distal latency and mixed nerve conduction velocity were measured before administration, after two, four, six and eight weeks' administration.