Octane

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 Dec 1999 - 11 Dec 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Principles of method if other than guideline:

Animals were exposed to the test atmosphere and checked for health, viability and clinical signs.

GLP compliance:

yes (incl. QA statement)

Remarks:

Ministry of Health, Welfare and Sport, State Supervisory Public Health Service, Veterinary Public Health Inspectorate, GLP Section

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Octane

EC Number:

203-892-1

EC Name:

Octane

Cas Number:

111-65-9

Molecular formula:

C8H18

IUPAC Name:

octane

Details on test material:

- Name of test material (as cited in study report): n-octane supplied by Boom, Meppel, The Netherlands
- Physical state: clear, volatile liquid
- Analytical purity: 99.3 %
- Lot/batch No.: S90753 802
- Storage condition of test material: ambient temperatures, in the dark

Test animals

Species:

rat

Strain:

other: WAG/RijCrlBR

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: 14 weeks
- Weight at study initiation: approximately 250 g at randomization

- Housing: Animals were housed in groups of 5 in suspended stainless steel cages under conventional conditions. After randomization animals were moved to the exposure chambers and housed individually in wire-mesh cages.
- Diet (ad libitum): commercial rodent diet (Rat & Mouse No. 3 Breeding Diet, RM3)
- Water (ad libitum): Tap water suitable for human consumption (quality guidelines according to Dutch legislation based on EEC Council Directive 80/778/EEC, see Annex 3) was supplied by N.V. Waterleidingbedrijf Midden-Nederland (WMN).
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24 (lowest 17.5 %)
- Humidity (%): 30-70 (maximum was 78)
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): artificially illuminated for 12 hours between 7.30 a.m. and 7.30 p.m.


IN-LIFE DATES: From: 1998-11-18 To: 1998-12-11

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: air

Remarks on MMAD:

MMAD / GSD: no data

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: modified H 1000 inhalation chambers (Hazleton Systems Inc., USA)
Each chamber had a pyramidal top and bottom and was constructed of stainless steel with glass doors on two sides.
- System of generating particulates/aerosols: test atmosphere was generated by pumping liquid n-octane into stainless steel tubing using peristaltic pumps (Watson and Marlowe).
- Temperature, humidity in air chamber: 19-24 °C, 40-70 %
- Air flow rate: 11.9 m3/h (results from earlier experiments)



TEST ATMOSPHERE
- Brief description of analytical method used: During exposure a total carbon analyzer (TCA, Ratfisch, Germany) was operated with 4 ports which weresuccessively sampled during 10 minutes. The ports were connected to exposure chamber A (control), B (lower concentration), C (mid concentration) and D (higher concentration). The TCA readings were calibrated using PET sample bags filled with 50 l air and n-octane corresponding to concentrations of 0.7, 1.4, 4.6, 8.8, 14.4 and 17.7 g/m3.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

During exposure a total carbon analyzer was operated with 4 ports for control and 3 test concentrations. Shortly after the experiment, a stability check of the concentrations was performed.

Duration of treatment / exposure:

8 hours

Frequency of treatment:

once daily for 3 consecutive days

Doses / concentrations

Remarks:

Doses / Concentrations:
0 g/m3; 1.4 g/m3 corresponding to 300 ppm; 4.2 g/m3 corresponding to 900 ppm; 14 g/m3 corresponding to 3000 ppm
Basis:
nominal conc.

No. of animals per sex per dose:

8

Control animals:

yes, concurrent vehicle

Details on study design:

- Rationale for animal assignment: The rat was selected because this species is considered suitable for this type of study and was the species specified in the TNO EZ Collective project proposal. The strain of rats used in these experiments has been used extensively in behavioral studies within TNO.

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least once daily
- Cage side observations checked: no details given

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: prior to randomization (no details given)


BODY WEIGHT: Yes
- Time schedule for examinations: body weight was recorded during randomization and on days of testing

Statistics:

All data were analyzed using the SAS® statistical software package (release 6.12). For each test measure, probability values of p≤0.05 were consideredsignificant. Treatment effects were analyzed using repeated measures analysis of variance. Group comparisons were made using Dunnett´s multiple comparison tests.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Behaviour (functional findings):

no effects observed

Details on results:

Exposure levels (once daily for 3 consecutive days) used in this study did not induce clear signs of general intoxication. No significant effects of exposure were observed on body weight or on body temperature.

CLINICAL SIGNS AND MORTALITY
No remarkable clinical signs were observed.

BODY WEIGHT AND WEIGHT GAIN
During the 3-day exposure period, mean body weights were only slightly changed. A small decrease was observed in the 14 g/m3 group during the exposure period. Repeated measures analysis of variance of body weight data indicated a significant treatment-by-time interaction. However, analysis of variance of body weight data at each test time point indicated that there were no significant differences between groups.

Effect levels

Key result

Dose descriptor:

NOAEC

Effect level:

> 14 000 mg/m³ air (nominal)

Sex:

male

Basis for effect level:

other: overall effects (no effects) highest dose tested

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In conclusion, short-term high-level exposure to n-octane did not induce any toxicologically significant effects. The highest exposure level used at which no effects were observed was 14 g n-octane/m3.

Executive summary:

In conclusion, short-term high-level exposure to n-octane did not induce any toxicologically significant effects. The highest exposure level used at which no effects were observed was 14 g n-octane/m3.