Octane-1,2-diol

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not indicated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Well documented and reported study adequate for assessment. The study was state of the art at the time and conducted according to internationally accepted literature references in a recognized industrial research facility. GLP was not implemented at that time. Read across of acute inhalation toxicity data is considered to be appropriate, because the chemical structures of the substance target chemical, octane-1,2-diol, and the substance analogue source chemical, pentane-1,2-diol (EC 226-285-3), are very similar and there is no difference in functional groups.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

of 1981

Deviations:

no

GLP compliance:

no

Test type:

other: standard acute limit test, but with 2 dose groups

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Pentane-1,2-diol

EC Number:

226-285-3

EC Name:

Pentane-1,2-diol

Cas Number:

5343-92-0

IUPAC Name:

pentane-1,2-diol

Test animals

Species:

rat

Strain:

other: Tif:RAI f (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Initial Age: Young adult rats
- Number and Sex: 10 males and 10 females per dose group
- Initial Weight Range: Males: 215 to 231 g, females: 196 to 224 g
- Housing: In groups of 5 by sex in Macrolon cages (type IV)*
- Diet (ad libitum*): Commercially available standard diet (NAFAG No. 890, NAFAG, Gossau, Switzerland).
- Water (ad libitum*): Tap water. (Periodically analysed)
- Acclimation period: Not specified, but the animals were bred in-house.

* except during the 4 h inhalation exposure

ENVIRONMENTAL CONDITIONS

Air conditioned room:
- Temperature (°C): 22 ± 2°C
- Relative Humidity (%): 50 ± 10%
- Photoperiod: 12 hrs light/day

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Concentrations:

Gravimetrically determined mean aerosol concentrations ± standard deviations of measurements at 0.5, 1, 2, 3 and 4 h post exposure start:
Group 1 (Control): --- (filtered air)
Group 2 (Low Dose): 3.380 ± 0.092 mg/L air
Group 3 (High Dose): 7.015 ± 0.100 mg/L air

Nominal aerosol concentrations (presumbably over the entire 4 h exposure period):
Group 1 (Control): --- (filtered air)
Group 2 (Low Dose): 96.7 mg/L air
Group 3 (High Dose): 290.0 mg/L air

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

Single 4 hour inhalation exposure followed by 14 days of observation.
Observations:
- Mortality / Clinical signs: 1, 2, & 4 h after exposure start (i.e. during & immediately after exposure), 2 h after end of exposure and daily thereafter
- Bodyweight: Immediately before exposure start, and 7 and 14 days after exposure
- Necropsy (gross pathology with particular attention to the respiratory tract) at 14 days after exposure on all animals.

- Gravimetric determination of aerosol concentrations by trapping of aerosol samples on filters.
- Gravimetric determination of particle size distribution twice during each exposure by use of a 4 stage cascade impactor (C.F. Casella & Co., London)
with Selectrom filters of 25 mm diamter and 0.2 µm pore size.
- Monitoring of temperature, relative humidity and oxygen content of the test aerosol.

Statistics:

Calculation of LC50 values and 95% confidence limits was inappropriate, as there were no deaths.
Bodyweights of treated animals and controls were compared by analysis of variance (Freund JE, Mathematical Statistics, Prentice Hall 1962).

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 7.015 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No deaths at this and lower gravimetrically determined mean aerosol concentrations. 95% CL could not be determined as there were no deaths.

Mortality:

There were no deaths at any of the aerosol concentrations tested in the present study.

Clinical signs:

other: Transient dyspnea confined to the day of exposure, ruffled fur and curved body position confined to the day of exposure and the day afterwards were evident in both dose groups, whereby at 7.015 mg/L air findings were slightly more severe or extended over

Body weight:

Body weight gain was not adversely affected by treatment. In male animals a dose related increase in bodyweight gain was apparent during the week after the inhalation exposure.

Gross pathology:

Macroscopic examination of each animal revealed mottled or reddish lungs in a number of treated animals, whereby the incidence of findings was not dose related.

Any other information on results incl. tables

Particle size distribution was considered to be acceptable for acute inhalation toxicity testing, as ca. 50% of the particle mass was ≤ 3 µm at each test aerosol concentration (derived from cascade impactor measurements).

Applicant's summary and conclusion

Conclusions:

Nose only inhalation exposure of male and female rats to Pentane-1,2-diol (a structural analogue to Octane-1,2-diol) over 4 hours at gravimetrically determined mean aerosol concentrations of 3.380 or 7.015 mg/L air and at an acceptable particle size did not induce any mortality. Minor transient clinical signs, and necropsy findings in a number of treated animals were attributed the the test material but not considered relevant for toxicity classification. According to EU classification rules (REGULATION (EC) 1272/2008) the outcome of the present study does not necessitate any classification or labelling regarding acute inhalation toxicity.