Octane-1,2-diol

Endpoint summary

Description of key information

Oral rat (standard acute method):                                                         LD50 > 2000 mg/kg bw  (no mortality at 2000 mg/kg bw).

Acute dermal rat:                                                                                      Waiving, as this study was considered to be scientifically unjustified.      

Acute inhalation rat - read-across from pentane-1,2-diol:              LC50 > 7015 mg/m^3 (no mortality at 7015 mg/m^3).

In addition octane-1,2-diol has quite a low vapour pressure (0.15 Pa at 20 °C, 0.28 Pa at 25°C) limiting the risk of human exposure to its vapour.

Conclusion:              No requirement of classification for acute oral, dermal or inhalation toxicity [DIRECTIVE 67/548/EEC & Reg. (EC) 1272/2008].

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a recognized contract research organization. Study is adequate for assessment with acceptable restrictions. Purity and stability of the test material were the responsibility of the sponsor and therefore were not reported for the batch of test material used.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

of 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

of 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sprague Dawley rats, strain: Crl:CD BR with appropriate range of bodyweight at study start.
- Source: Charles River UK Ltd., Margate, Kent, UK.
- Age at study initiation (day of dosing): 8 to 12 weeks.
- Weight at study initiation (day of dosing): Males: minimum 219 g, maximum 231 g,
Females: minimum 216 g, maximum 230 g.
- Housing: Group housing with up to 5 animals by sex in solid-floor propylene cages.
- Bedding material: Woodflakes.
- Fasting period: Overnight immediately prior to dosing until 3-4 hours after dosing.
- Diet (ad libitum, except for fasting period): Commercially available standard laboratory animal diet:
Rat and Mouse Expanded Diet No. 1 from Special Diets Services Limited, Witham, Essex, UK.
- Water (ad libitum*): Mains drinking water
- Acclimation period: At least 5 days before start of dosing.

* Remark: The study report does not clearly state whether or not water was supplied during the fasting period.

ENVIRONMENTAL CONDITIONS

The animal room was maintained at:
- Temperature (°C): 20 ± 1°C
- Relative Humidity (%): 42 to 67%
- Photoperiod (artificial lighting): 12 h day / 12 h night
- Rate of air exchange: Ca. 15 changes/h

Route of administration:

oral: gavage

Vehicle:

arachis oil

Remarks:

BP

Details on oral exposure:

VEHICLE
- Concentration of test material in vehicle: 200 mg/ml
- Amount (dose volume by gavage): 10 ml/kg bw
(individual dose volume was calculated based on individual fasted bodyweight at the time of dosing).

DOSAGE PREPARATION:
The dose formulation was freshly prepared by mixing the test material with the vehicle. A suspension was formed.
Homogeneity was assured by use of a Silverson Homogeniser and vortex mixer.

RATIONALE FOR DOSE SELECTED:
The choice of the limit dose of 2000 mg/kg bw was appropriate in the main study, because this dose did not induce any deaths and elicited only transient clinical signs in a preliminary range-finding study with 1 male and 1 female rat observed for 12 days after dosing.

Doses:

2000 mg/kg bw (5 males + 5 females)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Observation of clinical signs: 0.5, 1, 2 and 4 h post dosing on the day of administration (Day 0) and subsequently once daily for 14 days.
Weighing of each animal: Day 0 for dose calculation and on Days 7 and 14.
- Necropsy performed: yes, of all main study animals.

Statistics:

Not applicable, as there were no deaths and only one dose group.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths at the limit dose of 2000 mg/kg.

Mortality:

Single Dose at Mortality
2000 mg/kg 0/5 (f)
2000 mg/kg 0/5 (m)

Clinical signs:

other: In the main study, clinical signs comprised hunched posture, lethargy, ataxia, decreased respiratory rate and laboured respiration in all animals on the day of dosing (Day 0). By the day afterwards (Day 1) only hunched posture was still seen in four male

Gross pathology:

Necropsy of each animal at the end of the 14-day post treatment observation period did not reveal any macroscopic pathology findings.

Interpretation of results:

other: no mortality at the limit dose of 2000 mg/kg, no classification according to 1272/2008

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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.

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

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

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).

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.

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).

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In the acute oral toxicity study, all animals survived the limit dose of 2000 mg/kg. Therefore, classification of octane-1,2 -diol for acute oral toxicity is not required [REGULATION (EC) 1272/2008].

 

Based on the general low oral toxicity of octane-1,2 -diol (LD50 > 2000 mg/kg, no deaths at 1000 mg/kg/day in a repeated dose oral study during 90 days) high acute dermal toxicity is not to be expected. Therefore, classification of octane-1,2 -diol for acute dermal toxicity is not required.

Acute inhalation toxicity of octane-1,2 -diol is concluded by read-across from a study performed with pentane-1,2 -diol. The LC50 was > 7015 mg/m^3. Additionally, octane-1,2 -diol has a very low acute toxicity. Accordingly, classification of octane-1,2 -diol for acute inhalation toxicity is not required.