Octane-1,2-diol

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Well documented and reported study fully adequate for assessment. The study was conducted according to an internationally accepted technical guideline and in compliance with GLP in a recognized contract research organization. The present robust study summary is based only on a translation of the original study report, but both were written by the study director himself.

Qualifier:

according to guideline

Guideline:

other: Guide to Quasi-drug and Cosmetic Regulations in Japan, Yakuji Nippo, Ltd., Feb. 2006

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Species, Strain: Rabbit, NZW (Yac:NZW(KBL))
- Source: Yonam College of Agriculture
San 3-1, Suhyang-ri, Seonghwan-eup, Cheonan-si,
Chungcheongnam-do, Korea
- Number and Sex: 3 males were dosed in the study (selected from 5 males with suitable skin sites)
- Age at start of dosing (Day 1): 16 weeks
- Weight prior to dosing (Day 1): Minimum 2.71 kg, maximum 2.92 kg
- Housing: Individual housing in stainless steel cages (38 x 49 x 35 cm) with automated flush system
- Diet (ad libitum): Purina experimental diet for rabbits 5302 from Agribrands Purina Korea Inc.
- Water(ad libitum) : Filtered and purified public tap water (municipal supply), supplied in polycarbonate bottles
- Acclimation period: Ca. 2.5 months prior to study start under laboratory conditions.

Routine analysis of the diet used for nutrients and possible contaminants and of the drinking water for specified microorganisms and environmental contaminants were conducted or available at the testing facility. There were no known contaminants in the diet or water at levels that would be expected to interfere with or affect the results of the study.

ENVIRONMENTAL CONDITIONS IN THE ANIMAL ROOM

- Temperature (°C): 21.6 to 23.6°C
- Relative Humidity (%): 40.2 to 61.6%
- Photoperiod: 12 hours light, 12 hours dark per 24 hours
- Intensity of ilumination: 150 to 300 Lux
- Rate of air exchange: 10 to 15 changes/h (all fresh air)

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Remarks:

The neat test material was warmed to 40-50°C for 10 minutes for liquefaction and then kept at room temperature for 10 minutes until use for dosing

Controls:

not required

Amount / concentration applied:

0.5 mL undiluted pre-warmed liquid test material per approx. 6 cm2 intact or abraded, clipped skin

Duration of treatment / exposure:

24 hours

Observation period:

72 hours post exposure start (i.e. the final observation time point was 48 hours post patch removal)

Number of animals:

3 males

Details on study design:

TEST SITE PREPARATION AND ADMINISTRATION
On the day before treatment, hair was removed with clippers from the dorsal region (left and right side of the spine) of each animal. Samples of 0.5 mL of the liquefied, neat test material were applied to the clipped intact and to clipped and then abraded skin of albino rabbits by means of gauze patches each of approx. 6cm2 size (2.5cm x 2.5 cm each; 0.5 mL test material per gauze patch). Prior to use the neat test substance was liquefied by warming for approx. 10 minutes to 40-50°C and then left for 10 minutes at room temperature before being administered to the gauze patches. Patches were fixed with commercially available transparent sticking plaster, then with Lint cloth plaster and finally with paper masking tape and held in contact with the intact or abraded skin sites by occlusive dressing.

On each animal one additional clipped intact skin site and one clipped and then abraded site remained untreated but were covered and dressed occlusively in the same manner as the treated skin sites and acted as a controls.

REMOVAL OF TEST MATERIAL
At the end of the 24 hour exposure period, the occlusive dressing and gauze patches and residual test material were removed, the latter by use of absorbent cotton moistened with tepid water.

TIME POINTS OF SKIN EVALUATION:
The treated skin patches were evaluated 24, 48 and 72 h after exposure start, (i.e. immediately, 24 & 48 hours post patch removal). The study was terminated after the final reading (72 h after exposure start), as on all occasions all animals were entirely free from skin reactions (erythema or edema). The scoring system for the grading of skin reactions is listed in Table 1 (next field below).

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: Administered to intact skin for 24 hours

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: administered to intact skin for 24 h

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: administered to intact skin for 24 h

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: Administered to intact skin for 24 hours

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: administered to intact skin for 24 h

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: administered to intact skin for 24 h

Irritant / corrosive response data:

In each animal, clipped intact and clipped abraded skin patches treated with liquefied neat test material for 24 hours were free from erythema, scab or edema formation at any observation time point of the study, i.e. at 24, 48 and 72 hours after treatment start.

Other effects:

Mortality or clinical signs attributable to treatment with the test material were not evident and bodyweight development was normal in all animals.

Interpretation of results:

other: not irritating

Conclusions:

Occlusive administration of 1,2-octanediol to clipped, intact or clipped, abraded skin of three rabbits for 24 hours did not induce any skin reactions during the present study, i.e. during 72 hours after treatment start. According to EU classification rules [REGULATION (EC) 1272/2008] the outcome of this study does not necessitate any labelling regarding skin irritation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented and reported study fully adequate for assessment. The study was conducted according to an internationally accepted technical guideline and in compliance with GLP in a recognized contract research organization.

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

of 2004

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Species, Strain: Rabbits, New Zealand White (SPF Crl:NZW)
- Source: Charles River Wiga GmbH, D-97320 Sulzfeld, Germany
- Number and Sex: 2 males
- Age on day of dosing (Day 1): > ca. 3 months
- Weight prior to dosing (Day 1): Minimum 3790 g and 4545 g
- Housing: Individual housing in stainless steel cages (50 x55 x40 cm) with ovally peforated floor
- Bedding: ALTROMIN Type S8/15, granulated soft wood bedding
- Diet (ad libitum): Standard diet for rabbits (Brand: "ALTROMIN 2123"; Altromin, 32791 Lage/Lippe, Germany)
- Water(ad libitum): Tap water (municipal supply), in Makrolon® bottles, changed daily
- Acclimation period: Ca. 3 months prior to study start under laboratory conditions.

Routine analysis of the batch of diet used for nutrients and possible contaminants (heavy metals, aflatoxins, pesticides) and of the drinking water and bedding material for microbial contaminants, heavy metals and halogenated hydrocarbons were conducted or available at the testing facility.

ENVIRONMENTAL CONDITIONS

Air conditioned animal room set at:
- Temperature (°C): 21.5 to 22.5°C
- Relative Humidity (%): 40 to 70%
- Photoperiod: 12 hours artificial light, 12 hours dark per 24 hours

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 mL of the undiluted liquid test material was administered into the conjunctival sac of one eye per rabbit. The contralateral eye remained untreated to serve as a control.

Duration of treatment / exposure:

The treated eyes of both animals were carefully rinsed with deionised water at 1 hour after test material instillation, because of conjunctival redness and chemosis, grade 1 and 2, respectively. At 24 h after test material instillation, the treated eye of animal #1 was rinsed again, because of corneal opacity grade 2 in this eye.

Observation period (in vivo):

animal #1: 16 days
animal #2: 14 days

Number of animals or in vitro replicates:

2 male rabbits

Details on study design:

EYE EVALUATION:

Before treatment start both eyes of each animal were investigated after instillation of 2 or 3 drops of fluorescein sodium solution (0.5% in deionised water) into the conjunctival sac, to ensure that there were no pre-existing ocular defects. After 30 seconds the eyes were rinsed with deionised water.

One animal was initially treated and, in view of corneal opacity up to grade 2 and iridic swelling grade 1 for a number of days in this animal (#1), only one other animal (#2) was committed to the study for confirmation of the initial results 13 days afterwards.

Eyes were evaluated in both animals at approximately 1, 24, 48 and 72 hours after test material instillation adopting the numerical scoring system listed in Table 1 in the field below. Additional examinations were performed daily thereafter ending 16 and 14 days after test material instillation in animals #1 and #2, respectively. Grades attained at 48, 72 and 96 hours after instillation were included in the mean gradings of ocular lesions. Staining with fluorescein sodium solution supported the recognition of corneal lesions in animal #1 at 6 & 9 days after test material instillation and in #2 at 6, 8, 10 & 14 days after test material instillation.

Equipment used for eye evaluation: Hand slit-lamp (Heine OPTOTECHNIK)

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 16 days

Remarks on result:

other: A lesion of the superficial epithelium of the cornea, ca. 3 mm diameter, was seen from Day 5 to Day 8 after test material instillation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: A lesion of the superficial epithelium of the cornea, ca. 3 mm diameter, was seen from Day 5 to Day 8 after test material instillation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 12 days

Remarks on result:

other: associated with iridic swelling and/or circumcorneal hyperaemia in the iris, and on a number of days with an oval pupil

Irritation parameter:

iris score

Basis:

animal #1

Time point:

48 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 12 days

Remarks on result:

other: associated with iridic swelling and/or circumcorneal hyperaemia in the iris, and on a number of days with an oval pupil

Irritation parameter:

iris score

Basis:

animal #1

Time point:

72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 12 days

Remarks on result:

other: associated with iridic swelling and/or circumcorneal hyperaemia in the iris, and on a number of days with an oval pupil

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 9 days

Remarks on result:

other: associated with iridic swelling and/or circumcorneal hyperaemia in the iris, and on a number of days with an oval pupil

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 11 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 9 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24 h

Score:

1

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Corneal lesions, grade 1 or 2 in animal #1 and grade 1 in #2 were seen from 1 hour (Day 0) or 24 hours after test material instillation (Day 1) and had entirely disappeared by Day 16 in animal #1 and by Day 14 in animal #2. On a number of consecutive days, a lesion of the superficial epithelium of the cornea, ca. 3 mm in diameter, was recorded in each animal.

Swelling of the iris (grade 1) was evident in animal #1 from 48 hours until 11 days after test material instillation and in animal #2 from 1 hour until 8 days after instillation and associated with circumcorneal hyperaemia in the iris in animal #1 for 5 days and animal #2 for 4 days. The observation of an oval appearance of the pupil seen on a number of days in each animal was considered to be related to iris swelling.

In addition to the findings specified above and under "Overall irritation/corrosion results", conjunctival redness grade 1 and chemosis grade 2 followed by grade 1 were also seen in both animals at 1 and 24 hours after instillation, and on some occasions, mucous secretion from the eye was recorded.

All ocular findings seen in the present study were fully reversible. Control eyes (untreated) were without ocular findings throughout the observation period.

Other effects:

Mortality or signs of systemic toxicity were not evident and bodyweight was unaffected by treatment with the test material.

Interpretation of results:

other: irritating to eyes

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In eye irritation key study 1, classification has been based on the readings at 48, 72 and 96 hours after test material instillation, as during this time period the overall mean severity grade for iris lesion was higher than during 24 to 72 hours after instillation. In both animals the grades of corneal opacity and conjunctival redness and in animal #1 that of chemosis remained unchanged by this time shift. In animal #2, chemosis grade 1 at 24 h after instillation was followed by grade 0 thereafter.

Justification for selection of eye irritation endpoint:

Two in vivo eye irritation studies were selected as key studies, as adequate classification for eye irritation necessitated both of them. Endpoint study record "7.3.2 Eye irritation: in vivo_Eye_irrit_rabbit_KE_1549 SR” has been the most critical available eye irritation study with octane-1,2-diol, and both, this study and the study summarised in endpoint study record “in vivo_Eye irrit_rabbit_LPT_79_0026” are the only available eye irritation studies in which neat octane-1,2-diol was tested. In all other available eye irritation studies, dilutions containing ≤ 10 % of octane-1,2-diol were tested.

Effects on eye irritation: irritating

Justification for classification or non-classification

In view of the absence of any effects on clipped intact and clipped abraded skin treated for 24 hours with neat octane-1,2 -diol (key study) and the absence of relevant skin irritation findings in all other available skin irritation studies (supporting studies), classification regarding skin irritation or corrosion according to EU classification rules [REGULATION (EC) 1272/2008] is unnecessary.

 

The incidence and severity of iris lesions and/or corneal opacity attained in Key Study 1 of the in vivo eye irritation studies with neat octane-1,2 -diol necessitates classification as “Category 2 (irritating to eyes)" [REGULATION (EC) 1272/2008]. Although in Key Study 1 the eyes were rinsed with deionised water for removal of residual test material already at 1 hour after test material instillation, classification as "Risk of serious damage to eyes (R41)" suggested by ECETOC 1997 or consequently as "Category 1 (irreversible effects on the eye)" has been considered to be inappropriate by the author of this end point summary, because in Key Study 1 all ocular findings were of limited severity and fully reversible and in Key Study 2, instillation of neat octane-1,2–diol to eyes of six rabbits (eyes apparently not rinsed after treatment) did not induce an incidence or severity of ocular lesions warranting any classification or labelling according to the EU classification rules.

 

Reference:

ECETOC 1997, ECETOC Document No.37, EC Classification of Eye Irritancy.