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Description of key information

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
Study period:
2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no deviations from standard test guidelines and no methodological deficiences, which do not affect the quality of teh relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
On the day of treatment, the animals were 2 to 4 months old and had a mean body weight ± standard devition of 2.8 ± 0.4 kg.
Acclimatation: at least 5 days before the beginning of the study.
Identification : individual ear tag.

The conditions in the animal room were set as follows:
- temperature: 18±3°C
- relative humidity: 30 to 70%
- light/dark cycle: 12h/12h
The temperature and relative humidity were under continuous control and recording. In addition to these daily checks, the housing conditions and corresponding instrumentation and equipment were verified and calibrated at regular intervals.

The animals were housed individually in polystyrene cages (35 x 55 x 32 cm).
Each cage was equiped with a food container and a water bottle.

All the animals had free access to 110 C pelleted diet.
Food is analysed regularly by the supplier for composition and contaminant levels.

Drinking water filtered by a FG Millipore membrane (0.22 µm) was provided ad libitum.
Bacteriological and chemical analyses of water are performed regularly by external laboratories. These analyses include the detection of possible contaminants (pesticides, heavy metals and nitroamines).
No contaminants were known to have been present in the diet, drinking water or bedding material at levels which may be expected to have interfered with or prejudiced the outcome of the study.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: The left flank of each animal served as control
Amount / concentration applied:
Doses of 0.5 ml of the test item were placed on a 6 cm2 dry hydrophilic gauze pad, which then applied to the right flank of the animals.
Duration of treatment / exposure:
In first instance, duration of exposure was 4 hours on one flank on a single animal.

Since the test item was no irritant on the first animal, it was then applied for 4 hours to two other animals.
Observation period:
The skin was examined approximately 1 hour, 24, 48 and 72 hours after removal of the dressing.
SInce there was persistent irritation reactions at 72 hours, the observation period was extended to a maximum of 14 days (until day 15) in order to determine the progess of the lesions and their irreversibility.
Any change in the animals' behaviour was noted.
Number of animals:
One in fist instance and 2 for the second run.
Details on study design:
The day before treatment, both flanks of each animal were clipped using electric clippers and the skin of each animal was examined in order to check the absence of any signs of skin irritation.

The test item and the gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

The untreated skin served as control.

Subsequently, the dressings were removed and no residual test substance was oberved.

The animals were then replaced into their individual cages.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 h
Score:
2.7
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 h
Score:
3
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 h
Score:
2.7
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 h
Score:
2
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 h
Score:
3
Max. score:
4
Other effects:
From day 4, a dryness of the skin was observed at the treatment site for all 3 animals.
On day 15, a dryness of the skin persisted in 2 animals.
No ulceration or necrosis were noted.
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
As the mean scores for erythema, oedema for 2 out of 3 animals reached the criteria values for irritation, under our experimental conditions, n-Pentyl bromide was considered as irritant when administered by cutaneous route in rabbits.
Executive summary:

The skin irritation potential of the test material was determined according to the OECD 404 guidelines. Three rabbits were exposed to 0.5 ml of the test material for 4 hours, the site was them observed at intervals over a period of 15 days.

The mean scores over 24, 48 and 72 hours for indivudual animals were 3.7, 1.7 and 2.7 for erythema and 2.7, 0 and 2.7 for oedema.

Erytheam and oedema were reversible. From day 4, a dryness of the skin was observed at the treatment site.

The test material was determined to be irritating.

UnderRegulation 1272/2008 the test material should be classed as "Skin Irrit. 2" and assigned the hazard phrase "H315: Causes Irritation to the Skin" and signal word "Warning".

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no deviations from standard test guidelines and no methodological deficiences, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
At the start of the study the animals were in the weight range 2.0 to 3.5 kg and were twelve to twenty weeks of age.
After an acclimatization period of at least five days each animal was given a number unique within the study by indelible ink-marking on the inner surface of the ear and the cage label.

The animals were individualy housed in suspended cages.
Free access to mains drinking water and food was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

The temperature and relative humidity were set to acheive limits of 17 to 23°C and 30 to 70 % respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchenge was at least fifteen changes per hour and the ligjting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain anay contaminant of a level that might have affected the purpose or integrity of the study.
Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye served as control
Amount / concentration applied:
0.1 ml
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
Initially, a single rabbit was treated. A volume of 0.1 ml of the test material was placed into the conjonctival sac of the right eye, formed gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test material, an assessment of the initial pain reaction was made.
After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.
Assessment of ocular damage/irritation was made approximately 1 hourand 24, 48 and 72 hours following treatment.
Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophtalmoscope.
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 1 hour
Score:
10.7
Max. score:
110
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1 hour
Score:
10.7
Max. score:
80
Reversibility:
not fully reversible within: 72 hours
Irritant / corrosive response data:
Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24-hour observation. Minimal conjunctival irritation was noted in one treated eye at the 48-hour observation.
Two treated eyes appeared normal at the 48-hour observation while the remaining treated eye appeared normal at the 72-hour observation.
Other effects:
All animals showed expected gain in bodyweight during the study.
Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material produced a maximum group mean score of 10.7 and was classified as a mild irritant (class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.
Executive summary:

A single application of the test material to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. Two treated eyes appeared normal at the 48-hour observation while the remaining treated eye appeared normal at the 72-hour observation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
The two studies where conducted under GLP and according to OECD 404.
The study giving the greater effect is retained.

Justification for selection of eye irritation endpoint:
The two studies where conducted under GLP and according to OECD 404.
The study giving the greater effect is retained.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: moderately irritating

Justification for classification or non-classification