Registration Dossier

Administrative data

Description of key information

Skin irritation: The test material produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin.
Eye irritation: The test material produced a maximum group mean score of 4.7 and was classified as aminimal irritant (Class 3 on a 1-8 scale) to rabbit eye according to a modified Kay and Chalandra classification system. The test material did not meet the criteria for classification as irritant according to EU regulations and according to GHS classification.

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:
1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted using OECD guidelines
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Three rabbits were supplied by David Percival Ltd, Moston, Sandbach, Cheshire UK.
Weight at the start of the experiment: 2.67-3.02 kg; 12-16 weeks old.
After minimum acclimatisation of 5 days each animal was given a number.
The animals were housed individually in suspended metal cages, with free access to drinking water and food.
The animal room was maintained at a temperature of 17-19°C and relative humidity of 45-50%.
The air exchange was approx. 15 changes per hr and the lighting was controlled by a time switch to give 12 hr continous light and 12 hr darkness.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
0.5 gr of test material moistened with 0.5 ml of distilled water was applied
Duration of treatment / exposure:
4 hr
Observation period:
The sites were examined approx. 1, 24, 48 and 72 hr following the removal of the patches.
Number of animals:
3
Details on study design:
On the day before the test each rabbit was clipped free of fur from the dorsal flank area using vetrinary clippers.
On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5g of test material moistened with o.5 ml of distilled water, was introduced under 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin.
the patch was secured in position with a surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabitt was wrapped in an elastic corset, and the animals were returned to their cages for the duration of the exposed period.
Four hr after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool and soaked in distilled water.
Approx. 1 hr following the removal of the patches and 24, 48 and 72 hr later the test sites were examined for evidance of primary irritation and scored according to the scale from Draze JH (1977).


Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal #1
Time point:
other: 1, 24, 48 and 72 hr
Score:
0
Remarks on result:
other: Erythema/Eschar formation/Oedema formation
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal #2
Time point:
other: 1, 24, 48 and 72 hr
Score:
0
Remarks on result:
other: Erythema/Eschar formation/Oedema formation
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal #3
Time point:
other: 1, 24, 48 and 72 hr
Score:
0
Remarks on result:
other: Erythema/Eschar formation/Oedema formation
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material produced a primary irritation index of 0.0 and was classified as NON-IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
Executive summary:

Acute dermal irritation study was conducted on New Zealand White rabbits under OECD guideline 404 and EU method B4. A single 4 hr, semi-occluded application of the test material to the intact skin of 3 rabbits produced no evidence of skin irritation. The test material produced a primary irritation index of 0.0 and was classified as NON-IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

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
Study period:
1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted under OECD guidelines
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Three rabbits were supplied by David Percival Ltd, Moston, Sandbach, Cheshire UK.
Weight at the start of the experiment: 3.28-3.49 kg; 12-16 weeks old.
After minimum acclimatisation of 5 days each animal was given a number.
The animals were housed individually in suspended metal cages, with free access to drinking water and food.
The animal room was maintained at a temperature of 17-19°C and relative humidity of 49-640%.
The air exchange was approx. 15 changes per hr and the lighting was controlled by a time switch to give 12 hr continous light and 12 hr darkness.
Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye remained untreated and was used as control
Amount / concentration applied:
98 mg per 0.1 ml
Duration of treatment / exposure:
The test material was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after application, to prevent loss of material and then released. Immediately after administration of the test material an assessment of the initial pain reaction was made.
In orded to minimise pain on application of the test materail, one drop of local anasthetic was instilled into both eyes of all animals 1-2 minutes before treatment.
Observation period (in vivo):
Assessment of ocular damage/irritation was made approx. 1, 24, 48 and 72 hr following treatment.
Number of animals or in vitro replicates:
Three animals
Details on study design:
The numerical values corresponding to each animal, tissue and observation time was recorded. The data relating to the conjunctivae were designated by the letters A (redness), B (chemosis),and C (discharge), those relating to the iris designated by the letter D and those relating to the cornea by the letter E (degree of opacity) and F (area of opacity). For each tissue the score was calculated as follows:
Score for conjunctivae = (A+B+C) x 2
Score for iris = D x 5
Score for cornea = (E x F) x 5
Using the numerical data obtained a modified version of the system described by Kay JH and Calandra JC (1962) j. Soc. Cosmet. Chem.
was used to classify the ocular irritancy potential of the test material. This was achived by adding together the scores for the cornea, iris and conjunctivae for each time point for each rabbit. The group means of the total scores for each observation were calculated. The highest of these group means together with the persistence of the reactions enabled classification of the eye irritancy potential of the test material.
If any rabbit shows irrevesrsible ocular damage the test material will be classified as corrosive to the eye.
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 72
Score:
4.7
Reversibility:
not specified
Irritant / corrosive response data:
Minimal conjunctival irritation was noted in all treated eyes one hr after treatment and in one treated eye at 24 hr observations.
Treated eyes appeared normal at the 24 or 48 hr observations
Other effects:
No corneal or iridial effects were noted during the study.
Interpretation of results:
slightly irritating
Remarks:
Migrated information Class 3 on a 1-8 scale Criteria used for interpretation of results: EU
Conclusions:
The test material produced a maximum group mean score of 4.7 and was classified as MINIMAL IRRITANT (CLASS 3 ON A 1 TO 8 SCALE) to the rabbit eye according to a modified Kay and Calandra classification system.
The test material did not produce positive criteria in any rabbit according to the EU labelling regulations. No symbol and risk phrase are therefore required.
Executive summary:

Acute eye irritation test was conducted in New Zealand White rabbits using OECD guidelines 405 and method B5 of the commission Directive 92/69/EEC.

A single application of the test material to the non-irrigated eye of three rabbits produced minimal conjunctival irritation. Treated eyes appeared normal at the 24 or 48 hr observations.

The test material produced a maximum group mean score of 4.7 and was classified as MINIMAL IRRITANT (CLASS 3 ON A 1 TO 8 SCALE) to the rabbit eye according to a modified Kay and Calandra classification system.

The test material did not produce positive criteria in any rabbit according to the EU labelling regulations. No symbol and risk phrase are therefore required.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation: The test material produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin.

Eye irritation: The test material produced a maximum group mean score of 4.7 and was classified as aminimal irritant (Class 3 on a 1-8 scale) to rabbit eye according to a modified Kay and Chalandra classification system. The test material did not meet the criteria for classification as irritant according to EU regulations and according to GHS classification.


Justification for selection of skin irritation / corrosion endpoint:
Experimntal stuy available

Justification for selection of eye irritation endpoint:
The test material produced a maximum group mean score of 4.7 and was classified as aminimal irritant (Class 3 on a 1-8 scale) to rabbit eye according to a modified Kay and Chalandra classification system.

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

The maximum group mean score of 4.7. Based ont he experimental results of the Acute skin and eye irritation studies and according to the EEC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC, 27th April 1993), FR-720 does not have to be classified for skin or eye irritation and has no obligatory labelling requirement for skin irritation or eye irritation and the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No.1272/2008.