Registration Dossier

Administrative data

Description of key information

The substance is not irritating for intact and abraded rabbit skin.
The substance is not irritating for rabbit eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
An in vitro skin irritation study does not need to be conducted because adequate data from an in vivo study are available.
Type of information:
other: read across from supporting substance
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: "Hazardous Substances Regulations" under the U.S. Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965).
GLP compliance:
no
Remarks:
Study conducted before 1981
Control samples:
yes, concurrent no treatment
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Porton
- Age at study initiation: 9-15 weeks
- Weight at study initiation: 2.44 Kg (♂), 2.10 kg (♀)
- Housing: Bred oh the premises and maintained under a semi-barrier system.
- Diet: A commercial irradiated diet (Styles-Oxoid) was fed ad lib.
- Water: Sterile filtered water was available at all times.
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1°C
- Humidity (%): 50-70 %
- Photoperiod (hrs dark / hrs light): Animals were exposed to artificial light for 10 hours daily from 08:00 - 18.00 hours.
Type of coverage:
not specified
Preparation of test site:
other: shaved and abraded
Vehicle:
water
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 10 g of the test compound was mixed with 10 ml of water to make a solution of 15 ml, 0.75 ml of which was applied to each test site
Duration of treatment / exposure:
24 hours
Observation period:
24 and 72 hours
Number of animals:
Six rabbits (5 ♂ and 1 ♀)
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: 10 % of the total body surface.
- Type of wrap if used: The site were covered with aluminium foil secured with "Sleek" adhesive tape. The test sites were then enclosed by a 6" wide "Coban" self adhesive bandage the edges of which were fixed to the skin by strips of "Sleek" in order to retain the test substance in close contact with the skin.

SCORING SYSTEM: Draize et al.
Irritation parameter:
erythema score
Basis:
animal: 11, 12, 13, 14, 15
Time point:
other: mean score after 24, 48 and 72 hours
Score:
ca. 0
Max. score:
4
Reversibility:
other: no skin reaction observed
Remarks on result:
other: shaved skin
Irritation parameter:
erythema score
Basis:
animal: 16
Time point:
other: mean score after 24, 48 and 72 hours
Score:
ca. 0.66
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
animal: 11, 12
Time point:
other: Mean score after 24 ,48 and 72 hours
Score:
ca. 0.66
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
animal: 14, 16
Time point:
other: mean score after 24, 48 and 72 hours
Score:
ca. 0
Max. score:
4
Reversibility:
other: no skin reaction observed
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
animal: 13
Time point:
other: mean score after 24, 48 and 72 hours
Score:
ca. 1.33
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
animal: 15
Time point:
other: Mean score after 24, 48 and 72 hours
Score:
ca. 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: shaved skin
Irritant / corrosive response data:
The value assessed at 24 hours was used also for 48 hours in a protective manner because no observation was made at 48 hours after the beginning of test.

Slight erythema and very slight to moderate oedeme was seen in 2/6 and 6/6 rabbits respectively, 24 hours after application of the compound. Very slight oedema was still present on 1/6 abraded sites at 72 hours.

Interpretation of results:
other: Not classified according to the CLP Regulation (EC n. 1272/2008)
Conclusions:
The substance is not irritating for skin rabbit.
Executive summary:

The substance has been tested for skin irritation according to the method "Hazardous Substances Regulations" under the U.S. federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965). During the test 5 male and 1 female rabbits are tested with 10 g of test item on shaved and abraded skin after 24 hours of patch treatment. Under the conditions of the present experiment the substance was considered to be not irritant for rabbit skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation, other
Remarks:
An in vitro eye irritation study does not need to be conducted because adequate data from an in vivo study are available.
Type of information:
other: read across from supporting substance
Adequacy of study:
key study
Study period:
September 11, 1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
other: "Hazardous Substances Regulations" under the U.S.A. federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965)
Deviations:
not specified
GLP compliance:
no
Remarks:
Study conducted before 1981
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Strain: Porton strain
- Age at study initiation: 9-15 weeks old
- Weight at study initiation: 2.44 kgs. (♂) 30d 2.10 kgs. (♀)
- Housing: bred on the premises and maintained under a semi-barrier system
- Diet: A commercial irradiated diet (Styles-Oxoid) was fed ad libitum
- Water: Sterile filtered water was available at all times
- Acclimation period: one week prior to the start of the trial

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1°C
- Humidity (%): 50-70 %
- Photoperiod (hrs dark / hrs light): Animals were exposed to artificial light for 10 hours daily from 08.00-18.00 hours
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 100 mg
Duration of treatment / exposure:
Single injection
Observation period (in vivo):
The rabbits were examined 1, 24, 48 and 72 hours, 6, 10 and 14days after application of the test compound and for any further period that was considered necessary.
Number of animals or in vitro replicates:
5 male and 1 female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: yes, after 30 seconds the compound was, as far as possible, flushed out of the eye of three of the rabbits with warm water for 1 minute
Irritation parameter:
cornea opacity score
Basis:
animal: 14, 15, 16
Time point:
other: Mean score after 24, 48 and 72 hours
Score:
ca. 0
Max. score:
4
Reversibility:
other: no eye effect observed
Remarks on result:
other: Rinsed
Irritation parameter:
conjunctivae score
Basis:
animal: 14, 15
Time point:
other: Mean score after 24, 48 and 72 hours
Score:
ca. 1
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Rinsed
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 16
Time point:
other: Mean score after 24, 48 and 72 hours
Score:
ca. 1.33
Max. score:
3
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: Rinsed
Irritation parameter:
chemosis score
Basis:
animal: 14, 15
Time point:
other: Mean score after 24, 48 and 72 hours
Score:
ca. 0
Max. score:
4
Reversibility:
other: no eye effect observed
Remarks on result:
other: Rinsed
Irritation parameter:
chemosis score
Basis:
animal: 16
Time point:
other: Mean score after 24, 48 and 72 hours
Score:
ca. 0.66
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: Rinsed

A slight to mild conjunctival reaction was seen in all treated eyes one hour after application of the compound. Generally there was very little change by 24 hours and thereafter the reactions subsided slowly with 3/3 washed and 2/3 unwashed eyes returning to normal as follows:- 72 hours (2/3 washed eyes), 6 days (1/3 washed eyes) and 10 days (2/3 unwashed eyes). The remaining unwashed eye still showed a very slight reaction at the termination of the study on day 14. Staining of the conjunctivae by the compound was seen in all eyes for up to 48 hours in the washed eyes, 10 days for 2/3 unwashed eyes and the duration for the remaining eye.

A slight corneal reaction consisting of slight opacity and damage to the surface epithelium was seen in 2/3 unwashed eyes at 24 and 48 hours. Staining of the cornea by the compound was also seen in the unwashed eyes for up to 10 days for 2/3 and the duration for the remaining one.

Interpretation of results:
other: Not classified according to the CLP Regulation (EC n. 1272/2008)
Conclusions:
The substance is not irritating for rabbit eyes.
Executive summary:

The substance has been tested for eye irritation according to The method "Hazardous Substances Regulations" under the U.S. federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965). During the test 5 male and 1 female rabbits are treated with 100 mg of the test compound. After 14 days only one animal (n. 13) showed a redness score (1), nevertheless in order to evaluate the irritation potential of the test item this animal was not considerd because his eyes were not rinsed after application.

The substance is considered to be not irritant for rabbit eyes.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Test on skin and eye irritation are available on similar substance 1. The complete hypothesis and justification for the read across approach has been attached in section 13.

 

Skin irritation assessment:

The assessment was based on single study (Huntsman, 1975) according to the method of the U.S. Federal Hazardous Substances Labelling Act Sect. 191.11 (February 1965). During the study only one rabbit shows a signs of erythema on intact skin. Oedema formation was recorded with 4 rabbits from very slight to slight, but all signs of irritation are fully recovered within 72 hours.

No animal showed a mean value for erythema or edema reaction ≥ 2.3

 

Eye irritation assessment:

The assessment was based on single study (Huntsman, 1975) irritation according to the method of the U.S. Federal Hazardous Substances Labelling Act Sect. 191.12 (February 1965). During the study 5 male and 1 female rabbits were exposed to test article instilled into the conjunctival sac. After 30 seconds the compound was, as far as possible, flushed out of the eyes of three of the rabbits for one minute with warm water. At the end of the observation period (14 days) all the irritation effect were fully reversible except for one rabbit that showed a residual redness score (1).

Considering that the eye of the animal was not rinsed and the observation period has a duration of 14 days instead of 21 as reported in the CLP Regulation (EC n. 1272/2008), the score was not considered for the evaluation of the irritation potential according the CLP Regulation.

No animal showed a mean value ≥ 1 for corneal opacity, ≥ 2 for conjunctival redness or ≥ 2 for conjunctival opacity

 

Justification for classification or non-classification

According to the CLP Regulation (EC n. 1272/2008), skin Irritation means the production of reversible damage to the skin following the application of a test substance for up to 4 hours.

The substance shows a very low interaction between with the rabbit skin. The values of erythema and oedema are below the trigger values for classification, therefore no classification is warranted according to the CLP Regulation (EC n. 1272/2008).

According to the CLP Regulation (EC n. 1272/2008) eye irritation means the production of changes in the eye following the application of test substance to the anterior surface of the eye, which are fully reversible within 21 days of application.

The substance does not show eye effects with values above the trigger value for the classification. therfore the substance is not classified according to the CLP Regulation (EC n. 1272/2008).