[No public or meaningful name is available]

Endpoint summary

Description of key information

Skin irritation in vivo: application of 0.5 ml, undiluted, onto shaved skin of 3 young albino rabbits, occlusive, 4h exposure: not irritating to the skin (OECD 404, GLP)

Eye irritation in vivo: application of 0.1 ml, undiluted, into conjunctival sac of 3 albino rabbits, 24h exposure: not irritating to the eyes (OECD 405, GLP)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Remarks:

in vivo study was conducted prior to REACH implementation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994-12-08 - 1994-12-19 (experimental phase)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

OECD-Guideline for Testing of Chemicals, Section 4, 404 "Acute Dermal Irritation / Corrosion", adopted July 17, 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

other: Albino

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. Zimmermann, Schweizer Hof, D-73453 Untergröningen/Aalen
- Age at study initiation: young
- Housing: The rabbits housed individually in wire grating cages (area 2450 cm², height 42 cm) without bedding.
- Diet (e.g. ad libitum): Raiffeisen-Ringfutter, Kaninchen Trockenfutter 52/P, Raiffeisen Kraftfutterwerk Kehl, ad libitum.
- Water (e.g. ad libitum): Community tap water from Karlsruhe; free access for the animals by daily changing of the watering-bottles.
- Acclimation period: The animals were acclimated to the test conditions for 5 days prior to the administration.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23 ° C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES:
Acclimatization: December 08 1994 - December 12, 1994
Administration: December 13 1994
Observation: December 13,1994 - December 19 1994

Type of coverage:

occlusive

Preparation of test site:

shaved

Remarks:

On the fifth day the dorsal area of the trunk was shaved in an area of 3 x 5 cm².

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml / animal
- Concentration (if solution): undiluted

Duration of treatment / exposure:

4h

Observation period:

1 week

Number of animals:

3 animals, Identification numbers: 009 (male), 015 and 022 (female)

Details on study design:

TEST SITE
- Area of exposure: The test substance was dermally applied in a single dose of 0.5 ml/animal onto the dorso-lumbar region of 3 albino rabbits.
- Type of wrap if used: The region treated was protected with the non-stripped, non-irritating plastic material of the reverse of a patch (width 6 cm) (Werovil, No. 15 00 20 WERO-MEDICAL, D-65232 Taunusstein). It was held in place for a period of 4 hours by an occlusive bandage made from a dressing (width 8 cm, with selvages, coated completely with cellophane) (No. 09 00 22 WERO-MEDICAL). The bandage was fixed with 1.25 cm broad strips of Adhesive Tape ST (WERO-MEDICAL).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After removal of the bandage at the end of the exposure period the residual test substance was removed by gently washing with water.
- Time after start of exposure: 4h

OBSERVATION TIME POINTS
1 hour after bandage removal, then daily

SCORING SYSTEM:
- Method of calculation: Evaluation of the Skin Reaction according to table 1 in OECD-Guideline 404

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: day 4 or 5

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

other:

Remarks:

no animal showed any signs of edema

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

Rabbit 015 female

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: day 4 or 5

Remarks on result:

other:

Remarks:

Erythema score was 0 after 1h, each 1 at day 1, 2, and 3, and 0 at day 5 and 6

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

Rabbit 022 female

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

Rabbit 009, male

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: day 4 or 5

Remarks on result:

other:

Remarks:

Erythema score was 0 after 1h, each 1 at day 1, 2, and 3, and 0 at day 5 and 6

Irritant / corrosive response data:

After removing the occlusive bandage after a period of 4 hours, the exposure area was washed and cleaned with water. In the following observation period a dermal irritation of the exposure area in the form of an erythema (two rabbits) was noticed.
The control area did not show any pathological skin reaction. According to table 1 of OECD-Guideline 404 at all times of evaluation the value was classified as 0.

Under the conditions of this experiment the test substance produced skin lesions in the form of an erythema. Two rabbits showed this effect estimated at grade 1 (maximum possible 4). The erythemata were observed from day 1 to day 3. No oedema could be observed during the observation period. The effects observed turned out to be reversible.

Other effects:

Mortality: After the dermal administration of 0.5 ml test item per animal for a period of 4 hours none of the 3 rabbits died during the experiment.
Toxicological symptoms: During the observation period of 6 days none of the animals showed signs of toxicological symptoms.
Behaviour: The reaction of the rabbits treated was quiet and watchful. The behaviour pattern was not different to that of other rabbits which were not in the test.
Body weight: During the experiment the body weight of all three rabbits had an increase.

Interpretation of results:

GHS criteria not met

Conclusions:

This study was performed in compliance with OECD-Guideline 404 under GLP, is well-documented and with sufficient information for classification, the results can hence be considered as reliable. Under the conditions of this experiment the test substance produced skin lesions in the form of an erythema. Two rabbits showed this effect estimated at grade 1 (maximum possible 4). The erythemata were observed from day 1 to day 3. No oedema could be observed during the observation period. The effects observed turned out to be reversible. According to Regulation 1272/2008, a substance must be classified as skin irritant Cat. 2, if i.a.
(1) Mean value of ≥ 2,3 - ≤ 4,0 for erythema/eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or
(2) Inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling;
Those criteria are not met here, and so the substance does not need to be classified as irritating to the skin.

Executive summary:

This study was performed in compliance with OECD-Guideline 404 "Acute Dermal Irritation/Corrosion" with three albino rabbits under GLP.

Under the conditions of this experiment the test substance produced skin lesions in the form of an erythema. Two rabbits showed this effect estimated at grade 1 (maximum possible 4). The erythemata were observed from day 1 to day 3. No oedema could be observed during the observation period. The effects observed turned out to be reversible.

During the experiment all three rabbits had an increase in weight.

Visible toxicological signs could not be observed; none of the animals died during the observation period.

GHS criteria are not met, the substance does not need to be classified as irritating to the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Remarks:

in vivo study was conducted prior to REACH implementation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-01-05 - 1995-01-16 (experimental phase)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

OECD-Guideline for Testing of Chemicals 405 "Acute Eye Irritation / Corrosion", adopted February 24, 1987.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

other: Albino

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dr. Zimmermann, Schweizer Hof, D-73453 Untergröningen/Aalen
- Housing: The rabbits housed individually in wire grating cages (area 2450 cm², height 42 cm) without bedding.
- Diet (e.g. ad libitum): Raiffeisen-Ringfutter, Kaninchen Trockenfutter 52/P, Raiffeisen Kraftfutterwerk Kehl, ad libitum.
- Water (e.g. ad libitum): Community tap water from Karlsruhe; free access for the animals by daily changing of the watering-bottles.
- Acclimation period: The animals were acclimated to the test conditions for 5 days prior to the administration.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22 ° C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES:
Acclimatization: January 05, 1995 - January 09, 1995
Administration: January 10, 1995
Observation: January 10, 1995 - January 16, 1995

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:

24 h

Observation period (in vivo):

1 week

Number of animals or in vitro replicates:

3 animals, Identification numbers: female: 002, male: 007 and 008

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): 24 h after administration the eye was carefully rinsed with NaCl 0.9 % in order to remove the residual test substance.

SCORING SYSTEM: according to table 1 of OECD-Guideline 405

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

identical in all three animals

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: n/a

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

identical in all three animals

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: n/a

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

No. 002, female

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: day 3

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

No. 007, male

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: day 2

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

No. 008, male

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: day 2

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

No. 002, female

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: day 2

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

No. 007, male

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: day 2

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

No. 008, male

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: day 2

Irritant / corrosive response data:

EYE REACTION
The test substance was applied undiluted in a dose of 0.1 ml into the right eye to each of 3 albino rabbits.
After evaluation of the eye reaction according to table 1 of the OECD-Guideline 405, all three rabbits developed the diffuse, crimson colour of the conjunctivae. Individual vessels were not easily discernible. These effects were estimated at grade 2 (maximum possible 3). Hyperemic blood vessels were not observed any more on day 2 (rabbit No. 007 and 008) or on day 3 (rabbit No. 002).
Furthermore, all three animals showed swelling of lids. This effect was estimated at grade 3 (rabbit No. 002) or at grade 2 (rabbit No. 007 and 008) (maximum possible 4). Swelling of lids was not observed any more on the 48th hour.
No rabbit showed any exsudation after administration and during the observation period.
Irritations and lesions of cornea or iris could not be observed.
The effects on conjunctivae attributed to the test item are reversible which was revealed by the last four days of the observation period.
In the untreated left eye which was used as control pathological symptoms could not be noted.

Other effects:

- Other observations:

MORTALITY/TOXICOLOGICAL SYMPTOMS
After the administration of 0.1 ml test substance into the right eye none of the treated rabbits died during the experiment and observation period. Toxicological symptoms could not be observed.

BEHAVIOUR
The general behaviour of the rabbits treated was quiet and watchful. The behaviour pattern was not different to that of other rabbits which were not in the test.

BODY WEIGHT
During the experiment the body weight of all three rabbits increased.

Interpretation of results:

GHS criteria not met

Conclusions:

This study was performed in compliance with OECD-Guideline 405 under GLP, is well-documented and with sufficient information for classification, the results can hence be considered as reliable.
After evaluation of the eye reaction according to table 1 of the OECD-Guideline 405, all three rabbits developed the diffuse, crimson colour of the conjunctivae. Individual vessels were not easily discernible. These effects were estimated at grade 2 (maximum possible 3). Hyperaemic blood vessels were not observed any more on day 2 (rabbit No. 007 and 008) or on day 3 (rabbit No. 002).
Furthermore, all three animals showed swelling of lids. This effect was estimated at grade 3 (rabbit No. 002) or at grade 2 (rabbit No. 007 and 008) (maximum possible 4). Swelling of lids was not observed anymore on the 48th hour.
Irritations and lesions of cornea or iris could not be observed.
According to Regulation 1272/2008, a substance must be classified as eye irritant Cat. 2, if, when applied to the eye of an animal, a substance produces:
— at least in 2 of 3 tested animals, a positive response of:
— corneal opacity ≥ 1 and/or
— iritis ≥ 1, and/or
— conjunctival redness ≥ 2 and/or
— conjunctival oedema (chemosis) ≥ 2
— calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days
Those gradings were not observed in the test. Cornea opacity score and Iris score were zero in all animals and all observation time points. Conjunctivae redness scores, mean over 24, 48, and 72h, were 1.0, 0.33, and 0.33 in the individual animals, and chemosis scores were each 0.33.
So, the criteria set out in Regulation 1272/2008 are not met here, and the substance does not need to be classified as irritating to the eyes.

Executive summary:

This experiment was performed as an "Acute Eye Irritation/Corrosion"-study in compliance with the OECD-Guideline for Testing of Chemicals 405 under GLP. The test substance was applied undiluted in a single dose of 0.1 ml into the right eye to each of 3 albino rabbits.

After evaluation of the eye reaction according to table 1 of the OECD-Guideline 405, all three rabbits developed the diffuse, crimson colour of the conjunctivae. Individual vessels were not easily discernible. These effects were estimated at grade 2 (maximum possible 3). Hyperaemic blood vessels were not observed any more on day 2 (rabbit No. 007 and 008) or on day 3 (rabbit No. 002)

Furthermore, all three animals showed swelling of lids. This effect was estimated at grade 3 (rabbit No. 002) or at grade 2 (rabbit No. 007 and 008) (maximum possible 4). Swelling of lids was not observed any more on the 48th hour.

Irritations and lesions of cornea or iris could not be observed.

Cornea opacity score and Iris score were zero in all animals and all observation time points. Conjunctivae redness scores, mean over 24, 48, and 72h, were 1.0, 0.33, and 0.33 in the individual animals, and chemosis scores were each 0.33.

Under the conditions of this experiment the test substance did not cause mortality. Toxicological symptoms could not be noted.

All symptoms observed turned out to be reversible.

The left eye was not treated and was used for control. Symptoms of eye irritation did not occur on this eye.

During the experiment all three animals had a weight gain.

GHS criteria are not met, the substance does not need to be classified as irritating to the eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

According to Regulation 1272/2008, a substance must be classified as skin irritant Cat. 2, if i.a.

(1) Mean value of ≥ 2,3 - ≤ 4,0 for erythema/eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or

(2) Inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling;

The test substance produced skin lesions in the form of an erythema. Two rabbits showed this effect estimated at grade 1 (maximum possible 4). The erythemata were observed from day 1 to day 3. No oedema could be observed during the observation period. The effects observed turned out to be reversible.

 

According to Regulation 1272/2008, a substance must be classified as eye irritant Cat. 2, if, when applied to the eye of an animal, a substance produces:

— at least in 2 of 3 tested animals, a positive response of:

—corneal opacity≥1 and/or

—iritis≥1, and/or

—conjunctival redness≥2 and/or

—conjunctival oedema (chemosis)≥2

— calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days.

Cornea opacity score and Iris score were zero in all animals and all observation time points. Conjunctivae redness scores, mean over 24, 48, and 72h, were 1.0, 0.33, and 0.33 in the individual animals, and chemosis scores were each 0.33.

 

So, the criteria set out in Regulation 1272/2008 are not met here, and so the substance does not need to be classified as irritating to the skin or eyes.