Registration Dossier

Administrative data

Description of key information

The key study (Murmann, P 1993) examined the potential of HAB to cause irritation to skin. The undiluted test substance (0.5 mL) was placed on the intact skin of 6 male rabbits for four hrs, and covered with a semi-occlusive patch. After four hrs, the test substance was removed with warm water. The animals were scored for signs of edema and erythema according to the Draize scale at 3/4, 24, 48, and 72 hrs. All animals showed signs of erythema (maximum score of 2) by the 3/4 hr observation. Five of the six animals also showed edema (maximum score of 2) at that reading as well. Erythema and edema persisted through the 72 hr reading, though by the 6 day reading only 2 animals showed signs of erythema, and one animal still showed signs of edema. By the day 8 reading, all signs of erythema and edema had resolved. At the 72 hr observation, one animal display yellowish, and drying and cracking skin. At the 6 day observation, this animal, along with 3 others showed shedding skin. By the 8 day observation, most of these animals still showed shedding skin, though it was healing. By the 10 day observation, all symptoms had resolved. Because symptoms were not fully resolved at the end of 72 hrs, the study was extended through 10 days after exposure. The primary irritation index was 1.25, and all symptoms were fully reversible. Therefore, HAB is not classified as a skin irritant according to CLP Regulation.

The key study (Murmann, P 1993) examined the potential of HAB to cause irritation to eyes. A 0.1 ml sample of undiluted test substance was placed in one eye of each of three male rabbits. The untreated eye served as control. The animals were examined for signs of irritation at 1, 24, 48, and 72 hours after application. All three animals showed signs of conjunctival erythema (score of 1) at the 1 hr observation. By the 48 hr observation, these symptoms had resolved in all but one animal. This animal continued to show irritation at the 72 hr observation. For this reason, the study was extended to determine the reversibility of the symptoms. At the next observation at day 6, symptoms had resolved in all animals. The mean irritation score was 0.55. Therefore, HAB is not classified as an eye irritant under CLP Regulation.

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:
October 5, 1992-December 18, 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Fa. Dr. Karl Thomae GmbH, Biberach
- Age at study initiation: adult
- Weight at study initiation: 2-3 kg
- Housing: singly in stainless steel cages, identified by ear tags
- Diet (e.g. ad libitum): Ssniff K4, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 degree C
- Humidity (%): 30-70%
- Air changes (per hr): 15 changes/hr
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark


IN-LIFE DATES: From: December 12, 1992 To: December 18, 1992
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
There was one intact skin test site per animal. Each test site was treated with 0.5 mL of undiluted test material.
Duration of treatment / exposure:
4 hrs
Observation period:
Observations for dermal irritation and defects occurred at 3/4, 24, 48, and 72 hours, and 6, 8, and 10 days after the occlusion period.
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: dorsal
- Type of wrap if used: Aesculap Favorita II


REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with warm water
- Time after start of exposure: 4 hrs


SCORING SYSTEM: Draize
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24, 48, and 72 hrs
Score:
1.25
Irritant / corrosive response data:
All animals showed signs of erythema (maximum score of 2) by the 3/4 hr observation. Five of the six animals also showed edema (maximum score of 2) at that reading as well. Erythema and edema persisted through the 72 hr reading, though by the 6 day reading only 2 animals showed signs of erythema, and one animal still showed signs of edema. By the day 8 reading, all signs of erythema and edema had resolved. At the 72 hr observation, one animal display yellowish, and drying and cracking skin. At the 6 day observation, this animal, along with 3 others showed shedding skin. By the 8 day observation, most of these animals still showed shedding skin, though it was healing. By the 10 day observation, all symptoms had resolved.

Results of Skin Irritation Study

Animal

1

2

3

4

5

6

Erythema

¿ hr

2

1

2

1

2

2

24 hrs

2

2

1

2

2

1

48 hrs

2

2

1

1

2

1

72 hrs

3

2

1

2

3

1

6 days

2

0

0

0

1

0

8 days

0

0

0

0

0

0

10 days

0

0

0

0

0

0

Edema

¿ hr

1

1

2

1

1

0

24 hrs

1

1

1

1

1

0

48 hrs

1

1

0

1

1

0

72 hrs

2

1

0

1

1

0

6 days

1

0

0

0

0

0

8 days

0

0

0

0

0

0

10 days

0

0

0

0

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
The primary irritation index was 1.25 and all symptoms were fully reversible within 14 days. The test substance is not classified as a skin irritant according to EU GHS guidelines.
Executive summary:

This study examined the potential of the test substance to cause irritation to skin. The test substance was placed on the skin of 6 male rabbits for 4 hrs, and covered with a semi-occlusive patch. After 4 hrs, the test substance was removed with warm water. The animals were scored for signs of edema and erythema according to the Draize scale at 3/4, 24, 48, and 72 hrs. Because symptoms were not fully resolved at the end of 72 hrs, the study was extended through 10 days after exposure. Signs of erythema (maximum score of 2) and edema (maximum score of 2) were seen at the 3/4 hr observation. These symptoms were fully resolved by the day 8 observation. Signs of discoloration, drying and cracking were seen starting at the 72 hr observation. By the day 10 observation, all of these symptoms were resolved as well. The primary irritation index was 1.25, and all symptoms were fully reversible. The test substance is therefore not classified as a skin irritant according to EU GHS guidelines.

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:
1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Fa. Dr. Karl Thomae GmbH, Biberach
- Age at study initiation: adult
- Weight at study initiation: 2-3 kg
- Housing: individually in stainless steel cages, identified by ear tags
- Diet (e.g. ad libitum): Ssniff K 4, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 degree C
- Humidity (%): 30-70%
- Air changes (per hr): 15 air changes/hr
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark


IN-LIFE DATES: From: Oct. 19, 1992 To: Oct. 26, 1992
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye was used as control.
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:

24 hrs
Observation period (in vivo):
Readings were taken at 1, 24, 48, and 72 hours, and 6 days after the application.
Number of animals or in vitro replicates:
3
Details on study design:
A single application to the conjunctival sac of the right eyelid. The substance was not washed out.

SCORING SYSTEM: Draize


TOOL USED TO ASSESS SCORE: fluorescein stain
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 24, 48, and 72 hrs
Score:
0.55
Reversibility:
fully reversible within: 6 days
Irritant / corrosive response data:
All three animals exhibited conjunctival erythema (score of 1) at the 1 hr reading and through the 24 hr reading. By the 48 hr reading, these symptoms had resolved in all but one animal. This animal continued to show conjunctival erythema through the 72 hr reading, but by the day 6 reading, its symptoms had resolved as well.

Results of Eye Irritation Study

Animal

1 hr

24 hr

48 hr

72 hr

6 days

1

Conjunctiva - Erythema

1

1

1

1

0

Conjunctiva ¿ Chemosis

0

0

0

0

0

Iris

0

0

0

0

0

Cornea

0

0

0

0

0

2

Conjunctiva - Erythema

1

1

0

0

0

Conjunctiva ¿ Chemosis

0

0

0

0

0

Iris

0

0

0

0

0

Cornea

0

0

0

0

0

3

Conjunctiva - Erythema

1

1

0

0

0

Conjunctiva ¿ Chemosis

0

0

0

0

0

Iris

0

0

0

0

0

Cornea

0

0

0

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance is not classified as an eye irritant according to EU GHS guidelines.
Executive summary:

This study examined the potential of the test substance to cause irritation to eyes. 0.1 ml of test substance was placed in one eye of three male rabbits. The untreated eye served as control. The animals were examined for signs of irritation at 1, 24, 48, and 72 hours after application. All three animals showed signs of conjunctival erythema (score of 1) at the 1 hr observation. By the 48 hr observation, these symptoms had resolved in all but one animal. This animal continued to show irritation at the 72 hr observation. For this reason, the study was extended to determine the reversibility of the symptoms. At the next observation at day 6, symptoms had resolved in all animals. The mean irritation score was 0.55. The test substance is not classified as an eye irritant under EU GHS guidelines.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

HAB is not irritating to the skin or eyes of laboratory animals; inhalation is not a relevant route of exposure.


Justification for selection of skin irritation / corrosion endpoint:
Key guideline study reports experimental data.

Justification for selection of eye irritation endpoint:
Key guideline study reports experimental data.

Justification for classification or non-classification

HAB is not irritating to the skin or eyes of laboratory animals in a GLP study; inhalation is not a relevant route of exposure.