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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985/07/11 - 1985/07/31
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable well-documented study report which meets basic scientific principles: GLP.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
skin irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1985/07/11 - 1985/07/31
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable well-documented study report which meets basic scientific principles: GLP.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose:
read-across source
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
occlusive dressing used; 24 hour exposure
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles Rivers UK Ltd
-Sex: Male (10); Female (10)
- Age at study initiation: 6 weeks
- Weight at study initiation: Male: 125-135g; Female: 110-115g
- Housing: individually housed
- Diet (e.g. ad libitum): No. 1, expanded pelleted maintenance diet for rats and mice from Special Diet Services Ltd., ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6-day acclimatisation


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25
- Humidity (%): 58-90
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
Amount(s) applied (volume or weight): 2.0 ml
Concentration (if solution): neat
Duration of treatment / exposure:
On the day prior to application the trunk of each animal was clipped free of hair. For each treated animal, 2 mL/kg of BP83HF was applied to a patch of absorbent paper. The patch was applied to the trunk and held in place beneath a sleeve under a Poroplast bandage. The whole patch assembly was held in place with tape. The patches were left in position for approximately 24 hours. Patches were similarly applied to control animals with the omission of test material. To prevent the animals from gaining access to the sites of application (and hence possibly ingesting traces of test material), collars were applied around the animals heads for a further 24 hours (control and test animals).
Observation period:
Once per day for 14 days
Number of animals:
Control: (5) males; (5) female
2 ml/kg (converted 1.7 g/kg): (5) males; (5) females
Details on study design:
SCORING SYSTEM: Draize scale
- Dermal response observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
2
Max. score:
2
Reversibility:
fully reversible
Remarks:
after 72 hours
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
ca. 2
Max. score:
2
Reversibility:
fully reversible
Remarks:
after 72 hours
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
ca. 0.2
Max. score:
2
Reversibility:
fully reversible
Remarks:
after 72 hours
Remarks on result:
other: Only one female rabbit displayed an erythema score of 2.0 at the 72 hour observation. Reversed in all other 9 animals.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 1.35
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Irritant / corrosive response data:
There were no animal deaths prior to study termination. Well-defined erythema was noted upon removal of the test patches in all animals exposed to BP83HF, generally persisting for a further 24 hours. Scab formation was subsequently observed on Day 5 and skin flaking was noted on Day 6 in all treated animals, persisting for a few days only in most animals. Plaster marks were noted on all test and control animals following patch removal; this is an artifact of the test procedure and is commonly seen in studies of this type. No other significant signs of ill health, behavioral change or reaction to treatment were noted.
Other effects:
The body weight gain of male rats was unaffected by treatment with the test material. A marginally larger overall weight gain was recorded for treated female rats when compared with the controls; this was considered to have arisen fortuitously and not related to treatment with BP83HF.

Post mortem examination of all animals killed at termination revealed an area of diffuse subcutaneous haemorrhage beneath the dorsal patch site in one male exposed to BP83HF. However, no other findings considered to be related to treatment were observed and no tissues were processed further for histopathological examination.

Post mortem examination of all animals killed at termination revealed an area of diffuse subcutaneous haemorrhage beneath the dorsal patch site in one male exposed to BP83HF. However, no other findings considered to be related to treatment were observed and no tissues were processed further for histopathological examination.
Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The average erythema score (24, 48, and 72 hours) was 1.35.   Classification as a dermal irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

In this study, 10 rabbits were exposed to 2.0 ml of BP83HF via an occlusive patch. Dermal responses were evaluated once a day for 14 days.  Skin irritation was scored according to the Draize method of scoring. At the 24 and 48 hour observations, all animals were noted with a well defined erythema.  Only one animal was noted with well defined erythema at the 72 hour observation.  After 72 hours, all animals were free of dermal irritation.  The average erythema score (24, 48, and 72 hours) was 1.35.   This study was conducted to acceptable, well-documented scientific principles.  Classification as a dermal irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
occlusive dressing used; 24 hour exposure
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles Rivers UK Ltd
-Sex: Male (10); Female (10)
- Age at study initiation: 6 weeks
- Weight at study initiation: Male: 125-135g; Female: 110-115g
- Housing: individually housed
- Diet (e.g. ad libitum): No. 1, expanded pelleted maintenance diet for rats and mice from Special Diet Services Ltd., ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6-day acclimatisation


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25
- Humidity (%): 58-90
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
Amount(s) applied (volume or weight): 2.0 ml
Concentration (if solution): neat
Duration of treatment / exposure:
On the day prior to application the trunk of each animal was clipped free of hair. For each treated animal, 2 mL/kg of BP83HF was applied to a patch of absorbent paper. The patch was applied to the trunk and held in place beneath a sleeve under a Poroplast bandage. The whole patch assembly was held in place with tape. The patches were left in position for approximately 24 hours. Patches were similarly applied to control animals with the omission of test material. To prevent the animals from gaining access to the sites of application (and hence possibly ingesting traces of test material), collars were applied around the animals heads for a further 24 hours (control and test animals).
Observation period:
Once per day for 14 days
Number of animals:
Control: (5) males; (5) female
2 ml/kg (converted 1.7 g/kg): (5) males; (5) females
Details on study design:
SCORING SYSTEM: Draize scale
- Dermal response observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
2
Max. score:
2
Reversibility:
fully reversible
Remarks:
after 72 hours
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
ca. 2
Max. score:
2
Reversibility:
fully reversible
Remarks:
after 72 hours
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
ca. 0.2
Max. score:
2
Reversibility:
fully reversible
Remarks:
after 72 hours
Remarks on result:
other: Only one female rabbit displayed an erythema score of 2.0 at the 72 hour observation. Reversed in all other 9 animals.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 1.35
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Irritant / corrosive response data:
There were no animal deaths prior to study termination. Well-defined erythema was noted upon removal of the test patches in all animals exposed to BP83HF, generally persisting for a further 24 hours. Scab formation was subsequently observed on Day 5 and skin flaking was noted on Day 6 in all treated animals, persisting for a few days only in most animals. Plaster marks were noted on all test and control animals following patch removal; this is an artifact of the test procedure and is commonly seen in studies of this type. No other significant signs of ill health, behavioral change or reaction to treatment were noted.
Other effects:
The body weight gain of male rats was unaffected by treatment with the test material. A marginally larger overall weight gain was recorded for treated female rats when compared with the controls; this was considered to have arisen fortuitously and not related to treatment with BP83HF.

Post mortem examination of all animals killed at termination revealed an area of diffuse subcutaneous haemorrhage beneath the dorsal patch site in one male exposed to BP83HF. However, no other findings considered to be related to treatment were observed and no tissues were processed further for histopathological examination.

Post mortem examination of all animals killed at termination revealed an area of diffuse subcutaneous haemorrhage beneath the dorsal patch site in one male exposed to BP83HF. However, no other findings considered to be related to treatment were observed and no tissues were processed further for histopathological examination.

Applicant's summary and conclusion

Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The average erythema score (24, 48, and 72 hours) was 1.35.   Classification as a dermal irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

In this study, 10 rabbits were exposed to 2.0 ml of BP83HF via an occlusive patch. Dermal responses were evaluated once a day for 14 days.  Skin irritation was scored according to the Draize method of scoring. At the 24 and 48 hour observations, all animals were noted with a well defined erythema.  Only one animal was noted with well defined erythema at the 72 hour observation.  After 72 hours, all animals were free of dermal irritation.  The average erythema score (24, 48, and 72 hours) was 1.35.   This study was conducted to acceptable, well-documented scientific principles.  Classification as a dermal irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.