Registration Dossier

Administrative data

Description of key information

Skin Irritation – C14-C20 aliphatics, 2-30% aromatics are not dermal irritants for rabbit (OECD TG 404).

Ocular Irritation - C14-C20 aliphatics, 2-30% aromatics are not irritating for rabbits (OECD TG 405).

Respiratory Irritation - No studies were located to indicate that C14-C20 aliphatics, 2-30% aromatics are respiratory irritants.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

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.
Reason / purpose:
read-across: supporting information
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.

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985/07/22-1985/07/25
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: supporting information
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
no 72 hour observation, but material demonstrated no irritation at 24 and 48 hours
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Ranch Rabbits
- Sex: 3 females
- Weight at study initiation: 2.4 to 3.0 kg
- Housing: Individually
- Diet (e.g. ad libitum): Guinea Pig Maintenance Diet, from Special Diet Services, ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 46-71
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated contra-lateral eye
Amount / concentration applied:
Amount(s) applied (volume or weight): 0.1 ml
Concentration (if solution): neat
Duration of treatment / exposure:
Test material was introduced into one eye of each animal. The eyelids were held together for approximately one second, and then released to allow observation of the reaction of the animal.
Observation period (in vivo):
1, 24, and 48h post instillation and once per day on days 4 and 7. For each observation, reference was made to the contra-lateral (untreated) eye.
Number of animals or in vitro replicates:
3 female rabbits
Details on study design:
SCORING SYSTEM: Draize scale for ocular irritation.

The presence of damage to the tissues of the eye was investigated by fluorescein staining at each observation except those on the day of exposure. Any ocular reactions not adequately described by the scoring system or in structures not mentioned were recorded in full. At the completion of the observation period the rabbits were killed by cervical dislocation.
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 1 hour
Score:
1
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 1 hour
Score:
1
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 1 hour
Score:
1
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48 h
Score:
0
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: no irritation was noted after the 1 hour observation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48 h
Score:
0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: Mean score at 24-48 hour observation was 0
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: Mean score at 24-48 hour observation was 0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: Mean score at 24-48 hour observation was 0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: Mean score at 24-48 hour observation was 0
Irritant / corrosive response data:
All animals exhibited a conjunctival redness score of 1 at the 1 hour time point. All irritation scores were zero at the 24 and 48 hour observation time points.
Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The mean (24-48 hour) corneal opacity, iris lesion, conjunctivae redness, and chemosis scores for BP83HP were 0, 0, 0, and 0 respectively. Classification as an ocular 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:

This study was conducted to determine the potential of BP83HP to cause irritation to the eye in a rabbit model system. The eyes of six rabbits were instilled with 0.1 ml of BP83HP, neat. Ocular examinations occurred at 1h, 24h, and 48h post instillation. Ocular damage was assessed and scored according to the Draize method. All animals survived the exposure. There was slight irritation noted (conjunctivae score of 1) at the 1 hour observation point. There was no irritation at the 24 and 48 hour observations. The mean (24-48 hour) corneal opacity, iris lesion, conjunctivae redness, and chemosis scores for BP83HP were 0, 0, 0, and 0 respectively. Classification as an ocular 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.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

SKIN IRRITATION: Erythema and edema scores (24, 48, and 72 average) are below the classification threshold requirements for the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparation (cut off value of 2.0) and for the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) (cut off value of 2.3).

 

OCULAR IRRITATION: Ocular lesion scores (24, 48, and 72 average) are below the classification threshold requirements.

Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparation: 0, cornea opacity; 0, iris lesion; >2.5, redness of the conjunctivae; >2.0, oedema of the conjunctivae (chemosis).

Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP): 0, cornea opacity; 0, iris lesion; >2.0, redness of the conjunctivae; >2.0, oedema of the conjunctivae (chemosis).

 

RESPIRATORY IRRITATION - There are no studies that warrent classification as a respiratory irritant under either the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC or under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

Justification for classification or non-classification

These findings do not warrant the classification of C14-C20 aliphatics, 2-30% hydrocarbon solvents as a skin, ocular, or respiratory irritant under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.