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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985-07-11 to 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-referenceopen allclose all
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
acute toxicity: dermal
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1985-07-11 to 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
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
used occlusive wrap
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
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
Vehicle:
unchanged (no vehicle)
Details on dermal 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 polythene 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).
Duration of exposure:
24 hours
Doses:
Control: (5) males; (5) female
2 ml/kg (converted 1.7 g/kg): (5) males; (5) females
No. of animals per sex per dose:
Animals: (10) males; (10) female per dose for a total of 20 animals
Control animals:
yes
Details on study design:
SCORING SYSTEM: Draize scale
- Dermal response observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Differences between treated and control group mean values for bodyweight gain were analysed by Student's t-test. Where individual variance ratios were significant (P <0.05 or less), Cochran's approximation was applied (Snedecor and Cochran, Statistical Methods, 6th Ed. Iowa State. 1973). Where zero variance was found in one or more groups, intergroup comparison was performed by the Wilcoxon Rank Sum Test.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 700 mg/kg bw
Remarks on result:
other: (dose converted from >2 mL/kg bw)
Mortality:
There were no animal deaths prior to study termination.
Clinical signs:
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.
Body weight:
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.
Gross pathology:
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.
Other findings:
GROSS POSTMORTEM EXAMINATION

No alterations were noted.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The LD50 of BP83HF was > 2 ml/kg (converted 1.7 g/kg). Classification as an acute dermal toxicant 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:

Five male and five female rabbits were exposed to BP83HF for 24h via an occluded patch.  Dermal evaluations occurred at 24 hours post patch removal and once daily until the study termination at day14. Exposure had no effect on viability; all animals survived the exposure.  The LD50 of BP83HF was > 2 ml/kg (converted 1.7 g/kg). Classification as an acute dermal toxicant 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.

Reason / purpose:
reference to other study

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 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
used occlusive wrap
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
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

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal 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 polythene 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).
Duration of exposure:
24 hours
Doses:
Control: (5) males; (5) female
2 ml/kg (converted 1.7 g/kg): (5) males; (5) females
No. of animals per sex per dose:
Animals: (10) males; (10) female per dose for a total of 20 animals
Control animals:
yes
Details on study design:
SCORING SYSTEM: Draize scale
- Dermal response observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Differences between treated and control group mean values for bodyweight gain were analysed by Student's t-test. Where individual variance ratios were significant (P <0.05 or less), Cochran's approximation was applied (Snedecor and Cochran, Statistical Methods, 6th Ed. Iowa State. 1973). Where zero variance was found in one or more groups, intergroup comparison was performed by the Wilcoxon Rank Sum Test.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 700 mg/kg bw
Remarks on result:
other: (dose converted from >2 mL/kg bw)
Mortality:
There were no animal deaths prior to study termination.
Clinical signs:
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.
Body weight:
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.
Gross pathology:
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.
Other findings:
GROSS POSTMORTEM EXAMINATION

No alterations were noted.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The LD50 of BP83HF was > 2 ml/kg (converted 1.7 g/kg). Classification as an acute dermal toxicant 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:

Five male and five female rabbits were exposed to BP83HF for 24h via an occluded patch.  Dermal evaluations occurred at 24 hours post patch removal and once daily until the study termination at day14. Exposure had no effect on viability; all animals survived the exposure.  The LD50 of BP83HF was > 2 ml/kg (converted 1.7 g/kg). Classification as an acute dermal toxicant 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.