Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1987-07-27 to 1987-08-10
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across from a guideline study
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Test animals

Species:
rat
Strain:
other: CD (Crl:COBS CD(SD)BR)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7 - 10 weeks
- Weight at study initiation: 200 to 232 g
- Fasting period before study: no
- Housing: individually housing in metal cages with wire mesh floors
- Diet: ad libitum, standard laboratory rodent diet "Labsure LAD 1"
- Water: ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23
- Humidity (%): 66
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
One day prior to treatment hair was removed from the dorsolumbar region of each rat with electric clippers exposing an area equivalent to 10% of the total body surface. No shaving or chemical depilation was used.

The test substance was applied by spreading it evenly over the prepared skin. Total volume applied was 1.92 ml/kg bw. Test substance was applied in the original state (aqueous solution, a.i. 31 %) as delivered by the sponsor. The treated area was then promptly covered with gauze which was held in place with an impermeable dressing encircled firmly around the trunk.

At the end of the 24-hours exposure period, the dressings were carefully removed and the treated area of skin decontaminated by washing in warm (30°-40°C) water and blotting dry with absorbent paper.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw (based on product),
No. of animals per sex per dose:
5 males
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 d
- Body weights were recorded on Day 1 (day of dosing), 8 and 15
- Clinical observation: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days the animals were observed once in the morning and again at the end of the experimental day. This latter observation was at approximately 16.30 hours on week days or 11.30 hours on Saturday and Sunday. Clinical signs were recorded at each observation. The nature, severity, approximate time of
onset and duration of each toxic sign.
- Necropsy of the survivors performed: yes
- Other examinations performed: skin reactions - The treated areas of skin were examined daily for signs of dermal irritation and assessed according to the following arbitrary scoring system.
Erythema and eschar formation:
No erythema = score 0
Slight erythema = score 1
Well-defined erythema = score 2
Moderate to severe erythema = score 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) = score 4
Oedema formation:
No oedema = score 0
Slight oedema = score 1
Well-defined oedema (area well-defined by definite raising) = score 2
Moderate oedema (raised approximately 1 millimetre) = score 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) = score 4
A separate record was kept of dermal changes other than erythema and oedema.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: based on product
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 620 mg/kg bw
Remarks on result:
other: based on a.i.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: based on product; mortality 0/10
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 620 mg/kg bw
Remarks on result:
other: based on a.i.; mortality 0/10
Mortality:
0/10
Clinical signs:
- Application site: Sites of application of the test substance showed slight or well-defined erythema in all animals on Day 2 and/or 3. On Day 4 and Day 5, slight erythema were seen in three male and four female rats, sloughing in two male rats and one female rat and hyperkeratinisation in three female rats. All skin reactions were completely reversible by Day 6 in all animals.
Slough or hyperkeratinisation affected the treated skin of 4, 5, 6, 8, 9, 10 rats on Days 4 and 5 only.

- systemic: There were no clinical signs of systemic reaction to treatment.
Body weight:
Slightly low bodyweight gains were recorded for three females on Day 8.
All other rats achieved anticipated bodyweight gains throughout the study.
Gross pathology:
Terminal autopsy findings were normal.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
The acute lethal dermal dose to rats was found to be > 2000 mg/kg bodyweight (based on product).
Executive summary:

In an acute dermal toxicity study according to EU Method B.3 and OECD Guideline 402, 5 male and 5 female CD rats (Crl:COBS CD(SD)BR) were dermally exposed to Coco AAPB (a.i 31 %) as delivered by the sponsor for 24 hours to 10% of total body surface at a dose of 2000 mg/kg bw (limit test). Test sites were covered with an occlusive dressing. After 24 hours, the test sites were rinsed with warm water. Animals then were observed for 14 days after dosing.

There were no clinical signs of systemic reaction to treatment. Sites of application of the test substance showed slight or well-defined erythema in all animals on Day 2 and/or 3. On Day 4 and Day 5, slight erythema were seen in three male and four female rats, sloughing in two male rats and one female rat and hyperkeratinisation in three female rats. All skin reactions were completely reversible by Day 6 in all animals. Slightly low bodyweight gains were recorded for three females on Day 8. All other rats achieved anticipated bodyweight gains throughout the study. Terminal autopsy findings were normal.

Dermal LD0 Combined: 2000 mg/kg bw

Dermal LD50 Combined: > 2000 mg/kg bw

LD0 and LD50 determined refer to the test substance as delivered by the sponsor. Amount of active ingredient in test substance is 31 %. Therefore the calculated oral LD0and LD50 combined referring to 100 % active substance is 620 and > 620 mg/kg bw, respectively.

Coco AAPB (a.i. 31 %) is of low toxicity based on the LD50 in males and females.