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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 February 2019 to 06 March 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report date:
2019

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
09 October 2017
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
30 May 2008.
The guideline has not yet been revised in line with the OECD 2017 version. The study does not fully comply with the older version of the guideline, but the study design is considered to be acceptable for all OECD countries.
Deviations:
not applicable
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998.
The guideline has not yet been revised in line with the OECD 2017 version. The study does not fully comply with the older version of the guideline, but the study design is considered to be acceptable for all OECD countries.
Deviations:
not applicable
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Condensation products of phenol and salicylaldehyde
EC Number:
947-320-5
Molecular formula:
Variable as UVCB substance
IUPAC Name:
Condensation products of phenol and salicylaldehyde
Test material form:
solid: flakes
Details on test material:
- Appearance: Red-reddish brown solid flake
- Storage conditions: Controlled room temperature (15 - 25 °C, < 70 % relative humidity)
Specific details on test material used for the study:
FORM AS APPLIED IN THE TEST
- The test material was powdered into fine dust before the application. Sufficient water was used to moisten the test material to ensure good contact with the skin.
- Measurement of pH: If the pH is 2 or less or 11.5 or greater, a study cannot be conducted, unless there is evidence that the test material is not severely irritating or corrosive to the skin. The pH of the test material in this study was determined prior to the initiation of the experiment and it was found to be 5.36, therefore the experiment could be started.

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Crl: WI Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 11 weeks
- Weight at study initiation: 244 - 256 g
- Housing: Animals were housed in type II polypropylene/polycarbonate cages. Animals were housed individually during the treatment and were group housed after patch removal. Rodents were housed with deep wood sawdust bedding to allow digging and other normal rodent activities. Lignocel 3/4-S Hygienic Animal Bedding was available to animals during the study. The quality of the bedding was guaranteed by the supplier. Additionally, nest building material (Arbocel Crinklets natural) was available to animals during the study. The quality of the nest building material was guaranteed by the supplier.
- Diet: Ad libitum
- Water: Tap water ad libitum.
- Acclimation period: 25 or 27 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20.2 - 24.5 °C
- Humidity: 25 - 73 %
- Air changes: 15 - 20 air exchanges/hour
- Photoperiod: 12 hours light (from 6.00 a.m. to 6.00 p.m.) / 12 hours dark, daily.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Remarks:
Sufficient water was used to moisten the test material to ensure good contact with the skin.
Details on dermal exposure:
TEST SITE
- Area of exposure: The back of each animal was shaved approximately 24 hours prior to treatment. The test material was applied to the shaved skin as a single dose and remained in contact with the skin for the exposure period.
- % coverage: approximately 10 % area of the total body surface.
- Type of wrap if used: Sterile gauze pads were placed on the skin of rats to cover the test material. These gauze pads were kept in contact with the skin using a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 hours.

REMOVAL OF TEST SUBSTANCE
- Washing: At the end of the exposure period, the treated area of skin with the test material was washed with water at body temperature.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 0.50 ± 0.01 g
- For solids, paste formed: Sufficient water was used to moisten the test material to ensure good contact with the skin.
Duration of exposure:
24 hours
Doses:
2 000 mg/kg bw
No. of animals per sex per dose:
3 females
Initially one animal was dosed at the selected limit dose (2 000 mg/kg bw). As the animal survived, the second and third animal received the same dose.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/morbidity was checked twice daily during the 14-day observation period. Clinical observations were performed on the day of treatment at approximately 30 minutes, 1, 2 and 5 hours after application of the test material and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Adverse skin reactions at the site of application were recorded daily following the removal of the dressing.
The body weights were recorded on Day 0 (before the test material administration) and on Days 7 and 14 (before necropsy).
- Necropsy of survivors performed: Yes. Macroscopic examination was performed on all animals. All animals were anaesthetised with sodium pentobarbital and exsanguinated. Following confirmation of death, after examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed. All macroscopic changes were recorded.
Statistics:
The method used was not intended to allow the calculation of a precise LD50 value.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Mortality:
The test material did not cause mortality at the dose level of 2 000 mg/kg bw.
Clinical signs:
There were no adverse clinical signs noted in any animals during the 14-day observation period.
No adverse local dermal signs (erythema/oedema) were noted in any animals during the 14-day observation period.
Coloured skin (orange, on the back) was noted for all animals from Day 1 up to Day 5, which was related to the test material and was not identified as a local dermal sign. Test material residue on the back of the animals (in the treated area, not removable) was noted from Day 1 up to Day 9.
Body weight:
Slight decrease in body weight was observed in the animals of the main phase between Day 0 and Day 7. Body weights were within the range commonly recorded for this strain and age between Day 7 and Day 14 in case of all animals.
Gross pathology:
There was no evidence of any gross macroscopic changes at a dose level of 2 000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified according to EU criteria
Conclusions:
Under the conditions of the study the acute dermal LD50 of the test material was determined to be greater than 2 000 mg/kg body weight in female rats.
Executive summary:

The acute dermal toxicity of the test material was investigated in a study which was conducted in compliance with the standardised guideline OECD 402, under GLP conditions.

A single animal at a dose level of 2 000 mg/kg body weight (bw) was used in a range-finding phase, followed by two animals in the main phase to confirm the expected non-lethal dose level. The test material was applied as a single dermal 24-hour exposure followed by a 14-day observation period.

Clinical observations were performed on all animals at approximately 30 minutes, 1, 2, 5 hours after dosing and daily for 14 days thereafter. Body weight was measured on Day 0 (prior to dosing) and on Days 7 and 14 (before necropsy). Gross macroscopic examination was performed on all animals at necropsy at the end of the 2-week observation period (Day 14).

The test material did not cause mortality at the dose level of 2 000 mg/kg bw.

There were no adverse clinical signs noted in any animals during the 14-day observation period.

No adverse local dermal signs (erythema/oedema) were noted in any animals during the 14-day observation period.

Coloured skin (orange, on the back) was noted for all animals from Day 1 up to Day 5, which was related to the test material and was not identified as a local dermal sign. Test material residue on the back of the animals (in the treated area, not removable) was noted from Day 1 up to Day 9.

Slight decrease in body weight was observed in the animals of the main phase between Day 0 and Day 7. Body weights were within the range commonly recorded for this strain and age between Day 7 and Day 14 in case of all animals.

Additionally, there was no evidence of any macroscopic changes at a dose level of 2 000 mg/kg bw.

Under the conditions of the study the acute dermal LD50 of the test material was determined to be greater than 2 000 mg/kg body weight in female rats.