Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2020
Report date:
2020

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
1998
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japan MAFF 8147
Version / remarks:
2000
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Bioassay - Labor für biologische Analytik GmbH, Im Neuenheimer Feld 515-519; 69120 Heidelberg
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han) SPF
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: Young adult animals (male animals approx. 9 weeks, female animals approx. 13 weeks)
- Weight at study initiation: females: 210-233 g (mean: 222.8 g, SD: 8.7 g); males: 253-276 g (mean: 263.8 g, SD: 9.76 g)
- Housing: Single housing, in Makrolon cages, type III with wooden gnawing blocks
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 5 days before administration
- Microbiological status: SPF

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3
- Humidity (%): 30-70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: About 40 cm²
- % coverage: At least 10% of the total body surface

REMOVAL OF TEST SUBSTANCE
- Washing: With warm water
- Time after start of exposure: After 24 hours

TEST MATERIAL
- Amount applied: 2.27 mL/kg bw
- Concentration: Undiluted
- Constant volume or concentration used: Yes
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw (both males and females)
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Body weights: Shortly before application (day 0), weekly thereafter and on the last day of observation.
Clinical observations: Several times on the day of application and at least once during each workday thereafter.
Mortality: At least once each workday
Scoring of skin findings: 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), then several times until the last day of observation.

- Necropsy of survivors performed: yes
Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations.
Statistics:
not performed

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male
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
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mL/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
Very slight erythema (grade 1) in 5/5 females on day 1 and in 2/5 until day 3
Mortality:
No mortality occurred.
Clinical signs:
No systemic clinical signs were observed during clinical examination.
Body weight:
All animals gained weight in a normal range throughout the study period.
Gross pathology:
No macroscopic pathologic abnormalities were noted in any animal examined on the last day of observation (5 males and 5 females).
Other findings:
Local effects
- Males: No local effects were observed.
- Females: Very slight erythema (grade 1) was seen in all female animals on study day 1 and persisted in in two of these animals until study day 3.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met