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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
other: read across from analogue substance
Adequacy of study:
key study
Study period:
Since November 23,1989 to December
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Similar substance 1
IUPAC Name:
Similar substance 1
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG
- Age at study initiation: males 11 weeks , females 13 weeks
- Weight at study initiation: males: 256-282 g, females: 199-213 g
- Housing:Individually in Makrolon type-2 cages with standard softwood bedding
- Diet : Pelleted standard Kliba 343, Batch 34/88 rat maintenance diet
- Water : Community tap water from Itingen, ad libitum
- Acclimation period:7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22 ± 3
- Humidity (%): 40-70 %,
- Air changes (per hr): 10-15 air changes
- Photoperiod: 12 hours cycle dark/light

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: 10%
- Type of wrap if used: occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.
- Other: On test day 1 the test article was applied evenly on the skin with a syringe

REMOVAL OF TEST SUBSTANCE
- Washing : lukewarm tap water


TEST MATERIAL
- Amount(s) applied: 4 ml
- Constant volume or concentration used: yes

Duration of exposure:
24 h
Doses:
4 ml at 2000 mg/kg bw
No. of animals per sex per dose:
5 x sex x single dose
Control animals:
yes, concurrent no treatment
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations :
mortality/ viability: Four times during test day 1, and daily during days 2 - 15
Body Weights: Test days 1 (pre-administration), 8 and 15.
Symptons: Each animal had an examination for changes in appearance and behavior four times during day 1, and daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes

GENERAL BEHAVIOR
aggressiveness vocalization, restlessness/excitation nervousness, fear sedation, somnolence, sleep, coma

RESPIRATION
apnea ,dyspnea ,rales

EYE
chromodacryorrhea, exophthalmos, miosis, mydriasis, whitish discharge, lid adhesion, negative corneal reflex

NOSE
rhinorrhea, epistaxis

MOTILITY
akinesia, ataxia ,dropped head, hyperkinesia, hypokinesia, paralysis, flaccid paralysis, spastic , paddiing movements, stiff gait, rolling movements

BODY POSITION
ventral body position
latero-abdominai position
hunched posture

MOTOR SUSCEPTIBILITY
spasms, tonic muscle spasms, clonic muscle spasms, opisthotonus, saltatory spasms, trismus retching, "Straub" phenomenon ,tremor ,muscle-twitching ,muscle-twitching, generalized

SKIN
erythema edema, necrosis ,crusts ,scale formations

VARIDUS
loss of weight ,emaciation ,diarrhea ,ruffled fur ,necrosis of tissue of application area , salivation ,pallor, cyanosis


Test item preparation:
The test article was placed into a glass beaker on a tared Mettler PK 300 balance and the vehicle (distilled water) was added. A weight/volume dilution was prepared using .a homogenizer.
Homogeneity of the test article in the vehicle was maintained during treatment using a magnetic stirrer.
The preparation was made immediately prior to dosing.
Statistics:
The LOGIT-Model couid not be applied to the observed rate of death. The toxi¬city was estimated without use of a statistical model.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality observed during the test
Clinical signs:
at 2000 mg/kg: erythema, brown discolored application area, scales (females).
The described symptoms were partly observed until termination of test. No systemic symtoms were observed.
Body weight:
normal
Gross pathology:
No macroscopic organ changes.

Applicant's summary and conclusion

Interpretation of results:
other: not classified under Regulation 1272/2008
Conclusions:
The analogue substance was tested for acute dermal toxicity following OECd 402. Under the experimental conditions the LD50 (LD0) > 2000 mg/kg bw.
Executive summary:

The test article was applied to the skin of rats of both sexes for 24 hours at a dose of 2000 mg/kg. The following death rate was observed: 0 % at 2000 mg/kg.

Based on these observations, the LOGIT model could not be applied to the observed rate of death.

Therefore, the toxicity was estimated to be greater than 2000 mg/kg

SYMPTOMS

The following local findings were observed: 2000 mg/kg: erythema, brown discolored application area, scales (females). The described symptoms were partly observed until termination of test. No systemic symtoms were observed.

NECROPSY

The following macroscopic organ changes were observed: No macroscopic organ changes.