Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20.09. – 06.10. 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
Council Regulation (EC) No.440/2008, published in O.J. L 142, 2008
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Expiration: 03/2011
Storage condition of test material: at the room temperature in tightly closed container

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Breeding farm VELAZ s.r.o., Koleč u Kladna, Czech Republic, RČH CZ 21760152; with certificate of good health condition
- Age at study initiation: not specified
- Weight at study initiation: average F 212.6 g, M 235 g
- Fasting period before study: not specified
- Housing: individually in cage with sterilized shavings of soft wood, monitored conditions
- Diet (e.g. ad libitum): standard pelleted diet ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3°C, permanently monitored
- Humidity: 30 – 70 %, permanently monitored
- Photoperiod: 12 hour light/12 hour dark

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 6 × 6 cm on the back of animals (aprox. 10% of the body surface)
- Type of wrap if used: mull, plaster

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped off with water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/ kg bw
- For solids, paste formed: no, applied in delivered form

Duration of exposure:
24 h
Doses:
2000 mg/ kg bw
No. of animals per sex per dose:
5 males + 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Body weight: before application, 8th and 15th day of study
Mortality: daily
Clinical signs: daily
After application the animals were observed individually – at the first day: twice (30 minutes and 3 hours after application), at the second day: twice (in the morning and in the afternoon) and daily thereafter for 14 days.
Observations included changes in skin and fur, eyes, visible mucous membranes, nutritive condition, autonomic and central nervous systems, psychic activity, somatomotor activity, reactions to stimuli, function of respiratory, circulatory, digestive and urogenital system.
Also presence of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma was carefully observed.

- Necropsy of survivors performed: yes
Pathological examination: 15th day of study



Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat. (total fraction)
Mortality:
No death of animals was observed during the 14-day observation period.
Clinical signs:
No clinical signs of intoxication were observed.
Body weight:
The weight increments were adequate to species and age of animals in the experiment.
Only slight decreased body weight and body weight increment in female No.3 and No.4 was recorded.
Gross pathology:
No macroscopic changes were diagnosed during pathological examination in all animals. No irritation on the applied skin was observed during pathological examination.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance toxicity was evaluated on the basis of mortality, body weight changes, and clinical signs of toxicity during the observation period and necropsy findings at the end of study.
The test substance applied on skin at a dose of 2000 mg/kg of animal weight did not cause death of animals.
No clinical signs of intoxication were observed. No macroscopic changes were diagnosed during pathological examination of animals.
LD50> 2000 mg/kg
Executive summary:

The test substance, 2-(3',5'-Dichloro-2'-hydroxyphenyl)-4-quinazolinone, was tested for acute dermal toxicity using Wistar rats.

Testing was performed according to the Method B.3 Acute Toxicity (Dermal), Council Regulation (EC) No.440/2008, published in O.J. L 142, 2008.

The study was performed as limit test: two groups of animals – 5 males and 5 females at the dose of 2000 mg/kg of body weight. The pre-test was performed with 1 male and 1 female from each group. After end exposure test substance of these pilot animals, the other animals of the group were dosed.

The test substance was applied on the shaved skin of the test animals in delivered form for 24 hours.

The test animals were observed 14 days after exposure test substance, afterwards they were sacrificed, and the necropsy for macroscopic examination of the organs was performed.

The test substance applied at the dose of 2000 mg/kg of body weight did not cause death of animals. No clinical signs of intoxication were observed. No macroscopic change was diagnosed during pathological examination of animals.

According to the results of study, the value of LD50 (dermal) of the test substance, 2-(3',5'-Dichloro-2'-hydroxyphenyl)-4-quinazolinone, for rats of both sexes is higher than 2000 mg/kg of body weight.