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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study not performed according to GLP, but carried out in a quality environment and in repect of internal standard operating procedures, checked by regular Quality Assurance audits, and according to OECD 402 and 404 guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Remarks:
But audited by Quality Assurance
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
3,3'-(1,4-Phenylene)bis(5,6-diphenyl-1,2,4-triazine)
EC Number:
700-823-1
Cas Number:
55514-22-2
Molecular formula:
C36H24N6
IUPAC Name:
3,3'-(1,4-Phenylene)bis(5,6-diphenyl-1,2,4-triazine)
Details on test material:
- Name of test material (as cited in study report): CH022 WP30
- Physical state: powder
- Analytical purity: 99.8 %
- Purity test date: January 7th, 2012
- Lot/batch No.: LP140
- Stability under test conditions: stable
- Storage condition of test material: at room temperature in a dark and well ventilated place

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Weight at study initiation: males: approximately 250 g, females: approximately 200 g
- Housing: 1 animal per cage
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-2
- Humidity (%): between 40 and 70
- Air changes (per hr): > 10 full air changes
- 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: 6 x 5 cm
- % coverage: 10 %
- Type of wrap if used: Gauze patch held in close contact with the skin by means of a non occlusive tape Micropore

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the testsite was wiped with a cotton pad soaked with purified water
- Time after start of exposure: 24 +/- 1 hours

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

Duration of exposure:
24 +/- 1 hours
Doses:
2000 mg/kg
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: once daily during acclimation period and for 15 days after application, but on Day 1: 1h, 3h, ad 5 hours after application.
- Frequency ofweighing: on Day 1 (before application), and on days 3, 8, 15.
- Necropsy of survivors performed: yes
- A complete macroscopic examination was performed on all animals. This included examination of the thoracic, abdominal and pelvic cavities with their associated organs and tissues.
- skin examination according to OECD 404, for skin irritation checking

Results and discussion

Preliminary study:
The dose was selected considering 2000 mg/kg did not induce mortality by oral route and in vitro skin penetration of WP30 using human skin mounted on static cells did not exceed 0.49 %.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
No anomaly detected
Body weight:
See Table 2 in study report attached
Gross pathology:
None

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
As no mortality was observed, DL50 by dermal application is above 2000 mg/kg.
Executive summary:

The objective of this study was to evaluate the potential toxicity of the test item CH0222 WP30 after a single topical application for a 24-hour exposure period on Wistar rat skin.

5 male and 5 female Wistar rats (RjHan: WI, SPF albino rats from Janvier) were treated at 2000 mg/kg corresponding to the limit test.

On the day of application (Dl), a weight based quantity of test item was moistened with purified water and applied directly onto the dorsal part of the trunk of each animal which had been clipped the day before. The test item was evenly spread over the application site which represented at least lO% of the body surface. The application site was then covered with a gauze patch held in close contact with the skin by means of a non occlusive tape for a 24h exposure period. At the end of the exposure period, the patch was removed and the test site was wiped with a cotton pad soaked with purified water.

Animals were observed at least once daily for mortality and general clinical signs for 15 days and were weighed on Dl, D3, D8 and D15.

Skin reactions were evaluated for all animals approximately 1 hour (D2), 24h (D3), 48h (D4) and 72h (DS) after patch removal at the end of the contact period and on D8 and Dll. The responses, erythema and edema, were scored according to a table graded from 0 (no skin reaction) up to 4 (severe reaction).

No death occurred during the course of the study and no abnormal clinical sign was observed.

Body weight evolution was not affected by the treatment for males whereas a slight body weight loss was observed in 4/5 females between Dl and D3 but weight increase was restored thereafter. This transient observation on body weight evolution was most probably related to the non occlusive tape.

.

As no mortality was observed, CH0222 WP30 is not classified and the DL 50 by dermal application was estimated to be higher than 2000 mg/kg.