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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 05, 2012 - December 06, 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
other: Japan MAFF 8147
GLP compliance:
yes (incl. QA statement)
Remarks:
Bioassay Labor für biologische Analytik GmbH, Im Neuenheimer Feld 515/519, 69120 Heidelberg
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
bis(2-ethylhexyl)[(4-methyl-1H-1,2,3-benzotriazol-1-yl)methyl]amine; bis(2-ethylhexyl)[(4-methyl-2H-1,2,3-benzotriazol-2-yl)methyl]amine; bis(2-ethylhexyl)[(5-methyl-1H-1,2,3-benzotriazol-1-yl)methyl]amine; bis(2-ethylhexyl)[(5-methyl-2H-1,2,3-benzotriazol-2-yl)methyl]amine; bis(2-ethylhexyl)[(6-methyl-1H-1,2,3-benzotriazol-1-yl)methyl]amine
EC Number:
939-700-4
Molecular formula:
Unspecified
IUPAC Name:
bis(2-ethylhexyl)[(4-methyl-1H-1,2,3-benzotriazol-1-yl)methyl]amine; bis(2-ethylhexyl)[(4-methyl-2H-1,2,3-benzotriazol-2-yl)methyl]amine; bis(2-ethylhexyl)[(5-methyl-1H-1,2,3-benzotriazol-1-yl)methyl]amine; bis(2-ethylhexyl)[(5-methyl-2H-1,2,3-benzotriazol-2-yl)methyl]amine; bis(2-ethylhexyl)[(6-methyl-1H-1,2,3-benzotriazol-1-yl)methyl]amine
Test material form:
liquid
Details on test material:
- State of aggregation: liquid
- Storage conditions: Room temperature; avoid temperatures < 0°C
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, avoid temperature < 0°C

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: males animals approx. 230 g, female animals approx. 212 g
- Housing: single housing in Makrolon cage, type III; bedding: H 15005-29; Ssniff, Spezialitäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany); enrichment: NGM E-022; ABEDD® LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien – Austria
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 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: 10
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG)

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

TEST MATERIAL
- Amount applied: 2.11 mL/kg bw
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation. Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
- Necropsy of survivors performed: yes
- Other examinations performed: Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), several times until the last day of observation. The evaluation of skin reactions was performed according to Draize, J.H. (1959).

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
other: No systemic clinical signs were observed during clinical examination. Local effects: In all male animals well-defined erythema (grade 2) was noted on study day 1 and persisted in one animal until study day 3. In the other four animals moderate erythema
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of this study, the acute dermal median lethal dose (LD50) was determined to be greater than 2000 mg/kg bw,
Executive summary:

In an acute dermal toxicity study (Limit Test) following OECD guideline 402 and in compliance with GLP, young adult Wistar rats (5 males and 5 females) were dermally treated with a single dose of 2000 mg/kg bw of the undiluted test item to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. No mortality occurred and no signs of systemic toxicity were observed. The following test item-related local effects were recorded during the course of the study: very slight to moderate erythema (grade 1 to 3), very slight to slight edema (grade 1 to 2), incrustations and scaling. The mean body weight of the animals increased within the normal range throughout the study period. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. Accordingly, the acute dermal median lethal dose (LD50) was determined to be > 2000 mg/kg bw.