Registration Dossier

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:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
Version February 24, 1987
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
Version August 1998
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147 as this in line with the OECD Guideline 402
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Identifier: CAS 80675-49-6
- Lot/batch No.: L-7015-20
- Yellow powder
- Storage conditions: Ambient temperature, no protection from light necessary
Specific details on test material used for the study:
- Identifier: CAS 80675-49-6
- Lot/batch No.: L-7015-20
- Analytical purity: 95%
- Yellow powder
- Storage conditions: Ambient temperature, no protection from light necessary

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Crl:WI (Han) SPF rats from Charles River Deutschland GmbH, 97633 Sulzfeld, Germany.
- Age at study initiation: young adult animals (♂: ~8 weeks, ♀: ~12 weeks)
- Weight at study initiation: ♂: 259.6 ± 6.11 g, ♀: 215.8 ± 1.30 g
- Housing: single caging in Makrolon cages type III
- Diet: ad libitum, H 15005-29; Ssniff, Spezialitaeten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany)
- Water: ad libitum, tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): ø 22 - 26 (continuous control and recording)
- Humidity (%): ø 20 - 80 (continuous control and recording)
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
olive oil
Remarks:
suspension
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped epidermis (dorsal and dorsolateral parts of the trunk)
- % coverage: ~ 40 cm² (corresponds to at least 10 % of the body surface)
- Type of wrap if used: a semi occlusive dressing. The bandage consists of four layers absorbent gauze (Ph. Eur. Lohmann GmbH & Co. KG, Germany) and Fixomull stretch (adhesive fleece, Beiersdorf AG, Germany).

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing of the application site with warm water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 6.67 g/kg (The dosing was provided in g by using a scale, because the test substance preparation in a higher concentration is a paste and the preparation is not applicable in mL)
- Concentration: 30 g/100 mL (suspension)
- For solids, paste formed: yes

VEHICLE
- Amount applied: see above; the test-item preparation was prepared shortly before application. The homogeneity of the test item during application was achieved by stirring with an Ultraturrax and a magnetic stirrer.
- Reason for the vehicle: Good homogeneity in olive oil Ph.Eur./DAB
Duration of exposure:
24 h
Doses:
2000 mg/kg
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 were determined shortly before administration (day 0), weekly thereafter and on the last day of observation. Recording of clinical signs was performed several times on the day of administration and at least once daily thereafter each workday for the individual animals. A check for any dead or moribund animal was made at least once each workday; these records are archived by Bioassay.
- Necropsy of survivors performed: yes; necropsy with gross-pathology examination on the last day of the observation period after sacrifice with CO2 in a chamber with increasing concentrations over time
- Other examinations performed: Scoring of skin findings with individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), several times until the last day of observation and on the last day of observation.

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:
- Systemic effects: no systemic clinical observations were performed during clinical examination.
- Local effects: due to a yellowish discoloration of the application area caused by the test article, erythema could not be evaluated in all animals on study day 1 and 2 (♂) or 1, 2 and 6 (♀) after administration. A yellowish discoloration of the skin at the application site remained from study day 6 until day 9 (♂) or 7 until day 9 (♀) after administration in all animals.
Body weight:
Mean body weight of the female animals decreased or remained stable during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range. The mean body weight of the male animals increased throughout the study period within the normal range (Table 1).
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Any other information on results incl. tables

Table 1: Body weight changes

Sex

Mean body weight (g) ± SD at indicated time period

 

Day 0

Day 7

Day 14

Male animals

259.8 ± 6.11

279.4 ± 7.64

317.4 ±1 4.05

Female animals

215.8 ± 1.30

217.6 ± 2.97

225.2 ± 5.45

SD: Standard deviation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met