Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 31, 2016 - March 28, 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
Council Regulation (EC) No. 440/2008 laying down test methods pursuant to Regulation (EC) No. 1907/2006 of the European Parliament and the council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
The test item preparation was prepared directly before administration. Appropriate amounts of the test item were moistened sufficiently with the vehicle and grounded in a mortar using a pestle. The test item preparation was administered within less than 1 hour after preparation. The stability of the test item in the vehicle was not investigated.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Sulzfeld, Germany
- Age at study initiation: 9 weeks (males), 12 weeks (females)
- Weight at study initiation: The mean initial body weight at the start of study was 226 g (range from 199 to 265 g).
- Fasting period before study: no
- Housing: separately in type III Makrolon cages with a shelter, placed on mobile racks
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.4 – 23.1°C
- Humidity (%): 40.9 – 59.7%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12 h

IN-LIFE DATES: From: day 1 To: day 15

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
paraffin oil
Details on dermal exposure:
TEST SITE
- Area of exposure: 39 cm2
- % coverage: approx. 10%
- Type of wrap if used: self-adhesive fabric (Fixomull stretch, Beiersdorf)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50, 200, 1000 and 2000 mg/kg bw
- For solids, paste formed: yes

VEHICLE
Designation: Art. 1.07174
Synonym: Liquid paraffin
Supplier: Merck KGaA, Germany
Batch: K45409474
Released until: April 30, 2019


Duration of exposure:
24 h
Doses:
50, 200, 1000 and 2000 mg/kg bw
No. of animals per sex per dose:
50 mg/kg bw: 5 (f)
200 mg/kg bw: 5 (f)
1000 mg/kg bw: 5 (f)
2000 mg/kg bw: 5 (m) / 5 (f)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Standard statistical methods have been applied for data processing.

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 during the course of this study.
Clinical signs:
No clinical signs of toxicity were observed.
Body weight:
One female rat treated with 2000 mg/kg showed a decrease of the body weight during the observation period. The body weight development of all other rats was inconspicuous throughout the study.
Gross pathology:
Gross pathological examination revealed no organ alterations in all animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test item has no acute dermal toxic potential under the conditions of the present study, and the LD50 value exceeds 2000 mg/kg body weight after single dermal administration in rats.
Executive summary:

Objective

The objective of the present study was to identify potential toxic effects of the test item, after single dermal administration to rats in a stepwise procedure.

Study Design

Groups of 5 female rats each were dermally treated with the test item for 24 hours at dose levels of 50, 200, 1000 and 2000 mg/kg bw. The study was started with the lowest dose level of 50 mg/kg bw. As no mortalities were observed up to the highest dose, a further group of 5 male rats was exposed at a dose level of 2000 mg/kg bw.

Mortality and clinical signs were monitored for at least 6 hours after administration and then daily. All animals were weighed before treatment (day 1) and on days 2, 4, 6, 8, 11, 13, and 15. At the end of the observation period, all surviving rats were sacrificed and subjected to a detailed necropsy.

Results

No mortality occurred during the course of this study.

No clinical signs of toxicity were observed.

One female rat treated with 2000 mg/kg bw showed a decrease of the body weight during the observation period. The body weight development of all other rats was inconspicuous throughout the study.

Gross pathological examination revealed no organ alterations in all animals.

Conclusion

The test item has no acute dermal toxic potential under the conditions of the present study, and the LD50 value exceeds 2000 mg/kg body weight after single dermal administration in rats.