Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 April 2015 - 22 December 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted on 24 February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: EPA, OPPTS Methods 870.1000 “Acute Toxicity Testing - Background”
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- State of aggregation: Clear colorless liquid
- Storage Conditions: Room temperature, in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
Species and strain: Rat, Hsd: Sprague Dawley SD
Sex: Males and females (nulliparous and non-pregnant)
Age: 6 to 8 weeks old
Weight at order: 176 to 200 grams
Supplier: Charles River Italia S.p.A., Calco, Lecco, Italy
Breeder: Charles River Italia S.p.A., Calco, Lecco, Italy
Date of arrival: 09 April 2015
Weight range at arrival: 189 to 203 grams
Acclimatisation period: At least 5 days
Veterinary health check: During acclimatisation period

ENVIRONMENTAL CONDITIONS
Animals per cage: Up to 5 of one sex during acclimatisation; individually caged during the study
Housing: Clear polysulphone H-Temp solid bottomed cages (Tecniplast Gazzada S.a.r.l., Buguggiate, VA, Italy) measuring 59.5×38×20 cm during
acclimatisation period and 42.5×26.6×18.5 cm during the study with nesting material provided into suitable bedding bags.
Cage control: Daily inspected and changed as necessary (at least 3 times/week)
Water Drinking: water supplied to each cage via a water bottle
Water supply: Ad libitum
Diet: 4 RF 18 (Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI) Italy)
Diet supply: Ad libitum throughout the study
Room lighting: Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours
Air changes: Approximately 15 to 20 air changes per hour
Temperature range: 22 °C±2 °C
Relative humidity range: 55%±15%

Administration / exposure

Type of coverage:
semiocclusive
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal surface of the trunk
- % coverage: Approximately 10% of body surface
- Type of wrap if used: elastic adhesive bandage and gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, with cotton wool soaked with lukewarm water.
- Time after start of exposure: 24 hours
Duration of exposure:
The animals remained in contact with the test item for 24 hours.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females at 2000 mg/kg
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for clinical signs the day of dosing: on dosing, approximately 1 hour after dosing, 2 hours after dosing and 5 hours after dosing, daily thereafter. All animals were weighed at allocation to the study (Day -1), on the day of dosing (Day 1) and on Days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Mortality:
No mortality occurred.
Clinical signs:
No clinical signs were observed in male or female animals after treatment during the observation period.
Body weight:
Body weights and body weight changes were within the expected range for this species and age of animals at the end of the study.
Gross pathology:
No abnormalities were found at necropsy examination performed on all animals at termination of the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The results of an acute dermal toxicity study performed according to OECD.EC guidelines and GLP principles indicate that SAKURA SALICYLATE has no toxic effect on the rat following dermal exposure over a 24 hour period at 2000 mg/kg bw. It is therefore concluded that the dermal LD50 is greater than 2000 mg/kg bw.
Executive summary:

The acute toxicity of SAKURA SALICYLATE was investigated following dermal administration of a single dose to the rat. A single dose of 2000 mg/kg bw was administered to a group of 5 male and 5 female animals for 24 hours. After a 14-day observation period, all animals were killed and subjected to necropsy examination. No mortality occurred and no signs of toxicity were observed in male or female animals during the observation period. The body weight changes observed during the study were within the expected range for this species and age of animals. No internal abnormalities were found at necropsy in the animals at termination of the study. No abnormalities were observed at the treated site. These results indicate that the test item, SAKURA SALICYLATE, has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg bw. Based on these data, the dermal LD50 for Isopropoxyethyl salicylate was determined to exceed 2000 mg/kg bw, the substance is not classified for dermal toxicity in category 4 according to Regulation (EC) 1272/2008.