Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 04 December 2014 to 19 December 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
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

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Italy s.r.l., San Pietro al Natisone (UD), Italy
- Age at study initiation: approximately 8-10 weeks (at allocation)
- Weight at study initiation: 177 to 190 g
- Housing: individually caged during the study
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C+/-2°C
- Humidity (%): 55%+/-15%
- Air changes (per hr): Approximately 15 to 20 air changes per hour
- Photoperiod (hrs dark / hrs light): Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours

IN-LIFE DATES: From: 04 December 2014 (allocation day) To: 19 December 2014 (day of necropsy)

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal surfaces of the trunk
- % coverage: approximately 10% of body surface
- Type of wrap if used: A patch of surgical gauze covered by a strip of synthetic film was placed over the treated site and the whole assembly held in place by encircling the trunk of the animal with a length of elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): corn oil
- Time after start of exposure: approximately 25 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg/body weight
- For solids, paste formed: yes, using 1 mL of sterile water
Duration of exposure:
Approximately 25 hours
Doses:
2000 mg/kg/body weight
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 and weighing: All animals were observed for clinical signs on dosing, approximately 1, 2, 4 hours after dosing on the day of treatment and 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, gross necropsy examination for both external and internal abnormalities, with particular attention to the treatment site.

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:
not determinable due to absence of adverse toxic effects
Mortality:
No mortality occurred.
Clinical signs:
Blue staining in treated site, due to the colour of the substance, was observed in all male and female animals from Day 2 up
to Day 14. On Day 15, this finding was observed in 3 males and 4 females.
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:
Blue staining on the treatment site was observed in several animals during the external examination performed on all animals at termination of the
study. No internal abnormalities were noted during the necropsy procedure.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
These results indicate that the test item has no toxic effect on the rat following dermal exposure over a period of approximately
25 hours at a level of 2000 mg/kg body weight. The lack of mortality demonstrates the acute toxicity expected (ATE) to be greater than 2000 mg/kg
body weight.
European Directives concerning the classification, packaging and labelling of dangerous substances (Council Regulation (EC) No. 1272/2008 and
subsequent revisions) would suggest the following:
Classification: Not required
Signal word: None indicated
Hazard statement: None indicated
Executive summary:

The acute toxicity of was investigated following dermal administration of a single dose to the rat. A single dose of 2000 mg/kg body weight was administered to a group of 5 male and 5 female animals for approximately 25 hours. After 14 days, 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.

Only blue staining on the treatment site, due to the colour of the substance, was found at necropsy in several animals at termination of the study.

These results indicate that the test item has no toxic effect on the rat following dermal exposure over a period of approximately 25 hours at a level of 2000 mg/kg body weight. The lack of mortality demonstrates the acute toxicity expected (ATE) and the mean lethal dose (LD50) to be greater than 2000 mg/kg body weight.