Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 02 December 2014 to 02 January 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2015

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class 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:
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 9-10 weeks
- Weight at study initiation: 162-170 g
- Fasting period before study: approximately 16 hours prior to dosing
- Housing: 3 animals/cage
- Diet (e.g. ad libitum): ad libitum, except for the fasting period prior to dosing
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at leat 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: 09 December 2014 (Allocation of the animals to the first group) To: 02 January 2015 (Last necropsy procedure)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Peg 400-water 1:1 v/v
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 Ml/kg body weight
- Justification for choice of vehicle: solubility of the test item
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
2 x 3 females
Control animals:
no
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 0.5,
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 2, 8 and 15.
- Necropsy of survivors performed: yes, gross necropsy examination for both external and internal abnormalities,
with particular attention to the gastro-intestinal tract.

Results and discussion

Effect levels
Key result
Sex:
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 on muzzle, dorsal region or perianal region, due to the colour of the substance, was individually observed for a maximum of 10 days after dosing.
Body weight:
Changes in body weight observed during the study were within the expected range for this strain and age of animals.
Gross pathology:
No abnormalities were observed at necropsy examination.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
These results indicate that the test item did not induce toxic effects in the rat following oral administration of a single dose 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. The LD50 is > 2000 mg/kg body weight.
Executive summary:

The acute toxicity of the test item was investigated following a single oral administration to the Sprague Dawley rat followed by a 14-day observation period.

No mortality occurred in the first group of 3 animals dosed at 2000 mg/kg body weight or in the second one, similarly composed, dosed at the same dose level. Clinical signs were limited to blue staining on muzzle, dorsal region or perianal region individually observed for a maximum of 10 days after dosing, which is caused by the coloured test item. Body weight changes recorded during the study were within the expected range for this strain and age of animals.

No abnormalities were observed at necropsy examination performed at the end of the observation period on animals of both groups.

These results indicate that the test item did not induce toxic effects in the rat following oral administration of a single dose 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.