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Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
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
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)
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.
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
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
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
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)
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.
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

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.

The acute toxicity of the test item 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.

Justification for classification or non-classification

Classification:        No category

Signal word:        No signal word required

Hazard statement : No hazard statement required