Registration Dossier

Diss Factsheets

Administrative data

Description of key information

- Acute toxicity:
Oral: LD50: >2000 mg/kg in the rat
Dermal: LD50: > 2000 mg/kg in the rat

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:
June 7-29, 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant study conducted to recognised international test guidelines
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:Charles River Italia S.p.A.
- Age at study initiation:7 - 8 weeks old
- Weight at study initiation:180- 231 g
- Housing: Group hosed in polysulphone solid bottom cages
- N° of animal/cage: Up to 5/cage during acclimatisation; 3/cage during study period
- Diet: 4 RF 18 (Mucedola S.r,l)
- Diet supply: ad libitum except for an overnight fast prior to dosing and 4 hours following dosing.
- Water :ad libitum
- Acclimation period:at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°c +/- 2°c
- Humidity (%):55% +/- 15%
- Air changes: 15 to 25 air changes per hour
- Photoperiod: Artificial (fluorescent tubes) , daily light/dark cycle of 12/12 hours


IN-LIFE DATES: From: 2012-06-07 To: 2012-06-29
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bodyweight
- Justification for choice of vehicle: Substance non-soluble/miscible in aqueous vehicles

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

DOSAGE PREPARATION (if unusual): Admixture w/v

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Expected lack of toxcity sed on information from structurally analogous substances
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Examination of clinical signs 0.5, 2 and 4 hours after treatment and daily observations thereafter; bodyweights were determined before treatment and weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: no
Statistics:
no statistics performed
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
0/6 animals
Clinical signs:
Salivation in 1 animal following dosing, recoveryt within 4 hours of dosing.
Body weight:
Changes in body weight were not remarkable
Gross pathology:
No abnormal findings
Other findings:
none
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Acute oral toxicity of the substance has been investigated according to OECD/EU test guidelines. The LD50 was determined to be in excess of 2000 mg/kg body weight.
Executive summary:

Acute oral toxicity of the substance has been investigated according to OECD/EU test guidelines. The LD50 was determined to be in excess of 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

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:
June 12-27, 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant study conducted to recognised international test guidelines
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source Charles River Italia S.p.A.
- Age at study initiation:7 - 9 weeks old
- Weight at study initiation:224 - 299 g
- Housing: policarbonatecages measuring 42 .5 x 26.6 x 18 cm with stainless stell mesh lid and floor
- N° of animal/cage: Individually caged (both during acclimatisation and study)
- cage try control: Daily inspected and changed as necessary (at least 3 times/week)
- Diet: 4 RF 18 (Mucedola S.r,l)
- Diet supply: ad libitum
- Water :ad libitum
- Acclimation period:at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°c +/- 2°c
- Humidity (%):55% +/- 15%
- Air changes: 15 to 25 air changes per hour
- Photoperiod: Artificial (fluorescent tubes) , daily light/dark cycle of 12/12 hours

IN-LIFE DATES: From: 2012-06-12 To: 2012-06-27
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure:approximately 10% of body surface
- Type of wrap if used:synthetic film

REMOVAL OF TEST SUBSTANCE
- Washing : After exposure , the adhesive bandage and gouze patch were removed. The treatment area was cleaned by gentle swabbing of the skin with cotton wool soaked with lukewarm water.
- Time after start of exposure:24 hours

TEST MATERIAL
- Amount(s) applied : Aliquots were weighed accordingly to the body weight of each animal measured prior dosing
- Constant volume or concentration used: yes
- Frequency of treatment: once only , on the day of dosing
- Treatment area preparation: on the day before dosing

Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 male and 5 female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days , termination on day 15.
- Frequency of observations and weighing:Observations - 1,2 and 4 hours after first dosing and daily thereafter for 14 days. Weighing - Days -1, 1, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: necropsy was carried out on all animals (gross necropsy examination for both internal and external abnormalities, with particular attention to the treatment site. All abnormalities were recorded.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None during 14 day post-exposure observation period
Clinical signs:
No signs observed considered to be of significance
Body weight:
No abnormal changes considered to be of significance
Gross pathology:
No abnormal changes considered to be of significance
Other findings:
None

 

 

 

 

 

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute toxicity of the substance was investigated following dermal administration of a single dose to the rat at 2000 mg/kg. No mortality occurred following dosing and no signs of toxicity were observed. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg.
Executive summary:

The acute toxicity of the substance has been investigated following dermal administration of a single dose to the rat at 2000 mg/kg. utilising OECD/EU test methods. No mortality occurred following dosing and no signs of toxicity were observed. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg.

 

         

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Data are available from studies investigating effects following exposure via the oral and dermal routes of administration. No significant toxicities were apparent at limit doses of 2000 mg/kg body weight.


Justification for selection of acute toxicity – oral endpoint
Single study available for evaluation

Justification for selection of acute toxicity – dermal endpoint
Single study available for evaluation

Justification for classification or non-classification

Classification with regard to acute oral and dermal toxicity is not justified based on the observed lack of mortality at a dose level of 2000 mg/kg.