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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:
2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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: Harlan Netherlands BV
- Age at study initiation: 7 - 8 weeks old
- Weight at study initiation: 157 - 198 g
- Housing: Group hosed in polycarbonate cages 59x38.5x20 cm
- N° of animal/cage: Up to 5/cage during acclimatisation; 3/cage during study period
- Diet: 4 RF 18 (Mucedola Srl)
- 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: 2011-10-26 To: 2011-11-18
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5% aqueous
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 soluble/miscible in selected vehicle
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 toxicity based 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:
Soft faces noted in 3 animals following dosing. Recovery within 48 hours of dosing.
Body weight:
Changes in body weight were not remarkable
Gross pathology:
No abnormal findings
Other findings:
none
Interpretation of results:
GHS criteria not met
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:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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: 8 - 10 weeks old
- Weight at study initiation: 208 - 306 g
- Housing: Polysulphone solid bottomed cages measuring 42 .5 x 26.6 x 18 cm
- N° of animal/cage: Group caged (during acclimatisation period); Individually caged (study)
- Diet: 4 RF 18 (Mucedola Srl), available 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: 2012-09-10 To: 2012-09-25
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 gauze 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
- 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
Sex:
male/female
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 of systemic toxicity observed. Signs of local irritation at treatment site.
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:
GHS criteria not met
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 systemic 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 systemic 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 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.

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