Registration Dossier

Administrative data

Description of key information

In an acute oral toxicity study in female rats, conducted in accordance with OECD 423 (2001) and according to GLP principles, a LD50 oral of >2000 mg/kg bw was determined. In an acute dermal toxicity study with 10 rabbits, performed equivalent to OECD 402 (1981), a LD50 of >5000 mg/kg bw was determined.

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:
October 16, 2012 - November 15, 2012
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)
Version / remarks:
(2001)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
(2008)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
Identification: Citrathal
Description: Clear yellow liquid
Batch: SC00005944
Storage conditions: room temperature in the dark
Species:
rat
Strain:
other: Wistar (RccHan:WIST)
Sex:
female
Details on test animals and environmental conditions:
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 154-176 g
- Fasting period before study: overnight before dosing
- Housing: Group housing of 3 animals per cage in suspended solid-floor polypropylene cages
- Diet: Free access (2014C Teklad Global Rodent diet, Harlan Laboratories UK Ltd.)
- Water: Free access to tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
GAVAGE METHOD: metal cannula attached to a graduated syringe
Frequency: single dosage, on Day 1.

DOSE VOLUME APPLIED: 2.18 mL/kg body weight
Doses:
2000 mg/kg body weight

No. of animals per sex per dose:
6 (2 groups of three females in a stepwise manner)
Control animals:
no
Details on study design:
- Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality and Clinical signs: 0.5, 1, 2 and 4 hours after dosing and subsequently once daily
Body weights: prior to dosing and 7 and 14 days thereafter
- Necropsy of survivors performed: yes
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortalities and no clinical signs of toxicity occurred
Mortality:
No mortalities occurred
Clinical signs:
No clinical signs of toxicity occurred
Body weight:
No abnormalities were observed
Gross pathology:
No abnormalities were observed
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study in female rats, conducted in accordance with OECD 423 (2001) and according to GLP principles, a LD50 oral of >2000 mg/kg bw was determined.
Executive summary:

The acute oral toxicity in female rats has been studied in accordance with OECD 423 (2001), EU Method B.1 tris (2008) and according to GLP principles. The substance was dosed (undiluted) at 2 g/kg bw in 6 female rats, in 2 steps. No mortality and no clinical signs of toxicity occurred. Macroscopic examination of the animals did not reveal any abnormalities. The acute oral toxicity (LD50) was determined to be >2000 mg/kg bw. Based on this result, the substance does not need to be classified for acute toxicity by the oral route in accordance with the CLP Regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study has Klimisch score 1

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:
September, 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1981)
Deviations:
yes
Remarks:
lack of the study design and test material details in the report
GLP compliance:
no
Remarks:
(study performed prior to GLP was in place)
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
No data

ENVIRONMENTAL CONDITIONS
No data
Type of coverage:
not specified
Vehicle:
not specified
Details on dermal exposure:
No data
Duration of exposure:
No data
Doses:
5000 mg/kg


No. of animals per sex per dose:
10 animals (sex unknown)
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: no data
- Necropsy of survivors performed: yes
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
1 animal died on day 14
Clinical signs:
Diarrhea, difficulty in walking due to severe skin reaction, lethargy, emaciation, ataxia, yellow nasal discharge, adipsia, anorexia, tachypnea, mucous in stool, respiratory rattle (no data about which clinical sign when was observed in which animal).
Body weight:
No data
Gross pathology:
See section "Any other information on results incl. tables"
Other findings:
- Erythema (redness) (day 1): Moderate in 4 of the 10 animals; Severe in 6 of the 10 animals
- Edema (day 1): Moderate in 10 of the 10 animals

 

Necropsy observations; Number of animals

Normal

3

Exudate, nose/mouth yellow

1

Exudate, anogenital, brown

1

Intestines, areas yellow

1

Intestines, bloated

3

Liver dark

1

Liver, mottled

1

Lungs, areas dark

2

Lungs, bright orange

2

Kidney dark

2

Kidney, mottled

2

Kidney, white nodules

1

 

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study with 10 rabbits, performed equivalent to OECD 402 (1981), a LD50 of >5000 mg/kg bw was determined.
Executive summary:

The substance was tested in an acute dermal toxicity study (limit test) with 10 rabbits, performed equivalent to OECD 402 (1981). One animal died on day 14. Diarrhea, difficulty in walking due to severe skin reaction, lethargy, emaciation, ataxia, yellow nasal discharge, adipsia, anorexia, tachypnea, mucous in stool and respiratory rattle was observed among the animals. Moderate to severe erythema and moderate edema was observed on day 1. Based on the results, a LD50 of >5000 mg/kg bodyweight was determined. Based on this result, the substance does not need to be classified for acute toxicity by the dermal route in accordance with the CLP Regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The study has Klimisch score 2

Additional information

Acute toxicity: oral

The acute oral toxicity in female rats has been studied in accordance with OECD 423 (2001), EU Method B.1 tris (2008) and according to GLP principles. The substance was dosed (undiluted) at 2 g/kg bw in 6 female rats, in 2 steps. No mortality and no clinical signs of toxicity occurred. Macroscopic examination of the animals did not reveal any abnormalities. The acute oral toxicity (LD50) was determined to be >2000 mg/kg bw.

Acute toxicity: dermal

The substance was tested in an acute dermal toxicity study (limit test) with 10 rabbits, performed equivalent to OECD 402 (1981). One animal died on day 14. Diarrhea, difficulty in walking due to severe skin reaction, lethargy, emaciation, ataxia, yellow nasal discharge, adipsia, anorexia, tachypnea, mucous in stool and respiratory rattle was observed among the animals. Moderate to severe erythema and moderate edema was observed on day 1. Based on the results, a LD50 of >5000 mg/kg bodyweight was determined.


Justification for selection of acute toxicity – oral endpoint
The only study with a reliability of 1 that is available.

Justification for selection of acute toxicity – dermal endpoint
The only available study.

Justification for classification or non-classification

The substance does not need to be classified for acute oral and acute dermal toxicity in accordance with the CLP Regulation as the acute oral toxicity is >2000 mg/kg bw and as the acute dermal toxicity is >5000 mg/kg bw.