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Administrative data

Description of key information

LD50 Oral (rat): 3900mg/kg bw 
LD50 Dermal (rabbit): >5000mg/kg bw

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparing to guidelines/standards, basic data is given.
Qualifier:
according to
Guideline:
other: no data (see comments)
Principles of method if other than guideline:
In this acute oral toxicity study, no details test guideline was presented. However, it is indicated that 10 animals (unspecified sex) per dose and 4 dose levels: 1730 mg/kg, 2470 mg/kg, 3510 mg/kg, and 5000 mg/kg. The results provided were: mortality, time of death of individual animals at different dose levels, signs of toxicity at each dose, and necropsy findings at each dose.
GLP compliance:
not specified
Test type:
other: no data
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Doses:
1730 mg/kg, 2470 mg/kg, 3510 mg/kg, and 5000 mg/kg
No. of animals per sex per dose:
10 anmials per dose and unspecific sex
Control animals:
no
Details on study design:
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
not specified
Dose descriptor:
LD50
Effect level:
3 900 mg/kg bw
95% CL:
>= 2 900 - <= 5 100
Mortality:
At 1730 mg/kg: 3/10 deaths (2 animals by day 1 and 1 anmial by day 4);
At 2470 mg/kg: 1/10 deaths (by day 1);
At 3510 mg/kg: 3/10 deaths (2 animals by day 1 and 1 animal by day 2).
At 5000 mg/kg: 9/10 deaths (6 animals by day 1, 2 animals by day 2 and 1 animal by day 3)
Clinical signs:
At 1730 mg/kg: diarrhea, lethargy;
At 2470 mg/kg: lethargy, piloerection, diarrhea, ptosis;
At 3510 mg/kg: lethargy, diarrhea, piloerection, comatose;
At 5000 mg/kg: lethargy, piloerection, chromorhinorrhea

Table 1: Necropsy observation

Doses (mg/kg)  1730 2470  3510  5000 
Normal    4  
Cannibalized      1  
Exudate, nose/mouth, red 1    1  
Exudate, nose/mouth, yellow        5
Exudate, nose/mouth, clear     1  
Exudate, nose/mouth, brown   1 1 6
Intestines, areas red 2   10 
Intestines, areas yellow
Intestines, bloated   1 9
Stomach bloated       1
Liver dark 3  
Liver mottled   6 1 1
Lungs, areas dark 3  
Lungs, dark       6
Lungs, fourescent red        1
Kidney dark  4  4
Kidney mottled    
Spleen dark    
Spleen large      2  3
Spleen mottled       
Bladder, blood contained    
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute median lethal oral doses (LD50) and their 95% confidence limits to rats of test substance was estimated to be:
LD 50: 3900 mg/kg bw (2900 - 5100 mg/kg bw; 95% C.I)
Executive summary:

In an acute oral toxicity study (1699 02/03), 40 rats (10 per group) were given single oral doses of Ligustral/Cyclal C/Trigustral at 1730, 2470, 3510 and 5000 mg/kg bw and observed after dosing.

Oral LD 50: 3900 mg/kg bw (2900 - 5100 mg/kg bw; 95% C.I)

The following treatment-related effects were noted: clincal signs (lethargy, diarrhea with piloerection, chromorhinorrhea and ptosis noted with higher doses); mortality (at the lowest dosage, 3/10 animals dies; at the highest dosage, only one animal survived during 4 days observation period); necropsy observations (intestines, liver, lungs, kidney and spleen showed abnormalities that appeared dose related. The stomach and bladder showed sporadic abnormalities).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
3 900 mg/kg bw
Quality of whole database:
The key study was the only study available and was assigned a Klimisch score of 2. The overall quality of the database is high.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparing to guidelines/standards, basic data is given.
Qualifier:
according to
Guideline:
other: no data (see comments)
Principles of method if other than guideline:
In this acute dermal toxicity study, no details test guideline was presented. However, it is indicated that 10 animals (unspecified sex) were dosed in a limit test (5000 mg/kg). The results provided were: mortality, time of death of individual animals, signs of toxicity, necropsy findings.
GLP compliance:
not specified
Test type:
other: no data
Limit test:
yes
Species:
rabbit
Strain:
not specified
Sex:
not specified
Type of coverage:
not specified
Doses:
5000 mg/kg
No. of animals per sex per dose:
10 animals per dose and unspecific sex
Control animals:
no
Details on study design:
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
At 5000 mg/kg dose: 2/10 deaths (by day 2)
Clinical signs:
At 5000 mg/kg dose: anorexia, lessened mobility due to severe edema & eschar of exposure site, ptosis - Animal 1 - days 6 through day 14. Emaciated - Animal - day 14.

Table 1: Necropsy observations

Doses (mg/kg) 5000
Normal
Cannibalized
Exudate, nose/mouth, red
Exudate, nose/mouth, yellow 2
Exudate, nose/mouth, clear
Exudate, nose/mouth, brown
Intestines, areas red
Intestines, areas yellow 1
Intestines, bloated 1
Intestines, contained dark green substance 1
Stomach bloated
Liver dark 5
Liver mottled 1
Lungs, white nodules
Lungs, areas dark 2
Lungs, dark
Lungs, flourescent red
Kidney dark
Kidney mottled 2
Kidney pale 1
spleen dark
spleen large
spleen mottled
Skin, sloughing of exposure area 1
Skin edema 8
Skin redness
Skin, hard/thick
Bladder, blood contained
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of Ligustral/Cyclal C/Trigustral in rabbits was found to be greater than 5000 mg/kg bw.
Executive summary:

In an acute dermal toxicity study (1699 02/03), 10 rabbits were given single dermal dose of Ligustral/Cyclal C/Trigustral at 5000 mg/kg bw and observed up to 14 days after dosing.

Dermal LD 50: >5000 mg/kg bw

There were 2/10 deaths on day 1. Signs of toxicity noted in animal 1 from day 6 through day 14 were anorexia, lessened mobility due to severe edema & eschar of exposure site and ptosis; animal 1 was emaciated by day 14. The following observations were noted during necropsy of all animals: intestines, liver, lungs, kidney and spleen showed abnormalities that appeared dose related. The stomach and bladder showed sporadic abnormalities. Skin sloughing of the exposure area (1/10); skin oedema (7/8), skin redness (9/10) and skin hard/thickness (6/10) were also noted.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The key study was the only study available and was assigned a Klimisch score of 2. The overall quality of the database is high.

Additional information

Acute inhalation toxicity is waived as both oral and dermal studies are available. Both studies had a Klimisch score of 2 and the results from both studies are acceptable to use in the human health risk assessment.


Justification for selection of acute toxicity – oral endpoint
Only 1 key study available.

Justification for selection of acute toxicity – inhalation endpoint
In accordance with column 2 of REACH Annex VIII, the information under 8.5.2 and 8.5.3 shall be provided for at least one other route in addition to the oral route. As the information for 8.5.1 and 8.5.3 is already available, an acute inhalation test is not required.

Justification for selection of acute toxicity – dermal endpoint
Only 1 key study available.

Justification for classification or non-classification

Based on the available information in the dossier, the substance Ligustral/Cyclal C/Trigustral (CAS No. 68039-49-6) does not need to classified for acute toxiciy for specific target organ toxicity - single exposure when the criteria outlined in Annex I of 1272/2008/EC are applied.