Registration Dossier

Administrative data

Description of key information

LD 50 oral rat > 2000 mg/kg bw; LD 50 dermal rat > 2000 mg/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:
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)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
other: - Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han)
Vehicle:
water
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels:
No mortality occurred.


Hunched posture and/or piloerection were noted in all
animals on Day 1 and red faeces were noted in all animals on
Day 2.
Gross pathology:
Effects on organs:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 value of Everzol Orange ED-G Crude in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

Everzol Orange ED-G Crude was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).
No mortality occurred.

Hunched posture and/or piloerection were noted in all animals on Day 1 and red faeces were noted in all animals on Day 2.
The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of Everzol Orange ED-G Crude in Wistar rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline the LD5O cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results Everzol Orange ED-G Crude does not have to be classified and has no obligatory labelling requirement for oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2004) and EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Only one study is available and has the highest reliability. The experimental result of LC50 is more than 2000 mg/kg bw, according to the OECD 423 the LD50 cut-off value was considered to exceed 5000 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
other: JMAFF guidance (2000), including the most recent revisions
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar strain Crl:WI (Han)
Sex:
male/female
Type of coverage:
not specified
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: 5x7 cm on the back of the animal was clipped.
- % coverage: approx. 10% of the total body surface, i.e. approx. 25cm2 for males and 18 cm2 for females



Duration of exposure:
Single dosage, on Day 1.
Doses:
2000 mg/kg (10 mL/kg) body weight.
No. of animals per sex per dose:
No.1 of animals is male
No.2 of animals is male
No.3 of animals is male
No.4 of animals is male
No.5 of animals is male
No.6 of animals is female
No.7 of animals is female
No.8 of animals is female
No.9 of animals is female
No.10 of animals is female
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred.
Clinical signs:
Lethargy, hunched posture, uncoordinated movements, quick breathing labored respiration, piloerection chromodacryorrhoea, ptosis and/or hypothermia were shown by all animals between Days 1 and 3, and for one male hunched posture was also noted on Day 11.
The treated skin area of all animals showed scales and/or scabs between Days 4 and 15, and showed brown staining between Days 2 and 15. Due to brown-red discolouration of the treated skin on Day 2, no scoring of the treated skin area was possible on that observation day.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefor considered not indicative of toxicity.
Other findings:
No abnormalities were found at macroscopic post mortem examination of the animals.

TABLE 1 MORTALITY DATA
TEST DATE 1 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
HOURS AFTER TREATMENT 0 2 4                            
MALES 2000 MG/KG ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­
FEMALES 2000 MG/KG ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­ ­
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of Everzol Orange ED-G Crude in Wistar rats was established to exceed 2000 ma/kg body weight.
Executive summary:

Everzol Orange ED-G Crude was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred.

Lethargy, hunched posture, uncoordinated movements, quick breathing, labored respiration, piloerection, chromodacryorrhoea, ptosis and/or hypothermia were shown by all animals between Days 1 and 3, and for one male hunched posture was also noted on Day 11.

The treated skin area of all animals showed scales and/or scabs between Days 4 and 15, and showed brown staining between Days 2 and 15. The treated skin area of all animals showed scales and/or scabs between Days 4 and 15, and showed brown staining between Days 2 and 15. Due to brown-red discolouration of the treated skin on Day 2, no scoring of the treated skin area was possible on that observation day.

The body weight gain during the observation period was within the range expected for rats used in this type of study.
No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD5O value of Everzol Orange ED-G Crude in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, Everzol Orange ED-G Crude does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the: - Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007), - Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Only one study is available and has the highest reliability. The result was well described.

Additional information

Summary from report acute oral

Everzol Orange ED-G Crude was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred.

Hunched posture and/or piloerection were noted in all animals on Day 1 and red faeces were noted in all animals on Day 2. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of Everzol Orange ED-G Crude in Wistar rats was established to exceed 2000 mg/kg body weight. According to the OECD423 test guideline the LD5O cut-off value was considered to exceed 5000 mg/kg body weight.

Summary from report acute dermal

Everzol Orange ED-G Crude was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred. No abnormalities were found at macroscopic post mortem examination of the animals. The body weight gain during the observation period was within the range expected for rats used in this type of study.

Lethargy, hunched posture, uncoordinated movements, quick breathing, labored respiration, piloerection, chromodacryorrhoea, ptosis and/or hypothermia were shown by all animals between Days 1 and 3, and for one male hunched posture was also noted on Day 11.

The treated skin area of all animals showed scales and/or scabs between Days 4 and 15, and showed brown staining between Days 2 and 15. The treated skin area of all animals showed scales and/or scabs between Days 4 and 15, and showed brown staining between Days 2 and 15. Due to brown-red discolouration of the treated skin on Day 2, no scoring of the treated skin area was possible on that observation day.

The dermal LD5O value of Everzol Orange ED-G Crude in Wistar rats was established to exceed 2000 mg/kg body weight.

Justification for classification or non-classification

Based on these results, Everzol Orange ED-G Crude does not have to be classified and has no obligatory labelling requirement for acute oral toxicity and acute dermal toxicity according to CLP (EC1272/2008) and DSD (67/548/EEC).