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Description of key information

The substance has a rat LD50 > 2000 mg/kg bw by oral and dermal routes.

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:
Study Initiation Date : 29 September 2021
Experimental Starting Date : 30 September 2021
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)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
3 animals per Step (total 12 animals)
Age at treatment: 9-10 weeks
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The dose volume was 10 mL/kg body weight. Feed was offered after 3 to 4 hours of dosing.
Doses:
Step I and Step I- confirmation: 300 mg/kg
Step II and Step II- confirmation: 2000 mg/kg
No. of animals per sex per dose:
12
Control animals:
no
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality
Clinical signs:
other:
Body weight:
other body weight observations
Remarks:
No body weight changes
Gross pathology:
No gross pathology
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Based on the results of the experiment, it is concluded that the LD50 cut off value for the test item is 5000 mg/kg body weight when administered as a single dose by oral gavage to female Sprague Dawley rat as per OECD Guidelines for Testing of Chemicals (No. 423, Section 4: Health Effects) on conduct of “Acute Oral Toxicity - Acute Toxic Class Method” and classified as “Category 5 or Unclassified (2000 < ATE ≤ 5000)” as per the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).
Executive summary:

The test item, ESTERI METILICI ACIDI GRASSI DA OLIO ESSEBIOCHLOR45 was evaluated for Acute Oral Toxicity in Sprague Dawley rats.
A starting dose of 300 mg/kg body weight was selected from the four fixed dosen levels of 5, 50, 300 and 2000 mg/kg body weight, since there is no information available for the test item. A total of 12 females (3 females for each Step-I, Step-I confirmation, Step-II and Step-II confirmation) were used for the experiment. All the animals of Step-I and Step-I confirmation were administered with 300 mg/kg body weight and Step-II and Step-II confirmation were administered with 2000 mg/kg body weight of the test item by oral route. All the animals were observed for clinical signs of toxicity and mortality at 20 to 30 mins, 1 hr (±10 mins), 2 hrs (±10 mins), 3 hrs (±10 mins) and 4 hrs (±10 mins) post dosing on day 1 and once daily thereafter for clinical signs of toxicity and twice daily for mortality during the 14 days observation period. Body weights were recorded at receipt, on day 1 before test item administration, on day 8 and 15 during the observation period. At the end of observation period, all the animals were humanely sacrificed by carbon dioxide asphyxiation, subjected to necropsy and gross pathological examination.
In Step-I and Step-I confirmation, the animals dosed with 300 mg/kg body weight did not revealed any clinical signs of toxicity and no mortality was observed. Also in Step-II and Step-II confirmation, the animals dosed with 2000 mg/kg body weight did not revealed any clinical signs of toxicity and no mortality was observed. No treatment related changes were observed in body weight and percent change in body weight with respect to day 1 at 300 mg/kg body weight and 2000 mg/kg body weight. All the animals revealed physiologically normal increase in the body weight. No gross pathological changes were observed in any of the animals at 300 mg/kg body weight and 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw
Quality of whole database:
High quality of the database which is based on a GLP study.

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:
From 29 September 2021 to 30 September 2021
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
Animals were housed under standard laboratory conditions, in an environmentally monitored air-conditioned room with adequate fresh air supply (12 to 15 air changes per hour), room temperature 19.6°C to 22.9°C and relative humidity 47% to 65%, with 12 hours fluorescent light and 12 hours dark cycle. The temperature and relative humidity were recorded once daily.
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Topically application
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
two female rats
Control animals:
no
Details on study design:
Two animals were administered with the same dose level of 2000 mg/kg body weight. Exposure time 24 hours. All the animals were observed for clinical signs of toxicity and mortality at
20 to 30 mins, 1 hr (±10 mins), 2 hrs (±10 mins), 4 hrs (±10 mins) and
6 hrs (±10 mins) on treatment day 1 and thereafter once daily for clinical signs of
toxicity and twice daily for mortality during the 14 days observation period. The
treatment site was observed approximately at 24, 48 and 72 hours after removal of test
patch using the Draize scoring system.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality
Clinical signs:
other:
Body weight:
other body weight observations
Remarks:
No changes in body weight.
Gross pathology:
No gross pathology
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Under the experimental conditions employed and based on the above results, it is
concluded that the acute dermal median lethal dose (LD50) of test item, ESTERI
METILICI ACIDI GRASSI DA OLIO ESSEBIOCHLOR45 in Sprague Dawley rats
is >2000 mg/kg body weight and classified as “Category 5 / Unclassified (2000 <
ATE ≤ 5000 mg/kg body weight)” according to the Globally Harmonized System
(GHS) of Classification.
Executive summary:

The test item, ESTERI METILICI ACIDI GRASSI DA OLIO ESSEBIOCHLOR45 was evaluated for Acute Dermal Toxicity in Sprague Dawley Rats. The study was performed in two phases i.e. range finding study and main study. Range finding study was performed with three female rats (one rat per step) and main study was performed with two female rats. On the day before the application of the test item, fur on the dorso-lateral area of the trunk of the animals was removed by clipping closely with an electric hair clipper and care was taken to avoid abrading the skin. The required quantity of the test item was applied as uniform film over an area of approximately 10% of the total body surface. The test item was held on to the applied surface by covering with cotton gauze dressing and wrapped with non-irritating adhesive tape. Finally the application site was wrapped with semi-occlusive dressing using crepe bandage. The contact period of test item was 24 hours. At the end of the contact period, the residual test item was washed using distilled water and dried with absorbent cotton. As there was no information on the test item, a starting dose of 200 mg/kg body weight was selected from the fixed dose levels of 50, 200, 1000 and 2000 mg/kg body weight. No clinical signs and mortality was observed at the dose level of 200 mg/kg body weight in range finding study. Further, one animal was dosed at 1000 mg/kg body weight. No clinical signs and mortality was observed at the dose level of 1000 mg/kg body weight in range finding study. Next one animal was dosed at 2000 mg/kg body weight. No clinical signs and mortality was observed at the dose level of 2000 mg/kg body weight in range finding study. Hence, during main study, two animals were administered with the same dose level of 2000 mg/kg body weight. No clinical signs and mortality was observed at the dose level of 2000 mg/kg body weight. No mortality was observed at any of the dosed steps. Hence, no further testing was carried out. All the animals were observed for clinical signs of toxicity and mortality at 20 to 30 mins, 1 hr (±10 mins), 2 hrs (±10 mins), 4 hrs (±10 mins) and 6 hrs (±10 mins) on treatment day 1 and thereafter once daily for clinical signs of toxicity and twice daily for mortality during the 14 days observation period. The treatment site was observed approximately at 24, 48 and 72 hours after removal of test patch using the Draize scoring system. The body weights were recorded at receipt, on day 1 before test item application, on days 8 and 15. At the end of observation period, all the animals were sacrificed under carbon dioxide asphyxiation and subjected to necropsy and detailed gross pathological examination. No mortality and clinical signs were observed. No skin reactions were observed in the treatment sites at 24, 48 and 72 hours after removal of test item using draize method. No treatment related changes in body weight and percent change in body weight with respect to day 1 were noted. Normal increase in body weights were noted during the observation period. No treatment related gross pathological changes were noted in any of the dosed animals (range finding study and main study) during necropsy.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw
Quality of whole database:
High quality of the database which is based on a GLP study.

Additional information

Justification for classification or non-classification

Based on the data available, the substance should not be classified for acute oral and dermal toxicity under CLP Regulation.