Registration Dossier

Administrative data

acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From September 9, 2015 to October 1, 2015
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guidelineopen allclose all
according to
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
according to
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
according to
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
Test type:
acute toxic class method

Test material

Test material form:
semi-solid (amorphous): gel
Details on test material:
- Name of test material (as cited in study report): Vegetable or animal oil, hydrogenated, reaction products with diethanolamine, maleic anhydride and sodium sulphite
- Lot No.: CH 192435/01
- Purity: Not applicable (UVCB)
- Organic Carbon: 30.2%
- Hydrotox No.: 15/5241
- Origin: DACC
- Stability: Stable within the durability and with appropriate storage conditions
- Solubility in water: ~1 g/L
- Appearance: Light beige liquid/paste
- Storage conditions: Ambient temperature, dark, dry
- Expiration date: July 15, 2015
- Safety directions: H315, H319. Use protective clothing: gloves and protection goggles.

Test animals

Details on test animals and environmental conditions:
Animal supply and acclimatisation
- Supplier: Harlan Italy s.r.l., San Pietro al Natisone (UD), Italy
- Age and body weight at study initiation: 6-7 weeks old; 150-174 g
- Date of arrival: September 03, 2015
- Weight range at arrival: from 160 to 168 g
- Acclimatisation period: At least 5 d

Animal husbandry
- Animals per cage: 3 during the study; up to 5 during acclimatisation
- Housing: Polisulphone solid bottomed cages measuring 59.5x38x20 cm with nesting material provided into suitable bedding bags
- Diet: 4 RF 18 (Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI) Italy)
- Diet supply: ad libitum throughout the study except for the dosing procedure

Environmental conditions
- Water: ad libitum
- Air changes: Approximately 15 to 20 air changes per h
- Temperature: 22±2°C
- Humidity: 55±15%

Administration / exposure

Route of administration:
oral: gavage
CMC (carboxymethyl cellulose)
Details on oral exposure:
Fasting procedure: Food was removed from the cages overnight prior to dosing (Day 1) and was made available approximately 4 h after dosing.
Dosing method: The formulated test substance was administered, by gavage, at a dose volume of 10 mL/kg using a plastic feeding tube attached to a graded syringe
Dose preparation: The test substance was suspended in vehicle i.e. 0.5% aqueous solution of carboxymethylcellulose in concentration of 200 mg/mL.
2,000 mg/kg bw
No. of animals per sex per dose:
Control animals:
not specified
Details on study design:
- Dosing: First group of 3 female animals was dosed at a level of 2,000 mg/kg bw. No mortality was observed. A second group of 3 female animals was then dosed at the same dose level. No further doses were investigated since the objective of the study had been achieved.
- Duration of observation period following administration: 14 d.
- Frequency of observations: Mortality and morbidity-All animals were checked twice daily.
- Body weight: All animals were weighed at allocation to the study (Day 1), on the day of dosing (Day 1) and on Days 2, 8 and 15. Body weight change calculated for Days 2, 8 and 15 of the dosing phase was relevant to Day 1 of the phase.
- Termination: Animals were sacrificed on Day 15 by carbon dioxide narcosis
- Necropsy: Necropsy was carried out on all animals (gross necropsy examination for both external and internal abnormalities, with particular attention to the gastro-intestinal tract).
- Clinical signs observation: Approximately 0.5, 2 and 4 h after dosing and daily thereafter for 14 d.

Results and discussion

Effect levels
Key result
Dose descriptor:
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
No mortality occurred.
Clinical signs:
No clinical signs were observed in any of the treated animals.
Body weight:
Changes in body weight observed during the study were within the expected range for this strain and age of animals.
Gross pathology:
No abnormalities were observed at necropsy examination performed on all animals at the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:
other: CLP criteria not met
The LD50 of the test substance was determined to be ≥2,000 mg/kg bw.
Executive summary:

A study was conducted to assess the acute oral toxicity of the test substance in rats according to OECD Guideline 423, EU Method B.1 and EPA OPPTS 870.1100, in compliance with GLP. In this study, groups of females were administered the test substance by gavage in a stepwise manner. Treated animals were then observed for mortality, clinical signs and body weight changes for 14 d and were then culled and subjected to gross pathological examination. In the first step, the test substance was administered to a group of 3 females at 2,000 mg/kg bw. A second group of 3 females was then dosed at the same level. No mortality and no signs of toxicity were observed. No abnormalities were recorded at necropsy. Based on the findings of the study, the oral LD50 of the test substance was determined to be >2,000 mg/kg bw (Caruso R, 2015).