Esterification products of fatty acids, C18 (unsaturated) alkyl and adipic acid with pentaerythritol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 Jan 2022 - 26 Jan 2022

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2022

Report date:

2022

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted in 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Esterification products of fatty acids, C18 (unsaturated) alkyl and adipic acid with pentaerythritol

Molecular formula:

not applicable

IUPAC Name:

Esterification products of fatty acids, C18 (unsaturated) alkyl and adipic acid with pentaerythritol

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately 8 - 9 weeks old
- Weight at study initiation: 182 - 195 g
- Fasting period before study: Animals were deprived of food overnight (for a maximum of 20 h) prior to dosing and until 3 - 4 h after administration of the test item. Water was available.
- Housing: On arrival and following assignment to the study, animals were group housed (up to 3 animals of the same sex and same dosing group together) in polycarbonate cages (Makrolon
MIV type; height 18 cm) containing sterilized wooden fibers as bedding material (Lignocel S 8-15, JRS - J. Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles. Animals were separated during designated procedures / activities.
- Historical data: not given
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures. The feed was analyzed by the supplier for nutritional components and environmental contaminants. Results of the analysis were provided by the supplier. It is considered that there were no known contaminants in the feed that would interfere with the objectives of the study.
- Water: Municipal tap-water was freely available to each animal via water bottles. Periodic analysis of the water was performed. It is considered that there were no known contaminants in the water that would interfere with the objectives of the study.
- Acclimation period: The animals were allowed to acclimate to the Test Facility toxicology accommodation for at least 5 days before the commencement of dosing.
- Method of randomisation in assigning animals to test and control groups: Animals were assigned to the study at the discretion of the coordinating biotechnician, with all animals within ± 20% of the sex mean body weights. Animals in poor health or at extremes of body weight range were not assigned to the study. Before the initiation of dosing, a health inspection was performed, and any assigned animal considered unsuitable for use in the study were replaced by alternate animals obtained from the same shipment and maintained under the same environmental conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 (actual daily mean temperature during study period: 20 °C)
- Humidity (%): 40 - 70 (actual daily mean relative humidity: 50 - 56%)
- Air changes (per hr): ≥ 10 (with fresh air - no air recirculation)
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 05 Jan 2022 To: 26 Jan 2022

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: not specified; the dose volume for each animal was based on the body weight measurement prior to dosing; dose volume (mL/kg bw) was
calculated as follows: Dose level (g/kg bw) / spec.gravity or density (g/mL) * purity correction factor. Thus, 2 g/kg bw / 0.941 g/mL = 2.123 mL/kg bw (no purity correction factor required as UVCB).

DOSAGE PREPARATION: The dosing formulations were stirred continuously during dose administration.

CLASS METHOD:
- Rationale for the selection of the starting dose: The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg bw. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test item.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2 groups of 3 female animals (stepwise treatment)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Throughout the study, animals were observed for general health / mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed from their cages during observation, unless necessary for identification or confirmation of possible findings. Post-dose clinical observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate), particular attention being paid to the animals for the first hour after dosing. Animals were weighed individually on Day 1 (pre-dose), 8 and 15. A fasted weight was recorded on the day of dosing.
- Necropsy of survivors performed: yes

Statistics:

Not performed.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality occurred.

Clinical signs:

other:

Gross pathology:

The mean body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

Other findings:

No test item related abnormalities were found at macroscopic postmortem examination of the animals. Incidental findings included foci on the clitoral gland in two animals. This finding is more often seen in rats of this strain in this kind of studies and therefore considered not test item-related.

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

The oral LD50 value of Esterification products of fatty acids, C18 (unsaturated) alkyl and adipic acid with pentaerythritol in Wistar Han rats was established to exceed 2000 mg/kg bw.