Pentaerythritol tetrabenzoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10.04.2018 - 25.04.2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

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:

Pentaerythritol tetrabenzoate

EC Number:

224-079-8

EC Name:

Pentaerythritol tetrabenzoate

Cas Number:

4196-86-5

Molecular formula:

C33H28O8

IUPAC Name:

3-(benzoyloxy)-2,2-bis[(benzoyloxy)methyl]propyl benzoate

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Name: Pentaerythritol tetrabenzoate
Appearance: off-white solid
Composition: Pentaerythritol tetrabenzoate >96%
CAS No.: 4196-86-5
EINECS-No.: 224-079-8
Molecular formula: C33H28O8
Molecular weight: 552.576 g/mol
Purity: >96%
Homogeneity: homogeneous
Expiry date: Nov. 2018
Storage: Room Temperature (20 ± 5°C)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Age at First Dose: 8 - 9 weeks; female animals were non-pregnant and nulliparous
Animal Health: Health condition of animals was examined by a veterinarian before initiation of the study.
Acclimation: The animals were acclimated under the conditions identical to the conditions during the experiment 5 days prior to the start of treatment. The acclimation was according to the standard operation procedure.
Housing Condition: The animals were housed in plastic cages suspended on stainless steel racks, 3 animals per cage in a room equipped with central airconditioning. The average room temperature was maintained within the range of 22.85 ± 0.59 °C, relative humidity within 54.53 ± 3.30%. The light regimen was set to a 12-hour light /12-hour dark cycle. Sanitation was performed according to the standard operation procedures.
Diet: The laboratory food ssniff (Spezialdiäten GmbH, Germany) was offered at recommended doses each day approximately at the same time.
Water: The animals received tap water for human consumption ad libitum. The quality of drinking water is periodically analysed and recorded.
Bedding: Lignocel S3/4, Lufa - ITL GmbH, Germany
Animals Identification: The animals in the cage were marked by a line (I - III) on the tail with a waterproof marker. Each cage was marked with the study code, ID
of animals and date of administration of the test item.
Justification for the Choice of Species: Normally females are used for testing according to OECD TG 423 because females are typically the more sensitive gender.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

The test item was administered in a single dose by gavage using a metal stomach tube. Animals were fasted 10-12 h prior to dosing (food but not water was withheld over-night). Following a period of fasting, animals were weighed and the test item administered. After test item administration, food was withheld for further 3-4 hours.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

The starting dose could be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg body weight. A limit dose of 2000 mg/kg body weight was used as a starting dose. One group of 3 females was dosed. Test item related mortality was not observed within 24 hours after administration and therefore, in a second step, another 3 females were treated at the same dose.

The required amount of the test item (according to the body weight and dose) was mixed with vehicle (Olive oil) shortly before administration. The dose of 2000 mg/kg was administered in a volume of 5 mL/kg body weight.

The test item was administered in a single dose by gavage using a metal stomach tube. Animals were fasted 10-12 h prior to dosing (food but not water was withheld over-night). Following a period of fasting, animals were weighed and the test item administered. After test item administration, food was withheld for further 3-4 hours.

Animals were observed individually immediately after administration of the test item and 0.5, 1, 2, and 4 hours later. Each animal was inspected daily for the next 14 days. Observations included: changes in skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity, and behavioural pattern. Particular attention was given to potential neurologic endpoints such as tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Individual weights of animals were measured immediately prior to administration of the test item and weekly thereafter. Weight differences after the first and the second week after administration were calculated and recorded.

All test animals were subjected to gross necropsy and the results were recorded for each animal.

Statistics:

Not relevant

Results and discussion

Preliminary study:

All three animals survived the initial limit dose of 2000 mg/kg bw.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All (6/6 females) animals survived the limit dose of 2000 mg/kg body weight by oral gavage.

Clinical signs:

No mortality was observed during the study. During the follow up period, no animals displayed signs of intoxication, change of health, nor any other adverse reaction.

Body weight:

At the end of the study the body weights of all animals were higher than the initial body weights. A stagnation of body weight in animal No 2 within the 1st week was observed and a slight decrease of body weights in animals No 3 and No 4 was observed between the first and second week after administration of the test item.

Gross pathology:

During necropsy, no macroscopic findings were observed.

Other findings:

None

Any other information on results incl. tables

Sex	Dose	ID	Result
Female	2000 mg/kg bw	1	No mortality
Female	2000 mg/kg bw	2	No mortality
Female	2000 mg/kg bw	3	No mortality
Female	2000 mg/kg bw	4	No mortality
Female	2000 mg/kg bw	5	No mortality
Female	2000 mg/kg bw	6	No mortality

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test item Pentaerythritol tetrabenzoate is greater than 2000 mg/kg body weight after single oral administration to Wistar rats. Pentaerythritol tetrabenzoate does not require classification and labelling for acute oral toxicity according to CLP Regulation (EC) No. 1272/2008.

Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the test item Pentaerythritol tetrabenzoate when administered as a single oral dose to Wistar rats. The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used. A limit dose of 2000 mg/kg body weight was used as a starting dose. The test item administered to 6 females at the limit dose did not cause death. At the end of the study the body weights of all animals were higher than the initial body weights. A stagnation of body weight in one animal within the 1st week after administration was observed and a slight decrease of body weights in two animals was observed between the first and second week after administration of the test item. During necropsy, no macroscopic findings were observed.

The LD50 of the test item Pentaerythritol tetrabenzoate is greater than 2000 mg/kg body weight after single oral administration to female Wistar rats. Pentaerythritol tetrabenzoate does not require classification and labelling for acute oral toxicity according to CLP Regulation (EC) No. 1272/2008.