2,5-di-tert-butyl-p-benzoquinone

Endpoint summary

Description of key information

The purpose of the study was to evaluate the potential toxic effect of the Test Item 2,5-Di-tert-butyl- 1,4-benzoquinone when administered as a single oral dose to Wistar rats.

The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used. Available information indicated that the Test Item is likely to be non-toxic; therefore, a limit dose of 2000 mg/kg body weight was used as a starting dose.

At the dose of 2000 mg/kg bw signs of toxicity was observed on Day 2 after administration. On Day 5 two animals were found dead. One died on Day 3. On Day 6 the rest of the animals were sacrificed due to ethical reasons. At dose of 300 mg/kg bw no mortalities were found.

At dose of 2000 mg/kg bw four animals were sleepy and lethargic. On Day 3 and after mild tremor and hyperaemia of eyes, ears and mouth were observed in all animals. At dose of 300 mg/kg bw animals were lethargic from Day 1 to Day 6. On the subsequent days, negative reactions were not registered.

Body weights were reduced in the group of 2000 mg/kg bw, at week 1 (three animals ). No body weigh changes were observed in the group of 300 mg/kg bw.

To examine gross pathology in the animals of 2000 mg/kg bw group animals 1-3 could not be necropsied because of cadavers were autolyzed. Animals 4-6 were found to have pronounced hyperaemia of extremities, ears, eyes and mouth and hypertrophy of both adrenals (diameter about 5-7 mm) was recorded. In animals of 300 mg/kg bw group no findings macroscopic findings at necropsy.

Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that the 2,5-Di-tert-butyl-1,4-benzoquinone is classified in Category 4 with a LD50 cut off value 500 mg/kg body weight, after single oral administration to Wistar rats.

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:

6 July 2016 to 19 August 2016

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

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Females (if applicable) nulliparous and non-pregnant: [yes/no]
- Age at study initiation:
- Weight at study initiation:
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):

IN-LIFE DATES: From: To:

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE

- Lot/batch no. (if required): L52897


MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Available information on similar tested compounds indicate that the test item is likely to be nontoxic considering acute toxicity.

Doses:

300 mg/kg bw and 2000 mg/kg bw

No. of animals per sex per dose:

6+6 (all females)

Control animals:

no

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

500 mg/kg bw

Based on:

test mat.

Mortality:

At the dose of 2000 mg/kg bw signs of toxicity was observed on Day 2 after administration. On Day 5 two animals were found dead. One died on Day 3. On Day 6 the rest of the animals were sacrificed due to ethical reasons.
At dose of 300 mg/kg bw no mortalities were found.

Clinical signs:

other: At dose of 2000 mg/kg bw four animals were sleepy and lethargic. On Day 3 and after mild tremor and hyperaemia of eyes, ears and mouth were observed in all animals. At dose of 300 mg/kg bw animals were lethargic from Day 1 to Day 6. On the subsequent day

Gross pathology:

2000 mg/kg bw group: Animals 1-3 could not be necropsied because of cadavers were autolyzed. Animals 4-6 were found to have pronounced hyperaemia of extremities, ears, eyes and mouth and hypertrophy of both adrenals (diameter about 5-7 mm) was recorded.
300 mg/kg bw group: no findings macroscopic findings at necropsy.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 of the test Item 2,5-Di-tert-butyl-1,4-benzoquinone is higher than 300 mg/kg body weight and lower than 2000 mg/kg body weight after single oral administration to Wistar rats. Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that the test Item 2,5-Di-tert-butyl-1,4-benzoquinone is classified in Category 4 with a LD50 cut off value 500 mg/kg body weight, after single oral administration to Wistar rats.

Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the Test Item 2,5-Di-tert-butyl- 1,4-benzoquinone when administered as a single oral dose to Wistar rats.

The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used. Available information indicated that the Test Item is likely to be non-toxic; therefore, a limit dose of 2000 mg/kg body weight was used as a starting dose. Test item-related mortality was not observed during 24 hours and therefore in a second step another 3 females were treated at the same dose. Test item-related mortality was observed on Day 5 and Day 7 after administration. In the third step another 3 females were treated at the dose of 300 mg/kg body weight. All females survived 24 hours and 14-day observation period. Due to the delayed toxic effects of the Test Item, other females (fourth step) were treated 14 days after the first administration of the dose 300 mg/kg body weight. Toxicity sings were observed in females treated with the dose of 2000 mg/kg body weight on Day 2 after administration of the Test Item. Animals from the first group (No 1-3) were sleepy and lethargic. From Day 3 mild tremor and the hyperaemia of the eyes, ears and mouth were observed in all animals too. This behaviour was observed also next days. On Day 5 after administration of the test item,

animals No 2 and 3 were found dead. Female No 1 died on Day 7. Animals died probably during the night hours, their cadavers were found in a state of autolysis. Similar signs were observed in the same time period after test item administration in animals No 4-6. Animals No 1-3 could not be necropsied because their cadavers were autolysed. Due to ethical reasons, on Day 6, animals No 4-6 were sacrificed and were subjected to gross necropsy. Pronounced

hyperaemia of extremities, ears, eyes and mouth and hypertrophy of both adrenals (diameter about 5-7 mm) were recorded. No mortality was observed in females treated with the Test Item at the dose of 300 mg/kg body

weight. Animals were lethargic from Day 1 to the Day 6. On the subsequent days, negative reactions were not registered. Body weight losses or stagnation of body weight were observed after week 1 after administration of the Test Item. Between week 1and week 2 no body weight losses were registered in 5 females; in one female mild body weight decrease was registered during necropsy, no macroscopically findings were noticed. The LD50 of the Test Item 2,5-Di-tert-butyl-1,4-benzoquinone is higher than 300 mg/kg body weight and lower than 2000 mg/kg body weight after single oral administration to Wistar rats.

Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that the Test Item 2,5-Di-tert-butyl-1,4-benzoquinone is classified in Category 4 with a LD50 cut off value 500 mg/kg body weight, after single oral administration to Wistar rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

500 mg/kg bw

Quality of whole database:

Reliable without restrictions.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

According to the criteria in CLP Annex I, 2,5-Di-tert-butyl-1,4-benzoquinone is classified in Category 4 with a LD50 cut off value 500 mg/kg body weight.