[(2,4-dibromophenoxy)methyl]oxirane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February - May 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

[(2,4-dibromophenoxy)methyl]oxirane

EC Number:

243-606-2

EC Name:

[(2,4-dibromophenoxy)methyl]oxirane

Cas Number:

20217-01-0

Molecular formula:

C9H8Br2O2

IUPAC Name:

2-[(2,4-dibromophenoxy)methyl]oxirane

impurity 1

Reference substance name:

2,4-dibromophenol

EC Number:

210-436-5

EC Name:

2,4-dibromophenol

Cas Number:

615-58-7

Molecular formula:

C6H4Br2O

IUPAC Name:

2,4-dibromophenol

impurity 2

Reference substance name:

[(p-bromophenoxy)methyl]oxirane

EC Number:

218-656-3

EC Name:

[(p-bromophenoxy)methyl]oxirane

Cas Number:

2212-06-8

Molecular formula:

C9H9BrO2

IUPAC Name:

2-[(4-bromophenoxy)methyl]oxirane

impurity 3

Reference substance name:

[(2,4,6-tribromophenoxy)methyl]oxirane

EC Number:

226-140-4

EC Name:

[(2,4,6-tribromophenoxy)methyl]oxirane

Cas Number:

5296-40-2

Molecular formula:

C9H7Br3O2

IUPAC Name:

2-[(2,4,6-tribromophenoxy)methyl]oxirane

Test material form:

liquid

Details on test material:

sample used for testing,
no further details

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: CG272
- Expiration date of the lot/batch: 11. July 2018
- Purity test date: not stated

RADIOLABELLING INFORMATION (if applicable)
not applicable

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: assumed stable
- Solubility and stability of the test substance in the solvent/vehicle: assumed soluble and stable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dobrá Voda, Slovak Republic
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 13 weeks
- Weight at study initiation: 190 - 245 g
- Fasting period before study: no
- Housing: up to 3 animals per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.5 ± 0.3°C
- Humidity (%): 53.6 ± 2.2 %
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: according to calculated dose
- Amount of vehicle (if gavage): not stated
- Justification for choice of vehicle: Olive oil is a standard vehicle according to OECD TG 423
- Lot/batch no. (if required): L52897
- Purity: not stated


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Available information indicated that the test item is likely to be non-toxic with regard to acute toxicity. A limit dose of 2000 mg/kg body weight was used as a starting dose.

Doses:

300, 2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed individually immediately after the administration of the test item and then 0.5, 1, 2, and 4 hours later. Then each animal was inspected daily for the next 14 days. Weekly weighing
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

no statistics applied during study

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

3/6 females survived the limit dose of 2000 mg/kg body weight and 6/6 females survived dose of 300 mg/kg.
1 animal of 3 died in the first step of 2000 mg/kg bw testing, 2 animals of 3 died in the second step of 2000 mg/kg bw.

Clinical signs:

Test item-related mortality in females treated with the test item in dose of 2000 mg/kg body weight was observed within 24 hours in 2 females and one female on Day 5 post-treatment. Animal died presumably during the night hours, because cadaver was in a state of autolysis.
Lethargy was observed in one animal between 0.5 – 1 hour post-treatment. Other animals were lethargic from 2 hours to 5 days post-treatment.
No mortality was observed in females treated with the test item at dose of 300 mg/kg body weight Animals lived through observation period without signs of intoxication. Neither change of health nor negative reactions were registered.

Body weight:

The body weight of the surviving animals treated with the dose of 2000 mg/kg mildly increased in 2 animals and no change of body weight during the study was observed for one animal.
Stagnation of the body weight in animals (except one female) treated with the dose of 300 mg/kg was observed between first and second week after administration.

Gross pathology:

All animals (except No 4; cadaver was autolysed) treated with the dose of 2000 mg/kg body weight were necropsied. During necropsy, no macroscopic findings were noticed.
All animals treated with dose of 300 mg/kg body weight were necropsied. During necropsy, no macroscopic findings were noticed.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 of the test item DENACOL EX-147 is greater 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 DENACOL EX-147 is classified in Category 4 with a LD50 cut off value 2000 mg/kg body weight, after single oral administration to Wistar rats.

Executive summary:

The test itemDENACOL EX-147 administeredto 6 females at limit dose of 2000 mg/kg body weight caused death of 3 females.Lethargy was observed within the observation period of 5 days post-treatment.Mild increase or stagnation of the body weight was observed.During necropsy, no macroscopic findings were observed.

The test itemDENACOL EX-147 administeredto 6 females at dose of 300 mg/kg body weight did not cause death. Nosigns of toxicity were observed in females during the first 4 hours or the 14-day observation period thereafter. Body weight stagnation in all animals (except one animal) was observed between week 1 and week 2.During necropsy, no macroscopic findings were observed.