2-bromobutane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-09-27 to 2016-10-18

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)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF No 8147, 11/2000

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-bromobutane

EC Number:

201-140-7

EC Name:

2-bromobutane

Cas Number:

78-76-2

Molecular formula:

C4H9Br

IUPAC Name:

2-bromobutane

Test material form:

liquid

Details on test material:

- Name of test material (as cited in the report): JNJ-47961173-AAA
- Physical state: Liquid
- Colour: Colourless

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: M15IB3251
- Expiration date of the lot/batch: 2017-04-07 (retest date)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: no data
- Solubility and stability of the test substance in the solvent/vehicle: no data

OTHER SPECIFICS
- Correction factor: 1

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: 6 female rats (nulliparous and non-pregnant), Wistar strain Crl:WI (Han) (outbred, SPF-Quality); Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 8 weeks old
- Weight at study initiation: 133-153 grams
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test item. Water was available ad libitum.
- Housing: Group housing of 3 animals per cage in labeled Makrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS- J. Rettenmaier & Sohne GmbH + CO. KG, Rosenberg, Germany) and paper as cage enrichment (Enviro-dri, Wm. Lillico &Son (Wonham Mill Ltd.), Surrey, United Kingdom).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): at least 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12-hour light/12- hour dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1.64 mL/kg

DOSAGE PREPARATION (if unusual): The test item was dosed undiluted as delivered by the Sponsor. The test item was kept at room temperature for a maximum of 4 hours prior to dosing. No correction was made for purity of the test item as the correction factor is 1. Adjustment was made for specific gravity of the test item.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: the dose level was selected based on toxicity data (e.g. existing human and animal data, literature, substance data supplied by the Sponsor, analysis of structure activity relationships (SAR) and in vitro, ex-vivo and in vivo tests) of the test item (specified and approved by the Study Director in the study files).

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The signs were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
- Necropsy of survivors performed: yes- At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occurred.

Clinical signs:

other: Lethargy, flat posture, hunched posture, slow breathing, shallow respiration, piloerection, salivation, ptosis and/or uncoordinated movements were noted for all animals between Days 1 and 3.

Gross pathology:

Several dark red foci of the thymus were noted for one animal. Macroscopic post mortem examination of the other animals at termination did not reveal any abnormalities.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of 2-bromobutane in Wistar rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Based on these results, 2-bromobutane does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).