Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no deviations from standard test guidelines and no methodological deficiences, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Colourless liquid 99.2% purity
Storage at room temperature and in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
One control group and 3 test groups each of 5 male and 5 female rats.
The rats were selected so that males and females would be between 8 weeks and 12 weeks old on the day of exposure.
The rats were housed by sex in groups of 5 and acclimatisated to laboratory conditions for at least 5 days before the day of exposure.
The holding cages (size 35x53x25 cm) were made of stainless steel sheet and wire mesh and were suspended on a movable rack. While in their cages all rats had free access to a measured excess of food and tap water. Food and water supplies were analysed routinely to determine the levels of chemical or microbiological contaminants. Room lighting was by artificial light between 8 am to 8 pm daily.
The temperature and relative humidity of the hloding room air was monitired continuously. The temperature of the holding area during the study remained within the range of 21 °C ± 3°C and the relative humidity remained generally within the range 55% ± 15%. There were no extremes of temperature or humidity considered likely to have influenced the results of the study.

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
clean air
Details on inhalation exposure:
Three groups of rats were exposed continuously for 4 hours to a test atmosphere containing the vapour of the test substance. Each group was exposed to a different concentration of vapour.
A further group acting as a control received clean air only for 4 hours.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Concentrations were :
Group 2 2.08 mg/L
Group 3 6.34 mg/L
Group 4 4.21 mg/L
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
yes
Details on study design:
A supply of clean dried air was connected to the vapour generator and the supply pressure was adjusted to give a flow rate of 10 liters per minute measured at the generator outlet tube. An in-line flow meter was used to monitor air flow throughout the exposure.
A syringue filled with the test substance was fitted to the syringue pump and connected to the generator with PTFE tubing. A flow rate of 0.018 mL/minute was selected for the exposure of the first test group. This flow rate was expected to give a vapour concentration of approximatively 2 mg/L.
The rats to be exposed were placed into restraining tubes. The tubes were attached to the ports in the mid section of the chamber.
The syringue pump and air supply was switched on and the exposure timed for 4 hours, following a 7-minutes equilibration period.
Afetr 4 hours, the supply of test substance was discontinued and the exposure chamber was allowed to clear before the rats were removed for examination.
This procedure was repeated for groups 3 and 4 using flow rates of 0.055 mL/min and 0.039 mL/min respectively.
Following exposure, the rats were returned to the holding cages and food and water supplies were restored. The test rats were kept in a ventilated cabinet overnight and then returned to the holding room for the remainder of the observation period.
The control rats were returned to the holding room at the end of the exposure procedure.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
2.41 mg/L air
Based on:
test mat.
95% CL:
1.805 - 3.022
Exp. duration:
4 h
Mortality:
Group Level (mg/l) Mortality
M F Total
1 Control 0/5 0/5 0/10
2 2.08 1/5 2/5 3/10
3 6.34 5/5 5/5 10/10
4 4.21 5/5 5/5 10/10

One of the five males exposed to allyl bromide at 2.08 mg/L died on the day of exposure. Two of the five females exposed at this level were found dead at the early check on Day 1 of the observation period.
All male rats and 3/5 female rats exposed to allyl bromide at 6.34 mg/L died during the exposure. The 2 remaining females exposed at this level died shortly after exposure.
Two male and 2 female rats exposed at 4.21 mg/L died during exposure. Three male and 2 female rats exposed at this level died later on the day of exposure. The remaining female was found dead at the early check the following morning.
Clinical signs:
During the exposure
During exposure signs seen in rats exposed to allyl bromide were exaggerated respiratory movements and shallow breathing. Additional signs seen in rats exposed at 6.34 and 4.21 mg/L were restless behaviour and death.

During the observation period
Up to and including Day 1 of the observation period, signs seen in rats exposed to allyl bromide at 2.08 mg/L were wet fur around snout and jaws, gasping, exaggerated repiratory movements, slow and irregular respiration, occasional whole body tremors, lacrimation, staining around the uro-genital region, brown staining around the snout and/or jaws, pilo erection, hypothermia, half closed eyes, matted fur, clear discharge from the eyes and death. Surviving males and females exposed at this level were normal in appearance and behaviour by Days 5 and 4 of the observation period respectively.
One female exposed at 6.34 mg/L survived for 50 minutes after exposure to allyl bromide. Signs seen during this 50 minutes period were exaggerated repiratory movements, wet fur around the snout and jaws, lethargy and dark eyes.
Signs seen in rats following exposure to allyl bromide at 4.21 mg/L were gasping, occasional whole body tremors, lethargy and death.
Fur soiled with excreta was seen in all test and control rats during and immediately following exposure. This signs was attributed to the method of restraint.
Body weight:
In male rats surviving exposure to allyl bromide at 2.08 mg/L the rate of bodyweight gain for test rats was lower than that of the male control rats. The rate of body weight gain for female rats surviving exposure at this level was similar to that of the female control rats.
Gross pathology:
Slight to marked congestion of the lungs was found in all decedent rats exposed to allyl bromide. Dark or patchy congested areas on the lungs were seen in 1 male exposed at 2.08 mg/L, in 3 female rats exposed at 4.21 mg/L and 1 male and 1 female exposed at 6.34 mg/L. Areas of congestion were seen in rats exposed at 2.08 mg/L. The tracheas in decedent rats exposed at 4.21 mg/L were filled with a white frothy fluid. A dark appearance of the liver was seen in the majority of rats exposed at 6.34 mg/L.
Clear discharge from the snout was seen in the 2 decedent females exposed at 2.08 mg/L and yellow/brown staining was seen in one female rat exposed at 4.21 mg/L. Liquid in the mouth/nostrils was seen in decedent rats exposed at 4.21 mg/L.
There were no macroscopic abnormalities in surviving test rats and no abnormalities in the control rats.

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Allyl bromide does require labelling with the hazard statement H331 Toxic if inhaled in accordance with the CLP regulation
Executive summary:

In a GLP-compliant acute toxicity study conducted in accordance with standardised guideline OECD 403, the LD50 of the test material was calculated by exposing 5 males and 5 females Sprague-Dowley rats to three concentrations ranging from 2.08 to 6.34 mg/L via inhalation. Under the conditions of the test, mortality was observed even at the lower concentration. LD50 wa determined to be 2.41 mg/L of air.

Test material requires classification according to Regulation 1272/2008.