Bromomethane

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 83-1 (Chronic Toxicity)

Deviations:

yes

Principles of method if other than guideline:

This study appears to conform to EU test method B31 with the following deviations
1. This study was carried out in the dog as opposed to the preferred species mentioned in the guidance, i.e. the rat. However the guidance does state that other species (rodent or non-rodent) may be used based on the results of previously conducted studies.
2. This study is described as a safety study as opposed to a toxicity study, with the highest dose selected for US registration of Methyl Bromide following specific discussions with the US EPA, as opposed to being selected as the dose most likely to ensure toxic effects.
3. Clinical observations should be carried out once daily as opposed to weekly.
4. Urinalysis should be carried out at the same time intervals as haematological analysis. However in this study urinalysis was carried out at 6 months and prior to study termination.

This study contains one major deviation in that the highest dose level was not selected as the most likely to ensure toxic effects. However it is felt that the study contains scientifically valid information.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

74-83-2

IUPAC Name:

74-83-2

Constituent 2

Reference substance name:

Bromomethane

EC Number:

200-813-2

EC Name:

Bromomethane

Cas Number:

74-83-9

Molecular formula:

CH3Br

IUPAC Name:

bromomethane

Details on test material:

Methyl Bromide: batch no.: SLV; purity: 100%

Test animals

Species:

dog

Administration / exposure

Details on study design:

3 groups of 4 dogs per sex were dosed 0, 0.5 and 1.5 ppm (equivalent to 0, 0.06 and 0.13 mg/kg day) Methyl Bromide fumigated food and 1 group of 8 dogs per sex was dosed 5.0 ppm (equivalent to 0.27 mg.kg day) Methyl Bromide fumigated food which was presented to dogs for a one hour feeding period, 5 days per week for a period of 12 months.

Clinical observations were made at regular intervals, body weights and food consumption was measured. Haematological analysis, serum chemistry analysis and urinalysis were carried out. Ophthalmological examinations were also conducted pretest and at selected intervals during the treatment period. Macroscopic and microscopic examinations were carried out and specific organs were weighted at study termination.

Results and discussion

Results of examinations

Details on results:

Mortality and physical observations
There were no unscheduled deaths or Methyl Bromide related physical observations seen during the course of this study.

Ophthalmoscopic examinations
There was no indication of any Methyl Bromide-related ocular disease

Body weights and food consumption
There were no Methyl Bromide-related effect on body weight, body weight gain or food consumption

Methyl Bromide intake information
T90 data indicated that the dogs had consumed about 75% of the total feed that they were going to eat during the first 30 minutes. The Methyl Bromide residual data indicated that the Methyl Bromide residual was about 50% of its T60 value at T90. An estimate of actual Methyl Bromide intake, or dose, was calculated based upon a time-weighted average. (TWA). For the highest dose group the target Methyl Bromide TWA intake was 0.125 mg/kg/day (5 ppm). However the actual Methyl Bromide TWA intake was 0.27 mg/kg/day.

Haematolology
There was no toxicologically significant effect on any haematology parameter produced by exposure to Methyl Bromide.

Clinical chemistry
There was no toxicologically significant effect on any clinical chemistry parameter produced by exposure to Methyl Bromide.

Urinalysis
There was no Methyl Bromide related-effect on any parameter seen in the urinalysis.

Terminal organ and body weights/body weight and organ/brain weight ratios
There was no Methyl Bromide-related effect seen on the terminal absolute or relative organ weights.

Macroscopic findings
A small number of macroscopic post mortem changes were noted in various organs and tissues, bearing no obvious relationship to the exposure of the animals to Methyl Bromide.

Microscopic findings
The results of microscopic examination of selected organs and tissues revealed no morphological evidence of Methyl Bromide related toxicity.

Effect levels

Dose descriptor:

NOEL

Effect level:

> 0.27 mg/kg bw (total dose)

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Fumigation of feed with Methyl Bromide, which led to Methyl Bromide averages intakes of up to 0.27 mg/kg/day for a year had no effect on any parameter measured. Under the conditions of this study, the NOEL for Methyl Bromide fumigated feed in dogs would be greater than 0.27 mg/kg/day of Methyl Bromide.