PMID- 23800997
OWN - NLM
STAT- MEDLINE
DCOM- 20140829
LR  - 20151119
IS  - 1477-0903 (Electronic)
IS  - 0960-3271 (Linking)
VI  - 33
IP  - 1
DP  - 2014 Jan
TI  - The toxic chemistry of methyl bromide.
PG  - 81-91
LID - 10.1177/0960327113493299 [doi]
AB  - Methyl bromide (MeBr) is a chemically reactive compound that has found use as a 
      fire retardant and fumigant used for wood, soil, fruits and grains. Its use is 
      banned in many countries because of its ozone-depleting properties. Despite this 
      ban, the use of MeBr persists in some parts of the world (e.g. New Zealand) due 
      to its important role in maintaining strict biosecurity of exported and imported 
      products. Its high chemical reactivity leads to a broad toxicological profile 
      ranging from acute respiratory toxicity following inhalation exposure, through 
      carcinogenicity to neurotoxicty. In this article, we discuss the chemistry of 
      MeBr in the context of its mechanisms of toxicity. The chemical reactivity of 
      MeBr clearly underlies its toxicity. Bromine (Br) is electronegative and a good 
      leaving group; the delta+ carbon thus facilitates electrophilic methylation of 
      biological molecules including glutathione (GSH) via its delta- sulphur atom, leading 
      to downstream effects due to GSH depletion. DNA alkylation, either directly by 
      MeBr or indirectly due to reduction in GSH-mediated detoxification of reactive 
      alkylating chemical species, might explain the carcinogenicity of MeBr. The 
      neurotoxicity of MeBr is much more difficult to understand, but we speculate that 
      methyl phosphates formed in cells might contribute to its neurone-specific 
      toxicity via cholinesterase inhibition. Finally, evidence reviewed shows that it 
      is unlikely for Br(-) liberated by the metabolism of MeBr to have any toxicological 
      effect because the Br(-) dose is very low.
FAU - Bulathsinghala, A T
AU  - Bulathsinghala AT
AD  - Department of Chemistry, University of Canterbury, Christchurch, New Zealand.
FAU - Shaw, I C
AU  - Shaw IC
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20130625
PL  - England
TA  - Hum Exp Toxicol
JT  - Human & experimental toxicology
JID - 9004560
RN  - 0 (Disinfectants)
RN  - 0 (Flame Retardants)
RN  - 0 (Hydrocarbons, Brominated)
RN  - 0 (Mutagens)
RN  - 9V42E1Z7B6 (methyl bromide)
SB  - IM
MH  - Animals
MH  - Biological Transport
MH  - Biotransformation
MH  - Disinfectants/analysis/chemistry/pharmacokinetics/*toxicity
MH  - Flame Retardants/analysis/pharmacokinetics/*toxicity
MH  - Fumigation
MH  - Half-Life
MH  - Humans
MH  - Hydrocarbons, Brominated/analysis/chemistry/pharmacokinetics/*toxicity
MH  - Mutagens/analysis/chemistry/pharmacokinetics/*toxicity
MH  - Neurotoxicity Syndromes/etiology/physiopathology
MH  - Ozone Depletion
MH  - Tissue Distribution
OTO - NOTNLM
OT  - Methyl bromide
OT  - human toxicity
OT  - mechanisms of toxicity
OT  - neurotoxicity
EDAT- 2013/06/27 06:00
MHDA- 2014/08/30 06:00
CRDT- 2013/06/27 06:00
PHST- 2013/06/27 06:00 [entrez]
PHST- 2013/06/27 06:00 [pubmed]
PHST- 2014/08/30 06:00 [medline]
AID - 0960327113493299 [pii]
AID - 10.1177/0960327113493299 [doi]
PST - ppublish
SO  - Hum Exp Toxicol. 2014 Jan;33(1):81-91. doi: 10.1177/0960327113493299. Epub 2013 
      Jun 25.