PRINCIPLES OF TOXICOLOGY

16.13 TOXIC PROPERTIES OF REPRESENTATIVE HALOGENATED SOLVENTS 393
Figure 16.20 Methyl chloride and methyl bromide.
Chloromethane is metabolized to methanol and hydrochloric acid, and the methanol subsequently
is oxidized to formaldehyde. There is a remarkable difference in individual human response to methyl
chloride exposure, with some subjects consistently showing several times slower metabolism and hence
much greater blood and expired air concentrations compared with other subjects. Chronic and subacute
exposure to methyl chloride predominantly affects the CNS, producing ataxia, staggering gait,
weakness, tremors, vertigo, speech difficulties, drowsiness, blurred vision, diplopia, personality
changes, visual or auditory hallucinations, nausea, and EEG abnormalities. In addition, cardiac
degeneration and depression of bone marrow activity have been reported. Incidents of acute exposure
to methyl chloride concentrations below lethal levels has resulted in pulmonary congestion and edema
in laboratory animals. Methyl chloride is considered a weak to moderate irritant to the eyes and skin.
Liquid methyl chloride splashing in the eyes or on the skin may result in defatting of the affected
tissues, anesthesia through freezing of the tissues, erythema, and blistering.
PHYSIOLOGIC RESPONSES TO METHYL CHLORIDE
Concentration (ppm) Response
10 Odor threshold in humans
50 TLV
510 Irritation threshold
3000 Lethal concentration in animal studies
Testicular degeneration, renal adenocarcinoma, and male infertility have been produced in experimental
animals following chronic exposure to methyl chloride. Teratogenic effects have been produced
in mice and rats following high-level exposure to methyl chloride, but its role as a human reproductive
hazard is not proven. Renal tumors have been induced in mice, but there is insufficient evidence to
classify methyl chloride as an animal or human carcinogen. Methyl chloride induced unscheduled
DNA synthesis, mutations, sister chromatid exchanges, and oncogenic transformation in a variety of
short-term test systems, and is a weak, direct-acting mutagen for bacteria and human cells in culture.
Methyl bromide, the brominated analog, primarily is used as a soil fumigant, as well as in a wide
range of grains, mills, warehouses, and homes. It also is used as a chemical intermediate, principally
as a methylating agent. It has found use as a fire-extinguishing agent, particularly in automatic
equipment for the control of engine fires on aircraft, but due to the inhalation toxicity of this material,
use as a fire extinguisher was limited to specialized applications. Methyl bromide is a dangerous
cumulative poison with delayed symptoms of central nervous system intoxication that may appear as
long as several months after exposure.
PHYSIOLOGIC RESPONSE TO METHYL BROMIDE IN HUMANS
Concentration (ppm) Response
1 TLV ®
21 Odor threshold
35–100 Reported initial acute effects range
300 Lethal inhalation concentration