as a pesticide; however, approximately 50% of this amount was exported to other nations.20 Approximately 105,000 U.S. workers (Table 2) are potentially exposed to methyl bromide.15
Methyl iodide is produced on a limited commercial scale by any of the following methods: 1) the reaction of methanol and iodine in the presence of phosphorous; 2) the reduction of an aqueous solution of iodine with bisulfate ion to yield hydriodic acid, which reacts with dimethyl sulfate to form methyl iodide; or 3) the reaction of hydrogen gas, elemental iodine, and aqueous methanol,2 which is similar to the production method of methyl chloride and methyl bromide. Methyl iodide is used primarily as a methylating agent2 with approximately 400 U.S. workers (Table 2) potentially exposed.15
Exposure Standards and Guides
The current Occupational Safety and Health Administration (OSHA) permissible exposure limits (PEL's) (29 CFR 1910.1000) for occupational exposure to these monohalomethanes are as follows:21
|Methyl Chloride||100 ppm, 8-hr time-weighted average (TWA) concentration|
|200 ppm, acceptable ceiling concentration|
|300 ppm, acceptable maximum peak for 5 minutes in any 3-hr period above the acceptable ceiling for an 8-hr shift|
|Methyl Bromide||20 ppm (80 mg/m3), ceiling concentration; Skin|
|Methyl Iodide||5 ppm (28 mg/m3), 8-hr TWA; Skin|
The OSHA PEL's for occupational exposure to methyl chloride and methyl iodide are intended to protect against the neurotoxic effects of these compounds. For methyl bromide, the OSHA PEL is intended to protect against the development of pulmonary edema as well as neurotoxic effects. The PEL for methyl chloride is based upon ANSI Z37.18-1969 as developed by the American National Standards Institute (ANSI),22 while the PEL's for methyl bromide and methyl iodide are based upon the 1968 Threshold Limit Values (TLV®s) of the American Conference of Governmental Industrial Hygienists (ACGIH).23 At the present time, NIOSH has no recommended exposure limit for the monohalomethanes.
ACGIH in its 1984-85 edition of TLV®s makes the following recommendations:24
|Methyl Chloride||50 ppm (105 mg/m3), 8-hr TWA; 100 ppm (205 mg/m3), 15-minute TWA Short Term Exposure Limit (STEL)|
|Methyl Bromide||5 ppm (20 mg/m3), 8-hr TWA; 15 ppm (60 mg/m3), 15-minute STEL; Skin|
|Methyl Iodide||2 ppm (10 mg/m3), 8-hr TWA; 5 ppm (30 mg/m3), 15-minute STEL; A2; Skin|
The ACGIH has included methyl iodide in its list of suspected carcinogens, designated as Appendix A2 in the TLV® listing.24
The "Skin" notation for methyl bromide and methyl iodide in both the OSHA PEL's and the ACGIH TLV®s refers to the potential contribution to the overall exposure by the cutaneous route by either airborne or direct skin contact with the substance.
Results of Animal Studies
It has been reported that under similar testing conditions, the acute lethal concentrations capable of killing 50% of rats (LC50) exposed by inhalation for 30 minutes to methyl chloride, methyl bromide, or methyl iodide were 72,000 ppm, 2,800 ppm and 1,750 ppm, respectively.25 These data suggest that by this route of exposure methyl chloride is 26 times less toxic than methyl bromide and 41 times less toxic than methyl iodide.
Methyl chloride, methyl bromide, and methyl iodide were mutagenic for Salmonella typhimurium bacterial strains TA1535 and TA10.30,31 Because strain TA100 carries the same gene base-pair mutation as strain TA1535 and because both of these strains are sensitive to direct-acting, alkylating agents, a common mode of action for the three methylating agents is implied. An independent analysis of these data indicated that the relative mutagenic potencies of methyl chloride, methyl bromide, and methyl iodide were approximately in the ratios of 1:40:10.33 In addition, methyl bromide was found to be mutagenic in Escherichia coli bacteria,34 and methyl iodide was reported to be a direct-acting mutagen for mouse lymphoma L5178Y/TK+/-cells.35
Carcinogenic and Other Chronic Effects
In a 2-year methyl chloride inhalation study,26 male and female mice were exposed at concentrati