National Toxicology Program

Production and Producers:
Methylamines are produced by the interaction of methanol and ammonia over a catalyst (zinc chloride) at high temperature. The mono-, di-, and trimethylamines are all produced, and yields are regulated by reaction conditions. They are separated by azeotropic or extractive distillation. Methylamine can also be synthesized by heating ammonium chloride and formaldehyde (Budavari, 1989; Lewis, 1993).

Methylamine is listed in the EPA's TSCA Inventory (NLM, 1995). The production capacity of mono- di-, and trimethylamines in the United States is presented in Table 1. The relative production of the three can vary, but is roughly in a 2:3:1 ratio for 1988 and 1991 and in a 1.5:3:1.5 ratio for 1994. Most material is used captively for downstream products. Current producers of methylamine are Air Products & Chemicals, Inc. and E.I. DuPont de Nemours & Co., Inc. Air Products & Chemicals, Inc. increased capacity above 200 million lbs in 1993 as a result of a debottlenecking project in late 1993. E.I. DuPont de Nemours, & Co., Inc. raised capacity above 180 million lbs. through expanded distillation and planned to add capacity through debottlenecking in early 1995. Questra Chemicals, purchased by Rhone-Poulenc in late 1989, closed its 22-million-lb facility in 1991 (Anon., 1985, 1988, 1991, 1994).

Annual production of methylamine, according to information submitted to the US International Trade Commission (USITC, formerly the US Tariff Commission), grew from about 2 million lbs in 1957 to about 52 million lbs in 1987. Since that time the USITC has not disclosed annual production. According to non-confidential data received by the EPA, however, annual production of methylamine in 1989 was in the range of 51 to 106 million lbs (Walker, 1995a). Table 2 presents annual production and companies reporting manufacture of methylamine in the USITC publication Synthetic Organic Chemicals, United States Production and Sales (USTC, 1969, 1974; USITC, 1977, 1978, 1981-1994a,b; Walker, 1995a).

Distributors of methylamine listed in recent chemical directories include Allchem Industries, Inc., Coyne Chemical, Primachem, Inc., and UCB Chemical Sector (Hunter, 1994; Van, 1994). In addition, methylamine hydrochloride is available from Eastern Chemical, Esprit Chemical Co., R.S.A. Corp., and Spectrum Chemical Manufacturing Corp. (Hunter, 1994; Kuney, 1994; Van, 1994).

Demand for methylamines is presented in Table 3.

Use Pattern:
Methylamine has many applications in various industries. It is an important intermediate in the manufacture of a variety of products including pharmaceuticals (e.g., ephedrine), pesticides (e.g., 1-naphthyl-N-methyl carbamate, Vapam), explosives, surfactants, and accelerators. It is commonly used in the tanning and dyeing industries and as a fuel additive. It is also used as a polymerization inhibitor, a component of paint removers, a solvent, in the manufacture of photographic developers (e.g., N-methyl-p-aminophenol sulfate), and as a rocket propellant (Anon., 1963; Budavari, 1989; ACGIH, 1993; Lewis, 1993). Methylamine has also been reported to be a precursor chemical used in the illicit manufacture of methamphetamine (Skeers, 1992).

An overview of the use pattern for methylamine over the last decade is presented in Table 4..

Human Exposure
There is potential for occupational, consumer, and environmental exposure to methylamine.

Occupational

The National Occupational Exposure Survey (NOES), which was conducted by the National Institute for Occupational Safety and Health (NIOSH) between 1981 and 1983, estimated that 10,891 workers, including 1,410 female employees, were potentially exposed to methylamine in the workplace. The NOES database does not contain information on the frequency, level, or duration of exposure to workers of any chemical listed therein (NIOSH, 1990).

Consumer

There is the potential for consumer exposure to methylamine through the consumption of foods and beverages that contain methylamine as well as from the consumption of foods and beverages that contain substances that metabolize endogenously to methylamine.

Several studies contain data on estimated exposure to methylamine through the diet. Pfundstein and coworkers (1991) calculated a mean daily intake for Germans of primary amines of 29 mg/day for women and 37 mg/day for men, of which the contribution of methylamine was 13.6 and 16.6 mg/day, respectively. Siddiqi and coworkers (1992) reported increased exposure to dietary amines, including methylamine, and nitrate in a population at high risk for esophageal and gastric cancer in the Kashmir region in northern India. They concluded that regular consumption of the vegetable, Hak, and salted tea with indiscriminate use of sun-dried red chilies by the natives is responsible for their high exposure to methylamine (3.9 mg/day) and noted that the population has a high nitrate dietary burden (237 mg/day) which is largely due to the consumption of nitrate-accumulating Brassica vegetables. Specific information from these and other studies on the levels of methylamine in food is presented in the following section, Environmental Occurrence. In addition, Atawodi & Spiegelhalder (1994) found exposure to methylamine through the consumption of Nigerian medicinal plants and suggested that this might contribute to the endogenous formation of carcinogenic N-nitroso compounds and account for some of the cancer of unknown etiology in Nigeria.

There is also implication for exposure to methylamine as a metabolite of drugs containing N,N­dimethylamino groups. A study on the application of a method of assaying deaminase activity found that methylamine is a minor metabolite formed in the liver microsomes of rats, rabbits, and guinea pigs during in vitro deamination of drugs containing N,N-dimethylamino groups (Yamada et al., 1993).

Environmental

There is potential for exposure to methylamine in illicit methamphetamine manufacture because of its use as a precursor chemical. Heating of the chemicals to produce the drug produces vapors which permeate the interior materials of buildings, including sheetrock, carpets and other porous surfaces; and residues may continue to volatilize long after the illegal laboratory is dismantled (Skeers, 1992).

There is also potential for environmental exposure to methylamine through its occurrence in ambient air and rainwater.

Environmental Occurrence:
Methylamine occurs naturally in a variety of foods and beverages. Pfundstein and coworkers (1991) analyzed 264 food and beverage items purchased in 1989-1990 from supermarkets in West Germany for the presence of primary and secondary amines. They found that methylamine was the most abundant amine in the diet and was found at the highest concentrations. The main dietary sources were cooked and smoked fish products. High concentrations were also found in meat products, cheese, bread, vegetables, spices, and coffee. Table 5 presents the reported levels of methylamine in these foods and beverages. An earlier study by Neurath and coworkers (1977) also reported the presence of methylamine in fresh vegetables, grains, green salad, apples, bean salad, pickled cabbage, herring, cod roe, cheese, coffee, cocoa, and black tea purchased in Germany.

Methylamine has also been shown to occur as a metabolite following exposures of humans and animals to the industrial chemical methyl isocyanate (MIC) (Varma et al., 1990).

Siddiqui and coworkers (1992) identified methylamine as one of the most prevalent primary amines in foods and beverages in the Kashmir region of India. Table 6 presents the levels of methylamine detected in the various fresh and preserved vegetables, red chilies, and salted tea.

Methylamine has also been detected in milk (7.9 mol/100 g), cheese pizza (2.9mol/100 g), green beans (4.9mol/100 g), commercial samples of wine (0.19µg/mL in red wine, 0.14µg/mL in white wine), uncured and cured pork (1,490µg/kg and 730µg/kg, respectively), and at high levels in squid, octopus, and other seafoods (up to a mean of 255 ppm). Broiling of seafoods caused an elevation of methylamine (Patterson & Mottram, 1974; Lin & Chang, 1983a,b, 1984; Zeisel & DaCosta, 1986; Ibe et al., 1991).

Methylamine also occurs in herring brine, in certain plants such as Mentha aquatica, in crude methanol together with di- and trimethylamine (Budavari, 1989), and in Nigerian medicinal plants (Atawodi & Spiegelhalder, 1994).

In addition, methylamine has been detected in ambient air and rainwater. A Japanese study detected methylamine in air samples from a poultry farm (0.52 ppb) and a fermentation system for poultry wastes (0.97 ppb) and in emission gas from an incinerator of poultry wastes (12.4 ppb) (Kuwata et al., 1983). Methylamine was also identified in ambient air and rainwater samples collected in 1991 from several sites in southern Sweden. The concentration of methylamine in air samples collected about 1 kilometer from agricultural areas ranged from 150-1200 pmol/m³, was 480 and 1100 pmol/m³ in samples collected from rural areas, was 200 pmol/m³ in a sample collected from a coastal area, and ranged from 60-160 pmol/m³ in samples collected from residential areas. The concentration of methylamine in rainwater samples collected about 1 kilometer from agricultural areas ranged from 30-280 nM, was 90 nM in a sample collected from a rural area, was 40 nM in a sample collected from a residential area, and was <10 nM in a sample collected from a coastal area (Gronberg et al., 1992). Methylamine was measured at concentrations ranging from not detected to 231 nM in precipitation samples collected over a 1­year period (April 1988 - April 1989) in central Virginia (Gorzelska et al., 1992).

Following a rail accident that spilled the soil fumigant VAPAM into the Sacramento River in July, 1991, methylamine was identified at trace levels in Lake Shasta, California. It was not detected 1 week after the spill (del Rosario et al., 1994).

Regulatory Status:
The ACGIH-recommended threshold limit value-time weighted average (TLV-TWA) for methylamine is 5 ppm (6.4 mg/m³). The short-term exposure limit (STEL) is 15 ppm (19 mg/m³) (ACGIH, 1994). The OSHA permissible exposure limit (PEL) is 10 ppm (12 mg/m³) averaged over an 8-hour work shift. A STEL has not been determined (OSHA, 1994). The NIOSH-recommended exposure limit for methylamine is 10 ppm (12 mg/m³), averaged over a 10­hour work shift (NIOSH, 1994).

The following actions have been taken by the TSCA Interagency Testing Committee (ITC) on methylamine (Walker, 1995b).

• A dossier (IR-481) was completed in June 1986.
  

• Methylamine was deferred April 9, 1987 for environmental effects because releases of the chemical from manufacturing and processing do not appear to contribute significantly to the level of the chemical in the environment, where the amines are rapidly degraded.
  

• Relatively high levels of the methyl amines occur naturally in a variety of animal and plant species.
  

• Methylamine was deferred for health effects because a worker exposure assessment by EPA concluded that worker exposures to methylamines during production and use would be quite low.