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Appendix D PARAQUAT ISSUE Paraquat is a herbicide that is used throughout the world. It is available in an aerosol form, granules, and a water-soluble concentrate. As a result of accidental or suicidal swallowing of the water-soluble concentrate, more than 500 human fatalities have occurred (Barley et al., l977). In contrast, neither inhalation of the spray nor ingestion of paraquat granules has been shown to be of clinical importance (Fairshter and Wilson, l975). About 60 percent of the marijuana consumed in the United States is grown in Mexico. Since l975, in the attempt to reduce the illegal production of marijuana, the Mexican government has been spraying marijuana fields from airplanes. The herbicide kills the treated plants within l or 2 days. Marijuana producers have resorted to harvesting the plants soon after spraying, minimizing exposure to sunshine, so that they are not destroyed. The paraquat persists on the dried leaves. Samples of marijuana confiscated at the U.S.-Mexico border have disclosed that about 2l percent of the confiscated marijuana was contaminated with paraquat in varying concentrations. Paraquat damages the lungs, heart, kidneys, adrenal glands, central nervous system, liver, skeletal muscle, and spleen. In general, all effects but those on the lungs are transitory. The changes in the lungs of humans after ingestion appear to be dose-related: small amounts of the swallowed chemical may cause modest and reversible lung damage; in contrast, larger quantities cause lethal pulmonary fibrosis. An important element in paraquat toxicity is the fact that it is concentrated in the lungs where it does particular damage to the alveolar lining. In many respects, probably including the mechanism by which it damages the lungs, its effects resemble those of oxygen toxicity but seem to be less reversible (Smith and Heath, l976). With respect to marijuana, the use of paraquat as a herbicide entails the possibility of risk to two populations: (l) those who spray the paraquat and the workers in the fields who are exposed to an environment containing the paraquat spray, and (2) the marijuana smoker. To date, no toxic effects attributable to paraquat, per se, have been proved in either population. However, the observations thus far relate to the acute hazards of paraquat inhalation and do l86
l87 not provide any assurance about the long-term effects. Indeed, observations on other inhaled toxins suggest that exposure for many years may be prerequisite for the development of clinical disability. An important question with respect to the toxic effects of paraquat on the lungs is how much of the paraquat survives combustion and is transferred in the smoke to the gas-exchanging surfaces of the lungs. Studies conducted by NIDA indicate that as much as 0.2 percent of the paraquat in a marijuana cigarette appeared in a condensate of smoke prepared under laboratory conditions. The results suggested that a typical marijuana cigarette contaminated at approximately 500 ppmâa reasonable degree of contaminationâwould produce smoke containing up to l mg of paraquat. This experimental evidence has led to the prediction that a human smoker of five marijuana cigarettes per day would expose the lungs to approximately 5 mg of paraquat. Laboratory evidence derived from hamsters suggests the possibility of damaging the distal part of the airways (the bronchioles and the proximal alveolar ducts) by this exposure. These experiments and predictions suggest that an individual who continued to smoke paraquat-contaminated cigarettes would be a candidate for serious lung injury. The prospect probably would be greatly heightened by the toxic effects of the combusted marijuana. There are only a few observations of experimental animals that bear directly on the effects of inhaled paraquat (Kimbrough and Gaines, l970; Zavala and Rhodes, l978). These suggest that similar lesions are produced by ingested paraquat and by paraquat introduced into the airways. For example, the introduction of minute quantities of paraquat dichloride intrabronchially, in concentrations ranging from l0 mg to l00 mg, elicited focal pulmonary edema, hemorrhage, and fibrosis (Zavala and Rhodes, l978). The smaller doses are within the range to which a smoker of marijuana contaminated by paraquat might be exposed. However, the experimental evidence is not entirely relevant on several accounts: (l) paraquat arriving at the lung surfaces by inhalation from contaminated air or after smoking must be carried in the form of smoke, gas, or small droplets, because larger droplets, such as the aerosols used in agriculture, are apt to precipitate out in proximal airways, which are protected by cilia and mucus; (2) the intrabronchial installation of paraquat in a solution provides a different pattern of access to the gas-exchanging surfaces of the lungs than does inhalation of smoke, gas, or droplets; (3) because of its water solubility, paraquat that escapes pyrolyzation during smoking would be expected to be taken up by the tracheal bronchial tree and its branches before reaching the alveoli unless carried in the form of smoke, gas, or small droplets. In essence, the evidence concerning the injurious effects of paraquat inhaled after either spraying or smoking is too meager for conclusions. The observations available since l975 have not proved that paraquat, per se, is harmful to the lungs. On the other hand, the clinical experience to date, coupled with the increasing understanding of the biochemical basis for paraquat toxicity, raises the serious possibility that continued exposure to inhaled paraquat is likely to be harmful to the lungs, that the predominant effect
l88 will be diffuse interstitial fibrosis, and that if exposure is sufficiently intense over years, respiratory insufficiency, disability, and death may reasonably be expected to ensue. REFERENCES Fairshter, R.D. and Wilson, A.F. Paraquat poisoning: Manifestations and therapy. Am. J. Med. 59:75l-753, l975. Harley, J.B., Grinspan, S., and Root, R.K. Paraquat suicide in a young woman: Results of therapy directed against the superoxide radical. Yale J. Biol. Med. 50:48l-488, l977. Kimbrough, R.D. and Gaines, T.B. Toxicity of paraquat to rats and its effect on rat lungs. Toxicol. Appl. Pharmacol. l7:679-690, l970. Smith, P. and Heath, D. Paraquat. CRC Crit. Rev. Toxicol. 4:4ll-445, l976. Zavala, D.C. and Rhodes, M.L. An effect of paraquat on the lungs of rabbits. Chest 74:4l8-420, l978.