The assessment of Methyl disulfide on human health

Methyl disulfide is an organic chemical compound with the molecular formula CH3SSCH3 which is the simplest disulfide. It is a flammable liquid with an unpleasant, garlic-like odor. The CAS NO is 624-92-0.

Methyl disulfide is used as a food additive in onion, garlic, cheese, meats, soups, savory flavors, and fruit flavors. Industrially,it is used in oil refineries as a sulfiding agent. It is also an effective soil fumigant in agriculture, registered in many states in the U.S. as well as globally. In this capacity, it is an important alternative in replacing methyl bromide, which is being phased out. This pesticide is marketed as "Paladin" by Arkema.

The following assessment about human health was produced by staff within the Bureau of Toxic Substance Assessment at the New York State Department of Health (DOH): 

Acute toxicity studies conducted on the Paladin formulated product were used by the U.S. EPA  as representative of Methyl disulfide(CAS NO:624-92-0) since the end product is composed of approximately 99 percent of the active ingredient. In these acute studies, Paladin was moderately toxic to laboratory animals via the oral route of exposure, but not very toxic via the dermal and inhalation routes of exposure. Paladin was a moderate eye irritant, but not a dermal irritant or sensitizer. The Paladin EC formulated product (93.8 percent Methyl disulfide) was moderately acutely toxic via the oral route of exposure, but not very toxic via the dermal route of exposure. In addition, Paladin EC was a moderate eye and skin irritant (tested on rabbits). Acute inhalation toxicity and dermal sensitization studies were not conducted on the Paladin EC formulated product, but the U.S. EPA allowed the results for the Paladin product to bridge this data gap. 

Methyl disulfide caused some effects in special acute and subchronic inhalation toxicity studies in rats. In a 24-hour continuous inhalation exposure study, this active ingredient did not cause any systemic toxicity up to a dose level of 18 parts-per-million (ppm) Methyl disulfide, the highest dose tested. Port-of-entry effects were characterized by an increase in the incidence of microscopic lesions and degeneration of the nasal tissues as well as inflammation of the olfactory and respiratory epithelia at 12.5 ppm; the no-observed-effect-level was 9 ppm. Methyl disulfide caused port-of-entry effects of acute inflammation, degeneration and hyperplasia in the nasal tissues at 1-day and 5-days in a 1- and 5-day inhalation toxicity study (6 hours per day exposure) in rats at 50 ppm, the lowest dose tested. Systemic toxicity characterized by decreased body weights and body weight gains was observed at 50 ppm in the 5-day portion of this study. In a 13-week inhalation toxicity study in rats, systemic toxicity consisting of clinical signs of toxicity as well as decreased body weights, body weight gains and food consumption was observed at 50 ppm; the NOEL was 10 ppm. Methyl disulfide additionally caused port-of-entry effects including minimal to moderate atrophy and microcavitation of the olfactory epithelia and respiratory squamous metaplasia in the anterior nasal cavity at 10 ppm, the lowest dose tested. 

Methyl disulfide also caused some effects in acute and subchronic inhalation neurotoxicity studies in rats. In the acute study, port-of-entry effects included red deposits on the mouth in females at 200 ppm and closed eyelids in both sexes at 100 ppm, the lowest dose tested. Systemic effects in this study were characterized by decreased total session locomotor activity in males and decreased total session motor activity in females at 100 ppm. In the subchronic study, Methyl disulfide caused decreases in total motor activity and body weight in males and decreases in overall body weight gain and food consumption in both sexes at 80 ppm; the NOEL was 20 ppm. Port-of-entry effects were characterized by degeneration of the nasal olfactory epithelium at 20 ppm; the NOEL was 5 ppm. 

Methyl disulfide caused some developmental toxicity in the offspring of pregnant rats, but not pregnant rabbits, exposed via inhalation to this chemical during organogenesis. In rats, maternal toxicity consisting of rough haircoat and decreased body weight, weight gain and food consumption occurred at a concentration of 50 ppm; the NOEL was 15 ppm. Developmental toxicity characterized by decreased fetal body weights and multiple skeletal developmental retardations was observed at a maternal concentration of 50 ppm; the NOEL was 15 ppm. Port-of-entry effects were not reported for this study, so a NOEL could not be established for this endpoint. In rabbits, neither maternal systemic effects nor developmental toxicity was observed at concentrations up to 135 ppm, the highest dose tested. Port-of entry effects consisting of macroscopic lung lesions (dark red discoloration) were observed at all concentrations including 15 ppm, the lowest dose tested. Methyl disulfide did not cause any reproductive effects in a two-generation reproduction study in rats up to concentrations of 80 ppm, the highest dose tested. Parental toxicity consisting of decreased body weight, body weight gain and food consumption occurred in F1 males at 20 ppm; the NOEL was 5 ppm.

The carcinogenic potential of Methyl disulfide has not been evaluated. Neither chronic toxicity nor carcinogenicity studies have been conducted on this active ingredient via oral or inhalation routes of exposure. However, Methyl disulfide was negative in a number of genotoxicity studies and the U.S. EPA has stated that a cancer assessment is not warranted at this time given these results. 

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