The potential genotoxicity of methylsulfonylmethane, a crystalline organic sulfur, derived from chemically modified lignin from plants was evaluated using in vitro and in vivo assays. In the bacterial reverse mutation test using Salmonella typhimurium TA98. TA 100, TA 153 5, and TA 1538, methylsulfonylmethane did not induce any significant increase of His' revertants. In the in vitro chromosome aberration test using Chinese Hamster Lung (CHL) cells, no aberration effects were seen. In the in vivo evaluation using a micronucleus test, negative results were obtained. Accordingly, the results indicated that methylsulfonylmethane is not genotoxic and its use is unlikely to present a potential hazard.
Abstract: Methylsulfonylmethane is a type of organic sulfur compound found in minute amounts in foods, such as milk, vegetables, and fruits (Pearson et al., 1981) and it is approximately 34% of sulfur in composition. Next to calcium, phosphorus, and potassium, sulfur is the fourth most abundant mineral found in the body and it has been confirmed by research in guinea pigs that the sulfur in MSM is incorporated into the sulfur-containing amino acids, cysteine and methionine (Richmond, 1986). Recent studies report that MSM has a mitigating effect on arthritis (Hasegawa et al., 2004), an anti-inflammatory effect (Hasegawa et al., 2005), and an anti-allergy effect (Barrager et al., 2002) however, it has been brought to attention that the amount of MSM contained in food is minute because available MSM becomes damaged during processing and cooking (Steely, 1994), thus it is necessary to replace it with supplements in order to expect functionality of MSM. Furthermore, as a functional food in Japan, the target daily intake amount has been determined as 3g and it is equivalent to 0.06g/kg-BW estimating that a human’s weight is 50kg. It has been substantiated in toxicity tests with rats that there is no indication of any toxicity when administering 2.0g/kg-BW in a single dose as well as administering 1.5g/kg-BW daily, for 90 days (Horvath et al., 2002). Furthermore, 1.5g/kg-BW, the amount used for the 90-day repetitive dose test, is equivalent to the 25 times more than the target daily intake amount. In order to confirm safety with a dose that is higher than what Horvath et al. reports, single dose and 13-week repetitive administration toxicity tests of MSM were conducted.
Methylsulfonylmethane (MSM) is a sulfur-containing compound found in a wide range of human foods including fruits, vegetables, grains, and beverages. More recently, it has been marketed as a dietary supplement worldwide. The objective of this study was to evaluate the pharmacokinetic profile and distribution of radiolabeled MSM in rats. Male Sprague-Dawley rats were administered a single oral dose of [35S]MSM (500 mg/kg), and blood levels of radioactivity were determined at different time points for up to 48h. Tissue levels of radioactivity at 48 and 120h and urine and fecal radioactivity levels were measured at different time points for up to 120h following [35S]MSM administration to rats. Oral [35S]MSM was rapidly and efficiently absorbed with a mean tmax of 2.1h, Cmax of 622 µg equiv/mL, and AUC0-inf of 15124 h•μg equiv/mL. The t1/2 was 12.2h. Soft tissue distribution of radioactivity indicated a fairly homogeneous distribution throughout the body with relatively lower concentrations in skin and bone. Approximately 85.8% of the dose was recovered in the urine after 120h, whereas only 3% was found in the feces. No quantifiable levels of radioactivity were found in any tissues after 120h, indicating complete elimination of [35S]MSM. The results of this study suggest that [35S]MSM is rapidly absorbed, well distributed, and completely excreted from the body.
Methylsulfonylmethane (MSM) is a metabolite of dimethyl sulfoxide, and occurs naturally at low levels in many foods. MSM has received wide attention as a dietary supplement to promote joint health. The objective of these studies was to determine the developmental toxicity potential of MSM when administered orally to pregnant rats during the period of major organogenesis and histogenesis. In a preliminary dose-finding study, distilled MSM microprill (i.e., microspherical pellets of MSM) was administered by oral gavage at dose levels of 0 (vehicle control), 50, 250, 500, and 1000 mg/kg/day to 8-9 sperm-positive female Sprague-Dawley rats/group/day on gestation days 6-20. No evidence of maternal or fetal toxicity was observed. For the definitive developmental study, four groups of 24-25 timed-bred primiparous female rats were administered 0, 50, 500, or 1000 mg MSM/kg/day via gavage on gestation days 6-20. Maternal feed consumption, body weight, body weight gain, uterus weight and corrected body weight/body weight gain were unaffected by treatment. No evidence of maternal toxicity, and no significant differences in litter viability, litter size, or litter body weight were detected. Fetal evaluations failed to show any biologically significant increase in the incidence of anomalies in the MSM treated groups, and no malformations were seen in any of the fetuses. No evidence of fetal mortality, alterations to growth, or structural alterations were observed in the fetuses of dams administered 50-1000 mg/kg/day. Therefore, under the conditions of this study, the no-observed-adverse-effect level (NOAEL) for maternal and developmental toxicity was 1000 mg/kg/day.
ABSTRACT: Methylsulfonylmethane (MSM) is a sulfur donor compound occurring in nature and has been found in plants, milk, and urine of bovines and humans. MSM is a normal oxidation product of dimethylsulfoxide (DMSO). Sulfur is the sixth most abundant macro mineral in breast milk and the third most abundant mineral in the human body based upon percentage of total body weight and is an essential element for the structure of every living cell. MSM possess a broad range of health benefits including analgesic, anti-inflammatory, anti-allergy, while enhancing immune function by providing nutritionally essential organic sulfur and methyl groups. A scientific study has reported that 35S-labeled MSM was incorporated into essential sulfur-containing amino acids such as methionine and cysteine of guinea pig serum protein; thus MSM may provide a source of sulfur for essential sulfur-containing amino acids in animal and humans. Although the medicinal values of MSM have been studied, the cancer preventative effect of MSM remains unclear. In this study, the cancer preventative effect of MSM at the initiation state of multiple stage chemical carcinogenesis was investigated on a mammary breast carcinogenic animal model induced by DMBA in female SD rats. Forty-five female SD rats were divided onto three groups: age-matched control, DMBA, and DMBA+5%MSM. The experiment was started at the 35th postnatal day with water being given to the aged-matched control groups and the DMBA group and 5% MSM suppled to the MSM+DMBA group. DMBA (25mg/kg) was administered by mouth at the 50th postnatal day in the DMBA and DMBA+MSM groups. Five percent MSM was continuously supplied for an additional 90 days after DMBA administration. All animals were sacrificed at the 9th month after DMBA treatment to examine the pathological changes in the mammary glands by light microscopy. Compared to the age-matched control group, the DMBA treated group showd a variety of lesions, including epithelial hyperplasia (12.5%), benign tumors (25%), and carcinomas in-situ (25%). No benign tumor or carcinoma was observed in the MSM+DMBA and age-matched control group, which only showed normal histology or mild hyperplasia. Our preliminary results indicated that MSM may prevent mammary breast cancer at the initiation stage of chemical carcinogenesis. The mechanisms for this need further study.
Methylsulfonylmethane (MSM) is a popular dietary supplement used in a variety of conditions including pain, inflammation, allergies, arthritis, parasitic infections and the maintenance of normal keratin levels in hair, skin and nails. Despite its popularity, there is little published toxicology data on MSM. The objective of this study was to evaluate the acute and subchronic toxicity of MSM in rats at a dose five to seven times the maximum recommended dose in humans. MSM administered in a single gavage dose of 2 g/kg resulted in no adverse events or mortality. MSM administered as a daily dose of 1.5 g/kg for 90 days by gavage resulted in no adverse events or mortality. Necropsy did not reveal any gross pathological lesions or changes in organ weights. Renal histology of treated animals was normal. It is concluded that MSM is well tolerated in rats at an acute dose of 2 g/kg and at a subacute chronic dose of 1.5 g/kg.
Methionine, an essential amino acid, and cysteine are the major sulfur-containing amino acids in the body and both are thought to be synthesized predominantly in plants and micro-organisms. Methylsulfonylmethane (MSM) is a natural constituent of the environment in which it is found in plants, in milk and urine of both bovines and humans, is a normal oxidation product of dimethyl sulfoxide (DMSO) also in the natural environment and may be part of the natural global sulfur cycle. To determine whether sulfur from methylsulfonylmethane (MSM) is incorporated into sulfur amino acids, I fed 35S-MSM to guinea pigs. 35S was incorporated into peptidyl methionine and cysteine of guinea pig serum proteins. The specific activity of 35S-methionine was 30% greater than for 35S-cysteine, suggesting a precursor-product relationship. Total specific activity of serum proteins was increased by only 30% with a 100% increase of administered 35S-MSM, suggesting a limiting step in synthesis. Approximately 1% of the radioactivity was recovered in serum proteins, none in the feces and most was excreted in the urine. Microorganisms of intestinal lumen may be responsible for the incorporation of the 35S of MSM into sulfur amino acids. MSM may provide a source of sulfur for essential animal methionine by mechanisms not yet elucidated in either animals or micro-organisms.
An acute oral toxicity study was conducted on Sample No. 751, dimethyl sulfone, employing albino rats as test animals. The acute oral median lethal dose (LD50) was found to be ≥ 17020 mg/kg. The test material was administered in the form of a 25.0% (w/v) aqueous solution; however, the LD50 value is expressed in terms of actual Sample No. 751 received.