Mangansulfat

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants.

0.02 [mg/m3], as Mn (respirable fraction), 0.1 mg/m3, as Mn (inhalable fraction)

8 hr Time Weighted Avg: 0.2 mg/cu m /Manganese and inorganic compounds, as Mn/

Excursion Limit Recommendation: Excursions in worker exposure levels may exceed 3 times the TLV-TWA for no more than a total of 30 minutes during a work day, and under no circumstances should they exceed 5 times the TLV-TWA, provided that the TLV-TWA is not exceeded. /Manganese and compounds, as Mn/

8.2 [mg/m3]

14 [mg/m3]

430 [mg/m3]

EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. INHALATION: supply fresh air. If required provide artificial respiration.

The present study was designed primarily to investigate the biliary excretion of organic bile constituents following administration of the manganese-bilirubin combination. Experiments in hyperbilirubinemic Gunn rats were also performed to determine whether the unconjugated or the conjugated form of bilirubin is involved in this cholestatic interaction. Male Sprague-Dawley rats and male homozygous Gunn rats were given the following (iv.): (a) manganese (4.5 mg per kg); (b) unconjugated bilirubin (25 mg per kg); (c) bilirubin ditaurate (38 mg per kg); (d) manganese- unconjugated bilirubin, or (e) manganese-bilirubin ditaurate. Bile flow was measured and bile was analyzed for manganese, total bilirubin, bile salts, cholesterol and phospholipid content. The results show that: (i) manganese- unconjugated bilirubin treatment caused about manganese unconjugated bilirubin treatment caused about a 50% reduction in bile flow in Sprague Dawley rats, whereas in Gunn rats the manganese bilirubin ditaurate treatment resulted in about a 75% reduction, and (ii) in both strains, bile salt excretion was not appreciably modified during the cholestatic phase, as biliary bile salt concentration increased. The results suggest that although that although important differences regarding the form of bilirubin apparently exist, unconjugated bilirubin could be implicated in the cholestatic interaction in both strains of rats. Manganese bilirubin induced cholestasis is not related to a defect in bile salt excretion. The latter supports our contention that diminished canalicular membrane permeability to water is likely to be a key factor in this form of experimental cholestasis.

EFFECTS OF PARENTERAL METAL SUPPLEMENTS ON SALICYLATE TERATOGENICITY WAS STUDIED IN RATS. MANGANOUS SULFATE (10 MG/KG) SIGNIFICANTLY ENHANCED TERATOGENIC EFFECTS OF SODIUM SALICYLATE.

Manganese-bilirubin (Mn-BR)-induced cholestasis in rats is associated with altered lipid composition of various hepatic subcellular fractions. Increased bile canalicular (BCM) cholesterol content in Mn-BR cholestasis & the intracellular source of the accumulating cholesterol were investigated. To label the total hepatic cholesterol pool, male Sprague-Dawley rats were given ip 3H-cholesterol, followed 18 hr later by 2-14C-mevalonic acid (a precursor of cholesterol synthesis). To induce cholestasis, manganese (Mn, 4.5 mg/kg) & bilirubin (BR, 25 mg/kg) were injected iv; animals were killed 30 min after BR injection; canalicular and sinusoidal membranes, microsomes, mitochondria, & cytosol were isolated. Total cholesterol content of each fraction was determined by spectrophotometric techniques as well as radiolabeled techniques. In Mn-BR cholestasis, the total cholesterol concns of BCM & cytosol were significantly increased. Also, the contribution of 14C-labeled cholesterol (newly synthesized cholesterol) was enhanced in all isolated cellular fractions. The results are consistent with the hypothesis that accumulation of newly synthesized cholesterol in BCM is involved in Mn-BR cholestasis. An enhanced rate of synthesis of cholesterol, however, does not appear to be the causal event, as the activity of HMG-CoA reductase (rate-limiting enzyme in cholesterol synthesis), assessed in vitro, was decreased following Mn-BR treatment. Treatment with the Mn-BR combination may affect other aspects of intracellular cholesterol dynamics.

Manganese mainly affects the nervous system and may cause behavioral changes and other nervous system effects, which include movements that may become slow and clumsy. This combination of symptoms when sufficiently severe is referred to as “manganism”. (L228)

Manganese is a cellular toxicant that can impair transport systems, enzyme activities, and receptor functions. It primarily targets the central nervous system, particularily the globus pallidus of the basal ganglia. It is believed that the manganese ion, Mn(II), enhances the autoxidation or turnover of various intracellular catecholamines, leading to increased production of free radicals, reactive oxygen species, and other cytotoxic metabolites, along with a depletion of cellular antioxidant defense mechanisms, leading to oxidative damage and selective destruction of dopaminergic neurons. In addition to dopamine, manganese is thought to perturbations other neurotransmitters, such as GABA and glutamate. In order to produce oxidative damage, manganese must first overwhelm the antioxidant enzyme manganese superoxide dismutase. The neurotoxicity of Mn(II) has also been linked to its ability to substitute for Ca(II) under physiological conditions. It can enter mitochondria via the calcium uniporter and inhibit mitochondrial oxidative phosphorylation. It may also inhibit the efflux of Ca(II), which can result in a loss of mitochondrial membrane integrity. Mn(II) has been shown to inhibit mitochondrial aconitase activity to a significant level, altering amino acid metabolism and cellular iron homeostasis. (L228)

Manganese mainly affects the nervous system and may cause behavioral changes and other nervous system effects, which include movements that may become slow and clumsy. This combination of symptoms when sufficiently severe is referred to as “manganism”. (L228)

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. /Manganese sulfate monohydrate/ [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=10034-96-5]

MANGANESE SULFATE INJECTIONS STIMULATE HEMATOPOIESIS IN ANIMALS ... .

INTRAHEPATIC CHOLESTASIS CAN ... BE PRODUCED IN RATS BY ADMIN OF IV ... MANGANESE SULFATE ... THIS RESPONSE IS ASSOCIATED WITH DEVELOPMENT OF NECROTIC LESIONS, WHICH VARIES FROM FOCAL NECROSIS TO SUBTOTAL MIDZONAL NECROSIS. WIDESPREAD DILATATION OF BILE CANALICULI WITH LOSS OF MICROVILLI IS OBSERVED 20 HR AFTER TREATMENT. MAX BILIARY EXCRETION OF BILIRUBIN IS MARKEDLY DIMINISHED IN MANGANESE SULFATE-LOADED RATS; THERE IS NO CORRELATION BETWEEN EXTENT OF NECROSIS & CHOLESTATIC RESPONSE. /THIS/ TREATMENT FOLLOWED BY BILIRUBIN INFUSION CAN CAUSE MORE SEVERE CHOLESTASIS; RECOVERY OF BILE FLOW IS PARTIAL @ 24 HR & ESSENTIALLY COMPLETE @ 48 HR.

Manganese sulfate in sodium chloride has been tested for carcinogenic activity in the Strain A mouse lung tumor system. In this study, Strain A/Strong mice of both sexes, 6-8 weeks old, were injected intraperitoneally 3 times/week for a total of 22 injections. Three dose levels (132, 330, or 660 mg/manganese sulfate/kg) were employed that represented the maximum tolerated dose. Twenty mice were used at each dose level (10/sex) including vehicle (saline) and positive (urethan) controls. Mice were sacrificed 30 weeks after the first injection. A slight statistically significant increase (p= 0.068, Fisher Exact Test) in the number of pulmonary adenomas per mouse was associated with administration of the high dose. The response was somewhat elevated at the other doses, but was not statistically significant.

A comparison of the cytotoxic activity of cationic (MnSO4) and anionic (KMnO4) salts of inorganic manganese in the mouse in vivo indicated that the former was more strongly clastogenic than the latter. Mice were administered different doses of the salt orally over a period of 3 weeks. In general, both the frequencies of chromosomal aberrations in bone marrow cells and micronuclei were increasd significantly by both salts. Sperm-head abnormalities showed a significant enhancement as well. The clastogenic effects were directly related to the concentrations used and were not markedly influenced by the duration of treatment. In view of the known affinity of Mn2+ for chromosomal components, it has been suggested that the effects were mediated by these ions produced directly from MnSO4 and indirectly from KMnO4 following conversion under acidic pH of the gastric juices.

Male rats were exposed to manganese sulfate ip daily for a period of four weeks to see its effects on tissue levels and urinary excretion of total nicotinamide nucleotides. Increased levels of total nicotinamide nucleotides were observed in blood and brain while the levels were found to be decreased in liver. There was a progressive increase in the excretion of total nicotinamide nucleotides during the experimental period. Total nicotinamide nucleotides levels in blood and urine might serve as useful biological indicators of manganese toxicity.

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . /Manganese and related compounds/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or in severe respiratory distress. Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors for hypotension with a normal fluid volume. Watch for signs of fluid overload ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Manganese and related compounds/

... Toxicology and carcinogenesis studies were conducted by administering manganese (II) sulfate monohydrate (97% pure) in feed to groups of male and female F344/N rats and B6C3F1 mice for ... 2 yr. ... 2 YEAR STUDY IN RATS: Groups of 70 male and 70 female rats were fed diets containing 0, 1,500, 5,000, or 15,000 ppm manganese (II) sulfate monohydrate. Based on average daily feed consumption, these doses resulted in the daily ingestion of 60, 200, or 615 mg/kg body weight (males) or 70, 230, or 715 mg/kg (females). ... 2 YEAR STUDY IN MICE: Groups of 70 male and 70 female mice received diets containing 0, 1,500, 5,000, or 15,000 ppm manganese (II) sulfate monohydrate. These levels resulted in an average daily ingestion of 160, 540, or 1,800 mg/kg body weight (males) or 200, 700, or 2,250 mg/kg (females). ... CONCLUSIONS: Under the conditions of these 2-year feed studies, there was no evidence of carcinogenic activity of manganese (II) sulfate monohydrate in male or female F344/N rats receiving 1,500, 5,000, or 15,000 ppm. There was equivocal evidence of carcinogenic activity of manganese (II) sulfate monohydrate in male and female B6C3FI mice, based on the marginally increased incidences of thyroid gland follicular cell adenoma and the significantly increased incidences of follicular cell hyperplasia. /Mangansese sulfate monohydrate/

Manganese sulfate in nutrients and/or dietary supplements is generally recognized as safe when used in accordance with good manufacturing or feeding practices.

Substance added directly to human food affirmed as generally recognized as safe (GRAS).

Trace minerals added to animal feeds. These substances added to animal feeds as nutritional dietary supplements are generally recognized as safe when added at levels consistent with good feeding practice. Element: Manganese; Source compound: manganese sulfate. (All substances listed may be in anhydrous or hydrated form.)

Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. Manganese sulfate is included on this list.

... Substances for which a Federal Register notice has been published that included consideration of the serious health effects, including cancer, form ambient air exposure to the substance. Manganese (50 FR 32627; Aug. 13, 1985) is included on this list. /Manganese/

(IL) ILLINOIS 150 ug/l /Manganese/

(NY) NEW YORK 300 ug/l /Manganese/

(CA) CALIFORNIA 500 ug/l /Manganese/

(CT) CONNECTICUT 500 ug/l /Manganese/

(ME) MAINE 500 ug/l /Manganese/

(MN) MINNESOTA 300 ug/L /Manganese/