Toxic level

Exposure to manganese dusts, fume, and compounds should not exceed the ceiling value of 5 mg/ms for even short periods because of the element s toxicity level. 

The time-weighted average (TWA) concentrations for 8-h exposure to bromine ttifluoride, bromine pentafluoride, chlorine ttifluoride, chlorine pentafluoride, and iodine pentafluoride have been estabHshed by ACGIH on a fluoride basis to be 2.5 mg/m. NIOSH reports (121) the foUowing inhalation toxicity levels for chlorine ttifluoride LC q monkey, 230 ppm/h LC q mouse, 178 ppm/h for chlorine pentafluoride LC q monkey, 173 ppm /h mouse, 57 ppm/h. 

Sodium Nitrate and Sodium Nitrite. Nitrates and nitrites ate used in meat-curing processes to prevent the growth of bacteria that cause botulism. Nitrates have been shown to form low, but possibly toxic, levels of nitrosamines in certain cured meats. For this reason, the safety of these products has been questioned, and use is limited (80). 

Of the water-soluble vitamins, intakes of nicotinic acid [59-67-6] on the order of 10 to 30 times the recommended daily allowance (RE)A) have been shown to cause flushing, headache, nausea, and moderate lowering of semm cholesterol with concurrent increases in semm glucose. Toxic levels of foHc acid [59-30-3] are ca 20 mg/d in infants, and probably approach 400 mg/d in adults. The body seems able to tolerate very large intakes of ascorbic acid [50-81-7] (vitamin C) without iH effect, but levels in excess of 9 g/d have been reported to cause increases in urinary oxaHc acid excretion. Urinary and blood uric acid also rise as a result of high intakes of ascorbic acid, and these factors may increase the tendency for formation of kidney or bladder stones. AH other water-soluble vitamins possess an even wider margin of safety and present no practical problem (82). 

The hver of sharks and other oily fishes sometimes accumulate toxic levels of vitamin A, and cases of acute poisoning have been reported both among Eskimos and the Japanese. 

Since diketene is a strong eye irritant even at low levels, it has a strong warning effect. Diketene becomes unbearable before acute toxic levels are reached. Due to the risk of delayed lung edema, a physician should be consulted and the patient monitored carefully after exposure. 

Deficiency or Toxicity in Humans. Molybdenum deficiency in humans results in deranged metaboHsm of sulfur and purines and symptoms of mental disturbances (130). Toxic levels produce elevated uric acid in blood, gout, anemia, and growth depression. Faulty utiH2ation results in sulfite oxidase deficiency, a lethal inborn error. 

Parent substances and metaboHtes may be stored in tissues, such as fat, from which they continue to be released following cessation of exposure to the parent material. In this way, potentially toxic levels of a material or metaboHte may be maintained in the body. However, the relationship between uptake and release, and the quantitative aspects of partitioning, may be complex and vary between different materials. For example, volatile lipophilic materials are generally more rapidly cleared than nonvolatile substances, and the half-Hves may differ by orders of magnitude. This is exemplified by comparing halothane and DDT (see Anesthetics Insectcontholtechnology). 

Along with increasing evidence of health benefits from consumption of vitamins at levels much higher than RE) A recommendations comes concern over potential toxicity. This topic has been reviewed (19). Like all chemical substances, a toxic level does exist for each vitarnin. Traditionally it has been assumed that all water-soluble vitamins are safe at any level of intake and all fat-soluble vitamins are toxic, especially at intakes more than 10 times the recommended allowances. These assumptions are now known to be incorrect. Very high doses of some water-soluble vitamins, especially niacin and vitamin B, are associated with adverse effects. In contrast, evidence indicates that some fat-soluble micronutrients, especially vitamin E, are safe at doses many times higher than recommended levels of intake. Chronic intakes above the RDA for vitamins A and D especially are to be avoided, however. 

Detection. Many people can detect hydrogen cyanide by odor or taste sensation at the 1 ppm concentration in air, most at 5 ppm, but HCN does not have an offensive odor and a few people cannot smell it even at toxic levels. Anyone planning to work with hydrogen cyanide should be checked with a sniff test employing a known safe concentration. This test should be given periodically. Several chemical detection and warning methods can be employed. The most rehable are modem, electronic monitors based on electrolytes that react with hydrogen cyanide. 

Chemical Reactivity - Reactivity with Water. When potassiiun cyanide dissolves in water, a mild reaction occurs and poisonous hydrogen cyanide gas is released. The gas readily dissipates, however if it collects in a confined space, then workers may be exposed to toxic levels. If the water is acidic, toxic amounts of the gas will form instantly Reactivity with Common Materials Contact with even weak acids will result in the formation of deadly hydrogen cyanide gas Stability During Transport Stable Neutralizing Agents for Acids and Caustics Not pertinent Polymerization Not pertinent Inhibitor of Polymerization Not pertinent. 

Required locations of gas detectors (sensors) are often specified by the authority having jurisdiction. For example, API RP 14C recommends certain locations for combustible detectors. These recommendations have been legislated into requirements in U.S. Federal waters by the Minerals Management Service. RP 14C should be referred to for specific details, but, basically, combustible gas detectors are required offshore in all inadequately ventilated, classified, enclosed areas. The installation of sensors in nonenclosed areas is seldom either required or necessary. Ignitible or high toxic levels of gas seldom accumulate and remain for significant periods of time in such locations. 

A rare hereditary condition known as galactosemia involves defects in galac-tose-l-P uridylyltransferase that render the enzyme inactive. Toxic levels of... 

Sorbitan [C6H80(0H)4] products have a particularly low toxicity level, being derived from the hexahydric alcohol sorbitol [CH2OH (CHOH)4 CH2OH], which is, in turn, produced by the reduction of glucose sugar. 

Fhtients with kidney disease may exhibit drug toxicity and a longer duration of drug action. The dosage of drugp may be reduced to prevent the accumulation of toxic levels in the blood or further injury to the kidney. 

Thiabendazole is contraindicated in patients with known hypersensitivity. Thiabendazole is used with caution in patients with hepatic or renal disease. Thiabendazole is a Pregnancy Category C drug and is used during pregnancy only if the potential benefit outweighs the risk to the fetus. When thiabendazole is administered with the xanthine derivatives, the plasma level of the xanthine may increase to toxic levels. It is important to monitor xanthine plasma levels closely in case a dosage reduction is necessary. 

Most drugs can be expected to have potentially lethal effects, as their usefulness depends on their ability to infiuence physiological processes. However, the dose level at which toxic effects manifest should be significantly higher than those required to produce a pharmaceutical response, so that a good safety margin exists between therapeutic and toxic levels. 

Chambers JE, Ma T, Boone JS, et al. 1994. Role of detoxication pathways in acute toxicity levels of phosphorothionate insecticides in the rat. Life Sci 54 1357-1364. 

Rider JA, Moeller HC, Puletti EJ. 1967. Continuing studies on anticholinesterase effect of methyl parathion, initial studies with guthion, and determination of incipient toxicity level of dichlorvos in humans [Abstract]. Fed Proc 26 427. 

More rapid elimination was needed than could be provided by passive diffusion in order to prevent tissue concentrations reaching toxic levels. 

The ammonia produced by enteric bacteria and absorbed into portal venous blood and the ammonia produced by tissues are rapidly removed from circulation by the liver and converted to urea. Only traces (10—20 Ig/dL) thus normally are present in peripheral blood. This is essential, since ammonia is toxic to the central nervous system. Should portal blood bypass the liver, systemic blood ammonia levels may rise to toxic levels. This occurs in severely impaired hepatic function or the development of collateral links between the portal and systemic veins in cirrhosis. Symptoms of ammonia intoxication include tremor, slurred speech, blurred vision, coma, and ultimately death. Ammonia may be toxic to the brain in part because it reacts with a-ketoglutarate to form glutamate. The resulting depleted levels of a-ketoglutarate then impair function of the tricarboxylic acid (TCA) cycle in neurons. 

Ferritin, an iron-binding protein, prevents ionized iron (Fe ) from reaching toxic levels within cells. Elemental iron stimulates ferritin synthesis by causing the release of a cytoplasmic protein that binds to a specific region in the 5 nontranslated region of ferritin mRNA. Disruption of this protein-mRNA interaction activates ferritin mRNA and results in its translation. This mechanism provides for rapid control of the synthesis of a protein that sequesters Fe +, a potentially toxic molecule. 

The quantitative measurement of toxicity level is expressed by parameters like NOEL (no observed effect level), NOAEL (no observed adverse effect level), and ADI (acceptable daily intake). The NOEL values are divided by 100 to obtain ADI values. The 100 safety factor derives from 10 x 10, where the 10s represent the animal-to-human conversion rate and the human variability factor. Currently, the most useful index of safety is the ADI, expressed as milligrams of test substance per kilogram of body weight (ppm), with the recommendation not to eat more than the ADI per day. The FDA, EU, and WHO agree on the ADI principle. 

These codes can be combined when a substance has multiple risks. Codes are then separated by a siash (for different means of penetration) or a dash (for risks of different nature). Thus 20/21/22 means that a substance is harmful by inhalation, skin contact and ingestion, if the substance is inflammable as well, it is 10-20/21/22. A compound can have different acute and chronic toxicity levels. For example, for phenylamine 20/21/22-40-48/23/24/25, ie harmful by inhalation, skin contact, ingestion possibility of irreversibie effects risk of toxic effects by inhalation, skin contact and prolonged ingestion. 

---