Lethality absorption

As a class of compounds, the two main toxicity concerns for nitriles are acute lethality and osteolathyrsm. A comprehensive review of the toxicity of nitriles, including detailed discussion of biochemical mechanisms of toxicity and stmcture-activity relationships, is available (12). Nitriles vary broadly in their abiUty to cause acute lethaUty and subde differences in stmcture can greatly affect toxic potency. The biochemical basis of their acute toxicity is related to their metaboHsm in the body. Following exposure and absorption, nitriles are metabolized by cytochrome p450 enzymes in the Hver. The metaboHsm involves initial hydrogen abstraction resulting in the formation of a carbon radical, followed by hydroxylation of the carbon radical. MetaboHsm at the carbon atom adjacent (alpha) to the cyano group would yield a cyanohydrin metaboHte, which decomposes readily in the body to produce cyanide. Hydroxylation at other carbon positions in the nitrile does not result in cyanide release. 

Symptoms appear much more slowly from skin absorption. Skin absorption great enough to cause death may occur in 1-2 h. Respiratory lethal dosages kill in 1-10 min, and liquid in the eye kills nearly as rapidly. Very small skin dosages sometimes cause local sweating and tremors but little other effects. Nerve agents are cumulative poisons. Repeated exposure to low concentrations, if not too far apart, will produce symptoms. 

In a review of data on occupational chemicals that may contaminate breast milk (Byczkowski et al. 1994), it is stated that lead may be excreted in milk in amounts lethal to the infant and that the metal may be mobilized from bone stores to milk during the lactation period. Even when the concentration of lead in mother s milk is low, the absorption of metals into the systemic circulation of infants is generally high when they are on a milk diet. To better understand the sensitivity of the nursing infant to chemicals, epidemiological studies, chemical monitoring, and model development and application are needed. 

Exposure to solid or liquid cyanogen halides can cause skin and eye irritation. Otherwise, casualties exposed to cyanides experience few effects at sublethal doses. Percutaneous absorption of a lethal dose may produce temporary rapid and deep breathing followed by convulsions and unconsciousness. Under these circumstances, the casualty will stop breathing within 2-4 minutes after exposure. Death will occur 4-8 minutes later. 

Effects of Overexposure VX is a lethal cholinesterase inhibitor. Doses which are potentially life-threatening may be only slightly larger than those producing least effects. Death usually occurs within 15 minutes after absorption of a fatal dosage. 

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