Vesicants acute toxicity

Not only is the acute toxicity of CR extremely low, with an estimated human LCt5Q over 100,000 mg mln/m, but the overt signs of exposure are even more transitory than those of CS. Eye Irritation passes In 15-30 min, and skin Irritation in 15-20 min. Erythema, which develops only on contaminated skin, passes In about an hour and does not lead to vesication or to contact sensitization. The abrupt Increase in blood pressure, which has been observed after whole-body drenches of CR In solution, subsides rapidly. Although available results show no long-term health effects of exposure to CR, there are no available data on the mutagenicity and carcinogenicity of this compound, and the data on teratology are limited. 

The acute toxic effects of mustard vesicants are usually attributed to the consequences of alkylation reactions with organic compounds including nucleoproteins such as DNA. Alkylation reactions can result in physiological and metabolic disturbances as well as genotoxic effects. Several hypotheses have been advanced concerning the primary cause of cell death following acute exposures. As reviewed by Papirmeister et al. (1991), the three major hypotheses are ... 

Acute toxicity figures for man are not known but a lowest lethal concentration over 30 min of 6 ppm was quoted by Maynard (1989). The LD50 has been measured in a number of species (Table 3), while LCfsoS in a variety of species vary from 500 to 1500 mg min m 3 (Goldman and Dacre, 1989). The efficacy of lewisite, like that of mustard, depends partly upon its vesicant properties but lewisite is also a lethal systemic chemical weapon. About 30 drops (2.6 g), applied to the skin and not washed off or otherwise decontaminated would be expected to produce a fatal outcome in an average man. 

L Signs and Symptoms of Toxicity. Mustard vesicants (agents HD and HN2) are acutely toxic by direct contact, the skin, eyes, and upper respiratory tract... 

Mechanisms of Toxicity. The acute toxic effects of mustard vesicants are usually attributed to the consequences of alkylation reactions with organic com-... 

Acute Toxicity. Liquid lewisite applied by eye-dropper to the forearms of men caused blanching and discoloration of the skin followed by extensive erythema within 15-30 min and vesication within 12 hr (Wardell 1941 as cited in Goldman and Dacre 1989). The pain associated with these dermal exposures reportedly occurred within 2 min, and considerable discomfort persisted for about 1 wk. Other tests with human subjects and clinical reports also indicate a similar temporal sequence of events. Exposure to lewisite vapor (0.06-0.33 mg/ L) caused discoloration and blistering, with the maximum effect occurring by 36 8 hr after exposure (Wardell 1941). At a concentration of 0.01 mg/L, lewisite vapor caused inflammation of the eyes and swelling of the eyelids after 15 min of exposure, and inhalation of 0.5 mg/L for 5 min is considered to be potentially lethal. 

Myelosuppression (dose-related) mucositis (worse with continuous infusion) moderate emetogenic potential alopecia vesicant severe extravasation injury cardiac toxicities acute—not related to cumulative dose arrhythmias, pericarditis chronic— cumulative injury to myocardium (total dose greater than 550 mg/m2 lower total cumulative doses cause damage to myocardium in children (e.g., 350 mg/m2)... 

Human toxicity values have not been established or have not been published. However, based on available information, this material appears to have few, if any, acute vesicant or vomiting/sternatory properties. 

Sulfur mustard is a known human carcinogen, and some of its degradation products may also be carcinogenic (IOM, 1993). Sulfur mustard acts as a vesicant or blister agent and shows acute systemic toxicity in addition to its effects on skin, eyes, and the respiratory tract. 

The vesicant properties of lewisite result from direct contact with the skin. Signs of dermal toxicity (pain, inflammation) may be experienced within a minute after exposure. Acute lethality is usually the result of pulmonary injury. Ocular exposure may result in corneal necrosis. Due to its lipophilicity, percutaneous absorption of lewisite is rapid and, at a sufficient exposure, may be associated with systemic toxicity characterized by pulmonary edema, diarrhea, agitation, weakness, hypothermia, and hypotension (lOM, 1993). The threshold for severe systemic toxicity in humans following dermal exposure to lewisite has been estimated at lOmg/kg (9.1-13.4 mg/kg) (Sollman, 1957). 

Subcommittee on Toxicity Values for Selected Nerve and Vesicant Agents, Committee on Toxicology Review of Acute Human-Toxicity Estimates for Selected Chemical-Warfare Agents. National Academy Press, Washington, DC. 

Myelosuppression mucositis worse with continuous infusion moderately emetogenic may cause acute and delayed (by 24 8 hours) emesis vesicant severe extravasation injury cardiotoxicity (similar to other anthracyclines) may be less cardiotoxic than doxorubicin controversy about equ ivalent doses cardiac toxicity associated with cumulative doses >900 mg/m Myelosuppression moderately emetogenic may be worse with oral and high-dose regimens alopecia mucositis hypotension infusion rate-related etoposide phosphate can be given IV push without hypotension risk hypersensitivity reactions especially common in children... 

Myelosuppression mucositis moderately emetogenic vesicant extravasation alopecia cardiac toxicities acute and chronic, as with daunorubicin and doxorubicin (total cumulative dose not well established >150 mg/m reported to be associated with decreased LVEF Myelosuppression low... 

Is there evidence of excessive lachiymation and acute conjunctivitis (note, if there is circumstantial evidence of the release of a vesicant or a corrosive toxic substance, decontamination of the eyes by irrigation is an immediate priority) ... 

Longer latency production of toxic pulmonary oedema and later acute respiratory distress syndrome with associated type 1 respiratory failure Vesicant agents... 

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