Percutaneous toxicity

Percutaneous toxicities (LD50) both without and with decontamination were calculated statistically using the probit-numerical method by means... 

Table 1. Percutaneous toxicity of tested agents LD50 p.c. mg/kg [2] + standard deviation or (lower - upper confidence limit).

Wahlberg JE, Boman A. 1979. Comparative percutaneous toxicity of ten industrial solvents in the guinea pig. Scand J Work Environ Health 5 345-351. 

Burnett C et al Teratology and percutaneous toxicity studies on hair dyes. Toxicol Environ Health 1 1027, 1976... 

Dermal application of up to 2.6g/kg resulted in no deaths and no signs of percutaneous toxicity moderate irritation of the skin was observed. Instillation of the liquid into the eye of a rabbit produced erythema and edema of the conjunctiva, tearing, and mucous secretion but no corneal injury. 

Wahlberg JE Percutaneous toxicity of solvents. A comparative investigation in the guinea pig with benzene, toluene, and 1,1,2-trichloroethane. Ann Occup Hyg 19 226-229, 1976... 

Soluble Compounds Animals repeatedly exposed to dusts of soluble uranium compounds in concentrations from 3 to 20mg/m died of pulmonary and renal damage both feeding and percutaneous toxicity studies on animals indicated that the more soluble compounds are the most toxic. In animals, effects on the liver are a consequence of the acidosis and azotemia induced by renal dysfunction. ... 

Duprat P, Gradiski D. 1978. Percutaneous toxicity of hexachlorobutadiene. Acta Pharmacol Toxicol 43 346-353. 

Brrmett, C., Goldenthal, E.I., Harris, S.B., Wazeter, F.X., Strausbrrrg, J., Kapp, R. Voelker, R. (1976) Teratology and percutaneous toxicity studies on hair dyes. J. Toxicol, environ. Health, 1, 1027-1040... 

Table 5.2 Species Differences in the Relative Percutaneous Toxicity and Skin Penetration of Organophosphorus Compounds...

McCreesh AH. Percutaneous toxicity. Toxicol AppI Pharmacol 1965 7(suppl 2) 20-26. 

Wahlberg JE. 1965. Percutaneous toxicity of metal compounds. A comparative investigation in guinea pigs. Arch Environ Health 11 201-204. 

Benton et al. (2006b, 2007) experimentally determined the LCtso and LC50 in male and female adult SD rats exposed whole body to VX vapor for 10, 60, and 240 min in a dynamic exposure chamber (Table 6.3) study protocol was similar to that for agent GB in the studies conducted by Mioduszewski et al. (2001, 2002a). Experiments testing the role of decontamination less than 24 h post-exposure provided clear evidence for percutaneous toxicity induced by whole-body vapor exposure to the persistent nerve agent VX. For severe and lethal VX vapor exposure effects, females were not more susceptible than males for the exposure durations examined. 

Apart from this classic approach, it would be possible to improve the properties of known CWs, e.g. microencapsulation so that less stable or highly volatile substances can be used. Nanotechnology offers new possibilities, as described recently by Price and Peterson (2008). The other option is to improve penetration using known enhancers like dimethyl sulfoxide (DMSO). While the percutaneous toxicity (expressed as LD50 in rats) of one of the toxic organophosphates - O-isopropyl 5-2-diisopropylaminoethyl methyl phosphnothiolate - is 59.1 P-g/kg, in mixture with DMSO this value is decreased to 10.1 pg/kg (Bajgar, 1989). 

Lopez, R., Diaz Sylvester, P.L., Ubios, A.M., Cabrini, R.L. (2000). Percutaneous toxicity of uranyl nitrate its effect in terms of exposure area and time. Health Phys. 78 434-7. 

Czerwinski, S.E., Skvorak, J.P., Maxwell, D.M., Lenz, D.M., Baskin, S.I. (2006). Effect of octanoEwater partition coefficients of organophosphorous compounds on biodistrihution and percutaneous toxicity. J. Biochem. Mol. Toxicol. 20 241-6. 

McCreesh, A.H. (1965) Percutaneous toxicity. Toxicology and Applied Pharmacology, 7 (Suppl. 2), 20-26. 

It is unlikely that there will be significant percutaneous toxicity under the usual conditions of exposure to screening smokes. However, if primary and cumulative skin irritation tests suggest that there may be systemic effects, then it will be appropriate to conduct more detailed monitored studies for percutaneous toxicity. 

Wahlberg, J.E., Percutaneous toxicity of metal compounds. Arch. Environ. Health, 11, 201-204, 1965. Walker, J., Jr., Galdston, M., and Wexler, J., WP casualties at Edgewood Arsenal, Maryland, 1945, Report 103,... 

MOD6. The percutaneous toxicity of the G-compounds. Unpubhshed MOD report. 

The majority of substances listed on Schedule 1 of the Chemical Weapons Convention are considered to be percutaneous hazards (OPCW, 1993). In particular, sulphur mustard (HD) and VX are the most extensively studied agents of this genre and are representative of chemical warfare agents that exhibit mainly local or systemic percutaneous toxicity, respectively (Table 1). 

Vapour loss of a chemical warfare agent from the skin surface affects percutaneous toxicity by reducing the dose available for skin absorption. For agents of low volatility, such as VX, practically all of the applied dose may potentially be absorbed and so the percutaneous toxicity (LD50) approaches that of an intravenous (IV) LD50. In contrast, more volatile chemicals, such as G-agents, are subject to extensive vapour loss... 

Clearly, factors which reduce or prevent the skin-surface vapour loss of a chemical warfare agent will tend to enhance skin absorption and percutaneous toxicity. Occlusion of contaminated skin (for example, with ointments or impermeable dressings) is an obvious means of impeding vapour loss and has implications for the... 

Figure 10. Relationship between vapour pressure and the relative percutaneous toxicity (expressed as the ratio of the percutaneous LD50 to the intravenous LD50) of four nerve agents (VX, GF, GD and GB indicated by solid circles). A notable exception to this relationship is GA (indicated with a solid triangle) which may undergo dermal metabolism prior to systemic absorption...

Further development of antigas ointments ceased in the 1950s because of their eight-fold enhancement in the percutaneous toxicity of G-agents (Cullumbine el al., 1954). The UK military use of anti-gas ointments as decontaminants was formally discontinued in 1959, when it was recommended that the best means of mitigating skin absorption was by physical absorption onto powders. Instead, attention focused on the development of new decontaminants. 

The percutaneous toxicity of chemical warfare agents is primarily related to the rate and extent of percutaneous absorption which, in turn, is subject to a variety of environmental, biological and physicochemical factors. Understanding the basic mechanisms which control skin absorption is essential for developing effective pre- and postexposure medical countermeasures and progress in transdermal technology is likely to yield new challenges and opportunities in the future. 

TABLE 5.2 Species differences in the relative percutaneous toxicity and skin penetration of organophosphorus compounds... 

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