The Lower Limit of Irritation

The lower limit of irritation of a gas, also termed the threshold value of pathological sensitivity, is the minimum concentration provoking a painful sensation at those surfaces on which it acts in its characteristic manner. The surfaces are the conjunctiva, the nasal mucosa and the pharynx, the skin, etc. Experiments are made on human subjects and are continued until the appearance of signs of the specific action of the gas, generally lachryma-tion or sneezing, on all or nearly all the persons taking part in the experiment. 

The lower limit of irritation is generally expressed in mgm. of substance per cubic metre of air. 

In Table I the values of the lower limit of irritation are given for several substances. 

It will be seen from this table that the lower limit of irritation of the war gases may vary between fairly wide limits. The substance with the greatest irritant power known to the present is diphenyl chloroarsine. 

The lower limit of irritation, that is, the minimum concentration which produces lachrymation, is 14 mgm. per cu. m. The limit of insupportability is 40 mgm. per cu. m. The product of mortality is 500 (Muller). 

It may be classed among the strongest lachrymators. The lower limit of irritation is 2 mgm. per cu. m. of air (Muller). The maximum concentration which a normal man can support for a period of not more than i minute is 25-30 mgm. per cu. m. Mortality-product 3,000 (Muller). 

Veheity,— When cylinders and irritant candles are used, the velocity should not be leas than 3 miles per hour because winds liaving a lower velocity than this arc likely to be gusty and variable. They may die dowm or even reverse and blow the agent back on our owm troops. How ever, when the agent is delivered by artillery, mortars, projectors, or bombs, this lower limit of wind velocity need not be considered. 

The respiratory effects of irritant mixtures are not limited to complex ones such as those just described. Volunteers who were exposed to formaldehyde at concentrations as high as 2.0 pg/m3 (greater than the PEL of 1.2 pg/m3) did not experience lower airway irritation, 8 yet those exposed to mixtures of formaldehyde (Kqw = 0.35) and terpenes (Kqw = 2.42 to 4.83) did exhibit symptoms of lower airway irritation. 9 Additional examples of the effects of respiratory irritant mixtures are presented later in the case study Section (17.7) of this chapter. 

The lower swelling of the epidermis by an alkyl polyglycoside solution as compared with water is a sign of the functional compatibility of alkyl polyglycosides and contributes by way of compensation to limiting irritation mechanisms of other components in the formulation. In addition, on the basis of comeometer measurements [74], the loss of moisture content in the homy layer is lower by 30% to 40% under the effect of alkyl polyglycoside as compared with standard ether sulfate. This corresponds to the effect of the very mild zwitterionic amphodiacetates. 

We have observed that for the initiation of effective therapy, 50 to 100 mg have to be administered orally which is at the upper limit of toxic effects as mentioned above. In the last 2 years, we have treated patients for 2 weeks with local 0.1% vitamin A acid until this treatment becomes irritant and then we commence oral treatment. The oral dosage can be reduced to about 20 mg twice daily and after 4 weeks to about 10 mg twice daily. Simultaneously, local treatment can be reduced below the development of irritancy by application of 0.05% vitamin A acid ointment and in some cases we can reduce the vitamin A acid concentration in the ointment to 0.01% (Figure 22.2). Thus the side effects of local and oral therapy can be avoided by combination of both types of treatment which suggests that in the future when programming the therapy of ichthyotic patients, the combination of local and oral therapy should be considered. When we have stopped oral therapy and tried to initiate a maintenance treatment with local vitamin A acid at low concentrations, relapses occur within 2 months. After the re-appearance of ichthyotic lesions, oral administration of vitamin A acid at the lower dose was repeated with satisfactory results. 

Benzyl chloride [(chloromethyl)henzene, a-chlorotoluene], CgH CH2Cl, is a colorless Hquid with a very pungent odor. Its vapors are irritating to the eyes and mucous membranes, and it is classified as a powerfljl lacrimator. The physical properties of pure benzyl chloride are given in Table 2 (2—7). Benzyl chloride is insoluble in cold water, but decomposes slowly in hot water to benzyl alcohol. It is miscible in all proportions at room temperature with most organic solvents. The flash point of benzyl chloride is 67°C (closed cup) 74°C (open cup) autoignition temperature is 585°C lower flammability limit 1.1% by volume in air. Its volume coefficient of expansion is 9.72 x. ... 

As is apparent from the above information, there is no ideal disinfectant, antiseptic or preservative. All chemical agents have their limitations either in terms of their antimicrobial activity, resistance to organic matter, stability, incompatibility, irritancy, toxicity or corrosivity. To overcome the limitations of an individual agent, formulations consisting of combinations of agents are available. For example, ethanol has been combined with chlorhexidine and iodine to produce more active preparations. The combination of chlorhexidine and cetrimide is also considered to improve activity. QACs and phenols have been combined with glutaraldehyde so that the same effect can be achieved with lower, less irritant concentrations of glutaraldehyde. Some... 

Inhalation exposure of rats to mancozeb, exposed everyday for 4 months indicated an increase in irritation of the mucous membrane of the upper respiratory tract and concentration-related nonspecific changes to the liver and kidneys. Exposure was in the form of dispersed aerosols at concentrations ranging from 2 to 135 mg m. At the lower concentrations, there were no observable effects. In animals exposed repeatedly to high doses of mancozeb (dust) equivalent to 150-250 times the acceptable exposure limit (AEL), reduced body weight, inflammation of the lungs, and abnormal thyroid function were observed. 

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