The decay of solvated electrons in various aqueous solutions was studied using a stroboscopic pulse radiolysis technique with a time resolution of 24 psec. High concentrations of solutes such as H2O2, acetone, CdCl2, NaNO2, and NaNO3 decreased the initial solvated electron yield, while high acid concentrations did not. Reasons for this reduction in yield are discussed, and the conclusion reached is that the scavengers must be reacting with a precursor to the solvated electron. We believe that this precursor is probably a low-energy electron which reacts prior to solvation.

Publication costs assisted by the Ontario Cancer InstituteThe stroboscopic pulse radiolysis, spr, system has been used to determine the yield of electrons in aqueous solution 30 psec after irradiation in the presence of high concentrations of scavenger. Using Cd2+ and cystamine as efficient electron scavengers a yield, G (product), of at least 4.8 molecules/100 eV is found for electrons compared to ag(eaq-)30psec of 4.0. The yield of eaq_ has also been investigated in high concentration of base. There is found to be very little, if any, increase in initial yield at concentrations up to 1 M NaOH. Small increases (~13%) are noted in initial yield at concentrations up to 5 M which are attributed to recombination of species in the radiation "spurs" or to hole reactions. Very little increase in yield was noted when high concentrations (5 M) of NaCl were used (~3%). By taking into account both the fast electron addition to scavengers observed in this paper and assuming the spur yield can be given by a simple equation, g (eaq"")t = 2.7 + 1.3 exp(-108f), excellent agreement was obtained between these pulse radiolysis studies and steady-state yields. The total yield of electrons can be described by the equation, G (product) = 4.8(1 -exp(-[S]/C37) + exp(-[S]/C37)(2.7 + 1.3/z [S])/(108 + k [S])), again in agreement with other product yield studies.

This paper reviews technical issues related to the toxicologic testing of inhaled pharmaceuticals. Although there are commonalities between approaches to general and inhalation toxicity testing, there also are specific challenges in the toxicity testing of inhaled pharmaceuticals. A major issue is that of dose; inhaled dose is more difficult to determine than intravenous or oral doses. Also, it is harder to relate dose in laboratory animals to that in man for inhalation exposure than for other routes of administration. Additionally, in the case of inhaled pharmaceuticals, people generally inhale through the mouth, whereas most laboratory animals inhale primarily through the nose. This presents significant challenges in exposure methodology and technology that often need innovative approaches involving alteration to particle size of the agent or dosing procedure. Because the respiratory tract is the site of deposition, local respiratory toxicity and possible damage to lung cells need to be assessed. Systemic toxicity also needs to be evaluated and may be an issue in some cases. Special studies on pulmonary function, mucociliary clearance, or immune response may be needed, depending on the nature of the inhaled pharmaceutical. This review explores the main issues involved in toxicity testing of inhaled pharmaceuticals, the approaches that have been used, and the current and future challenges.

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