Michael A Dorato

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Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists(More)
The no-observed-adverse-effect-level (NOAEL) is an important part of the non-clinical risk assessment. It is a professional opinion based on the design of the study, indication of the drug, expected pharmacology, and spectrum of off-target effects. There is no consistent standard definition of NOAEL. This is based, in part, on the varied definitions of what(More)
Monkeys and rats were exposed to 11.6, 112.5, or 1152 microgram Mn/m3 as an Mn3O4 aerosol twenty-four hours per day for nine months. Various serum biochemical, and hematologic evaluations were conducted on both specie. Body weight gain was accelerated in rats exposed to 1152 microgram Mn/m3. Hemoglobin concentrations were slightly elevated for both sexes(More)
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(More)
Inhalation toxicology technology has provided the scientific community with important advances in studies of inhaled toxicants. These advances include new and more efficient exposure systems (e.g., flow-past nose-only exposure systems), and improved approaches to inhalation chamber environmental control (e.g., temperature, humidity, air quality). Practical(More)
The use of a newly developed head dome system has allowed measurement of pulmonary function in conscious monkeys. Such information is often desired, so that pharmacological or toxicological effects of administered compounds can be measured in the absence of effects from anesthetic agents. The current study was conducted to gain experience with this method(More)
An adaptation of the method reported by Amdur and Mead (1958, Amer. J. Physiol. 192, 364-368) was used to evaluate pulmonary mechanics in conscious rats, utilizing a flow plethysmograph and intraesophageal catheter to determine compliance, resistance, respiratory flow, thoracic pressure, tidal volume, frequency, and minute volume. The procedure did not(More)
The choice of an appropriate high dose for nonclinical toxicology studies continues to generate significant discussion and debate. Typically, use of the term "high dose" reflects a consideration of a Maximum Tolerated Dose (MTD) or a Maximum Feasible Dose (MFD), inexact terms applied to the design of nonclinical studies conducted to support human clinical(More)
The primary objective of toxicology studies in the drug development process is to evaluate the safety of potential drug candidates. This is accomplished using relevant animal models and validated procedures. The ultimate goal is to translate the animal model responses into an understanding of the risk for human subjects. To this end, the toxicologist must(More)