Modified in vivo comet assay detects the genotoxic potential of 14-hydroxycodeinone, an α,β-unsaturated ketone in oxycodone.

14-Hydroxycodeinone (14-HC) is an α,β-unsaturated ketone impurity found in oxycodone drug substance and has a structural alert for genotoxicity. 14-HC was tested in a combined Modified and Standard Comet Assay to determine if the slight decrease in % Tail DNA noted in a previously conducted Standard Comet Assay with 14-HC could be magnified to clarify if the response was due to cross-linking activity. One limitation of the Standard Comet Assay is that DNA cross-links cannot be reliably detected.

Regulating and assessing risks of cholinesterase-inhibiting pesticides: divergent approaches and interpretations.

This document presents a revised framework for conducting worker and dietary risk assessments for less-than-lifetime exposures to organophosphate or carbamate pesticides based on red blood cell (RBC) or brain acetylcholinesterase (AChE) inhibition or the presence of clinical signs and symptoms. The proposals for appropriate uncertainty factors are based on the biological significance of the cholinesterase (ChE) inhibition noted at the lowest-observed-effect level (LOEL) and the degree of uncertainty in the extrapolation between human and animal data. An extensive evaluation of industry data, not previously summarized, and the available literature indicate that the following risk assessment principles are supportable and protective of human health: Plasma ChE inhibition is not an adverse effect, and therefore should not be utilized in risk assessments.

Inhibition of ozone-induced nitric oxide synthase expression in the lung by endotoxin.

Inhalation of the pulmonary irritant ozone is associated with an accumulation of macrophages in the lung. These cells, along with type II epithelial cells, are activated to release increased quantities of hydrogen peroxide and nitric oxide, two reactive mediators that have been implicated in tissue injury. In the present studies we determined whether pretreatment of rats with bacterially derived endotoxin, which modulates oxidant levels in tissues, could abrogate the effects of ozone on lung injury and nitric oxide production.

Stimulation of nitric oxide production in rat lung lavage cells by anti-Mac-1beta antibody: effects of ozone inhalation.

Acute inhalation of the pulmonary irritant ozone is associated with an inflammatory response characterized by increased numbers of macrophages in the lung that release elevated quantities of nitric oxide. The accumulation of phagocytes in the lung is dependent on expression of leukocyte adhesion molecules including Mac-1. In the present studies, we determined whether activation of the Mac-1 receptor is involved in regulating nitric oxide production by lung phagocytes, and whether this response is modified following acute ozone inhalation.

Taurine protects rat bronchioles from acute ozone-induced lung inflammation and hyperplasia.

Ozone is a potent respiratory irritant known to induce lung injury in humans and experimental animals. The present studies determined if ozone-induced lung inflammation was modified by pretreatment of animals with taurine, a detoxifying antioxidant. Rats were pretreated for 10 days with 5% taurine in their drinking water (controls received water only) prior to exposure to 2 ppm ozone for 3 h.