Showing papers in "Toxicology and Industrial Health in 1993"

Paradoxical behavior of antioxidants in food and biological systems.

Abstract: Scope of the Paper This paper cites the paradoxical actions of antioxidants in processed foods and in living biological systems. Essentially, it is a recognition of patterns of contradictory behavior. Limitations of space prevent detailed treatment of the paradoxes, their mechanistic basis, or citation of any more than one or two illustrative references. It is hoped that these will lead the interested reader to further substantiation of the paradoxes cited.

Chlorine Gas Exposure and the Lung: A Review

Abstract: We conducted a review of the literature detailing the respiratory effects of chlorine, an extremely important but toxic halogen. Historically, the heaviest mass inhalational exposures to chlorine resulted from World War I gassing. Currently potential human exposure to chlorine inhalation occurs in a variety of settings in the workplace, as a result of inadvertent environmental releases, and even in the home due to household cleaning mishaps. Chlorine species are highly reactive; tissue injury results from exposure to chlorine, hydrochloric acid, hypochlorous acid, or chloramines. Acute, high level exposure to chlorine gas in occupational or environmental settings results in a variety of dose-related lung effects ranging from respiratory mucus membrane irritation to pulmonary edema. Pulmonary function testing can reveal either obstructive or restrictive deficits immediately following exposure, with resolution over time in the majority of cases. However, some of those exposed may demonstrate long-term persistent obstructive or restrictive pulmonary deficits or increased nonspecific airway reactivity after high level exposure to chlorine gas. Symptoms and signs following inhalation of mixtures of chlorine-containing cleaners in the home are similar to those after occupational exposures and environmental releases. Although generally less severe, these events may be extremely common. Controlled human exposure data suggest that some subjects may be more responsive to the effects of chlorine gas; epidemiologic data also indicate that certain subpopulations (e.g., smokers) may be at greater risk of adverse outcome after chlorine inhalation. Although these findings are intriguing, additional study is needed to better delineate the risk factors that predispose toward the development of long-term pulmonary sequelae following chlorine gas exposure.

Environmental equity and pesticide exposure.

Abstract: Although people of color and low-income groups bear a disproportionate share of the health risks from exposure to pesticides, research attention has been meager, and data on acute and chronic health effects related to their toxic exposures are generally lacking. Increased resources are needed both to study this issue and to mitigate problems already identified. People of color should be a major research focus, with priority on long-term effects, particularly cancer, neurodevelopmental and neurobehavioral effects, long-term neurological dysfunction, and reproductive outcome. Suitable populations at high risk that have not been studied include noncertified pesticide applicators and seasonal and migrant farm workers, including children.

Environmental Justice for all: Community Perspectives on Health and Research:

Abstract: Some individuals, groups, and communities are at special risk from environmental threats. This is especially the case for low income persons, the working class, and people of color whose health may be imperiled by lead in their houses, pollution in their neighborhoods, and hazards in their workplace. Moreover, many of their children face potential health threats in the parks where they play. The environmental justice perspective unmasks the ethical and political questions of “who gets what, why, and in what amounts.” An environmental and public health strategy is needed to ensure that all Americans are protected.

Air pollution health risks: do class and race matter?

Abstract: Air pollution is not spread evenly across demographic groups. Exposures and associated health risks appear to fall disproportionately on populations that are poor and nonwhite. Although scientific evidence documenting disparities in air pollution exposures, doses, and health effects is scant, the available data strongly support the contention that disadvantaged groups, many of whom are ethnic and racial minorities, routinely encounter levels of air pollution that are higher than average. The extent to which exposure differentials contribute to observed differences in health status by class and race is unknown, but worthy of further investigation. We recommend several steps, all of them feasible and most of them relatively inexpensive, to improve our understanding and ability to address environmental health disparities.

Primary Aromatic Amines from Side-Stream Cigarette Smoke are Common Contaminants of Indoor Air

Abstract: A very sensitive mass-spectrometry method has been developed for the analysis of aromatic amines in tobacco smoke and in indoor air. Cigarettes were smoked with a smoking machine; the amines from the smoke were trapped in a 5% HCl water solution containing internal standards and detected by gas chromatography/mass spectrometry in the selected-ion-monitoring (SIM) mode. The amines measured were the following: aniline, 2-toluidine, 3-toluidine, 4-toluidine, 2-ethylaniline, 3-ethylaniline, 4-ethylaniline, 2,3-dimethylaniline, 2,4-dimethylaniline, 2,5-dimethylaniline, 2,6-dimethylaniline, 1-naphthylamine, 2-naphthylamine, 2-methyl-1-naphthylamine, 2-aminobiphenyl, 3-aminobiphenyl and 4-aminobiphenyl. We analyzed nine brands of cigarettes sold commercially in Italy (Gauloise, Nazionali, Marlboro, Camel, MS, MS mild and MS lights), with and without filter. Main-stream smoke contained a lower amount of aromatic amines than side-stream smoke: the total level of these amines in main-stream smoke ranged from 200 to 1300 ng/cigarette, whereas the level of aromatic amines in side-stream smoke varied from 20,000 to 30,000 ng/cigarette. The smoke of black-tobacco cigarettes had higher levels of aromatic amines compared to light-tobacco cigarettes and the filters significantly reduced aromatic amines in main-stream smoke. We also determined the levels of aromatic amines in ambient air, offices and houses. Some aromatic amines (aniline and toluidine) were detected in ambient air, as well as in rooms of non-smokers. Most measurements showed a considerable contamination of aromatic amines derived from side-stream smoke, which was detected also in parts of the buildings in which smoking was not allowed.

Effects of Acute and Subchronic Exposure of Topically Applied Fullerene Extracts on the Mouse Skin

Abstract: The recent discovery that fullerenes (C60) can be produced in macroscopic quantities has sparked much interest in the chemistry of this unusual molecule. Concerns have also arose about the potential carcinogenic effects of this molecule. We have addressed the potential acute and subchronic toxic effects of fullerenes applied in benzene on the mouse skin. The acute toxic effects measured in this study included epidermal DNA synthesis and the induction of ornithine decarboxylase activity in the epidermis. At the topical dose of fullerenes used in these studies (i.e., 200 ug), we found no effect on either DNA synthesis or ornithine decarboxylase activity over a 72 hour time course after treatment. The subchronic effects of the fullerenes as a mouse skin tumor promoter was assessed by repeatedly applying the chemical to the skin after initiation with the polycyclic aromatic hydrocarbon, 7,12-dimethlybenz-anthracene (DMBA). Repeated administration of the fullerenes for up to 24 weeks post-initiation did not re...

'Environmental justice': The central role of research in establishing a credible scientific foundation for informed decision making

Abstract: Although much of the evidence is anecdotal and circumstantial, there are mounting concerns that environmental health risks are borne disproportionately by members of the population who are poor and nonwhite. We examine the central role of environmental health research in defining the dimensions of the problem, understanding its causes, and identifying solutions. Environmental health sciences, including epidemiology, exposure analysis. pharmacokinetics, toxicology, and surveillance monitoring, must be employed to determine the extent to which society has achieved "equity" and "justice" in safeguarding the health and safety of its citizens. By improving our ability to identify, evaluate, prevent, and/or reduce risks for all members of society, environmental health research can contribute directly to fair and equitable protection for everyone, regardless of age, ethnicity, gender, race, or socioeconomic status.

Oxidation and aging: impact on vision.

Abstract: The function of the eye lens is to focus lighton the retina (Figures Ia.d). Upon aging there are compromises in the function of both these tissues. Age related cataractand age related macular degeneration (AMD) are the major causes of blindness among the elderly. This review will address relationships between pathobiology of age related or senile cataract and, to a lesserextent, age related degeneration of the retina and nutritional approaches to the delay of these disorders. Only studies which found associations between nutritional status and eye disease are reviewed here. Readers are referred to other recent reviews or summaries for data regarding cataract and AMD, which are not treated here (Taylor et al., 1991b; Jacques and Taylor, 1991; West, 1991; Taylor, 1989; Bunce et al., 1990; Varma, 1984; Sperduto, 1990; Third National Eye Institute Symposium on Eye Disease Epidemiology, 1991). Since more is known about etiology of cataract, this is reviewed first, followed by discussion regarding AMD. Much work is in progress.

Health Status by Social Class and/or Minority Status: Implications for Environmental Equity Research:

Abstract: Much of the epidemiologic research in the United States has been based only on the categories of age, sex and race; thus, race has often been used in health statistics as a surrogate for social and economic disadvantage. Few multivariate analyses distinguish effects of components of social class (such as economic level) from the relative, joint, and independent effects of sociocultural identifiers such as race or ethnicity. This paper reviews studies of social class and minority status differentials in health, with a particular emphasis on health status outcomes which are known or suspected to be related to environmental quality and conditions which increase susceptibility to environmental pollutants. Sociodemographic data are presented for the U.S. population, including blacks, Asian American/Pacific Islanders, American Indian/Alaska Natives, and Hispanics. Four areas of health status data are addressed: mortality, health of women of reproductive age, infant and child health, and adult morbidity. Conceptual and methodological issues surrounding various measures of position in the system of social strata are discussed, including the multidimensionality of social class, in the context of the importance of these issues to public health research. Whenever possible, multivariate studies that consider the role of socioeconomic status in explaining racial/ethnic disparities are discussed.

Sources of Free Radicals

Abstract: Ischemic heart disease is the leading cause of death in the United States. Atherosclerosis (which itselfmay be initiated by oxidative freeradical damage to low density lipoprotein (Quinn et al., 1987» results in coronary arteries lined with subendothelial deposits known as plaque. These deposits thicken the wall and narrow the lumen of the affected artery. Ultimately, the plaque mayrupture, exposing thrombogenic surface. A blood clot forms at the site, and may completely occlude the artery, resulting in an area in the wall of the myocardium with no blood flow. Some loss of function is immediate, perhaps enough to result in sudden death. If the area neverreperfuses, or if reperfusion occurs too late, an infarcted area of necrotic tissue results, and full function is never regained. If reperfusion can be brought about quickly by thrombolysis, angioplasty, or coronary artery bypass graft, then the affected area may recover with little or no infarct. The heartmay, however, develop transient arrhythmias and a reversible loss of function known as \"stunning\" (Braunwald and Kloner 1982). Hence, iatrogenic reperfusion is a goalof modern cardiology, but with it comesa price tag. Hearse (1977) described theoxygen paradox as injury sustained by the anoxic myocardium upon simple reintroduction of molecular oxygen.

The role of metal ions in oxidative processes and aging.

Abstract: Recent research clearly shows that oxidative damage in brain increases significantly with age and that oxidative damage is most likely mediated by the metal ions Fe and possibly Cu. These facts clearly suggest that processes involved in the regulation and/or control of metal ions may play an important role in aging. Specific control points where Fe metabolism could possibly play a key role in oxidative damage are assessed with a view of identifying possible modes for intervention in the processes leading to increased oxidative damage in brain with age. We conclude that the use of agents that would interfere with the action of trace metals in causing oxidative damage appears to be limited. On the other hand, recent research has shown that agents which scavenge free radicals may be very useful. Research with gerbils has shown that the chronic administration of the spin-trapping agent, a-phenyl-tert butyl nitrone (PBN), causes; A) a decrease in the ageassociated elevated levels of oxidized protein in brain, B) an increase in the age-associated depressed levels of the enzymes glutamine synthetase and neutral protease in brain, and C) a decrease in the ageassociated elevation in errors committed in a radial arm maze which tests spatial and short-term memory. It is highly likely that PBN manifests its action by reacting with, and scavenging, crucial free radicals but probably does not interfere with the action of Fe or Cu in oxidative events.

The chemistry of free radicals

Abstract: ing hydrogen atoms from fatty acid side chains of lipids. However, most scientists find that addition of catalase or scavengers of OH' to isolated cellular membrane fractions (e.g. plasma membrane fractions, microsomes) or to liposomes undergoing peroxidation in the presence of ferrous salts, or of ferric salts plus reducing agents (such as ascorbate), does not inhibit the peroxidation (Halliwell and Gutteridge, 1984b; Aust et al., 1985). This lack of effect is despite the fact that OH' radicals can usually be detected in the reaction mixtures by such techniques as aromatic hydroxylation, spin trapping, or the deoxyribose method, and detection of these OH' radicals is inhibited by catalase or scavengers. It follows that OH' is being generated in the reaction mixtures, but is not required for peroxidation to be proceed. How can this be explained? It is unlikely that the lack of action of ·OH scavengers means that the required ·OH formation is site specific, involving iron ions bound to the membrane, so that any OH formed reacts immediately with the membrane components and is not available for scavenging. Membrane-bound iron certainly does participate in lipid peroxidation (Borg and Schaich, 1988). However, a source of H202 would still be required, and so catalase should still inhibit. The fact that it does not has led several scientists to suggest that the first chain initiation of lipid peroxidation in membrane systems incubated with iron salts in the presence of 02 is achieved by reactive species other than ·OH (reviewed by Aust et al.,

Susceptibility to environmental pollutants among minorities

Abstract: Susceptibility to environmental pollutants involves both biological and nonbiological factors. Individuals belonging to minority groups are much more likely to be subject to a number of these factors. This paper examines biological susceptibility of minorities to environmental pollutants and provides specific examples of susceptibility resulting from: genetic makeup; occupation; other factors such as compromised health status, exposure to mixtures of pollutants, substance abuse, and unemployment; and social inequality of access to health care, education, and communication skills. Recommendations are made for specific actions and for additional studies.

Liver carcinogenesis is not a predicted outcome of chemically induced hepatocyte proliferation.

Abstract: Cell proliferation has long been recognized as a basic component of multistage carcinogenesis. Based largely on the finding that certain nongenoloxic chemical carcinogens induce cell proliferation ...

Effects on Neurobehavioral Performance of Chronic Exposure to Chemically Contaminated Well Water

Abstract: Occupational exposure to trichloroethylene (TCE) and other solvents impairs neurobehavioral performance. Use of well water contaminated with TCE and solvents has been associated with excessive symptoms, cancers, birth defects and impaired blink reflex. We extended these observations by measuring the neurophysiological (NPH) and neuropsychological (NPS) status of subjects who used water contaminated with 6 to 500 ppb of TCE for 1 to 25 years. The 170 well-water exposed subjects who resided in southwest Tucson, Arizona overlying the Santa Cruz River aquifer, were compared to 68 referent subjects for NPH and NPS tests. Also, 113 histology technicians (HT) were referents for blink reflex latency only. Affective status was assayed by a Profile of Mood States (POMS). Exposed subjects were statistically significantly impaired when compared to referents for NPH tests. These impairments included sway speed with eyes open and closed, blink reflex latency (R-1), eye closure speed, and two choice visual reaction time. NPS status was statistically significant impaired for Culture Fair (intelligence) scores, recall of stories, visual recall, digit span, block design, recognition of fingertip numbers, grooved pegboard and Trail making A and B. POMS scores were elevated. Prolonged residential exposure to well-water containing TCE at lower levels than occupational exposures, but without time away from exposure for metabolism and excretion of toxins, was associated with neurobehavioral impairment.

Oil-soluble antioxidants in foods.

Abstract: Rancidity results from an essentially spontaneous reaction of lipid material in foods with oxygen. This reaction was elucidated in the 1940s as a free-radical chain reaction and was termed "autoxidation". During the same period, the antioxidant properties of gallates and butylated hydroxyanisole were recognized and these compounds were usedcommercially as the first synthetic antioxidants. A number of otherantioxidants, produced by chemical synthesis, were developed in the following years. While antioxidant activity in naturally occurring substances was recognized much earlier (Blanck 1955), and sources of these substances were used commercially, it was until much later that their active components were isolated andcharacterized.

Occupational skin hazards from synthetic plastics.

Abstract: Epoxy and acrylic resins have numerous industrial applications but are also widely used in the household environment. These compounds are presently one of the most important sources of occupational contact dermatitis.Contact sensitization to epoxy resins is usually caused by the resin itself but hardeners or other additives, such as reactive diluents, plasticizers, fillers and pigments, can occasionally be responsible. Since completely cured epoxy resins are not sensitizers, epoxy resin sensitization is always due to the presence, in the final polymer, of uncured allergenic low molecular weight oligomers.Acrylates are now considered the fourth most common cause of contact sensitization due to resins. Unpolymerized monomers of acrylic compounds are known to be responsible for the contact allergy. Accelerators, inhibitors and catalysts, which are usually added to the acrylates to promote the polymerization process, can also sensitize.Both allergic and irritant contact dermatitis may be caused by exposure to...

Health risks from contaminated water: do class and race matter?

Abstract: The impact of contaminants in water on minorities and economically disadvantaged persons was reviewed. Environmental legislation governing water was summarized as background information against which relevant studies were evaluated. The majority of the available information was anecdotal or case study and did not lend itself to making quantitative comparisons or analyses. However, the data did present certain trends that led to the conclusion that inequities concerning exposure to contaminants in water may exist. The following recommendations were made: current data bases should be analyzed and new data bases created to facilitate assessments of exposure to waterborne contaminants to all populations; an analysis of populations not covered by the Safe Drinking Water Act should be undertaken; a survey should be conducted of the drinking water infrastructure and the results evaluated to identify any impacts to minorities and economically disadvantaged persons; the social, cultural and economic characteristics that influence human exposure to waterborne contaminants need to be identified; and better educational and community outreach programs need to be developed and implemented.

Genotoxicity of phenolic antioxidants.

Abstract: Among the array of protective mechanisms is that of antioxidants. Endogenous antioxidants include ascorbate, urate, a-tocopherol, andalbumin-bound bilirubin, Frie et al., (1988). In addition to these endogenous agents, there are phenolic derivations widely distributed among plant species which constitute an exogenous source of antioxidants, Stich (1991). Synthetic antioxidants such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BRT) and phydroxybenzoic acid (pHBA) plus some of the naturally occurring phenolic antioxidants are usedextensively in thepreservation of food products.

Hazardous wastes, hazardous materials and environmental health inequity.

Abstract: This paper reviews issues associated with the equity of locating hazardous waste sites and hazardous materials. Reports and case studies indicate that hazardous waste sites and the locations of hazardous materials are disproportionately situated near minority communities, especially African-American communities. This inequitable placement of hazardous waste sites is of concern, since exposure to toxic waste can adversely affect human health. Proximity to these sites may place these minority communities at higher risk of developing cancers and respiratory, cardiovascular, and neurological diseases, and of incurring increased levels of individual and family stress. The health of persons in minority communities near hazardous waste sites is further compromised by their lack of access to adequate health care. The potential health risks borne by racial and ethnic minorities and by low income communities as a consequence of exposure to toxic waste constitutes environmental inequity. In order to decrease the burden of these risks, we recommend developing environmental policies that address environmental inequity; conducting detailed demographic and health studies that assess the impact of exposure to toxic waste on minority populations; and devising educational programs to sensitize professional service providers and prevent exposure by community residents. This paper identifies research needs and opportunities.

Tissue injury by free radicals.

Abstract: In the last twenty fiveyears wehaveprogressed from theposition of freeradicals being considered a curiosity or even a myth in biological systems, to the point where free radical biochemistry has become a focus of intense scientific effort. The interest in this subject has spawned the publication of two specialist scientific journals,an increasingly large number of international conferences and an international society: the Society For FreeRadical Research, whosemembers come from all disciplines concerned with the study of free radicals and their properties. Whilst the fieldof free radical research is truly multi-disciplinary the fuel that drives its engine at presentis the intense research directed towards the study of the involvement of free radicals in human disease. Twenty years ago, Trevor Slater published his seminal monograph \"Free Radical Mechanisms in Tissue Injury\" (Slater, 1972). Today, the resources of industry and governments are being poured intolaboratory research andclinical trials directed at elucidating the role of free radicals in the development of human disease and the role of antioxidants as protective agents, preventing disease. .

Carcinogenicity of TCDD in laboratory animals: implications for risk assessment.

Abstract: Today, there is more scientific information relevant to the use of animal cancer data for the estimation of human risks than ever before. However, much of the data concerning tumor incidence in experimental animals that was available in 1988 demonstrated that TCDD is a carcinogen at multiple sites in both sexes of rats and mice. Some of the cancers occurred following particularly low doses. Since 1988, TCDD has been shown to be a carcinogen in hamsters, and some of the tumor incidence data in rat liver has been reevaluated during the last three years.

Oxisterol Determination in Selected Coffees

Abstract: The main aim of green-coffee processing techniques, such as decqffeination and roasting, is always to maintain a very high level of quality in taste and flavor, the beverage's most important cliaracteristics to consumers. Oxidative alterations of coffee lipids, which can occur in roasting, exert a very marked influence on these quality traits. Determining the extent of oxidation thus can provide an indication of the product's potential shelf-life and reveal traces of any newly-formed oxidative products that might prove nutritionally unsafe.Yet, while much attention has recently been focused on certain by-products induced by cholesterol oxidation and their proven toxicity as risk factors in atherosclerosis and cancer, oxidated phytosterols have largely gone unnoticed, being considered along with β-sitosterol as not very dangerous in that neither is absorbed by the intestinal tract. The present study investigates the substances derived from phytosterol oxidation (oxisterols) in samples of regular and decaff...

The Importance of Cellular Proliferation Induced by BHA and BHT

Abstract: Phenolic antioxidants have been used for many years to prevent oxidative spoilage of food (rancidity). They are of major importance in protecting foodstuffs during transportation and storage. Antioxidants thus constitute an essential element in the modem centralized food processing and distribution industries. In Canada, only three phenolic antioxidants are permitted to be added to food: butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and propyl gallate (PG). The mean dietary intake of BHA and BHT, as a result of their useas food additives, is relatively low; in Canada the intake overall ages is 7.40 mg/person/day for bothBHA and BHT, leading to a combined totalof 0.26 mg/kg/day (Kirkpatrick andLauer, 1986).

Age-related oxidation reaction in proteins.

Abstract: In the course of investigations to determine how the degradation of various enzymes is regulated, it was demonstrated that one mechanism involves oxidative modification (inactivation) of the enzyme, and thereby its conversion to a form that is highly susceptible to degradation by a variety of intracellular cytosolic proteases (Oliver et al., 1981, Levine et al., 1981, Stadtman 1986). As illustrated in Figure 1, oxidation of enzymes is achieved by metal ion catalyzed reactions in which 02 is reduced to H202 and Fe(III) is reduced to Fe(II). Both processes are catalyzed by anyone of several different electron donor systems, including: enzymic systems comprised of NAD(P)H and a flavoprotein (NAD(P)H oxidase, cytochrome P450 reductase/oxidase) or xanthine and xanthine oxidase, as wellas nonenzymic systems comprised of ascorbate/Fe(III) (Stadtman 1986, Oliver et al., 1987) or mercaptans/Fe(III) (Kim et al., 1985). Theavailable evidence (Stadtman 1990, Stadtman and Oliver 1991) is consistent with the view that protein modification is a site-specific process in which H202 and Fe(II) react at a metal binding site on the enzyme to generate an active oxygen species (·OH, ferryl, perferryl) which reactwith the side chainsof amino acid residues at the metal binding site. In some cases (e.g., lysine, arginine, proline) this leads to the generation of carbonyl derivatives, and as noted above converts the enzymes to forms that are highly susceptible to proteolytic degradation. Among otherchanges, it has beenestablished that histidyl residues are converted to asparaginyl residues, arginyl and prolyl residues are converted to glutamylsemialdehyde residues, prolyl residues arealso converted to glutamyl or pyroglutamyl residues, lysyl residues are converted to 2-amino adipylsemialdehyde residues, methionyl residues are converted to methionyl sulfoxamide residues and cysteinyl residues are converted to disulfide derivatives (mixeddisulfides, protein-protein cross-links) (for review see Stadtman 1990). A plausible mechanism by which Fe(II) mightcatalyze the oxidation of a protein aminoacid side chain is illustrated in Figure 2. In this illustration, it is assumed that the e-amino (-CH2NH2) of a lysyl residue in the protein serves as one of several ligands to which theFe(II) is bound. In the presence of H202, the Fe(II) protein complex is oxidized to a Fe(III) protein complex with concomitant formation of ·OH and OH-. Due to its high reactivity, the ·OH does not escape but reacts preferentially to abstract a H atom from the carbon bearing the eamino group forming an alkyl radical. Transfer of the lone electron of this MD

Inhibition of chemical-induced experimental cancer by synthetic phenolic antioxidants.

Abstract: The anticarcinogenic properties of synthetic phenolic antioxidants were discovered by Wattenberg (1972) who showed that butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) at 5000 ppm in the diet inhibited polycyclic aromatic hydrocarbon-induced forestomach tumors in mice and mammary tumors in rats. Subsequently, inhibitory effects, usually at the level of 5000 ppm or greater, were shown against a variety of chemical carcinogens (Table 1).At these high levels, phenolic antioxidants are inducers of carcinogen biotransformation systems and there is considerable evidence that their anticarcinogenic effects at such doses are dueto a blocking action resulting from increased carcinogen detoxification (Wattenberg, 1985).

Antioxidants in lung disease.

Abstract: Respiratory disease is a major cause of death anddisability in theU.S.and most industrialized countries. The etiology of most non-infectious lung diseases remains elusive despite a major increase in research on the respiratory system. Environmental causes are suspected for many lung diseases including chronic obstructive lung disease (COLD). Environmental agents are suspected to exacerbate existing lung disease (Van Bree et al., 1990). During the great air pollution episodes of London in the 1950s, patients with pre-existing lung disease were those most likely to die or suffer exacerbation of theirlung disease (Amdur, 1980). .

Biological antioxidant defenses.

Abstract: Under physiological conditions, aerobic organisms consume nearly 98% of molecular oxygen (dioxygen, 02) at cytochrome a3, the terminal cytochrome of the mitochondrial respiratory chain (Chance, Sies and Boveris, 1979). During this process dioxygen is reduced by four electrons, with no release of partially reduced oxygen intermediates (Malmstrom, 1982). Still, there is a fraction of 02 (1-2%) not consumed at cytochrome a3 which is monoor divalently reduced to superoxide radical (02-) or hydrogen peroxide (R202). Different perturbations of cell homeostasis result in a dramatic enhancement of the production of 02-, R202 and of the closely related species hydroxyl radical (·OR) (Freeman and Crapo 1981). 02-, R202 and the highly reactive ·OR are potentially cytotoxic reactive intermediates. These molecules can attack and irreversibly damage a diverse spectrum of biomolecules including proteins, phospholipids, nucleic acids and sugars-virtually any biomolecule. Pathophysiological situations such as hyperoxia (Freeman and Crapo, 1981), ischemia-reperfusion (Flohe, 1988) and inflammatory processes (Zweier, Kupusamy and Lutty, 1988) are known to increase cellular production of partially reduced oxygen intermediates which participate in tissue damage.