Toxicology and Industrial Health current issue

A review of conflict of interest, competing interest, and bias for toxicologists

Claxton, L. — 2008-06-20

One of the issues often associated with scientific misconduct is conflict of interest. Although there is a lack of uniformity in the definition of conflict of interest, many express concerns that competing interests may bias research methods and the interpretation of data and conclusions. In extreme cases, conflict of interest activity could contribute to scientific misconduct, hinder the training of scientists, delay the dissemination of research results, lead to the harming of human health and the environment, and misdirect society’s decisions that rely on science. This article is not a commentary or editorial but an attempt to supply an overview of what has been said, researched, and accomplished in the area of conflict of interest for toxicologists. Discussion of the financial, professional, and philosophical concerns associated with conflict of interest will be followed by brief discussion of general management approaches and the roles of scientists and organizations from all sectors (i.e., academia, industry, non-profit organizations, and government).

Protective effect of melatonin against formaldehyde-induced kidney damage in rats

Zararsiz, I, Sarsilmaz, M, Tas, U, Kus, I, Meydan, S, Ozan, E — 2008-06-20

This study was undertaken to investigate the protective effects of melatonin against formaldehyde-induced renal damage in rats. For this purpose, 21 male Wistar rats were divided into three groups. The animals in Group I were used as a control, whereas the rats in group II were injected every other day with formaldehyde. The rats in group III received melatonin daily while exposed to formaldehyde. At the end of the 14-day experimental period, all rats were killed by decapitation, and the kidneys were removed. Some of the renal tissue specimens were used for determination of superoxide dismutase, glutatione peroxidase enzyme activities, and malondialdehyde levels. The remaining kidney tissue specimens were used for light microscopic evaluation. The renal tissue activities of superoxide dismutase and glutatione peroxidase were significantly decreased, and malondialdehyde levels were significantly increased in rats treated with formaldehyde compared with those of the control animals. In the light microscopic evaluation of this group, degenerative glomerules, vacuolization and dilatation of distal tubules, and vascular congestion were detected. However, an increase was observed in activities of superoxide dismutase and glutatione peroxidase enzymes, and a decrease of malondialdehyde levels in animals treated with formaldehyde plus melatonin was observed. Furthermore, the histopathological changes caused by formaldehyde were disappeared except for minimal tubular dilatation in this group. In conclusion, the biochemical and histological findings of our study suggest that melatonin administration prevents formaldehyde-induced oxidative renal damage in rats.

Levels of retinyl palmitate and retinol in the skin of SKH-1 mice topically treated with retinyl palmitate and concomitant exposure to simulated solar light for thirteen weeks

Yan, J, Xia, Q, Wamer, W., Boudreau, M., Warbritton, A, Howard, P., Fu, P. — 2008-06-20

Retinyl esters account for more than 70% of the endogenous vitamin A found in human skin, and retinyl palmitate is one of the retinyl esters in this pool. Human skin is also exposed to retinyl palmitate exogenously through the topical application of cosmetic and skin care products that contain retinyl palmitate. To date, there is limited information on the penetration and distribution of retinyl palmitate and vitamin A within in the skin. In this study, the accumulation of retinyl palmitate and generation of retinol in the skin of male and female SKH-1 mice that received repeated topical applications of creams containing 0.0%, 0.1%, 0.5%, 1.0%, 5.0%, 10%, or 13% of retinyl palmitate 5 days a week for a period of 13 weeks were studied. Because products containing retinyl palmitate are frequently applied to sun-exposed skin, and because it is well established that exposure to sunlight and UV light can alter cutaneous levels of retinoids, mice in this study were additionally exposed 5 days a week to simulated solar light. The results showed that retinyl palmitate diffused into the skin and was partially hydrolyzed to retinol. The levels of retinyl palmitate in the skin of mice that were administered retinyl palmitate cream were higher than control values, and levels of both retinyl palmitate and retinol increased with the application of higher concentrations of retinyl palmitate in the cream. Our results indicate that topically applied retinyl palmitate may alter the normal physiological levels of retinyl palmitate and retinol in the skin of SKH-1 mice and may have a significant impact on vitamin A homeostasis in the skin.

Preventive role of folic acid on the developmental toxicity of phenol in Drosophila melanogaster

Askin, H, Uysal, H, Altun, D — 2008-06-20

Phenol (PN), obtained from coal tar, is used commonly in medical treatments, industrial areas, petroleum refineries, production of glue, fiber, and nylon. PN is used in the production of benzene and it is emitted in the atmosphere by motor vehicles. Folic acid (FA) is an essential nutrient among the B complex group of vitamins. The main aim of this study was to investigate the effects of PN and PN + FA on various developmental stages of Drosophila melanogaster. Different concentrations of PN and PN + FA were administered during the developmental periods of the fly (egg, larva and pupa). When F₁ progeny of control and experimental groups were compared, PN was found to extend the process of metamorphosis and decrease the total offspring numbers. However, these negative effects were inhibited by FA treatment at different concentrations (0.25–2.50 mg/kg). These results suggest that FA could effectively inhibit PN-induced abnormalities in developmental stages of Drosophila melanogaster.

The periodontal status of indirectly lead-exposed apprentices working in autorepair workshops

2008-06-20

The aim of this study was to evaluate the periodontal health status of lead-exposed apprentices and to search the correlation between clinical periodontal parameters and either blood lead or oxidative stress/damage indices in erythrocytes. Sixty male subjects were recruited for this study (30 apprentices and 30 controls). The periodontal health status was determined with gingival index, plaque index, gingival bleeding time index, probing depth, and clinical attachment level records. Additionally, blood lead level and indices of oxidative stress (glutathione peroxidase, superoxide dismutase), catalase activities and damage (malondialdehyde concentration) in erythrocytes were determined. The results showed that lead level was significantly higher in apprentices than in controls (P < 0.05). None of the clinical periodontal parameters and oxidative stress/damage indices were significantly different between the groups (P > 0.05). Significant correlation between plaque index and catalase, probing depth and superoxide dismutase, clinical attachment level and superoxide dismutase, and clinical attachment level and malondialdehyde in apprentices group (P < 0.05), and gingival bleeding time index and glutathione peroxidase in control group were found (P < 0.05). In multiple regression analysis, there were statistically significant associations between gingival index and working status, family income and either probing depth or clinical attachment level (P < 0.05). The results of this study showed significant association between the clinical periodontal parameters and oxidative stress/damage indices in apprentices indirectly exposed to low levels of lead.

Redefining idiopathic interstitial lung disease into occupational lung diseases by analysis of chemical composition of inhaled dust particles in induced sputum and/or lung biopsy specimens

Fireman, E., Lerman, Y, Ben Mahor, M, Ganor, E, Kramer, M. — 2008-06-20

There has been increased public awareness of the potential danger from exposure to hazardous dust in various occupations. This study aims to validate the qualitative analysis of scanning electron microscopy (SEM) of lung samples by 1) correlation of induced sputum (IS) findings to clinical findings, 2) comparing hazardous particles in IS to those in biopsied lung specimens, and 3) assessing whether the particles present in the lungs of transplanted patients correlate with occupational history of dust exposure. Forty patients with occupational history were included; of whom 35 filled in questionnaires. Twenty-four of them had SEM analysis of their IS, and 11 of these 24 also had SEM analysis of their lung tissue. Another 11 lung biopsies from patients with occupational history were scanned by SEM and compared with 10 lung biopsies from patients with no occupational history. SEM analysis of IS was as efficient for detecting hazardous particles as was SEM analysis of lung tissue; silica was detected better in sputum. Exposure to silica was the main chemical element associated with a high likelihood to show abnormalities in IS (Odds ratio 19.41 CI = 0.270–1398.33). The average number of detected hazardous chemical elements in patients with an occupational history of exposure was 4 ± 1.61 in IS and 3.55 ± 2.02 in lung tissue (P = 0.57); it was 1.5 ± 0.85 from transplanted occupationally exposed patients compared with 0.36 ± 0.67 in transplanted non-exposed patients (P = 0.003). SEM analysis of particles in IS and lung tissue can elucidate the causative agent(s) of otherwise idiopathic interstitial lung disease among occupationally exposed workers.

JP-8 jet fuel exposure potentiates tumor development in two experimental model systems

Harris, D., Sakiestewa, D, Titone, D, He, X, Hyde, J, Witten, M — 2008-06-20

The US Air Force has implemented the widespread use of JP-8 jet fuel in its operations, although a thorough understanding of its potential effects upon exposed personnel is unclear. Previous work has reported that JP-8 exposure is immunosuppressive. Exposure of mice to JP-8 for 1 h/day resulted in immediate secretion of two immunosuppressive agents; namely, interleukin-10 (IL-10) and prostaglandin E2 (PGE2). Thus, it was of interest to determine if jet fuel exposure might promote tumor growth and metastasis. The syngeneic B16 tumor model was used for these studies. Animals were injected intravenously with tumor cells, and lung colonies were enumerated. Animals were also examined for metastatic spread of the tumor. Mice were either exposed to 1000 mg/m³ JP-8 (1 h/day) for 7 days before tumor injection or were exposed to JP-8 at the time of tumor injection. All animals were killed 17 days after tumor injection. In the present study, JP8 exposure potentiated the growth and metastases of B16 tumors in an animal model. Exposure of mice to JP-8 for 1 h/day before tumor induction resulted in an approximately 8.7-fold increase in tumors, whereas those mice exposed to JP8 at the time of tumor induction had a 5.6-fold increase in tumor numbers. Thus, low concentration JP-8 jet fuel exposures have significant immune suppressive effects on the immune system that can result in increased tumor formation and metastases. We have now extended the observations to an experimental subcutaneous tumor model. JP8 exposure at the time of tumor induction in this model did not affect the growth of the tumor. However, JP8-exposed, tumor-bearing animals died at an accelerated rate as compared with air-exposed, tumor-bearing mice.

UVA photoirradiation of anhydroretinol - formation of singlet oxygen and superoxide

Yin, J., Xia, Q, Fu, P. — 2008-06-20

Anhydroretinol is a metabolite of vitamin A (retinol) and a major photodecomposition product of retinyl palmitate and retinyl acetate. Anhydroretinol is biologically active, inducing cell death in lymphoblastoid cells, prevention of N-methyl-N-nitrosourea-induced mammary cancer, and inhibition of cell growth in lymphocytes. We have previously determined that photoirradiation of anhydroretinol in the presence of a lipid, methyl linoleate, with UVA light-induced lipid peroxidation. In the present study, electron spin resonance (ESR) spin-trap techniques were employed to explore the mechanism of lipid peroxidation initiation. Irradiation of anhydroretinol by UVA in the presence of 2,2,6,6-tetramethylpiperidine (TEMP), a specific probe for singlet oxygen, resulted in the formation of TEMPO, indicating that singlet oxygen was generated. During photoirradiation in the presence of 5,5-dimethyl N-oxide pyrroline (DMPO), a specific probe for superoxide, ESR signals for DMPO-OOH were formed, and these signals were quenched by superoxide dismutase. The involvement of singlet oxygen on the induction of lipid peroxidation was also evidenced by the observation that lipid peroxidation was inhibited by sodium azide and enhanced by deuterium oxide. Our overall results provide evidence that photoirradiation of anhydroretinol with UVA light generates reactive oxygen species, e.g. singlet oxygen and superoxide, which mediate the induction of lipid peroxidation.