Journal of Toxicology & Environmental Health Part B: Critical Reviews

Gulumian, M.; Borm, P. J. A.; Vallyathan, V.; Castranova, V.; Donaldson, K.; Nelson, G.; Murray, J.

doi: 10.1080/15287390500196537pmid: 16990219

Clinical detection of silicosis is currently dependent on radiological and lung function abnormalities, both late manifestations of disease. Markers of prediction and early detection of pneumoconiosis are imperative for the implementation of timely intervention strategies. Understanding the underlying mechanisms of the etiology of coal workers pneumoconiosis (CWP) and silicosis was essential in proposing numerous biomarkers that have been evaluated to assess effects following exposure to crystalline silica and/or coal mine dust. Human validation studies have substantiated some of these proposed biomarkers and argued in favor of their use as biomarkers for crystalline silica- and CWP-induced pneumoconiosis. A number of “ideal” biological markers of effect were identified, namely, Clara cell protein-16 (CC16) (serum), tumor necrosis factor-α (TNF-α) (monocyte release), interleukin-8 (IL-8) (monocyte release), reactive oxygen species (ROS) measurement by chemiluminescence (neutrophil release), 8-isoprostanes (serum), total antioxidant levels measured by total equivalent antioxidant capacity (TEAC), glutathione, glutathione peroxidase activity, glutathione S-transferase activity, and platelet-derived growth factor (PDGF) (serum). TNF-α polymorphism (blood cellular DNA) was identified as a biomarker of susceptibility. Further studies are planned to test the validity and feasibility of these biomarkers to detect either high exposure to crystalline silica and early silicosis or susceptibility to silicosis in gold miners in South Africa.

Exon, J. H.

doi: 10.1080/10937400600681430pmid: 17492525

Acrylamide (ACR) is a chemical used in many industries around the world and more recently was found to form naturally in foods cooked at high temperatures. Acrylamide was shown to be a neurotoxicant, reproductive toxicant, and carcinogen in animal species. Only the neurotoxic effects were observed in humans and only at high levels of exposure in occupational settings. The mechanism underlying neurotoxic effects of ACR may be basic to the other toxic effects seen in animals. This mechanism involves interference with the kinesin-related motor proteins in nerve cells or with fusion proteins in the formation of vesicles at the nerve terminus and eventual cell death. Neurotoxicity and resulting behavioral changes can affect reproductive performance of ACR-exposed laboratory animals with resulting decreased reproductive performance. Further, the kinesin motor proteins are important in sperm motility, which could alter reproduction parameters. Effects on kinesin proteins could also explain some of the genotoxic effects on ACR. These proteins form the spindle fibers in the nucleus that function in the separation of chromosomes during cell division. This could explain the clastogenic effects of the chemical noted in a number of tests for genotoxicity and assays for germ cell damage. Other mechanisms underlying ACR-induced carcinogenesis or nerve toxicity are likely related to an affinity for sulfhydryl groups on proteins. Binding of the sulfhydryl groups could inactive proteins/enzymes involved in DNA repair and other critical cell functions. Direct interaction with DNA may or may not be a major mechanism for cancer induction in animals. The DNA adducts that form do not correlate with tumor sites and ACR is mostly negative in gene mutation assays except at high doses that may not be achievable in the diet. All epidemiologic studies fail to show any increased risk of cancer from either high-level occupational exposure or the low levels found in the diet. In fact, two of the epidemiologic studies show a decrease in cancer of the large bowel. A number of risk assessment studies were performed to estimate increased cancer risk. The results of these studies are highly variable depending on the model. There is universal consensus among international food safety groups in all countries that examined the issue of ACR in the diet that not enough information is available at this time to make informed decisions on which to base any regulatory action. Too little is known about levels of this chemical in different foods and the potential risk from dietary exposure. Avoidance of foods containing ACR would result in worse health issues from an unbalanced diet or pathogens from under cooked foods. There is some consensus that low levels of ACR in the diet are not a concern for neurotoxicity or reproductive toxicity in humans, although further research is need to study the long-term, low-level cumulative effects on the nervous system. Any relationship to cancer risk from dietary exposure is hypothetical at this point and awaits more definitive studies.

Rollison, Dana E.; Helzlsouer, Kathy J.; Pinney, Susan M.

doi: 10.1080/10937400600681455pmid: 17492526

Hair dyes are widely used, and permanent hair dye is the most commonly used type of product. Permanent hair dye colors are formed by an oxidative process involving arylamines, giving rise to concerns about the potential adverse health effects of long-term exposure, especially cancer. A 1993 International Agency for Cancer Research (IARC) review concluded that evidence was inadequate to evaluate the carcinogenicity of personal hair dye use. This systematic review synthesizes the results from studies of personal hair dye use and cancer published since 1993, taking into consideration the quality of exposure assessment. Thirty-one English-language articles published in January 1992–February 2005 that investigated the association between personal hair dye use and cancer were identified through the PubMed search engine. Quality of exposure assessment was rated between 1+ (lowest quality: assessed ever use of hair dyes) and 4+ (highest quality: assessed dye type [permanent/nonpermanent], dye color/shade, frequency and duration of use). Because of the heterogeneity of the exposure assessment across the studies, a formal meta-analysis was not conducted. Associations between personal hair dye use and non-Hodgkin's lymphoma, multiple myeloma, acute leukemia, and bladder cancer were observed in at least one well-designed study with detailed exposure assessment (rated 3+ or 4+), but were not consistently observed across studies. Results for bladder cancer studies suggest that subsets of the population may be genetically susceptible to hair dye exposures, but these findings are based on small subgroups in one well-designed case-control study. Replication of these findings is needed to determine whether the reported associations are real or spurious.