Flame-retardant contamination of firefighter personal protective clothing - A potential health risk for firefighters.

There is a high incidence of cardiovascular disease and certain cancers in firefighters that may be related to their occupational exposure to hazardous substances. Exposure may result from contaminated personal protective gear, as well as from direct exposure at fire scenes. This study characterized flame-retardant contamination on firefighter personal protective clothing to assess exposure of firefighters to these chemicals. Samples from used and unused firefighter protective clothing, including gloves, hoods and a coat wristlet, were extracted with methylene chloride and analyzed by EPA method 8270D Specific Ion Method (SIM) for polybrominated diphenyl ethers (PBDEs). Until recently PBDEs were some of the most common flame-retardant chemicals used in the US. Fifteen of the seventeen PBDEs for which analysis was performed were found on at least one clothing swatch. Every clothing sample, including an unused hood and all three layers of an unused glove, held a detectable concentration of at least one PBDE. These findings, along with previous research, suggest that firefighters are exposed to PBDE flame retardants at levels much higher than the general public. PBDEs are found widely dispersed in the environment and still persist in existing domestic materials such as clothing and furnishings. Firefighter exposure to flame retardants therefore merits further study.

Evaluating Endocrine Disruption Activity of Deposits on Firefighting Gear Using a Sensitive and High Throughput Screening Method.

OBJECTIVE: Adverse health outcomes related to exposure to endocrine disrupting chemicals, including increased incidences of coronary heart disease, prostate and testicular cancers, and congenital disabilities, have been reported in firefighters or their offspring. We, therefore, measured the estrogenic and antiestrogenic activity of extracts of used firefighter gear to assess exposure to these agents. METHODS: Extracts and known chemical contaminants were examined for estrogenicity and antiestrogenicity in yeast cells expressing the estrogen receptor. RESULTS: Most extracts of used gear and phthalate diesters detectable on this gear displayed strong antiestrogenic effects. Notably, new glove and hood extracts showed significant estrogenic activity. CONCLUSIONS: Overall, our data suggest that firefighters are exposed to both estrogenic and antiestrogenic agents, possibly phthalates that may lead to health risks observed in this occupation as a result of perturbation of hormone homeostasis.

Exposure of firefighters to particulates and polycyclic aromatic hydrocarbons.

Firefighting continues to be among the most hazardous yet least studied occupations in terms of exposures and their relationship to occupational disease. Exposures are complex, involving mixtures of particles and chemicals such as polycyclic aromatic hydrocarbons (PAHs). Adverse health effects associated with these agents include elevated incidences of coronary heart disease and several cancers. PAHs have been detected at fire scenes, and in the firehouse rest area and kitchen, routinely adjoining the truck bay, and where firefighters spend a major part of each shift. An academic-community partnership was developed with the Cincinnati Fire Department with the goal of understanding active firefighters' airborne and dermal PAH exposure. PAHs were measured in air and particulates, and number and mass concentrations, respectively, of submicron (0.02-1 µm) and PM2.5 (2.5 µm diameter and less) particles during overhaul events in two firehouses and a University of Cincinnati administrative facility as a comparison location. During overhaul firefighters evaluate partially combusted materials for re-ignition after fire extinguishment and commonly remove Self-Contained Breathing Apparatus (SCBA). Face and neck wipes were also collected at a domestic fire scene. Overhaul air samples had higher mean concentrations of PM2.5 and submicron particles than those collected in the firehouse, principally in the truck bay and kitchen. Among the 17 PAHs analyzed, only naphthalene and acenaphthylene were generally detectable. Naphthalene was present in 7 out of 8 overhaul activities, in 2 out of 3 firehouse (kitchen and truck bay) samples, and in none collected from the control site. In firefighter face and neck wipes a greater number of PAHs were found, several of which have carcinogenic activity, such as benzofluoranthene, an agent also found in overhaul air samples. Although the concentration for naphthalene, and all other individual PAHs, was very low, the potential simultaneous exposure to multiple chemicals even in small quantities in combination with high ultrafine particle exposure deserves further study. It is recommended that personal respiratory and skin protection be worn throughout the overhaul process.

Plasticizer contamination of firefighter personal protective clothing--a potential factor in increased health risks in firefighters.

Chemical exposures may be responsible for firefighters' elevated incidences of cancer and cardiovascular disease. This study characterized semivolatile chemical contamination on firefighter personal protective clothing to assess exposure of firefighters to these chemicals. Samples from used firefighter protective clothing, including gloves, hood, and one coat wristlet, were extracted with methylene chloride and analyzed by EPA method 8270 for semivolatile contaminants, including 20 polycyclic aromatic hydrocarbons (PAHs) and 6 phthalate diesters. Twenty-two of the chemicals of interest were found on at least one clothing swatch. Only di-(2-ethylhexyl) phthalate (DEHP), a plasticizer, added to polyvinyl chloride (PVC) to increase flexibility, was found on every swatch. DEHP concentrations were the highest of any chemical measured, and were 52 to 875 times higher than any PAH concentration measured. DEHP was also detected on most items of unused firefighter personal protective clothing, although at much lower levels. These findings suggest that firefighters are exposed to high levels of DEHP, a probable human carcinogen, and at levels much higher than PAHs, the semivolatile toxic combustion products most extensively studied historically. Firefighter exposure to DEHP and other phthalate diesters therefore merits further study.

Hypomethylation of dual specificity phosphatase 22 promoter correlates with duration of service in firefighters and is inducible by low-dose benzo[a]pyrene.

OBJECTIVE: Firefighters (FFs) are chronically exposed to smoke and products of incomplete combustion, which frequently contain polycyclic aromatic hydrocarbons (PAHs). This study examined the possibility of an association between PAH-induced epigenetic alterations and occupational firefighting exposure. METHODS: Promoter methylation was analyzed in four genes in blood DNA from 18 FFs and 20 non-FFs (controls). Jurkat and human normal prostate epithelial cells were treated with benzo[a]pyrene to ascertain the epigenetic effects of this type of agent. RESULTS: Firefighters had a higher prevalence of dual specificity phosphatase 22-promoter hypomethylation in blood DNA (P = 0.03) and the extent of hypomethylation correlated with duration of firefighting service (P = 0.04) but not with age. Benzo[a]pyrene reduced promoter methylation and increased gene expression of the same gene in Jurkat and normal prostate epithelial cells. CONCLUSIONS: Cumulative occupational exposure to combustion-derived PAHs during firefighting can cause epigenetic changes in promoters of specific genes.

Ultrafine particle exposure during fire suppression--is it an important contributory factor for coronary heart disease in firefighters?

OBJECTIVE: Coronary heart disease (CHD) is the primary cause of death among US firefighters during fire suppression. In other populations, exposure to respirable particles, including ultrafine particles, has been widely implicated as a risk factor for CHD. This study is the first to report detailed characterization of respirable particles released by combustion of an automobile and model residential structures under firefighter exposure conditions. METHODS: Characterization was performed when feasible during knockdown and routinely during overhaul. RESULTS: Ultrafines accounted for >70% of particles in all fire suppression stages, occurring in concentrations exceeding background by factors between 2 (automobile) and 400 (bedroom), consistent among all structures. CONCLUSIONS: Exposure to ultrafine particles during fire suppression should be considered a potential contributing factor for CHD in firefighters. Of major significance is their predominance during overhaul, where firefighters frequently remove respiratory protection.

Identification of mouse SLC39A8 as the transporter responsible for cadmium-induced toxicity in the testis.

Testicular necrosis is a sensitive endpoint for cadmium (Cd(2+), Cd) toxicity across all species tested. Resistance to Cd-induced testicular damage is a recessive trait assigned to the Cdm locus on mouse chromosome 3. We first narrowed the Cdm-gene-containing region to 880 kb. SNP analysis of this region from two sensitive and two resistant inbred strains demonstrated a 400-kb haplotype block consistent with the Cd-induced toxicity phenotype; in this region is the Slc39a8 gene encoding a member of the solute-carrier superfamily. Slc39a8 encodes SLC39A8 (ZIP8), whose homologs in plant and yeast are putative zinc transporters. We show here that ZRT-, IRT-like protein (ZIP)8 expression in cultured mouse fetal fibroblasts leads to a >10-fold increase in the rate of intracellular Cd influx and accumulation and 30-fold increase in sensitivity to Cd-induced cell death. The complete ZIP8 mRNA and intron-exon splice junctions have no nucleotide differences between two sensitive and two resistant strains of mice; by using situ hybridization, we found that ZIP8 mRNA is prominent in the vascular endothelial cells of the testis of the sensitive strains of mice but absent in these cells of resistant strains. Slc39a8 is therefore the Cdm gene, defining sensitivity to Cd toxicity specifically in vascular endothelial cells of the testis.

Gene expression profiles of mouse aorta and cultured vascular smooth muscle cells differ widely, yet show common responses to dioxin exposure.

Exposure to environmental toxicants may play a role in the onset and progression of cardiovascular disease. Many environmental agents, such as dioxin, are risk factors for atherosclerosis because they may exacerbate an underlying disease by altering gene expression patterns. Expression profiling of vascular tissues allows the simultaneous analysis of thousands of genes and may provide predictive information particularly useful in early disease stages. Often, however, in vivo experiments are unfeasible for material or ethical reasons, and data from cultured cells must be used instead, even though it may not be known whether cultured cells and live tissues share common global responses to the same toxicant. In a search for genes responsive to dioxin exposure, we used oligonucleotide microarrays with DNA sequences from 13,433 genes to compare global gene expression profiles of C57BL/6 mice aortas with cultured vascular smooth muscle cells (vSMCs) of the same mice. Aorta segments and vSMCs differed in the expression of more than 4500 genes, many showing expression differences greater than 1000-fold. Integration of microarray data into Gene Ontology Project annotations showed that many of the genes differentially expressed belonged to the same biological process or metabolic pathway. Notwithstanding these results, a subset of 35 genes responded in the same fashion to dioxin exposure in both systems. Genes in this subset encoded phase I and phase II detoxification enzymes, signal transduction kinases and phosphatases, and proteins involved in DNA repair and the cell cycle. We conclude that vSMCS may be useful aorta surrogates to study early gene expression responses to dioxin exposure, provided that analyses focus on this subset of genes.

Mutational biases associated with potential iron-binding DNA motifs in rodent lacI and human p53 mutational databases.

The role of Fenton oxidants in DNA damage, aging, and cancer is appreciated, but not well understood. Six potential iron-binding (PIB) DNA motifs were previously identified as sites of preferential strand cleavage. Since DNA-metal binding domains are a known determinant of oxidative DNA damage, and the location of strand breaks explains where oxidant attack occurs, we sought to determine whether the likelihood of base change mutations is a function of neighboring PIB motifs. We developed a sliding window function that computes the density of PIB motifs on both strands, within 4-12bp, for each location along a target gene. This range of window sizes reflects known diffusion distances of Fenton reaction products. Using mutational databases, odds of mutation at each base were calculated relative to PIB motif density, for all PIB motif types in aggregate, or for individual PIB motifs. Using mutational data from lacI transgenic animals, we observed a non-random distribution of PIB motifs, associated with increased odds of mutation, showing a strand bias. Sensitivity analysis confirmed that the optimum association between PIB motif density and mutations occurs when a 7bp radius is used for the window size. Randomly simulated mutations showed no association with PIB motif density. When the method was applied to human TP53 mutation data, we saw similar results, but no strand bias. As PIB motif density rises, linear trends are observed for increasing odds of mutation. Sensitivity analysis revealed associations between PIB motifs and GC --> AT transitions and GC --> TA transversions-the most commonly observed types of mutations arising from oxidative DNA damage. DNA-metal binding motifs are found in a wide variety of biological contexts, including many where conformational sensitivity to redox state is important. These techniques can help elucidate how DNA-iron-binding may affect lesions and subsequent mutations from multiple agents.

Phylogenetic analysis of Hoxa 11 sequences reveals absence of transposable elements, conservation of transcription factor binding sites, and suggests antisense coding function.

Nine thousand and eighty-eight base pairs of the chicken Hoxa 11 gene, including 8470 bases 5' of the translation start site were sequenced, and the characteristics of the upstream sequence investigated. Consistent with previous findings that middle repetitive elements are rare in the HoxA cluster, no repetitive elements were found other than simple oligonucleotide repeats. Multiple and pairwise alignments of the chicken upstream sequence with its human and mouse orthologs revealed multiple regions of 80% or higher homology across species. For the chicken, these regions were separated by sequences with no significant homology to human, mouse, or in most cases any other Genbank sequences. Selective clustering of transcription factor binding motifs was found to occur within the conserved homologous regions, suggesting evolutionary conservation of critical regulatory sequences. Of particular interest, seven conserved Cdx binding sites were found in the Hoxa 11 promoter, suggesting regulation by a non-clustered Caudal homeobox gene. Previous analysis of the mouse and human Hoxa 11 genes found a conserved antisense transcript, of unknown function. The chicken Hoxa 11 antisense strand included a conserved open reading frame capable of encoding 168 amino acids. Comparison of this region in mouse and chicken showed seven insertion/deletions, with each a multiple of three bases, thereby preserving open reading frame.