Total Aromatic Content in Petroleum Solvents Modifies Headspace Benzene Vapor Concentrations: Implications for Exposure Assessments

This study evaluates how equilibrium vapor concentrations above petroleum solvent mixtures are affected by total aromatic content and the implications for estimating benzene vapor exposures. Headspace vapor concentrations over mixtures with liquid benzene content ranging from 0.001 to 1.0% and varying percentages of 1,2,4-trimethylbenzene and n-nonane were studied using a direct-injection gas chromatography/flame ionization detection method that showed good precision. The measured values were compared to predictions based on Raoult's Law, with and without non-ideality corrections using activity coefficients. Ratios of vapor to liquid benzene concentrations decreased with increasing total aromatic content; that is, mixtures with 10% to 20% trimethylbenzene simulating non-hydrotreated mineral spirits had much lower ratios compared to the ≥99% aliphatic mixtures that simulate hydrotreated mineral spirits. Positive deviations from Raoult's Law were greatest at liquid benzene concentrations less than 0.1%, particularly in the predominantly aliphatic mixtures. Correcting for non-ideality using activity coefficients resulted in predicted vapor concentrations that were closer to measured values. The data indicate that higher aromatic content and higher liquid benzene content suppress benzene vapor concentrations due to benzene's greater affinity for similar aromatic molecules in solution. Benzene exposure reconstructions should consider actual composition of the historic material with respect to aromatic content.     

Biological monitoring of benzene exposure during maintenance work in crude oil cargo tanks

We investigated the association between the individual concentrations of benzene in the breathing zone and the concentrations of benzene in the blood and urine among workers maintaining crude oil cargo tanks. Benzene exposure was measured during three consecutive 12h work days among 13 tank workers and 9 unexposed referents (catering section). Blood and urine samples were collected pre-shift on the first day, post-shift on the third day, and pre-next shift on the following morning. The workers used half-mask air-purifying respirators, but not all workers used these systematically. The individual geometric mean benzene exposure in the breathing zone of tank workers over 3 days was 0.15 ppm (range 0.01-0.62 ppm). The tank workers' post-shift geometric mean benzene concentrations were 12.3 nmol/l in blood and 27.0 nmol/l in urine versus 0.7 nmol/l for both blood and urine among the referents. Benzene in the work atmosphere was highly correlated with the internal concentration of benzene both in post-shift blood (r=0.87, P<0.001) and post-shift urine (r=0.90, P<0.001), indicating that the varying use of respirators did not explain much of the variability in absorbed benzene. The results showed that, despite low benzene exposure in this work atmosphere and the use of personal protective equipment to a varying degree, the tank workers had a significant uptake of benzene that correlated highly with benzene exposure. The internal concentration of benzene was higher than expected considering the measured individual benzene exposure, probably due to an extended work schedule of 12h and physical strain during tank work. Control measures should be improved for processes, which impose a potential for increased absorption of benzene upon the workers.     

Exposure Monitoring and Health Risk Assessment of 1-Bromopropane as a Cleaning Solvent in the Workplace

This study was conducted to estimate the health risk to workers exposed to 1-bromopropane (1-BP) used as a cleaning solvent in their workplaces. Fifty samples from 10 workplaces that use 1-BP as a cleaning solvent were obtained to assess 1-BP concentrations. An exposure assessment revealed central tendency exposure (CTE) and reasonable maximum exposure (RME) levels of 82.1 and 214.8 mg/m³, respectively. For risk characterization, the 1-BP exposure concentrations for reproductive and developmental toxicities were calculated as 2.8 and 8.5 mg/m³, respectively, and compared with the reference concentrations in the workplace. The CTE and RME hazard quotients (HQ) were, respectively, 29.4 and 77.0 for reproductive toxicity and 9.6 and 25.2 for developmental toxicity. The results of our 1-BP risk assessment indicated that the CTE-HQs for both categories were higher than the acceptable risk value of 1, indicating that 1-BP may be considered as harmful to workers.     

Maternal Benzene Exposure during Pregnancy and Risk of Childhood Acute Lymphoblastic Leukemia: A Meta-Analysis of Epidemiologic Studies

Background

The prevalence of childhood leukemia is increasing rapidly all over the world. However, studies on maternal benzene exposure during pregnancy and childhood acute lymphoblastic leukemia (ALL) have not been systematically assessed. Therefore, we performed a meta-analysis to investigate the association between maternal solvent, paint, petroleum exposure, and smoking during pregnancy and risk of childhood ALL.

Methods

Relevant studies up to September 1^st, 2013 were identified by searching the PubMed, EMBASE, Cochrane library and the Web of Science databases. The effects were pooled using either fixed or random effect models based on the heterogeneity of the studies.

Results

Twenty-eight case-control studies and one cohort study were included for analysis, with a total of 16,695 cases and 1,472,786 controls involved. Pooled odds ratio (OR) with 95% confidence interval (CI) for ALL was 1.25 (1.09, 1.45) for solvent, 1.23 (1.02, 1.47) for paint, 1.42 (1.10, 1.84) for petroleum exposure, and 0.99 (0.93, 1.06) for maternal smoking during pregnancy. No publication bias was found in this meta-analysis and consistent results were observed for subgroup and sensitivity analyses.

Conclusions

Childhood ALL was associated with maternal solvent, paint, and petroleum exposure during pregnancy. No association was found between ALL and maternal smoking during pregnancy. Avoidance of maternal occupational and environmental benzene exposure during pregnancy could contribute to a decrease in the risk of childhood ALL.     

DNA damage in leukocytes of workers occupationally exposed to 1-bromopropane

1-bromopropane (1-BP; n-propyl bromide) (CAS No. 106-94-5) is an alternative to ozone-depleting chlorofluorocarbons that has a variety of potential applications as a degreasing agent for metals and electronics, and as a solvent vehicle for spray adhesives. Its isomer, 2-brompropane (2-BP; isopropyl bromide) (CAS No. 75-26-3) impairs antioxidant cellular defenses, enhances lipid peroxidation, and causes DNA damage in vitro. The present study had two aims. The first was to assess DNA damage in human leukocytes exposed in vitro to 1- or 2-BP. DNA damage was also assessed in peripheral leukocytes from workers with occupational exposure to 1-BP. In the latter assessment, start-of- and end-of-work week blood and urine samples were collected from 41 and 22 workers at two facilities where 1-BP was used as a solvent for spray adhesives in foam cushion fabrication. Exposure to 1-BP was assessed from personal-breathing zone samples collected for 1-3 days up to 8h per day for calculation of 8h time weighted average (TWA) 1-BP concentrations. Bromide (Br) was measured in blood and urine as a biomarker of exposure. Overall, 1-BP TWA concentrations ranged from 0.2 to 271 parts per million (ppm) at facility A, and from 4 to 27 ppm at facility B. The highest exposures were to workers classified as sprayers. 1-BP TWA concentrations were statistically significantly correlated with blood and urine Br concentrations. The comet assay was used to estimate DNA damage. In vitro, 1- or 2-BP induced a statistically significant increase in DNA damage at 1mM. In 1-BP exposed workers, start-of- and end-of-workweek comet endpoints were stratified based on job classification. There were no significant differences in DNA damage in leukocytes between workers classified as sprayers (high 1-BP exposure) and those classified as non-sprayers (low 1-BP exposure). At the facility with the high exposures, comparison of end-of-week values with start-of-week values using paired analysis revealed non-sprayers had significantly increased comet tail moments, and sprayers had significantly increased comet tail moment dispersion coefficients. A multivariate analysis included combining the data sets from both facilities, log transformation of 1-BP exposure indices, and the use of multiple linear regression models for each combination of DNA damage and exposure indices including exposure quartiles. The covariates were gender, age, smoking status, facility, and glutathione S-transferase M1 and T1 (GSTM1, GSTT1) polymorphisms. In the regression models, start-of-week comet tail moment in leukocytes was significantly associated with serum Br quartiles. End-of-week comet tail moment was significantly associated with 1-BP TWA quartiles, and serum Br quartiles. Gender, facility, and GSTM1 had a significant effect in one or more models. Additional associations were not identified from assessment of dispersion coefficients. In vitro and in vivo results provide limited evidence that 1-BP exposure may pose a small risk for increasing DNA damage.     

Does age affect the relationship between control at work and sleep disturbance for shift workers?

Among miners, shift work, aging and lack of control at work may be factors leading to increased sleep problems. Such risk factors may also operate in interaction, resulting in an even increased harm for sleep disruption. The present study aims at evaluating these relationships drawing on a sample of Australian mine and energy workers and their partners. The workers were mainly men. All performed shift work that included either nights (95%) or multiple shifts (92%), usually both (87%), while 36% were aged 50 years or above. The results show that low latitude over work activities is associated with higher sleep disturbances across the sample, though the effects are clearer amongst younger workers. By contrast, for younger workers, control over shift scheduling is not associated with sleep disturbances but for workers aged 50 or more, low control results in more sleep disturbance. Misalignment between shift workers and partner work schedules, and partner dissatisfaction with shift worker's employment and shift worker's work-life balance, are also associated with more sleep disturbances amongst shift workers.     

Subtoxic and toxic concentrations of benzene and toluene induce Nrf2‐mediated antioxidative stress response and affect the central carbon metabolism in lung epithelial cells A549

Since people in industrialized countries spend most of their time indoors, the effects of indoor contaminants such as volatile organic compounds become more and more relevant. Benzene and toluene are among the most abundant compounds in the highly heterogeneous group of indoor volatile organic compounds. In order to understand their effects on lung epithelial cells (A549) representing lung's first line of defense, we chose a global proteome and a targeted metabolome approach in order to detect adverse outcome pathways caused by exposure to benzene and toluene. Using a DIGE approach, 93 of 469 detected protein spots were found to be differentially expressed after exposure to benzene, and 79 of these spots were identified by MS. Pathway analysis revealed an enrichment of proteins involved in Nrf2‐mediated and oxidative stress response glycolysis/gluconeogenesis. The occurrence of oxidative stress at nonacute toxic concentrations of benzene and toluene was confirmed by the upregulation of the stress related proteins NQO1 and SOD1. The changes in metabolism were validated by ion chromatography MS/MS analysis revealing significant changes of glucose‐6‐phosphate, fructose‐6‐phosphate, 3‐phosphoglycerate, and NADPH. The molecular alterations identified as a result of benzene and toluene exposure demonstrate the detrimental effect of nonacute toxic concentrations on lung epithelial cells. The data provided here will allow for a targeted validation in in vivo models.     

Cross-Sectional Relationship Between Chronic Stress and Mineral Concentrations in Hair of Elementary School Girls

Chronic stress exposure is associated with diverse negative health outcomes. It has been hypothesised that stress may also negatively affect the body's mineral status. This study investigates the association between chronic stress and long-term mineral concentrations of calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), phosphorus (P) and zinc (Zn) in scalp hair among elementary school girls. Complete information on child-reported stress estimates (Coddington Life Events Scale (CLES)), hair cortisone and hair mineral concentrations, and predefined confounders in the stress–mineral relationship (i.e. age, body mass index, physical activity, diet, hair colour and parental education) was provided cross-sectionally for 140 girls (5–10 years old). The relationship between childhood stress measures (predictor) and hair minerals (outcome) was studied using linear regression analysis, adjusted for the abovementioned confounders. Hair cortisone concentrations were inversely associated with hair mineral concentrations of Ca, Mg, Zn and the Ca/P ratio. Children at risk by life events (CLES) presented an elevated Ca/Mg ratio. These findings were persistent after adjustment for confounders. This study demonstrated an independent association between chronic stress measures and hair mineral levels in young girls, indicating the importance of physiological stress–mineral pathways independently from individual or behavioural factors. Findings need to be confirmed in a more heterogeneous population and on longitudinal basis. The precise mechanisms by which stress alters hair mineral levels should be further elucidated.     

Benzene and the risk of non-Hodgkin lymphoma: A review and meta-analysis of the literature

Benzene, an accepted leukemogen, has been suggested to cause other hemato- and lymphopoietic cancers. Here we review the published literature for non-Hodgkin lymphoma (NHL) and occupational exposure to benzene. Six cohorts, sixteen case–control studies and two studies of other designs were identified through keyword searches of bibliographic databases. Twenty-two of twenty-four studies found no association between NHL and ever exposed to benzene compared to never; a random-effects meta-analysis gave a pooled risk estimate of 1.11 (95% confidence interval 0.94–1.30). Our finding of no effect agrees with one of two previous meta-analyses. The other meta-analysis examined if high benzene exposure increased NHL risk but a lack of consistent exposure categories within the same metric should have precluded pooling risks by exposure level. Instead, we reviewed whether dose–response relationships existed. The best available data came from six studies where exposure was estimated from historical measurements and on the whole, no trends in risks of NHL with rising cumulative, average, peak, or duration of benzene exposure were found. NHL is a heterogeneous group of malignancies and although less well-studied, benzene was not associated with any NHL subtype. In conclusion, benzene at either low or high doses does not increase the risk of NHL.     

Surface contamination artificially elevates initial sweat mineral concentrations

Several sweat mineral element concentrations decline with serial sampling. Possible causes include reduced dermal mineral concentrations or flushing of surface contamination. The purpose of this study was to simultaneously sample mineral concentrations in transdermal fluid (TDF), sweat, and serum during extended exercise-heat stress to determine if these compartments show the same serial changes during repeat sampling. Sixteen heat-acclimated individuals walked on a treadmill (1.56 m/s, 3.0% grade) in a 35°C, 20% relative humidity (RH), 1 m/s wind environment 50 min each hour for 3 h. Mineral concentrations of Ca, Cu, Fe, K, Mg, Na, and Zn were measured each hour from serum, sweat from upper back (sweat pouch) and arm (bag), and TDF from the upper back. Sites were meticulously cleaned to minimize surface contamination. Mineral concentrations were determined by spectrometry. TDF remained stable over time, with exception of a modest increase in TDF [Fe] (15%) and decrease in TDF [Zn] (-18%). Likewise, serum and pouch sweat samples were stable over time. In contrast, the initial arm bag sweat mineral concentrations were greater than those in the sweat pouch, and [Ca], [Cu], [Mg], and [Zn] declined 26-76% from initial to the subsequent samples, becoming similar to sweat pouch. Nominal TDF mineral shifts do not affect sweat mineral concentrations. Arm bag sweat mineral concentrations are initially elevated due to skin surface contaminants that are not removed despite meticulous cleaning (e.g., under fingernails, on arm hair), then decrease with extended sweating and approach those measured from the scapular region.     

Formation of Nitrated and Hydroxylated Aromatic Compounds from Benzene and Peroxynitrite, A Possible Mechanism of Benzene Genotoxicity

Peroxynitrite, the reaction product of nitric oxide (NO*) and superoxide anion (O*-) produced during immune activation by a variety of inflammatory cells, may contribute to genotoxicity of benzene through its ability to carry out hydroxylation and nitration. After exposure of benzene to synthesised peroxynitrite, phenol, nitrophenols (p-nitrophenol, o-nitrophenol and m-nitrophenol) and nitrobenzene were identified in the reaction mixture by HPLC separation and single UV wavelength and diode array detection. The formation of phenol, nitrophenols and nitrobenzene showed a linear relationship with both benzene and peroxynitrite concentrations. The molar ratio for phenol/(nitrobenzene and nitrophenols) was approximately 9/5 with a total product yield of 14% hydroxylated and nitrated products as based on peroxynitrite. The physiological relevance of the chemical reaction between benzene and peroxynitrite was tested by detecting the reaction products in human neutrophils (2.5 ± 10⁷ cells/ml) incubated with 10 mM benzene for 25 min. The concentration of phenol and p-nitrophenol were found to be 1.29 ± 0.22 and 1.56 ± 0.61 μM mean ± SD) in the incubation medium of the neutrophils pretreated with phorbol myristate acetate (500 nM) for 5 min, respectively, whereas no metabolites were detected if the neutrophils were not pretreated. Nitrated aromatic compounds are known to be more carcinogenic than the parent compounds. It is reported that acute and chronic infection increases the risk of cancer at various sites; and that anti-inflammatory agents decrease benzene myelotoxicity. We suggest that the increased production of peroxynitrite during chronic inflammation combined with benzene exposure may increase the carcinogenicity of benzene by a mechanism that includes the formation of metabolites from the chemical reaction between benzene and peroxynitrite. Thus, peroxynitrite mediated hydroxylation and nitration of benzene during immune activation represent a novel in vivo mechanism for generation of proximal carcinogens of benzene.     

Personal exposure to different levels of benzene and its relationships to the urinary metabolites S-phenylmercapturic acid and trans,trans-muconic acid

This report is part of an extensive study to verify the validity, specificity, and sensitivity of biomarkers of benzene at low exposures and assess their relationships with personal exposure and genetic damage. The study population was selected from benzene-exposed workers in Tianjin, China, based on historical exposure data. The recruitment of 130 exposed workers from glue-making or shoe-making plants and 51 unexposed subjects from nearby food factories was based on personal exposure measurements conducted for 3-4 weeks prior to collection of biological samples. In this report we investigated correlation of urinary benzene metabolites, S-phenylmercapturic acid (S-PMA) and trans,trans-muconic acid (t,t-MA) with personal exposure levels on the day of urine collection and studied the effect of dose on the biotransformation of benzene to these key metabolites. Urinary S-PMA and t,t-MA were determined simultaneously by liquid chromatography-tandem mass spectrometry analyses. Both S-PMA and t,t-MA, but specifically the former, correlated well with personal benzene exposure over a broad range of exposure (0.06-122 ppm). There was good correlation in the subgroup that had been exposed to <1 ppm benzene with both metabolites (P-trend <0.0001 for S-PMA and 0.006 for t,t-MA). Furthermore, the levels of S-PMA were significantly higher in the subgroup exposed to <0.25 ppm than that in unexposed subjects (n=17; P=0.001). There is inter-individual variation in the rate of conversion of benzene into urinary metabolites. The percentage of biotransformation of benzene to urinary S-PMA ranged from 0.005 to 0.3% and that to urinary t,t-MA ranged from 0.6 to approximately 20%. The percentage of benzene biotransformed into S-PMA and t,t-MA decreased with increasing concentration of benzene, especially conversion of benzene into t,t-MA. It appears that women excreted more metabolites than men for the same levels of benzene exposures. Our data suggest that S-PMA is superior to t,t-MA as a biomarker for low levels of benzene exposure.     

Health Risk Assessment of Inhalation Exposure to Formaldehyde and Benzene in Newly Remodeled Buildings,Beijing

Objective

To assess health risks associated with inhalation exposure to formaldehyde and benzene mainly emitted from building and decoration materials in newly remodeled indoor spaces in Beijing.

Methods

We tested the formaldehyde and benzene concentrations in indoor air of 410 dwellings and 451 offices remodeled within the past year, in which the occupants had health concerns about indoor air quality. To assess non-carcinogenic health risks, we compared the data to the health guidelines in China and USA, respectively. To assess carcinogenic health risks, we first modeled indoor personal exposure to formaldehyde and benzene using the concentration data, and then estimated the associated cancer risks by multiplying the indoor personal exposure by the Inhalation Unit Risk values (IURs) provided by the U.S. EPA Integrated Risk Information System (U.S. EPA IRIS) and the California Office of Environmental Health Hazard Assessment (OEHHA), respectively.

Results

(1) The indoor formaldehyde concentrations of 85% dwellings and 67% offices were above the acute Reference Exposure Level (REL) recommended by the OEHHA and the concentrations of all tested buildings were above the chronic REL recommended by the OEHHA; (2) The indoor benzene concentrations of 12% dwellings and 32% offices exceeded the reference concentration (RfC) recommended by the U.S. EPA IRIS; (3) The median cancer risks from indoor exposure to formaldehyde and benzene were 1,150 and 106 per million (based on U.S. EPA IRIS IURs), 531 and 394 per million (based on OEHHA IURs).

Conclusions

In the tested buildings, formaldehyde exposure may pose acute and chronic non-carcinogenic health risks to the occupants, whereas benzene exposure may pose chronic non-carcinogenic risks to the occupants. Exposure to both compounds is associated with significant carcinogenic risks. Improvement in ventilation, establishment of volatile organic compounds (VOCs) emission labeling systems for decorating and refurbishing materials are recommended to reduce indoor VOCs exposure.     

Survival of Listeria monocytogenes in commercial food-processing equipment cleaning solutions and subsequent sensitivity to sanitizers and heat

AIMS: To determine the ability of Listeria monocytogenes to survive exposure to commercial food-processing equipment cleaning solutions and subsequent treatment with sanitizers or heat. METHODS AND RESULTS: Cells of five strains of L. monocytogenes were suspended in 1% solutions of eight commercial cleaners (pH 7.1-12.5) or in water (control) and incubated at 4 degrees C for 30 min or 48 h before populations were determined by plating on tryptose phosphate agar. After exposure of cells to cleaning solutions for 30 min, populations of the most resistant strain of L. monocytogenes were reduced by < or = 1.63 log10 cfu ml(-1). In only three highly alkaline cleaning solutions (pH 11.6-12.4) were populations reduced significantly (P < or = 0.05) compared with reductions in water. After 48 h, populations were significantly higher in one cleaning solution (pH 10.4) than in water, while populations in six of the other seven cleaning solutions were reduced by > or = 4.72 log10 cfu ml(-1). Cells exposed to cleaning solutions for 30 min became sensitive to 4.0 or 6.0 mg l(-1) free chlorine and to 50 or 100 mg l(-1) benzalkonium chloride and cetylpyridinium chloride, common components of quaternary ammonium sanitizers. Cells exposed to four of the five test cleaners had D56 degrees C values less than or equal to those of the control cells. CONCLUSIONS: Listeria monocytogenes tolerates exposure to a high concentration of alkaline cleaning solutions but consequently becomes sensitized to sanitizers. SIGNIFICANCE AND IMPACT OF THE STUDY: The elimination of L. monocytogenes surviving exposure to alkaline cleaning solutions widely used for food-processing equipment is essential and the appropriate use of sanitizers for subsequent application to equipment is important in achieving this goal.     

Biochemical characterization of the small heat shock protein IbpB from Escherichia coli

Escherichia coli IbpB was overexpressed in a strain carrying a deletion in the chromosomal ibp operon and purified by refolding. Under our experimental conditions, IbpB exhibited pronounced size heterogeneity. Basic oligomers, roughly spherical and approximately 15 nm in diameter, interacted to form larger particles in the 100-200-nm range, which themselves associated to yield loose aggregates of micrometer size. IbpB suppressed the thermal aggregation of model proteins in a concentration-dependent manner, and its CD spectrum was consistent with a mostly beta-pleated secondary structure. Incubation at high temperatures led to a partial loss of secondary structure, the progressive exposure of tryptophan residues to the solvent, the dissociation of high molecular mass aggregates into approximately 600-kDa oligomers, and an increase in surface hydrophobicity. Structural changes were reversible between 37 and 55 degrees C, and, up to 55 degrees C, hydrophobic sites were reburied upon cooling. IbpB exhibited a biphasic unfolding trend upon guanidine hydrochloride (GdnHCl) treatment and underwent comparable conformational changes upon melting and during the first GdnHCl-induced transition. However, hydrophobicity decreased with increasing GdnHCl concentrations, suggesting that efficient exposure of structured hydrophobic sites involves denaturant-sensitive structural features. By contrast, IbpB hydrophobicity rose at high NaCl concentrations and increased further at high temperatures. Our results support a model in which temperature-driven conformational changes lead to the reversible exposure of normally shielded binding sites for nonnative proteins and suggest that both hydrophobicity and charge context may determine substrate binding to IbpB.     

Lifetime exposure to environmental lead and children's intelligence at 11-13 years: the Port Pirie cohort study.

OBJECTIVE--To examine the association between environmental exposure to lead and children''s intelligence at age 11-13 years, and to assess the implications of exposure in the first seven years of life for later childhood development. DESIGN--Prospective cohort study. SUBJECTS--375 children born in or around the lead smelting town of Port Pirie, Australia, between 1979 and 1982. MAIN OUTCOME MEASURE--Children''s intelligence quotient (IQ) measured at 11-13 years of age. RESULTS--IQ was inversely associated with both antenatal and postnatal blood lead concentrations. Verbal, performance, and full scale IQ were inversely related to blood lead concentration with no apparent threshold. Multivariate analyses indicated that after adjustment for a wide range of confounders, the postnatal blood lead concentrations (particularly within the age range 15 months to 7 years) exhibited inverse associations with IQ. Strong associations with IQ were observed for lifetime average blood lead concentrations at various ages. The expected mean full scale IQ declined by 3.0 points (95% confidence interval 0.07 to 5.93) for an increase in lifetime average blood lead concentration from 0.48 to 0.96 mumol/l (10 to 20 micrograms/dl). CONCLUSION--Exposure to environmental lead during the first seven years of life is associated with cognitive deficits that seem to persist into later childhood.     

LCA of cleaning and degreasing agents in the metal industry

An LCA of cleaning and degreasing agents in the metal industry was carried out. A comparison was made between a solvent product (VOC: a mixture of dearomatised hydrocarbons) and two products derived from vegetable oils (VOFA: rapeseed methyl ester and ethylhexyl laurate derived from coconut oil). The comparison was based on 1000 kg of used product. Results from the inventory and characterisation show that VOFA are environmentally favourable on aspects related to their low volatility and their use of renewable resources. However, they are less favourable on aspects predominantly related to cultivation of the crops. The environmental favourability of VOFA compared to VOC is strongly dependent upon the amounts needed for the task to be performed. Incorporation of data from practical experience concerning the use and waste treatment of VOFA in the metal industry may possibly further improve the environmental profile of VOFA. This work was presented at the 17th Annual Meeting of the Society of Environmental Toxicology and Chemistry (SETAC), November 19,1996, in Washington, DC. It was one of a series of presentations during the LCA session.     

Monitoring protein expression by proteomics: human plasma exposed to benzene

Low levels and long term exposure to benzene is associated with hematotoxicity including aplastic anemia, acute myelogenous leukemia, and lymphoma. Current biomonitoring methods such as urinary phenol, S-phenylmercapturic acid, and trans-trans muconic acid were found to be unreliable as analytical methods to detect benzene exposure. Therefore, to search for a specific protein for biomonitoring benzene exposure, we investigated plasma proteins from workers (n = 50) at a printing company who were exposed to benzene, by two-dimensional gel electrophoresis. The protein profiles are significantly different (p < 0.05) between benzene exposed and unexposed groups, as identified by matrix-assisted laser desorption ionization/time of flight mass spectrometry and confirmed by Western blot analyses. T cell receptor beta chain (TCR beta), FK506-binding protein, and matrix metalloproteinase-13 were expressed only in benzene exposed workers. In addition, interleukin-4 receptor alpha chain and T cell surface glycoprotein CD1b precursor were found to be up-regulated in the plasma of benzene exposed workers. When we treated Jurkat cells with benzene (10 microM-10 mM), TCR beta expression was increased in the membrane more than 6-9-fold compared to untreated cells. In addition, the amount of TCR beta released into the culture media, at benzene concentrations greater than 50 microM, increased up to 10 mM. Therefore, TCR beta levels in plasma could be used as a biomarker and a possible therapeutic target for benzene exposure.     

Cleaning characterization of protein drug products using UV-vis spectroscopy

This study uses on-line absorbance monitoring to evaluate cleanability of protein drug products. Characterization and validation of equipment cleanliness is a key requirement for a biopharmaceutical facility. A manufacturing-scale cleaning cycle has to be developed and validated for its ability to clean all of the equipment parts for a given soil. Cleaning validation in a multiproduct fill-finish facility could benefit from using a worst-case-based approach that involves validating the cleaning process for the most difficult to clean product. Such an approach minimizes the number of required validation runs. Scaled-down cleaning evaluations can provide helpful information for evaluating multiple products and determine the worst case. This study presents a simple and rapid technique for bench-scale characterization of cleanability of protein drug products. On-line A280 (UV absorbance at 280 nm) measurements are performed using a fiber optic probe, and the data are used to establish the dynamics of protein dissolution in cleaning solution. The model not only helps to estimate cleaning time of different formulated proteins (and peptides) but also provides insights into the kinetics of cleaning under different thermal and chemical conditions. Protein product degradation during cleaning is also evaluated through gel electrophoresis. Such information is useful in designing new cleaning cycles. While the study is performed using drug products, the model as well as the findings are also applicable for characterization of final purified bulk soils relevant to bulk drug manufacturing.