bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addendum to Trimethylbenzene [BAT Value Documentation, 2009]
Authors: Kraus T. , Schaller K.H. , Knecht U. , Csanády G. , Drexler H. , Hartwig A. ,   MAK Commission
Published: January 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the biological tolerance value at the work place (BAT value) for trimethylbenzene, considering dimethylbenzoic acids in urine to characterize the internal exposure.
The BAT value for trimethylbenzene from 2007 was established based on the 95th percentiles. After redefinition of the BAT value as correlate for the mean value from several investigations in one worker, a reevaluation of the BAT value has become necessary.

Inhalation chamber studies by Kostrzewski et al. (1997) and Knecht et al. (2000, 2003) provide mean values for dimethylbenzoic acid (DMBA) excretion. With a trimethylbenzene concentration at the MAK value level of 100 mg/m
3
(20 ml/m
3
), Kostrzewski et al. (1997) found a mean sum concentration of the DMBA metabolites of 450 mg/g creatinine, and Knecht et al. (2000) of 417 mg/g creatinine. With a trimethylbenzene concentration of 90 mg/m
3
(18 ml/m
3
), 269 mg DMBA metabolites/g creatinine were determined (Knecht et al. 2003).

Based on these studies by Kostrzewski et al. (1997) and Knecht et al. (2000, 2003) the sum concentration (mean value) of the DMBA metabolites of 400 mg dimethylbenzoic acids (sum of all isomers after hydrolysis)/g creatinine is established as BAT value.
Samples should be taken at the end of exposure or the end of the shift, and after several shifts for long‐term exposures, because Jones et al. (2006) described cumulative effects after repeated exposure, whereas this phenomenon was not observed by Knecht et al. (2000).
Addendum to Aluminium [BAT Value Documentation, 2009]
Authors: Letzel S. , Drexler H. , Hartwig A. ,   MAK Commission
Published: January 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the biological tolerance value at the work place (BAT value) for aluminium.

In persons with workplace‐related aluminium exposure, central nervous effects and lung effects were observed. The former BAT‐value was evaluated on a linear correlation between external and internal exposure to aluminium at the MAK value of 6 mg/m
3
(measured as fine dust). The lowering of the MAK value to 1.5 mg/m
3
(respirable fraction) and 4 mg/m
3
(inhalable fraction) made re‐evaluation of the BAT value necessary. The present MAK value of 1.5 mg/m
3
serves as a correlate for this reevaluation. Investigations by Mussi et al. (1984), Sjögren et al. (1988) as well as Letzel and Roßbach (2008) indicate that a total dust concentration of 1.5 mg/m
3
corresponds to a urinary aluminium concentration in the range of about 50–66 μg aluminium/g creatinine. Thus, a BAT‐value of 60 µg aluminium/g creatinine was established.

The creatinine‐related urinary excretion is used as biological parameter, because urinary aluminium concentrations related to creatinine show closer correlations to the airborne aluminium exposure than volume‐related urinary aluminium concentrations.
No restrictions apply for the time of sampling taking account of the long biological half‐life after cumulative aluminium exposure.
Benzidine [BAT Value Documentation, 2000]
Authors: Lewalter J. , Drexler H. , Hartwig A. ,   MAK Commission
Published: January 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area evaluated benzidine. Benzidine is a proven human carcinogen inducing papillomas and transitional cell carcinomas.External exposure can result from inhalation or percutaneous absorption. Internal exposure consists of the biologically relevant concentration of reactive metabolites in the target tissue, especially in the liver and in the efferent urinary tract. The benzidine concentrations in biological body fluids, such as blood, plasma and urine are exposure parameters. Exposures to benzidine can be determined via the excretion of free and conjugated benzidine with the urine. Benzidine adducts in erythrocytes (Hb adducts), plasma (HSA adducts) or leukocytes (DNA adducts) are considered to be parameters for a benzidine effect.Unlike the Hb adducts in erythrocytes, the biological half‐life of HSA adducts of aromatic amines in the serum is significantly shorter than that of free HSA. Already after three days, the HSA adduct level is generally lower than that of corresponding Hb adducts. This fact allows a differentiation of actual individual exposures to aromatic amines. Within up to three days after exposure to aromatic amines, the value of the ratio Hb adduct:HSA adduct is below 10. Earlier exposures are recognized by ratios above 10.Due to the nonlinearity between the air concentration and the biological values, exposure equivalents for carcinogenic substances (EKA) could neither be established for benzidine in urine nor for benzidine adducts at present.
Addendum to Creatinine as Reference Parameter for the Concentration of Substances in Urine [BAT Value Documentation, 2011]
Authors: Bader M. , Ochsmann E. , Drexler H. , Hartwig A. ,   MAK Commission
Published: January 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has supplemented the definition of creatinine as reference parameter for the concentration of substances in urine.Barr et al. (2005) investigated the creatinine concentration of representative urine samples from the US general population (n = 22 245 persons, aged 6 up to > 70 years old, different ethnic groups). An evaluation focussing on the results for white, non‐hispanic volunteers in the age group 20–60 years, showed that approximately 10% of the creatinine concentrations in urine were outside the WHO reference range of 0.3–3 g/l.In agreement with the WHO criteria (1996) for biomonitoring in the field of occupational medicine, the Commission basically recommends using only those urine samples which have creatinine concentrations between 0.3–3 g/l for substance analyses and the assessment of individual measurements based on a statistically derived lower and upper reference value (5th or 95th percentile) for the creatinine concentration in urine. In addition, the working group “Setting of Threshold Limit Values in Biological Materials” considers it useful to continue to use the narrower target range of 0.5–2.5 g/l for urine samples, for further improving the reliability of analytical results with and without creatinine adjustment, and the validity of studies on the correlation between external and internal exposure. This aspect should already be considered in the preanalytical phase of a biomonitoring investigation.
Haemoglobin adducts of ethylene oxide (N‐(2‐hydroxyethyl)valine), propylene oxide (N‐(2‐hydroxypropyl)valine), acrylonitrile (N‐(2‐cyanoethyl)valine), acrylamide (N‐(2‐carbonamide ethyl)valine) and glycidamide (N‐(2‐hydroxy‐2‐carbonamide ethyl)valine) [Biomonitoring Methods, 2015]
Authors: Schettgen T. , Müller J. , Ferstl C. , Angerer J. , Göen T. , Hartwig A. ,   MAK Commission
Published: January 2016

The method permits the simultaneous quantification of the N‐terminal haemoglobin adducts N‐(2‐hydroxyethyl)valine (HEV), N‐(2‐hydroxypropyl)valine (HPV), N‐(2‐cyanoethyl)valine (CEV), N‐(2‐carbonamide ethyl)valine (AAV), and N‐(2‐hydroxy‐2‐carbonamide ethyl)valine (GAV) of the carcinogens ethylene oxide, propylene oxide, acrylonitrile, acrylamide, as well as of glycidamide the metabolite of acrylamide in blood.The adducts which are covalently bound to the N‐terminal valine of the globin chain are cleaved off from the globin chain by a modified Edman degradation. The resulting pentafluorophenyl thiohydantoine derivatives of the valine adducts are extracted with diethyl ether, purified and then subjected to tandem mass spectrometric detection. To protect the vicinal hydroxyl group of the glycidamide adduct, the modified Edman degradation is followed by a second derivatization using sulphuric acetone. For calibration, standards are prepared in non‐smoker pooled globin, adding solutions of dipeptide standards simulating the adduct‐bearing latter two N‐terminal amino acids of the haemoglobin chain. They are processed in the same way as the samples to be analyzed. As internal standards, solutions of isolated globin, which has prior been transformed with the deuterated compounds d3‐acrylo‐nitrile, d3‐acrylamide or d3‐propylene oxide, are used. As internal standard for glycidamide, the d8‐labeled, acetonized pentafluorophenyl thiohydantoine of the glycidamide valine adduct is used.
Triethanolamin [MAK Value Documentation in German language, 2016]
Authors: Laube B. , Bartsch R. , Leibold E. , Schriever‐Schwemmer G. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for Triethanolamine
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) of triethanolamine, considering the endpoints respiratory tract irritation and developmental toxicity.

The critical effect of triethanolamine is respiratory tract irritation (focal larynx inflammation). The previous MAK value of 5 mg/m
3
for the inhalable fraction is based on 5‐day and 28‐day aerosol studies in rats with a LOAEC of 20 mg/m
3
. A benchmark calculation gives a BMDL05 of 14,1 mg/m
3
. Since 2014, the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. Based on this approach, a concentration of 4,7 mg/m
3
for the work place air can be calculated from this BMDL05. Therefore the MAK value of 5 mg/m
3
is retained.

As local effects are critical, Peak Limitation Category I is retained. At an excursion factor of 2, the allowable maximum concentration is still below the BMDL05.
NOAEL for fetotoxicity are 300 mg/kg bw and day in rats and 1125 mg/kg bw and day in mice. Teratogenicity was not tested. Nevertheless, because the calculated margins between NOAEL and MAK value are very high, and alkylamines lack teratogenicity, damage to the embryo or foetus is unlikely when the MAK value is observed. Therefore, triethanolamine is assigned to Pregnancy Risk Group C.
Glycerin [MAK Value Documentation in German language, 2016]
Authors: Laube B. , Bartsch R. , Schriever‐Schwemmer G. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for Glycerol
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) of glycerol, considering the endpoints irritation of the respiratory tract and developmental toxicity.

Since 2014, the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. However, examination of the study results showed that this approach does not apply for glycerol, because glycerol is not an eye irritant and the minimal to slight metaplasia of the squamous epithelium of the larynx seen in rats at 662 mg/m
3
with glycerol aerosol is not interpreted as adverse. The response does not increase with the exposure duration. Therefore, the MAK value is raised to 200 mg glycerol/m
3
for the inhalable fraction.

Peak Limitation Category I for local effects with an excursion factor of 2 is retained, as the effect is hardly concentration‐dependent, a sensory irritation is not known, and glycerol is, if at all, only slightly irritating to the eye.

After scaling the oral NOAELs for developmental toxicity of 1310, 1280 and 1180 mg/kg bw and day for rats, mice, and rabbits, respectively, to a concentration at the work place (2293, 1280, and 3442 mg/m
3
), the differences to the MAK value are considered so large, that damage to the embryo or foetus is unlikely when the MAK value is observed. The classification in Pregnancy Risk Group C is therefore retained.
Trimethylamin [MAK Value Documentation in German language, 2016]
Authors: Kreis P. , Michaelsen S. , Bartsch R. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for Trimethylamine

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) of trimethylamine of 2 ml/m
3
, considering the endpoints local and systemic toxicity as well as developmental toxicity. Available publications are described in detail. Daily exposure of rats to trimethylamine for 14 days resulted in inflammation of the respiratory epithelium at 74 ml/m
3
, the lowest concentration tested. Since 2014, the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. According to this approach, the MAK value would have to be lowered to 1 ml/m
3
. However, several data show, that the previous MAK value can be retained. Workers reported no irritation at 5 ml trimethylamine/m
3
. In addition cyclohexylamine and dimethylamine with a MAK value of 2 ml/m
3
are used as a read‐across due to similar alkalinity and RD
50
values, and in a recent volunteer study a NOAEC of 2 ml cyclohexylamine/m
3
is found. The MAK value will also protect from possible blue hazy vision which is caused by other tertiary amines since trimethylamine is assumed to be less effective than N,N‐dimethylethylamine with a MAK value of 2 ml/m
3
. The assignment is to Peak Limitation Category I, because local effects are critical, and the excursion factor of 2 is confirmed. Developmental toxicity studies with trimethylamine show that damage to the embryo or foetus is unlikely if the MAK value is observed, and the assignment to Pregnancy Risk Group C is retained.
Methylacetat [MAK Value Documentation in German language, 2016]
Authors: Michaelsen S. , Kreis P. , Bartsch R. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for Methyl acetate

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value) of methyl acetate of 100 ml/m
3
considering the critical endpoint respiratory tract irritation. A 28‐day study with rats shows a NOAEC for degeneration and necrosis of the olfactory epithelium of 350 ml/m
3
. A chronic NAEC of 125 to 167 ml/m
3
can be extrapolated. Since 2014, the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. According to this approach, the NAEC would correspond to a concentration of 63 to 84 ml/m
3
for work place air. However, acetic acid resulting from the local enzymatic cleavage of methyl acetate by carboxylesterases is responsible for the effects to the olfactory epithelium, and not the substance itself. Thus, the activity of rat and human carboxylesterases is decisive in the respiratory tract irritation of methyl acetate. Based on a comparative analysis on vinyl acetate, in which rat olfactory enzyme activity was shown to be almost equivalent to that in humans, the same is assumed for methyl acetate and the interspecies extrapolation step is deemed unnecessary. The MAK value is retained at 100 ml/m
3
. As local effects are critical, the assignment to Peak Limitation Category I and the excursion factor of 4 are also retained.
Medication Persistence of Disease‐Modifying Antirheumatic Drugs and Anti–Tumor Necrosis Factor Agents in a Cohort of Patients With Rheumatoid Arthritis in Brazil
Authors: Acurcio Francisco A. , Machado Marina A. A. , Moura Cristiano S. , Ferre Felipe , Guerra Augusto A. , Andrade Eli I. G. , Cherchiglia Mariangela L. , Rahme Elham 
Published: January 2016

ObjectiveTo assess the use and persistence of anti–tumor necrosis factor (anti‐TNF) versus disease‐modifying antirheumatic drug (DMARD) therapies in patients with rheumatoid arthritis (RA) in Brazil.MethodsThis was a new‐user cohort study of RA patients from 2003 to 2010, using administrative data. Individuals were classified as being persistent using a drug at the first year and the first 2 years after cohort entry, if they did not discontinue that drug during that period. Cox regression was used to identify potential determinants of discontinuation of therapy in each medication group.ResultsAmong 76,351 patients, 14,313 were using anti‐TNF (+/− DMARD) therapy. At the end of the first year of followup, 48.2% continued using anti‐TNF (+/− DMARD) therapy compared to 42.6% who persisted with DMARDs only. At the end of the second year, 23.1% of anti‐TNF (+/− DMARD) users and 19.3% of DMARD‐only users continued with therapy. Infliximab users had the lowest persistence rates. Multivariate Cox regression analysis showed that among anti‐TNF (+/− DMARD) users, higher discontinuation rates were observed in female patients, in patients with lower income (only at the first 2 years of followup), in nonresidents of the region with the highest Human Development Index (HDI) rates, in those with a higher comorbidity score, and in those enrolled in the 2003–2006 period. Among DMARD‐only users, younger patients, patients with lower income, nonresidents in regions with high HDI, those with a higher comorbidity score, and those enrolled in the 2003–2006 period were also more likely to discontinue therapy.ConclusionBrazilian patients with RA showed low rates of medication persistence for DMARDs and anti‐TNF agents, particularly at the first 2 years of followup. Future work could determine what other factors might contribute to drug persistence in RA.
Influence of Multiwalled Carbon Nanotubes on Biodegradable Poly(lactic acid) Nanocomposites for Electroactive Shape Memory Actuator
Authors: Mohan Raja , Subha J. , Alam Javed 
Published: January 2016

ABSTRACTPoly(lactic acid)/epoxidized soybean oil/carbon nanotubes (PLA/ESO/CNTs) nanocomposites were prepared by the solution blending process, and the influence of ESO on the properties of the composites was studied. Differential scanning calorimetry and X‐ray diffraction revealed that the addition of CNTs improved the crystallinity of the nanocomposites. The modulus increased with the addition of CNTs content in the composites. Morphological characterizations were done by scanning electron microscopy and transmission electron microscopy. Electrical conductivity of PLA/ESO/CNT composites increased with the addition of CNTs. This study revealed that the addition of ESO facilitated the dispersion of the CNTs in the PLA matrix.
Integrated approach to health screening of former department of energy workers detects both occupational and non‐occupational illness
Authors: Stange Bill , McInerney John , Golden Ashley , Benade Wendy , Neill Barbara , Mayer Annyce , Witter Roxana , Tenney Liliana , Stinson Kaylan , Cragle Donna , Newman Lee S. 
Published: January 2016

BackgroundThe National Supplemental Screening Program (NSSP) uses a Total Worker HealthTM approach to address U.S. Department of Energy (DOE) former worker health. This article provides the design of the integrated occupational health screening and promotion program.MethodsThe NSSP implemented a web‐based relational health records system to process demographic, exposure, and clinical data. We present medical findings for 12,000 DOE former workers that completed an initial NSSP medical screening between October 1, 2005 and October 4, 2013. We discuss the DOE former worker participant population and the exposure‐based and non‐occupational medical screening tests used.ResultsThe NSSP identified potential occupationally related health conditions in 40.5% of those screened. Notably, we identified 85.8% of participants with addressable non‐occupational health conditions, many of which were previously undiagnosed.ConclusionThe NSSP demonstrates that the identification of potential occupational health issues in conjunction with addressable non‐occupational health conditions provides former workers with information to more effectively manage health. Am. J. Ind. Med. 59:200–211, 2016. © 2016 Wiley Periodicals, Inc.
Botulinum toxin type A for neuropathic pain in patients with spinal cord injury
Authors: Han Zee‐A , Song Dae Heon , Oh Hyun‐Mi , Chung Myung Eun 
Published: January 2016

ObjectiveTo evaluate the analgesic effect of botulinum toxin type A (BTX‐A) on patients with spinal cord injury‐associated neuropathic pain.MethodsThe effect of BTX‐A on 40 patients with spinal cord injury‐associated neuropathic pain was investigated using a randomized, double‐blind, placebo‐controlled design. A 1‐time subcutaneous BTX‐A (200U) injection was administered to the painful area. Visual analogue scale (VAS) scores (0–100mm), the Korean version of the short‐form McGill Pain Questionnaire, and the World Health Organization WHOQOL‐BREF quality of life assessment were evaluated prior to treatment and at 4 and 8 weeks after the injection.ResultsAt 4 and 8 weeks after injection, the VAS score for pain was significantly reduced by 18.6 ± 16.8 and 21.3 ± 26.8, respectively, in the BTX‐A group, whereas it was reduced by 2.6 ± 14.6 and 0.3 ± 19.5, respectively, in the placebo group. The pain relief was associated with preservation of motor or sensory function below the neurological level of injury. Among the responders in the BTX‐A group, 55% and 45% reported pain relief of 20% or greater at 4 and 8 weeks, respectively, after the injection, whereas only 15% and 10% of the responders in the placebo group reported a similar level of pain relief. Improvements in the score for the physical health domain of the WHOQOL‐BREF in the BTX‐A group showed a marginal trend toward significance (p = 0.0521) at 4 weeks after the injection.InterpretationThese results indicate that BTX‐A may reduce intractable chronic neuropathic pain in patients with spinal cord injury. Ann Neurol 2016;79:569–578
Cause and prevention of demyelination in a model multiple sclerosis lesion
Authors: Desai Roshni A. , Davies Andrew L. , Tachrount Mohamed , Kasti Marianne , Laulund Frida , Golay Xavier , Smith Kenneth J. 
Published: January 2016

ObjectiveDemyelination is a cardinal feature of multiple sclerosis, but it remains unclear why new lesions form, and whether they can be prevented. Neuropathological evidence suggests that demyelination can occur in the relative absence of lymphocytes, and with distinctive characteristics suggestive of a tissue energy deficit. The objective was to examine an experimental model of the early multiple sclerosis lesion and identify pathogenic mechanisms and opportunities for therapy.MethodsDemyelinating lesions were induced in the rat spinal dorsal column by microinjection of lipopolysaccharide, and examined immunohistochemically at different stages of development. The efficacy of treatment with inspired oxygen for 2 days following lesion induction was evaluated.ResultsDemyelinating lesions were not centered on the injection site, but rather formed 1 week later at the white–gray matter border, preferentially including the ventral dorsal column watershed. Lesion formation was preceded by a transient early period of hypoxia and increased production of superoxide and nitric oxide. Oligodendrocyte numbers decreased at the site shortly afterward, prior to demyelination. Lesions formed at a site of inherent susceptibility to hypoxia, as revealed by exposure of naive animals to a hypoxic environment. Notably, raising the inspired oxygen (80%, normobaric) during the hypoxic period significantly reduced or prevented the demyelination.InterpretationDemyelination characteristic of at least some early multiple sclerosis lesions can arise at a vascular watershed following activation of innate immune mechanisms that provoke hypoxia, and superoxide and nitric oxide formation, all of which can compromise cellular energy sufficiency. Demyelination can be reduced or eliminated by increasing inspired oxygen to alleviate the transient hypoxia. Ann Neurol 2016;79:591–604