bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addendum zu 2‐Butoxyethanol [BAT Value Documentation in German language, 2016]
Authors: Göen T. , Rettenmeier A.W. , Drexler H. , Hartwig A. ,   MAK‐Kommission
Published: July 2016

2‐Butoxyethanol (Ethylene glycol monobutyl ether): Addendum BAT value documentation (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 2‐butoxyethanol (ethylene glycol monobutyl ether), considering butoxyacetic acid in urine to characterize the internal exposure. The main systemic adverse effects of 2‐butoxyethanol are on the haematopoietic system (haemolytic effects), followed by possible teratogenic and testicular effects. 2‐Butoxyethanol was classified in category 4 for carcinogenic substances, which enables the evaluation of a health based exposure limit. It can easily pass through the skin, so biological monitoring is necessary for a valid individual risk assessment.
A considerable part of the absorbed 2‐butoxyethanol is excreted in form of the glutamine conjugate of butoxyacetic acid, i. e. N‐butoxyacetyl glutamine. The relative amount of this conjugate in the total excretion of butoxyacetic acid varied considerably intra‐ and inter‐individually depending on the exposure levels and possibly on enzyme polymorphisms. On average half of the total butoxyacetic acid is excreted in the form of the glutamine conjugate (factor 2). Various studies indicate that at high exposure levels the capacity of the conjugate reaction is exceeded and lower conjugated amounts appear. Due to the high variability of conjugated amounts of the butoxyacetic acid and the limitation of conjugated amounts at high exposure levels the previous BAT value for free 2‐butoxyacetic acid is converted with a factor of  1.5 to the total amounts of 2‐butoxyacetic acid. Additionally, the impact of diuresis is considered by the relation to the creatinine concentration.
Therefore, a BAT value for the total butoxyacetic acid excretion of 150 mg butoxyacetic acid (after hydrolysis)/g creatinine was established. Sampling should be performed at the end of exposure and shift, respectively, after several previous shifts. This BAT value applies also for combined exposure to 2‐butoxyethanol and 2‐butoxyethylacetate.
Addendum to 2‐Butoxyethyl acetate (Ethylene glycol monobutyl ether acetate) [BAT Value Documentation, 2009]
Authors: Drexler H. , Hartwig A. ,   MAK Commission
Published: July 2016

2‐Butoxyethylacetate (Ethylene glycol monobutyl ether acetate): Addendum BAT value documentation (2008)
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 2‐butoxyethylacetate (ethylene glycol monobutyl ether acetate), considering butoxyacetic acid in urine to characterize the internal exposure.
The previous BAT value for free butoxyacetic acid of 100 mg butoxyacetic acid/l urine*, intended to protect against systemic effects (especially haemolytic effects), is retained. The sampling time is at the end of exposure/shift after several previous shifts.
For the total excretion of butoxyacetic acid a further BAT value of 200 mg butoxyacetic acid (after hydrolysis)/l urine* is established.
As the effects of the two glycol ethers 2‐butoxyethyl acetate and 2‐butoxyethanol, are largely the same in the human organism, the BAT values apply to both and the two substances are also discussed together in the addendum of 2‐butoxyethanol.
* no longer valid
Addendum zu Anilin [BAT Value Documentation in German language, 2016]
Authors: Bolt H. M. , Leng G. , Drexler H. , Hartwig A. ,   MAK‐Kommission
Published: July 2016

Aniline
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 aniline, considering aniline in urine to characterize the internal exposure and the methemoglobin formation as critical effect. Available publications as well as unpublished study reports are described in detail.

In a new chamber study, 19 individuals were exposed to the present MAK‐value of 2 ml aniline/m
3
for 6 hours with defined physical activity. The background level of methemoglobin was 0.7 ± 0.2%. At the end of exposure, an increase of up to 1.2 ± 0.3% (range 0.8–2.1%) was observed. The mean excretion of aniline in urine after hydrolysis at the end of exposure was 168 ± 52 µg/l (range 79.5–418 µg/l).

The BAT‐value relates to an air concentration of 2 ml/m
3
and a methemoglobin level of 5%. Considering this study, a BAT‐value of 500 µg/l urine (after hydrolysis) was evaluated. This value is a maximum concentration because of acute toxic effects of methemoglobin. Sampling time is at the end of exposure or the end of the working shift.

For the hemoglobin adduct of aniline, a “Biologischer Leitwert” (BLW) of 100 µg aniline (released from aniline‐haemoglobin conjugate)/l blood was evaluated based on occupational‐medical experiences in field studies.
Addendum zu 1‐Butanol [BAT Value Documentation in German language, 2016]
Authors: Weistenhöfer W. , Leng G. , Drexler H. , Hartwig A. ,   MAK‐Kommission
Published: July 2016

1‐Butanol (n‐Butyl alcohol): Addendum BAT value documentation (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 1‐butanol.
A capillary gas chromatographic head space technique developed by the Working Group “Analyses in Biological Materials” of the German Research Foundation (DFG) was used for determining 1‐butanol in urine. For this method hydrolysis is recommended neither for blood nor for urine investigation.

The BAT values of 10 mg 1‐butanol/g creatinine (sampling time at the end of exposure or end of shift) and 2 mg 1‐butanol/g creatinine (sampling time 16 hours after the end of shift (at the beginning of the next shift)) related to the MAK value of 100 ml/m
3
were confirmed.
Iron oxides (inhalable fraction) [MAK Value Documentation, 2011]
Authors: Hartwig A. ,   MAK Commission
Published: July 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated iron oxides, considering all toxicity endpoints. Publications and available unpublished studies are the basis for the evaluation.Following exposure to iron oxide dusts (poorly soluble particles) effects on the lungs are considered to be the critical effects. However, although iron oxides are poorly soluble, it cannot be excluded that small amounts of soluble Fe(II) or Fe(III) ions are also present in the lungs after inhalation. Toxic effects of iron oxides are only expected when the homeostasis of iron in the body is deregulated or exceeded. Under these conditions iron ions may cause an increased formation of reactive oxygen species via the Fenton reaction. These ions can trigger genotoxic and carcinogenic changes.Although an increased risk for lung cancer has been observed in employees at workplaces with exposures to dust containing iron oxides this is probably due to simultaneous exposure to other toxic compounds, and no final statement can be made on the carcinogenicity of iron oxides in humans. After intratracheal application of iron oxides in high doses an increased tumour incidence in the lungs of rats was observed. Therefore, and on the indication for a genotoxic effect of iron ions inin vitrostudies, iron oxides are classified in Carcinogen Category 3B. Skin contact is not expected to contribute to systemic toxicity. Practically no risk of sensitization is to be expected, although the data to support this statement are scarce.
3‐Iod‐2‐propinylbutylcarbamat (IPBC) [MAK Value Documentation in German language, 2016]
Authors: Hartwig A. ,   MAK Commission
Published: July 2016

3‐Iodo‐2‐propynyl butylcarbamate (IPBC)

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration of 3‐iodo‐2‐propynyl butylcarbamate at the workplace (MAK value), considering the endpoints respiratory tract irritation and developmental toxicity. No new studies have been published since the supplement from 2011. 3‐Iodo‐2‐propynyl butylcarbamate is irritating to the skin, eyes and airways and has skin‐sensitizing effects.

In a 5‐day aerosol inhalation study, hyperplasia, squamous cell metaplasia and necrosis occurred in the larynx of rats at 1 mg/m
3
with a NOAEC of 0.3 mg/m
3
. These effects were more pronounced in the 13‐week study with a NOAEC of 0.23 mg/m
3
. The systemic effect dose in long‐term feeding studies in rats and mice extrapolated to a concentration in air at the workplace is around 100 times higher.

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 MAK value of 0.005 ml/m
3
(0.058 mg/m
3
) can be calculated from the 13‐week study. Since the critical effect is irritation, Peak Limitation Category I is retained. As this effect is immediate and not a form of sensory irritation , but a change to the tissue, and because the margin between the MAK value and the histological NOAEC of 0.3 mg/m
3
is sufficiently large, the excursion factor of 2 has been retained.

There are no new data on prenatal toxicity available. Pregnancy Risk Group C has therefore been retained.
Distillates (petroleum), hydrotreated light [MAK Value Documentation, 2012]
Authors: Hartwig A. ,   MAK Commission
Published: July 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated hydrotreated light distillates (petroleum), considering all toxicity endpoints. Available publications and unpublished study reports are described in detail. The distillates are a complex hydrocarbon mixture. As there are no studies on materials with the same boiling range are available, studies on other hydrocarbon mixtures consisting mainly of aliphatic and alicyclic alkanes with a similar boiling range were used for the evaluation. In a 13‐week gavage study in rats the critical effects of an aromatics‐free hydrocarbon product are higher relative liver weight and changes in clinico‐chemical parameters observed at 500 mg/kg body weight per day. Based on the NOAEL of 100 mg/kg body weight per day that corresponds to 40 ml/m
3
and taking the preferred value approach a MAK value of 20 ml/m
3
is determined. As systemic effects are critical, the mixture is assigned to Peak Limitation Category II. The default excursion factor of 2 is set as no half‐life in blood is known. Pregnancy Risk Group C is assigned, as the NOAEC in a developmental toxicity study in rats is 364 ml/m
3
and thus damage to the embryo or foetus is unlikely when the MAK value is observed. Hydrotreated light distillates are not genotoxic. After chronic epicutaneous application of hydrodesulfurized kerosene, malignant skin tumours arose in mice. Since the relevance of these tumours for humans in this model cannot be excluded, Carcinogen Category 3 B was assigned. Skin contact does not contribute to systemic toxicity and sensitization is not expected.
Dichloromethane [MAK Value Documentation, 2015]
Authors: Hartwig A. ,   MAK Commission
Published: July 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated dichloromethane to derive a maximum concentration at the work place (MAK value), considering all toxicity endpoints. Available unpublished study reports and publications are described in detail.

Dichloromethane is a central nervous system depressant. A MAK value of 50 ml/m
3
is derived based on acute behavioural effects indicative for CNS depression assessed by visual‐manual tasks in humans. Peak Limitation Category II is assigned due to the critical systemic effects and at an excursion factor of 2 the resulting concentration in blood is below the NOAEC.

Dichloromethane is genotoxic in
in vitro
test systems in which the GSH‐dependent metabolic pathway is active. Genotoxicity studies in vivo indicated positive results only in somatic cells of mice in high concentrations. However, compared with humans, in mice the GSTT1 isoenzyme is of higher activity as well as the RNA‐adduct formation and the mRNA expression of GSTT1 in prostate, ovaries and placenta is higher. Due to lower sensitivity of humans compared with mice, dichloromethane is not expected to be mutagenic in germ cells of humans.

Available epidemiological studies show no association between dichloromethane and cancer in humans. In mice adenomas and carcinomas are seen in the liver and the lung which can be explained by the rapid metabolism of dichloromethane via the GSH‐dependent pathways in this species and these organs. Using physiologically based pharmacokinetic models in mice and humans, unit risks for humans have been published. Linear extrapolation of the median unit risk by the Commission yields a median risk for liver and lung tumours of 2.5 x 10
‐5
(0‐6.67 x 10
‐5
) for work place exposure to 50 ml dichloromethane/m
3
.

Dichloromethane is classified in Carcinogen Category 5 because the genotoxicity is of prime importance for carcinogenicity of dichloromethane, the genotoxic mode of action is well‐understood and data to calculate the carcinogenic potency in man are available, showing a very slight contribution to human cancer risk, if the MAK value of 50 ml/m
3
is observed.

According to available information of CO‐Hb formation in blood, damage to the embryo or foetus cannot be excluded even if the MAK value is observed and dichloromethane is assigned to Pregnancy Group B.
Dichloromethane is designated with an “H” notation since percutaneous absorption can contribute significantly to the systemic toxicity. Dichloromethane is not expected to be a sensitizer.
Terminal complement activation is increased and associated with disease severity in CIDP
Authors: Quast Isaak , Keller Christian W. , Hiepe Falk , Tackenberg Björn , Lünemann Jan D. 
Published: July 2016

AbstractChronic inflammatory demyelinating polyneuropathy (CIDP) is the most common chronic autoimmune neuropathy. While both cell‐mediated and humoral mechanisms contribute to its pathogenesis, the rapid clinical response to plasmapheresis implicates a circulating factor responsible for peripheral nerve injury. We report that treatment‐naïve patients with CIDP show increased serum and CSF levels of the anaphylatoxin C5a and the soluble terminal complement complex (sTCC). Systemic terminal complement activation correlates with clinical disease severity as determined by the Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale. These data indicate that complement activation contributes to peripheral nerve injury and suggest that complement inhibition should be explored for its potential therapeutic merit in CIDP.
Progression of Friedreich ataxia: quantitative characterization over 5 years
Authors: Patel Maya , Isaacs Charles J. , Seyer Lauren , Brigatti Karlla , Gelbard Sarah , Strawser Cassandra , Foerster Debbie , Shinnick Julianna , Schadt Kimberly , Yiu Eppie M. , Delatycki Martin B. , Perlman Susan , Wilmot George R. , Zesiewicz Theresa , Mathews Katherine , Gomez Christopher M. , Yoon Grace , Subramony Sub H. , Brocht Alicia , Farmer Jennifer , Lynch David R. 
Published: July 2016

AbstractObjectiveFriedreich ataxia (FRDA) is a progressive neurodegenerative disorder of adults and children. This study analyzed neurological outcomes and changes to identify predictors of progression and generate power calculations for clinical trials.MethodsEight hundred and twelve subjects in a natural history study were evaluated annually across 12 sites using the Friedreich Ataxia Rating Scale (FARS), 9‐Hole Peg Test, Timed 25‐Foot Walk, visual acuity tests, self‐reported surveys and disability scales. Cross‐sectional outcomes were assessed from recent visits, and longitudinal changes were gaged over 5 years from baseline.ResultsCross‐sectional outcomes correlated with measures of disease severity. Age, genetic severity (guanine‐adenine‐adenine [GAA] repeat length), and testing site predicted performance. Serial progression was relatively linear using FARS and composite measures of performance, while individual performance outcomes were nonlinear over time. Age strongly predicted change from baseline until removing the effects of baseline FARS scores, when GAA becomes a more important factor. Progression is fastest in younger subjects and subjects with longer GAA repeats. Improved coefficients of variation show that progression results are more reproducible over longer assessment durations.InterpretationWhile age predicted progression speed in simple analyses and may provide an effective way to stratify cohorts, separating the effects of age and genetic severity is difficult. Controlling for baseline severity, GAA is the major determinant of progression rate in FRDA. Clinical trials will benefit from enrollment of younger subjects, and sample size requirements will shrink with longer assessment periods. These findings should prove useful in devising gene therapy trials in the near future.
Prenatal Earthquake Exposure and Midlife Uric Acid Levels Among Chinese Adults
Authors: Ji Chunpeng , Li Yanping , Cui Liufu , Cai Jianfang , Shi Jihong , Cheng Feon W. , Li Yuqing , Curhan Gary C. , Wu Shouling , Gao Xiang 
Published: July 2016

ObjectiveTo test whether prenatal exposure to earthquake (as a surrogate for acute prenatal stress) could have unfavorable effects on uric acid levels later in life.MethodsWe included 536 individuals who had been prenatally exposed to the Tangshan earthquake in 1976, and 536 sex‐ and age‐matched individuals without that exposure. Serum uric acid concentrations were measured based on fasting blood samples, which were repeatedly collected in 2006, 2008, and 2010. Mean uric acid concentrations in 2010 and the increasing rate from 2006 to 2010 were compared between the 2 groups, after adjustment for age, sex, body mass index, serum concentrations of glucose, triglycerides, C‐reactive protein level, estimated glomerular filtration rate, and other potential confounders. We also used multiple logistic regression to estimate the risk of hyperuricemia (>416 μmole/liter in men or >357 μmole/liter in women) in 2010 by calculating the odds ratios (ORs) and 95% confidence intervals (95% CIs) after adjustment for the previously mentioned covariates.ResultsParticipants with prenatal exposure to the earthquake had higher concentrations of serum uric acid (adjusted means 315 μmole/liter versus 296 μmole/liter; P = 0.001) and a higher likelihood of having hyperuricemia (multivariate adjusted OR 1.70 [95% CI 1.09–2.66]) in 2010 relative to those without the exposure. Prenatal exposure to the earthquake was consistently significantly associated with a faster increase in uric acid concentration from 2006 to 2010 (P < 0.001).ConclusionPrenatal exposure to the earthquake was associated with higher serum uric acid and higher odds of hyperuricemia in early adulthood.
A modified super‐twisting sliding mode control with inner feedback and adaptive gain schedule
Authors: Yang Yi , Qin Shiyin , Jiang Ping 
Published: July 2016

SummaryIn order to deal with the overestimation of matched uncertainty and improve the convergence of sliding variable in sliding mode control, a modified structure of super‐twisting algorithm (STA) with inner feedback and adaptive gain schedule is presented in this paper. The foremost characteristic of the modified STA is that an inner feedback mechanism is built in the standard STA so as to regulate the dynamic behavior of sliding variable effectively. The damping effect produced by the inner feedback can restrain the overshoot and enhance the performance of faster convergence of the sliding variable. Furthermore, the adaptive gain schedule can effectively decrease the chattering amplitude without knowing the upper bound of uncertainty. The numerical simulations and experiments on DC servo system with low speed are carried out to validate the effectiveness and performance advantages of the proposed methodology. Copyright © 2016 John Wiley & Sons, Ltd.
Biosourced Ligands from Isosorbide for the Ethylation of Aldehydes or Alkynylation of Imines
Authors: Huynh Khanh‐Duy , Ibrahim Houssein , Bouchardy Lucie , Bournaud Chloée , Kolodziej Emilie , Toffano Martial , Vo‐Thanh Giang 
Published: July 2016

Abstractβ‐Amino alcohol and diamine ligands were prepared from isosorbide as a chiral renewable resource. The efficiencies of these ligands were evaluated for the metal‐catalyzed enantioselective ethylation of aldehydes and the alkynylation of aldimines.
Pseudo‐obstruction, stroke, and mitochondrial dysfunction: A lethal combination
Authors: Ng Yi Shiau , Feeney Catherine , Schaefer Andrew M. , Holmes Carol Ellen , Hynd Paula , Alston Charlotte L. , Grady John P. , Roberts Mark , Maguire Mellisa , Bright Alexandra , Taylor Robert W. , Yiannakou Yan , McFarland Robert , Turnbull Doug M. , Gorman Gráinne S. 
Published: July 2016

ObjectivesThe m.3243A>G MTTL1 mutation is the most common cause of mitochondrial disease; yet there is limited awareness of intestinal pseudo‐obstruction (IPO) in this disorder. We aimed to determine the prevalence, severity, and clinical outcome of patients with m.3243A>G‐related mitochondrial disease manifesting with IPO.MethodsIn this large, observational cohort study, we assessed the clinical, molecular, and radiological characteristics of patients with genetically determined m.3243A>G‐related mitochondrial disease, who presented with severe symptoms suggestive of bowel obstruction in the absence of an occluding lesion.ResultsBetween January 2009 and June 2015, 226 patients harbouring the m.3243A>G mutation were recruited to the Medical Research Council Centre Mitochondrial Disease Patient Cohort, Newcastle. Thirty patients (13%) presented acutely with IPO. Thirteen of these patients had a preceding history of stroke‐like episodes, whereas 1 presented 27 years previously with their first stroke‐like episode. Eight patients developed IPO concomitantly during an acute stroke‐like episode. Regression analysis suggested stroke was the strongest predictor for development of IPO, in addition to cardiomyopathy, low body mass index and high urinary mutation load. Poor clinical outcome was observed in 6 patients who underwent surgical procedures.InterpretationOur findings suggest, in this common mitochondrial disease, that IPO is an under‐recognized, often misdiagnosed clinical entity. Poor clinical outcome associated with stroke and acute surgical intervention highlights the importance of the neurologist having a high index of suspicion, particularly in the acute setting, to instigate timely coordination of appropriate care and management with other specialists. Ann Neurol 2016;80:686–692
Preparation and characterization of novel organic chelating resin and its application in recovery of Zn(II) from aqueous solutions
Authors: Zheng Qunxiong , Li Zhuoli , Miao Xixi , Li Jionghui , Huang Yifeng , Xia Haina , Xiong Chunhua 
Published: July 2016

An organic polymeric resin was synthesized by anchoring p‐aminobenzoic acid onto macroporous chloromethylated polystyrene beads, and was used for Zn(II) removal from aqueous solutions. The resin exhibited an initially rapid adsorption property for Zn(II) with equilibrium time of 10 h and the maximum adsorption capability approached 184.5 mg g−1. Optimum pH was 4.5. The mechanism of adsorption was investigated using kinetic, isotherm and thermodynamic models. The adsorption kinetic data were described well by a pseudo second‐order model with R2 of 0.997. There was a negative ΔG (−17.98 kJ mol−1) and positive ΔH (13.58 kJ mol−1). HCl solution (1.0 mol l−1) could achieve an elution rate of 100%. The experimental data were well fitted by the Thomas model with R2 of 0.9826. Copyright © 2016 John Wiley & Sons, Ltd.