bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addendum zu Tetrachlorethen [BAT Value Documentation in German language, 2018]
Authors: Bolt H.M. , Drexler H. , Hartwig A. ,   MAK Commission
Published: October 2018

Abstract

In 2017, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated tetrachloroethylene [CAS No.
127‐18‐4
] considering tetrachloroethylene in blood to characterize the internal exposure at the workplace. Available publications are described in detail.

The exposure equivalents for carcinogenic substances (EKA) of tetrachloroethylene uptake by inhalation and tetrachloroethylene in blood were confirmed and extended due to recent data.

The evaluation of the BAT value was based on the relationship between tetrachloroethylene uptake by inhalation at the MAK value and the corresponding concentration of tetrachloroethylene in blood. An eight‐hour exposure to the present MAK value of 10 ml tetrachloroethylene/m
3
correlates 16 hours after exposure with a mean tetrachloroethylene concentration in blood of approximately 200 µg/l. Therefore, a BAT value of 200 µg tetrachloroethylene/l blood was evaluated. Sampling time is 16 hours after exposure.
Addendum zu Ethylenglykoldinitrat [BAT Value Documentation in German language, 2018]
Authors: Klotz K. , Drexler H. , Hartwig A. ,   MAK Commission
Published: October 2018

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the biological tolerance value (BAT value) for ethylene glycol dinitrate [CAS No.
628‐96‐6
] in 2017.

Aim of this re‐evaluation was the lowering of the MAK value from 0.05 to 0.01 mL/m³ (for the sum of ethylene glycol dinitrate, nitroglycerin and propylene glycol dinitrate). The former BAT value of 0.3 µg ethylene glycol dinitrate/L blood was based on a correlation between external and internal exposure to the former MAK value of 0.05 ml/m³. The limit of detection of the applied analytical method was 0.2 µg ethylene glycol dinitrate/L blood. Correlating values of ethylene glycol dinitrate to the present MAK value would result in values below the limit of detection. Further studies and more sensitive analytical methods are missing. Therefore, the BAT value was withdrawn.
Addendum zu Aluminium [BAT Value Documentation in German language, 2018]
Authors: Klotz K. , Meyer‐Baron M. , van Thriel C. , Pallapies D. , Nasterlack M. , Letzel S. , Roßbach B. , Triebig G. , Weistenhöfer W. , Drexler H. , Hartwig A. ,   MAK Commission
Published: October 2018

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the biological tolerance value (BAT value) for aluminium [CAS No.
7429‐90‐5
] in 2017. Available publications are described in detail.

The BAT value of 60 µg aluminium/g creatinine evaluated in 2009 was based on the linear correlation between external and internal exposure. Aim of this re‐evaluation was the derivation of a health‐based BAT value considering the most sensitive critical effect of aluminium, the neurotoxicity. For this purpose, the available studies of aluminium‐exposed workers were taken into account, when the internal aluminium exposure as well as the occurrence of subclinical neurotoxic effects were determined. The effects had been measured with standardised neuropsychological test procedures. From these studies, a no observed adverse effect level (NOAEL) of 50 µg/g creatinine for the occurrence of subtle neurotoxic effects of humans was estimated. Therefore, a BAT value of 50 µg aluminium/g creatinine was evaluated. Sampling time for long‐term exposures is at the end of the shift after several shifts.
Arsen und Arsenverbindungen – Bestimmung von Arsenspezies (As(III), As(V), Monomethylarsonsäure, Dimethylarsinsäure und Arsenobetain) in Urin mittels HPLC‐ICP‐MS [Biomonitoring Methods in German language, 2018]
Authors: Schramel P. , Michalke B. , Emons H. , Göen T. , Hartwig A. ,   MAK Commission
Published: October 2018

AbstractThe working group “Analyses in Biological Materials” of the Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area verified the presented biomonitoring method.The analytical method described hereinafter permits the simple and specific determination of the arsenic species arsenic (III) (As3+), arsenic (V) (As5+), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and arsenobetaine in urine. The limits of quantitation allow the quantification of the above‐mentioned arsenic species in both occupational and environmental medicine.To this end, the arsenic species are separated by anion‐exchange high‐performance liquid chromatography (anion‐exchange HPLC) and detected by inductively coupled plasma mass spectrometry (ICP‐MS). Sample preparation is done by diluting the urine with water. Calibration is performed using either single or mixed standards of the different arsenic species or using the standard addition method.The method was extensively validated and the reliability data were confirmed by an independent laboratory, which has established and cross‐checked the whole procedure.
Methyl vinyl ether [MAK Value Documentation, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: October 2018

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the workplace (MAK value) and the Pregnancy Risk Group of methyl vinyl ether [
107‐25‐5
].

There are no new data. Methyl vinyl ether was assessed in two 28 day inhalation studies, the first with 5 male and 5 female rats each and concentrations of 0, 500, 3500, 25 000 ml/m
3
and a second with 10 male rats each and concentrations of 0, 150, 500, 1500 ml/m
3
. In the first study 3500 ml/m
3
was the systemic NOAEC for females and local NOAEC for males and females. In male rats, changes in haematological and clinico‐chemical parameters were observed in all exposure groups independent of the concentration. These effects could not be reproduced in the second study. At 3500 ml/m
3
the body weight gains of male rats were reduced. This reduction was not seen in the second study with a higher number of animals. Therefore the commission now evaluates the effects at 3500 ml/m
3
as incidental, maybe due to the lower number of animals, and defined 3500 ml/m
3
as NOAEC. As the margin of the MAK value of 200 ml/m
3
to slight effects at 25 000 ml/m
3
is large enough it also accounts for the increased respiratory volume at the workplace (the blood:air partition coefficient of methyl vinyl ether is > 5; see List of MAK‐ and BAT Values, Sections I b and I c). Therefore the MAK value of 200 ml/m
3
is confirmed.

Since a systemic effect is critical, Peak Limitation Category II is retained. No data concerning half‐life are available; therefore the default excursion factor of 2 is confirmed.

For rats, the NOAEC for developmental toxicity after inhalation is 5000 ml methyl vinyl ether/m
3
, at 10 000 ml/m
3
variations and retarded ossification were observed. Even considering the increased respiratory volume at the workplace the difference of the NOAEC for developmental toxicity to the MAK value is sufficient so that methyl vinyl ether remains assigned to Pregnancy Risk Group C.
1‐Ethoxy‐2‐propanol [MAK Value Documentation, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: October 2018

Abstract

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), the Pregnancy Risk Group and absorption through the skin of 1‐ethoxy‐2‐propanol [
1569‐02‐4
].

1‐Ethoxy‐2‐propanol is irritating to the eyes of rabbits and can damage the cornea. The critical systemic effects are pale foci in the lung and increased urine volume in rats after 13 weeks inhalation. The NAEC of these effects is estimated at 250 ml/m
3
, which results in a decreased MAK value of 20 ml/m
3
(88 mg/m
3
). This value also protects against possible irritation, as local effects are not observed up to 2000 ml/m
3
in the 13‐week rat inhalation study.

Since the critical effect of 1‐ethoxy‐2‐propanol is systemic, Peak Limitation Category II is retained. There is no specific toxicokinetic data available, so that the default excursion factor of 2 is confirmed.
New data on reproduction toxicity with 1‐ethoxy‐2‐propanol are not available. 1‐Ethoxy‐2‐propanol remains assigned to Pregnancy Risk Group C.
Skin contact is expected to contribute significantly to systemic toxicity and 1‐ethoxy‐2‐propanol remains designated with “H”.
Nitroglycerin [MAK Value Documentation, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: October 2018

AbstractThe 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) and the Pregnancy Risk Group of nitroglycerin [55‐63‐0].The critical effect in volunteers after a 25‐minute exposure to 0.05 ml/m3of a mixture of ethylene glycol dinitrate and nitroglycerin was vasodilation, as indicated by the development of headaches or decreases in blood pressure. In workers, headaches were reported at nitroglycerin concentrations of 0.03 to 0.11 ml/m3with a NOAEC below 0.01 ml/m3nitroglycerin. Based on this data, the MAK value for nitroglycerin was established at 0.01 ml/m3. As the MAK value is derived from experiences in workers, the increased respiratory volume at the work place is considered.The MAK value also applies to the sum of the concentrations of the three nitrate esters nitroglycerin, ethylene glycol dinitrate and propylene glycol dinitrate in the air. As systemic effects are critical, the assignment to Peak Limitation Category II and the excursion factor of 1, due to the short half‐life, are retained.In rats, the NOAEL for developmental toxicity after oral application is 86 mg/kg body weight and day. After toxicokinetic scaling this dose corresponds to a concentration of 16 ml/m3at the work place. The difference of this concentration to the MAK value is sufficient, therefore, nitroglycerin remains assigned to Pregnancy Risk Group C.Skin contact may contribute significantly to systemic toxicity and nitroglycerin continues to be designated with an “H”. Sensitization is not expected from the limited data.
Ethylene glycol dinitrate [MAK Value Documentation, 2017]
Authors: Hartwig A. ,   MAK Commission
Published: October 2018

AbstractThe German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the workplace (MAK value) of ethylene glycol dinitrate [628‐96‐6] of 0.05 ml/m3, considering all toxicity endpoints. A detailed description of the underlying studies is given.The critical effect in volunteers after a 25‐minute exposure to 0.05 ml/m3of a mixture of ethylene glycol dinitrate and nitroglycerin was vasodilation, as indicated by the development of headaches or decreases in blood pressure. The effects were very slight. In occupational situations it is very difficult to assess the levels of exposure to ethylene glycol dinitrate that induce symptoms and effects, not only because exposure is usually to mixtures of organic nitrate esters, but also because of both respiratory tract and skin absorption of ethylene glycol dinitrate vapours. In workers, headaches were reported at nitroglycerin concentrations of 0.03 to 0.11 ml/m3with a NOAEC below 0.01 ml/m3nitroglycerin. Based on this data, the MAK value for nitroglycerin was established at 0.01 ml/m3. Because of the same mode of action and the similar LOAEC of the two substances, the MAK value for ethylene glycol dinitrate has been lowered to 0.01 ml/m3. The MAK value also applies to the sum of the concentrations of the two substances in the air. As systemic effects are critical, the assignment to Peak Limitation Category I and the excursion factor of 1, due to the short half‐life, are retained. Although there are no studies on developmental toxicity, ethylene glycol dinitrate is assigned to Pregnancy Risk Group C in analogy to nitroglycerin. No data are available for genotoxicity or carcinogenicity. Skin contact may contribute significantly to systemic toxicity and ethylene glycol dinitrate continues to be designated with an “H”. Sensitization is not expected from the limited data.
Acetonitrile [MAK Value Documentation, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: October 2018

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the workplace (MAK value) and the Pregnancy Risk Group of acetonitrile [
75‐05‐8
].

Acetonitrile causes an increased incidence of liver adenomas and carcinomas in rats at 400 ml/m
3
with a statistically significant trend. The number of basophilic foci in the liver is positively correlated with the exposure concentration. At 100 ml/m
3
the elevation is not statistically significant, however, these foci are regarded as preneoplastic lesions. From this concentration the former MAK value of 20 ml/m
3
was derived. It is now lowered to 10 ml/m
3
taking into account the increased respiratory volume at the workplace because the blood:air partition coefficient of acetonitrile is > 5 (see List of MAK and BAT Values, Sections I b and I c). Since a systemic effect is critical, Peak Limitation Category II is retained. As the effects are probably due to the metabolites, the default excursion factor of 2 is confirmed despite the long half‐life of acetonitrile.

For rabbits, the NOAEL for developmental toxicity after gavage is 15 mg/kg body weight and day. After toxicokinetic scaling this dose corresponds to a concentration of 34 ml/m
3
at the workplace. Rabbits are more sensitive to acetonitrile than rats and humans and the developmental toxicity of acetonitrile is higher after gavage than after inhalation exposure as shown with rats. Therefore, the rabbit gavage data are not used to assign a Pregnancy Risk Group. The NOAEC for developmental toxicity in rats is 1600 ml/m
3
and after considering the increased respiratory volume at the workplace the difference to the MAK value is sufficient. Therefore, damage to the embryo or foetus is unlikely when the MAK value is observed and acetonitrile remains assigned to Pregnancy Risk Group C.
Trimethylamine [MAK Value Documentation, 2016]
Authors: Hartwig A. ,   MAK Commission
Published: October 2018

Abstract

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 [
75‐50‐3
] 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 RD50 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.
Citric acid and its alkali metal salts [MAK Value Documentation, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: October 2018

AbstractThe German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated citric acid [77‐92‐9] and its alkali metal salts, considering all toxicological endpoints.The critical effect of citric acid is the irritation of the respiratory tract with an acute LOAEC of 225 mg/m3in humans and 81 mg/m3in guinea pigs. At this concentration coughing is induced due to the lowering of the pH value. The NOAEC in guinea pigs is 31 mg/m3, the corresponding NOAEC in humans is not known. Studies with repeated inhalation are not available. Therefore, the maximum concentration at the workplace (MAK value) has been set by analogy with the MAK value for phosphoric acid of 2 mg/m3as inhalable fraction. Since a local effect is critical, Peak Limitation Category I is designated. The excursion factor of 2 is set by analogy with phosphoric acid.The alkali metal salts of citric acid are not irritating, which precludes setting the same MAK value for the salts as for citric acid. However, a higher MAK value cannot be established because the systemic NOAEL is unclear. Therefore, no MAK value can be set for the alkali metal salts of citric acid.The oral NOAEL for developmental toxicity in rats, mice, rabbits and hamsters is higher than 200 mg citric acid/kg body weight, which after toxicokinetic scaling corresponds to more than 200 mg/m3at the workplace. Therefore, damage to the embryo or foetus is unlikely when the MAK value is observed and citric acid is assigned to Pregnancy Risk Group C.Citric acid does not possess a relevant genotoxic potential in vivo. The same is assumed for its alkali metal salts. There are no valid carcinogenicity studies with citric acid. A tumour promoting effect of sodium citrate but not citric acid in the rat urinary bladder is due to excessively high sodium concentration in the urine and is therefore not relevant for humans at the workplace.According to skin absorption models, percutaneous absorption of citric acid does not contribute significantly to systemic toxicity. The same is assumed for its alkali metal salts. Citric acid and its alkali metal salts are not sensitizing to skin or airways.
N‐Vinyl‐2‐pyrrolidone [MAK Value Documentation, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: October 2018

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the workplace (MAK value) and the Pregnancy Risk Group of N‐vinyl‐2‐pyrrolidone [
88‐12‐0
].

N‐Vinyl‐2‐pyrrolidone is a non‐genotoxic carcinogen in liver, nose and larynx of rats. In 28‐day inhalation studies it was shown that cell proliferation in liver and hyperplasia in the nasal epithelia of rats is increased at 0.5 ml/m
3
with a NOAEC of 0.2 ml/m
3
. The former MAK value of 0.02 ml/m
3
was derived from this concentration, the MAK value is now lowered to 0.01 ml/m
3
. This takes into account the increased respiratory volume at the workplace, because the blood:air partition coefficient of N‐vinyl‐2‐pyrrolidone is > 5 (see List of MAK and BAT Values, Sections I b and I c). Since a systemic effect is critical, Peak Limitation Category II is retained. As the critical metabolite is not known, the default excursion factor of 2 for systemically acting compounds is confirmed.

For rats, the NOAEC for developmental toxicity after inhalation is 5 ml N‐vinyl‐2‐pyrrolidone/m
3
, where reduced maternal body weight gain occurred. At 20 ml/m
3
reduced foetal bodyweight and an increase of variations were observed. Taking into account the increased respiratory volume at the work place the NOAEC for developmental toxicity is 250 times higher than the MAK‐value. Therefore, N‐vinyl‐2‐pyrrolidone remains assigned to Pregnancy Risk Group C.
An algorithm for automated modulation transfer function measurement using an edge of a PMMA phantom: Impact of field of view on spatial resolution of CT images
Authors: Anam Choirul , Fujibuchi Toshioh , Budi Wahyu Setia , Haryanto Freddy , Dougherty Geoff 
Published: October 2018

AbstractPurposeThe purpose of this study was to introduce a new algorithm for automated measurement of the modulation transfer function (MTF) using an edge of a readily available phantom and to evaluate the effect of reconstruction filter and field of view (FOV) on the spatial resolution in the CT images.MethodsOur automated MTF measurement consisted of several steps. The center of the image was established and an appropriate region of interest (ROI) designated. The edge spread function (ESF) was determined, and a suitably interpolated ESF curve was differentiated to obtain the line spread function (LSF). The LSF was Fourier transformed to obtain the MTF. All these steps were accomplished automatically without user intervention. The results of the automated MTF from the edge phantom were validated by comparing them with a point image, and the results of the automated calculation were validated by the standard fitting method. The automated MTF calculation was then applied to the images of two polymethyl methacrylate (PMMA) phantoms and a wire phantom which had been scanned by a Toshiba Alexion 4‐slice CT scanner and reconstructed with various filter types and FOVs.ResultsThe difference in the 50% MTF values obtained from the edge and point phantoms were within ±4%. The values from the automated and fitted methods agreed to within ±2%, indicating that the automated MTF calculation was accurate. The automated MTF calculation was able to differentiate MTF curves for various filters. The spatial resolution values were 0.37 ± 0.00, 0.71 ± 0.01, and 0.78 ± 0.01 cycles/mm for FC13, FC30 and FC52 filters, respectively. The spatial resolution of the images decrease linearly (R2 > 0.98) with increasing FOVs.ConclusionAn automated MTF method was successfully developed using an edge phantom, the PMMA phantom. The method is easy to implement in a clinical environment and is not influenced by user experience.
Self‐Assembled Aptamer Nanoconstruct: A Highly Effective Molecule‐Capturing Platform Having Therapeutic Applications
Authors: Lee Jihyun , Lee Junseok , Ree Brian J. , Lee Yeong Mi , Park Hyeongmok , Lee Tae Geol , Kim Jeong Hun , Kim Won Jong 
Published: October 2018

AbstractAlthough the aptamer is a promising tool for binding and controlling the activity of a specific target molecule, its relatively low stability and capturing efficiency are major obstacles for its direct use in therapeutic applications. Herein, a 3D molecular capture system named the “constructed aptamer (CA)” is reported, which is formulated by the self‐assembly of the human vascular endothelial growth factor (hVEGF) aptamer block and Y‐shaped DNA blocks. The serum stability and target capturing efficiency exhibited by the CA are greater than that observed with the oligomeric aptamer and randomly amplified aptamer. In addition, successful intracellular uptake is observed by confocal laser scanning microscopy using fluorescence labeled CA. Finally, an enhanced antitumor effect is demonstrated in vivo, owing to the efficient inhibition of angiogenesis. Overall, the designed CA has great potential as a therapeutic platform for capturing a specific disease‐related molecule such as VEGF.