bluuebunny/crossref_metadata_2025_split huggingface dataset:
Method for the determination of arsenic and its compounds [Air Monitoring Methods, 2015]
Authors: Hahn J.‐U. , Parlar H. , Hartwig A. ,   MAK Commission
Published: January 2016

The analytical method is validated for the determination of arsenic and its compounds in the air of workplaces averaged over the sampling period after personal or stationary sampling. Sampling is performed by drawing a defined volume of air through a membrane filter located in the sampling head of a total dust sampling system (
G
esamt‐
S
taub‐
P
robenahme – GSP) using a suitable pump. The flow rate is adjusted to 10 L/min whereby the definition of the inhalable dust is fulfilled by this volumetric flow according to EN 481. After acid digestion the sample solution is analysed by means of graphite furnace atomic absorption spectrometry (GFAAS). Calibration solutions are prepared with the help of an autosampler by dilution with a constant injection volume. The determination of the limit of quantification (LOQ) is based on the blank value method and the method of the calibration function in the lower measurement range according to DIN 32645. The measurement range is between 0.25 and 3.3 µg/m
3
for an air sample volume of 1.2 m
3
. The LOQ is 0.25 µg/m
3
for an air sample volume of 1.2 m
3
.The expanded uncertainty of 26% was calculated for a validation concentration of 1.7 µg/m
3
. The sample preparation procedure described here was checked with elemental arsenic and arsenic(III) oxide.
Trimethylbenzene (all isomers) [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 evaluated the biological tolerance value at the work place (BAT value) for trimethylbenzene, considering the sum of dimethylbenzoic acids in urine to characterize the internal exposure. The evaluation is based on the relationship between external and internal exposure to the present MAK value of 100 mg/m
3
.

The BAT value was derived on the basis of the inhalation chamber studies of Kostrzewski et al. (1997) and Knecht et al. (2000, 2003). For an air concentration at the level of the MAK value of 100 mg/m
3
, Kostrzewski et al. (1997) found a mean sum concentration of dimethylbenzoic acid metabolites of 450 mg/g creatinine, Knecht et al. (2000) of 417 mg/g creatinine, and for an air concentration of 90 mg/m
3
269 mg/g creatinine (Knecht et al. 2003). Only Knecht et al. (2000, 2003) cited a 95th percentile and during the exposure, a defined physical activity was carried out, so that the conditions were more realistic compared with the study by Kostrzewski et al. (1997).

Altogether, the mean value was about 400 mg total dimethylbenzoic acids per gram creatinine. Considering the 95th percentiles in the studies of Knecht et al. (2000, 2003), a BAT‐value of 600 mg total dimethylbenzoic acids (after hydrolysis)/g creatinine was evaluated.
Samples should be taken at the end of exposure or end of shift, and, for long‐term exposures, after several shifts. Hydrolysis of the urine samples is necessary for the analytical determination of the metabolites.
N‐Methyl‐2‐pyrrolidone [BAT Value Documentation, 2009]
Authors: Bader M. , Wrbitzky R. , 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 evaluated a biological tolerance value at the work place (BAT value) for N‐methyl pyrrolidone (NMP), considering 5‐Hydroxy‐N‐methyl‐2‐pyrrolidone (5‐HNMP) in urine to characterize the internal exposure.A BAT value for 5‐HNMP in urine can at present not be derived from effect parameters, but only on the basis of the correlation to the MAK value.According to Bader et al. (2007), an 8‐hour exposure to NMP at the level of the MAK value of 82 mg/m3with an activity of 75W for one hour during the exposure interval results in a 5‐HNMP concentration of 153 mg/g creatinine (186 mg/l).According to Åkesson and Jönsson (2000) the expected 5‐HNMP concentration after 8 hours exposure to 82 mg NMP/m3is 183 mg/g creatinine or 220 mg/l assuming a mean creatinine concentration of 1.2 g/l, performed at rest. Possibly, the differences of the corresponding results by Bader et al. (2007) can be attributed to the influence of an additional dermal absorption.On the basis of the results by Bader et al. (2007), a BAT value of 150 mg 5‐Hydroxy‐N‐methyl‐2‐pyrrolidone/l urine corresponding to the MAK value of 82 mg/m3has been derived. Sampling time is at the end of exposure.
Mercapturic acids of 2‐chloroprene, epichlorohydrin, and 1,3‐butadiene in urine [Biomonitoring Methods, 2015]
Authors: Eckert E. , Göen T. , Hartwig A. ,   MAK Commission
Published: January 2016

The analytical method permits simultaneous determination of the mercapturic acid of epichlorohydrin i.e. N‐acetyl‐S‐(3‐chloro‐2‐hydroxypropyl) cysteine (CHPMA) and of four mercapturic acids of 2‐chloroprene in urine: N‐acetyl‐S‐(4‐chloro‐3‐oxobutyl) cysteine (Cl‐MA I), N‐acetyl‐S‐(3‐chloro‐2‐hydroxy‐3‐butenyl) cysteine (Cl‐MA III), N‐acetyl‐S‐(4‐hydroxy‐3‐oxobutyl) cysteine (HOBMA) and N‐acetyl‐S‐(3,4‐dihydroxybutyl) cysteine (DHBMA). The mercapturic acids HOBMA and DHBMA are also formed after exposure to 1,3‐butadiene.For determination, the urine samples are buffered to pH 2.5, spiked with isotopelabeled internal standards (d3‐CHPMA, d3‐Cl‐MA I, d3‐Cl‐MA III, d3‐HOBMA and d7‐DHBMA), processed using online solid phase extraction (online SPE) and LC–MS/MS. For that purpose the analytes are enriched on a C18 pre‐concentration column [RAM (Restricted Access Material) phase]. Subsequently, the analytes are transferred in backflush mode from the RAM phase to the analytical column, separated chromatographically and finally subjected to tandem mass spectrometric detection. Calibration is carried out using standard solutions in pooled urine which are processed and analyzed in the same way as the samples to be analyzed.
n‐, sec‐, iso‐, tert‐Butylamin [MAK Value Documentation in German language, 2016]
Authors: Meischner V. , Laube B. , Bartsch R. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for n‐, sec‐, iso‐, tert‐Butylamine

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 n‐, sec‐, iso‐ and tert‐butylamine, considering local and systemic toxicity as well as developmental toxicity. Daily exposure of rats to n‐butylamine for 14 days resulted in inflammation of respiratory epithelium at 17 ml/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, which would result in lowering the MAK‐value for n‐butylamine. However, workers reported no irritation at 1 to 2 ml n‐Butylamine/m
3
. Therefore, the MAK value of 2 ml/m
3
is confirmed, also for sec‐ and iso‐butylamine due to similar structure, pKa and RD
50
values. With tert‐butylamine the LOAEC of 66 ml/m
3
in rats in a 13‐week study resulted in nasal tissue inflammation and liver weight increase. Following the empirical approach, the same MAK value of 2 ml/m
3
is set for tert‐butylamine. As local effects might be or are critical, Peak Limitation Category I and an excursion factor of 2 and momentary value of 5 ml/m
3
is assigned for all butylamine isomers. Developmental toxicity studies with n‐butylamine show that damage to the embryo or foetus is unlikely if the MAK value is observed and thus n‐butylamine is assigned to Pregnancy Risk Group C. Due to the lack of developmental toxicity studies, sec‐, iso‐ and tert‐butylamine are assigned to Pregnancy Risk Group D.
Phosphorylchlorid [MAK Value Documentation in German language, 2016]
Authors: Kreis P. , Bartsch R. , van Thriel C. , Brüning T. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for Phosphorus oxychloride

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 phosphorus oxychloride of 0.2 ml/m
3
, considering the endpoints local and systemic toxicity as well as developmental toxicity. Available publications are described in detail. Phosphorus oxychloride is corrosive to eyes and skin and hydrolyses in water to hydrogen chloride and phosphoric acid, similar to phosphorus trichloride. There is not enough data for phosphorus oxychloride to set a MAK value because valid inhalation studies with repeated exposure are missing. Therefore, the MAK value of phosphorus oxychloride is derived by using a read‐across to phosphorus trichloride for which a MAK value of 0.1 ml/m
3
has been set based on a 28‐day inhalation study. Considering the fivefold higher NOAEC of phosphorus trichloride for sensory irritation in volunteers and rats the MAK value for phosphorus oxychloride is lowered accordingly to 0.02 ml/m
3
. The assignment to Peak Limitation Category I, because local effects are critical, and the excursion factor of 1 are confirmed. The assignment to Pregnancy Risk Group C is retained as damage to the embryo or foetus is unlikely when the MAK value is observed.
Tetrahydronaphthalene [MAK Value Documentations, 2013]
Authors: Jahnke G. , Schwabe R. , Hartwig A. ,   MAK Commission
Published: January 2016

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated tetrahydronaphthalene to derive a maximum concentration at the workplace (MAK value), considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. In animal studies, the target organs of the toxicity of tetrahydronaphthalene are the liver and kidneys and, after inhalation, also the respiratory tract. The relative kidney weights of female rats were increased at tetrahydronaphthalene concentrations of 15 ml/m
3
and above in both a 14‐week study and a 14‐day study. The NOAEC was 7.5 ml/m
3
in both studies, and 15 ml/m
3
for effects on the olfactory epithelium in the 14‐week study. In mice, NOAEC of 15 and 30 ml/m
3
were obtained for female and male animals, respectively, after exposure for 14 weeks. From the NOAEC of 15 ml/m
3
for effects in the nose of rats and the NOAEC of 7.5 ml/m
3
for increased relative kidney weights in female rats, a MAK value of 2 ml/m
3
is derived. Both systemic and local effects lead to the same MAK value and no data for local effects or the half‐life are available for humans. The classification in Peak Limitation Category I is therefore based on the lower default excursion factor of 1 as compared to 2 for Peak Limitation Category II. The NOAEL for developmental toxicity and maternal toxicity in rats was 45 mg/kg body weight and day. The difference between the MAK value and the calculated NAEC for developmental toxicity together with the difference between the MAK value and the calculated LAEC for developmental toxicity is, in view of the low severity of the findings and the simultaneous occurrence of maternal toxicity, sufficiently large. Thus, damage to the embryo or foetus is unlikely when the MAK value is observed and the substance is classified in Pregnancy Risk Group C. Tetrahydronaphthalene is not genotoxic and not carcinogenic in 2‐year inhalation studies in rats and mice. Tetrahydronaphthalene is not a contact sensitizer in guinea pigs and no clear results for sensitization in humans are available. Skin contact is not expected to contribute significantly to systemic toxicity.
Ethylacrylat [MAK Value Documentation in German language, 2016]
Authors: Kreis P. , Michaelsen S. , Bartsch R. , van Thriel C. , Lessmann H. , Schnuch A. , Göen T. , Bader M. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for Ethyl acrylate

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) of ethyl acrylate of 5 ml/m
3
, considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. The critical effect of ethyl acrylate is irritation of eye and nose in humans and the olfactory mucosa in rats and mice. The chronic NOAEC in rats is 5 ml/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. Accordingly, the MAK value has to be lowered to 2 ml/m
3
, which is confirmed in a recent volunteer study with a NOAEC of 2.5 and a LOAEC of 5 ml ethyl acrylate/m
3
. As local effects are critical, the assignment to Peak Limitation Category I and the excursion factor of 2 are confirmed. Developmental toxicity studies with ethyl acrylate 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. Ethyl acrylate is not genotoxic in vivo and not carcinogenic. Skin contact may contribute significantly to systemic toxicity and ethyl acrylate is designated with an “H” notation. The available data confirm that the substance is a skin sensitizer and the designation with “Sh” is retained. There are no data concerning the potential for respiratory sensitization.
2‐Aminoethanol [MAK Value Documentation in German language, 2016]
Authors: Laube B. , Bartsch R. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for 2‐Aminoethanol
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 2‐aminoethanol, considering the endpoints respiratory tract irritation, developmental toxicity, and skin absorption. Available unpublished study reports are described in detail.

Critical effect of 2‐aminoethanol is the local respiratory tract irritation. New 5‐day and 28‐day‐guideline‐studies with rats show time‐ and dose‐dependent effects in larynx (squamous metaplasia, inflammation, necrosis), trachea (squamous metaplasia, inflammation), and lung (hyperplasia of mucous and goblet cells). The NOAEC is 10 mg/m
3
(3,95 ml/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 0.22 ml/m
3
for the work place air can be calculated from this study, resulting in a MAK value of 0.2 ml/m
3
. Since the critical effect is irritation, Peak Limitation Category I is retained with an excursion factor of 1 as the substance is corrosive.

After scaling the oral NOAEL for developmental toxicity of 75, 225, and 500 mg/kg body weight and day for rabbits (dermal) and rats (dermal, oral), respectively, to an inhalation concentration at the work place, the differences to the MAK value, are considered sufficient, and damage to the embryo or foetus is unlikely when the MAK value is observed. Therefore, classification in Pregnancy Risk Group C is confirmed.
Absorption via skin does not contribute significantly to the systemic toxicity of 2‐aminoethanol.
4‐Methyl‐3‐penten‐2‐on [MAK Value Documentation in German language, 2016]
Authors: Meischner V. , Laube B. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for 4‐Methyl‐3‐pentene‐2‐one

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) for 4‐methyl‐3‐pentene‐2‐one of 5 ml/m
3
, considering local and systemic toxicity as well as developmental toxicity. As described in the last evaluation from 2006, 4‐methyl‐3‐pentene‐2‐one is irritating to eyes and skin. Starting at the lowest concentration of 31 ml/m
3
in a 49‐day‐inhalation‐study with daily exposure exudate in the olfactory epithelium is observed in 10 of 24 rats. A NAEC of 10 ml/m
3
is 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. Taking into consideration exposure of rats took place 7 days a week and no chronic study is available, it is assumed, that the chronic NAEC is 5 ml/m
3
. As olfactory epithelium is the target tissue, according to the empirical approach, the MAK‐value is reduced to 2 ml/m
3
. The assignment to Peak Limitation Category I, because local effects are critical, and the excursion factor of 2 are confirmed. As there are no developmental toxicity studies, the assignment to Pregnancy Risk Group D is confirmed.
Dipropylenglykol [MAK Value Documentation in German language, 2016]
Authors: Michaelsen S. , Kreis P. , Bartsch R. , Roßbach B. , Bader M. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for Dipropylene glycol

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) for dipropylene glycol has been set at 100 mg/m
3
for the inhalable fraction, considering the endpoints respiratory tract irritation and systemic toxicity as well as absorption through the skin. A 2‐year drinking water study with rats shows a NOAEL for focal inflammation of the liver in males of 115 mg/kg body weight and day and a NOAEL for olfactory epithelium degeneration in males and females of 470 and 530 mg/kg body weight and day, respectively. This raises the question, whether the olfactory epithelium could also be a local target tissue after inhalation. Inhalation studies with dipropylene glycol are not available. The substance shows very slight irritation of skin and eyes, if any. Thus, there are no indications of a potential local irritative effect to the upper airways. Therefore, the MAK value of 100 mg/m
3
derived from systemic effects is validated. As systemic effects are critical, the assignment to Peak Limitation Category II and the excursion factor of 2 are retained. A recent in‐vitro study with human skin shows that skin contact does not contribute significantly to systemic toxicity and the former designation with an “H” notation is withdrawn.
N‐Ethyl‐2‐pyrrolidon (Dampf) [MAK Value Documentation in German language, 2016]
Authors: Lohmann R. D. , Meischner V. , Leibold E. , Schriever‐Schwemmer G. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for N‐Ethyl‐2‐pyrrolidone

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 N‐ethyl‐2‐pyrrolidone of 2 ml/m
3
, considering the endpoints irritation of the respiratory tract and developmental toxicity.

The critical effect of N‐ethyl‐2‐pyrrolidone is degeneration of the olfactory epithelia in rats in a new 13‐week‐inhalation study. 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 these proposals, the NOAEC of 62.6 mg/m
3
(13.3 ml/m
3
vapour) corresponds to a work place air concentration of 31 mg/m
3
(6.6 ml/m
3
). The irritating response in the 13 week study is not more pronounced than after shorter exposition times. Therefore the MAK‐value is increased to 5 ml/m
3
for the vapour phase only. Local effects are critical and only minimal irritation occurs at the LOAEC, therefore the assignment of N‐ethyl‐2‐pyrrolidone to Peak Limitation category I and excursion factor 2 established in 2014 are retained. Also with the increased MAK value, damage to the embryo or foetus is unlikely when the MAK value is observed. Therefore, classification of N‐ethyl‐2‐pyrrolidone in Pregnancy Risk Group C is confirmed.
Phosphortrichlorid [MAK Value Documentation in German language, 2016]
Authors: Kreis P. , Bartsch R. , van Thriel C. , Brüning T. , Hartwig A. ,   MAK Commission
Published: January 2016

MAK Value Documentation for Phosphorus trichloride

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 phosphorus trichloride of 0.5 ml/m
3
, considering the endpoints local and systemic toxicity as well as developmental toxicity. Available publications are described in detail. As described in the previous evaluation of 2006, phosphorus trichloride is corrosive to eyes and skin and in a 28‐day‐inhalation‐study irritative to the respiratory tract of rats with a NOAEC of 3 ml/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. According to this approach, a concentration of 0.17 ml/m
3
for the work place air can be calculated from this study. Therefore, the MAK value is lowered to 0.1 ml/m
3
. The assignment to Peak Limitation Category I, because local effects are critical, and the excursion factor of 1 are confirmed. A developmental toxicity study with phosphorus trichloride in rats shows that damage for the embryo or foetus is unlikely if the MAK‐value is observed, and the assignment to Pregnancy Risk Group C is retained.
Development and First Validation of a Disease Activity Score for Gout
Authors: Scirè Carlo A. , Carrara Greta , Viroli Cinzia , Cimmino Marco A. , Taylor William J. , Manara Maria , Govoni Marcello , Salaffi Fausto , Punzi Leonardo , Montecucco Carlomaurizio , Matucci‐Cerinic Marco , Minisola Giovanni ,   and the Study Group for the Kick‐Off of the Italian Network for Gout Study
Published: January 2016

ObjectiveTo develop a new composite disease activity score for gout and provide its first validation.MethodsDisease activity has been defined as the ongoing presence of urate deposits that lead to acute arthritis and joint damage. Every measure for each Outcome Measures in Rheumatology core domain was considered. A 3‐step approach (factor analysis, linear discriminant analysis, and linear regression) was applied to derive the Gout Activity Score (GAS). Decision to change treatment or 6‐month flare count were used as the surrogate criteria of high disease activity. Baseline and 12‐month followup data of 446 patients included in the Kick‐Off of the Italian Network for Gout cohort were used. Construct‐ and criterion‐related validity were tested. External validation on an independent sample is reported.ResultsFactor analysis identified 5 factors: patient‐reported outcomes, joint examination, flares, tophi, and serum uric acid (sUA). Discriminant function analysis resulted in a correct classification of 79%. Linear regression analysis identified a first candidate GAS including 12‐month flare count, sUA, visual analog scale (VAS) of pain, VAS global activity assessment, swollen and tender joint counts, and a cumulative measure of tophi. Alternative scores were also developed. The developed GAS demonstrated a good correlation with functional disability (criterion validity) and discrimination between patient‐ and physician‐reported measures of active disease (construct validity). The results were reproduced in the external sample.ConclusionThis study developed and validated a composite measure of disease activity in gout. Further testing is required to confirm its generalizability, responsiveness, and usefulness in assisting with clinical decisions.