bluuebunny/crossref_metadata_2025_split huggingface dataset:
2,3‐Pentanedione – Method for the determination of 2,3‐pentanedione in workplace air using high performance liquid chromatography (HPLC) [Air Monitoring Methods, 2017]
Authors: Schuh C. , Nitschke L. , Hebisch R. , Brock T.H. , Hartwig A. ,   MAK Commission
Published: July 2018

Abstract

This analytical method is a validated measurement procedure for the determination of 2,3‐pentanedione in workplace air in a concentration range of a tenth up to twice the currently valid MAK value of 0.083 mg/m
3
. Sampling is performed by drawing a defined volume of air through a cartridge filled with silica gel impregnated with 2,4‐dinitrophenylhydrazine (DNPH) using a suitable flow‐regulated pump with a volumetric flow rate of 1 L/min. For sampling 1 hour or 15 min (checking the short‐term value) can be used. The formed hydrazones are desorbed with acetonitrile containing a defined amount of DNPH and analysed by means of liquid chromatography (HPLC‐UV or HPLC‐MS). Quantitative evaluation is based on a 10‐point calibration using an internal standard for analysis with HPLC‐MS and an external standard for analysis via HPLC‐UV. The limit of quantification for 2,3‐pentanedione is 0.00078 mg/m
3
based on an air sample volume of approx. 60 L or 0.0031 mg/m
3
based on an air sample volume of approx. 15 L (for short‐term value).

Joint Publication of the Analytical Subcommittee of the Chemistry Board of Experts of the Expert Committee Raw Materials and Chemical Industry of the German Social Accident Insurance and the working group “Air Analyses” of the Permanent Senate Commission of the DFG for the Investigation of Health Hazards of Chemical Compounds in the Work Area.
Sampling and analysis of substances and substance mixtures which may occur simultaneously as vapours and particles in workplace air [Air Monitoring Methods, 2018]
Authors: Breuer D. , Dragan C.G. , Hebisch R. , Bartsch R. , Giesen Y. , Krämer W. , Nitschke L. , Nitz G. , Pannwitz K.‐H. , Tschickardt M. , Brock T.H. , Hartwig A. ,   MAK Commission
Published: July 2018

AbstractDue to their physical properties semi‐volatile substances can occur as particle/vapour mixtures in workplace air. Such mixtures are formed, e.g. as a result of mechanical processes such as the processing of metals or ceramics, during dipping processes in electroplating or during spraying processes. For that reason workplace air measurements must be carried out with a suitable sampling system for the collection of particles and vapours in workplace air. This report sets out the general principles of the physical behaviour of airborne aerosols and explains the different toxic effects of both phases by inhalation. Sampling strategies for collection of particle/vapour mixtures in workplace air using generally accepted combined sampling systems are described. In addition, several approved sampling heads and sampling systems such as GSP, GSP‐Mini, GGP/GGP‐U are presented. Influences on the measurement results such as temperature, humidity, sampling, transport and storage are discussed and the calculation of the expanded uncertainty when measuring these special kinds of substances is explained.Joint Publication of the Analytical Subcommittee of the Chemistry Board of Experts of the Expert Committee Raw Materials and Chemical Industry of the German Social Accident Insurance and the working Group “Air Analyses” of the Permanent Senate Commission of the DFG for the Investigation of Health Hazards of Chemical Compounds in the Work Area.
Iodine and inorganic iodides [BAT Value Documentation, 2016]
Authors: Nasterlack M. , Drexler H. , Hartwig A. ,   MAK Commission
Published: July 2018

Abstract

In 2015 the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated iodine [CAS No.
7553‐56‐2
] and inorganic iodides. Available publications are described in detail.

There is no reproducible quantitative relation between iodine exposure, absorption and resulting body burden. The association between iodine absorption and the incidence of thyroid dysfunction seems to be U‐shaped. Therefore, no sharp boundary can be drawn between iodine oversupply and iodine deficiency relating to individual health. No harmless range could be indicated, so a BAT value (biological tolerance value) for iodine and inorganic iodides could not be derived.
There are major regional differences due to different geological deposits of iodine, different concentrations of iodine in drinking water, iodine‐containing aerosols and nutritional habits. Furthermore, there is a high variability in the urinary analysis. Therefore, a BAR (“Biologischer Arbeitsstoff‐Referenzwert”) for iodine and inorganic iodides could not be derived.
Benzol, Toluol, o‐Xylol, m‐Xylol, p‐Xylol, Ethylbenzol, Styrol und iso‐Propylbenzol (Cumol) – Bestimmung von Aromaten in Urin mittels dynamischer Headspace‐GC‐MS [Biomonitoring Methods in German language, 2018]
Authors: Van Pul J. , Roßbach B. , Göen T. , Hartwig A. ,   MAK Commission
Published: July 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 simultaneous determination of the following unmetabolised aromatic compounds in urine: benzene, toluene, o‐xylene, m‐xylene, p‐xylene, ethylbenzene, styrene and isopropylbenzene (cumene). Prior to the determination of the analytes by GC‐MS, the analytes are extracted and enriched using ITEX (In Tube Extraction) or SPDE (Solid Phase Dynamic Extraction). To this end, the urine samples are incubated at 50 °C, the analytes extracted from the gas phase and then the enriched analytes are transferred to the gas chromatograph and analysed using mass spectrometry. Calibration standards are prepared in water and processed in the same way as the samples to be analysed. Deuterated benzene is used as internal standard.The method was extensively validated and the reliability data were confirmed by an independent laboratory, which has established and cross‐checked the whole procedure.
Benzene, toluene, o‐xylene, m‐xylene, p‐xylene, ethylbenzene, styrene, isopropylbenzene (cumene) – Determination of aromatic compounds in urine by dynamic headspace GC‐MS [Biomonitoring Methods, 2018]
Authors: Van Pul J. , Roßbach B. , Göen T. , Hartwig A. ,   MAK Commission
Published: July 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 simultaneous determination of the following unmetabolised aromatic compounds in urine: benzene, toluene, o‐xylene, m‐xylene, p‐xylene, ethylbenzene, styrene and isopropylbenzene (cumene). Prior to the determination of the analytes by GC‐MS, the analytes are extracted and enriched using ITEX (In Tube Extraction) or SPDE (Solid Phase Dynamic Extraction). To this end, the urine samples are incubated at 50 °C, the analytes extracted from the gas phase and then the enriched analytes are transferred to the gas chromatograph and analysed using mass spectrometry. Calibration standards are prepared in water and processed in the same way as the samples to be analysed. Deuterated benzene is used as internal standard.The method was extensively validated and the reliability data were confirmed by an independent laboratory, which has established and cross‐checked the whole procedure.
Komponenten von Kühlschmierstoffen, Hydraulikflüssigkeiten und anderen Schmierstoffen [MAK Value Documentation in German language, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: July 2018

Abstract
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has been evaluating components of metal‐working fluids since 1982. A list of these compounds has been published and updated regularly in cooperation with German manufacturers of lubricants. As significant amounts of hydraulic fluids as well as other lubricants can leak into metal‐working fluids during their application, these components are also listed. The list contains about 360 components or component groups; however, it is not complete because there is no obligation to declare all components. This is especially true for metal‐working fluids. CAS numbers and structural formulae as well as the use concentration are given, if known. Compounds which are no longer allowed to be used in metal‐working fluids are mentioned in a “historical” list with the reason for their discontinuation. The reader is advised to check whether an evaluation of the toxicity by the Commission exists for the component of interest.
Faserstäube, anorganisch [MAK Value Documentation in German language, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: July 2018

AbstractThe German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has reevaluated the general aspects of the toxicity of inorganic fibrous dusts. As a first step a documentation on the effects caused by inhalation of inorganic fibrous dusts and the mode of action for their toxicity was set up. For the elucidation of the mechanism of the toxicity and carcinogenicity of fibers, data derived from studies with asbestos fibers were also considered, in order to obtain some knowledge with regard to the biological effects of the other inorganic fibrous dusts. The formation of tumors in the lungs and on serous membranes is mainly the result of inflammatory processes. Chronic inflammation and cell proliferation are caused by the impairment of fiber clearance, whereby inflammation‐promoting cytokines, growth factors, reactive oxygen (ROS) and nitrogen species (RNS) and chlorine radicals are released from the macrophages, inflammatory cells, alveolar cells and mesothelial cells. The generation of these radicals leads to genotoxic effects. In addition intracellular formation of ROS and RNS can be caused by the fibers themselves, as a result of their own surface reactivity. Fibers can stimulate cell receptors and inflammasomes.Each fiber dust group will be evaluated individually and, depending on the data available, may be classified in one of the categories for carcinogens. The Commission has already begun this procedure.
Benzyl alcohol [MAK Value Documentation, 2017]
Authors: Hartwig A. ,   MAK Commission
Published: July 2018

AbstractThe German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated benzyl alcohol [100‐51‐6] to derive a maximum concentration at the workplace (MAK value), considering all toxicological endpoints. Available publications and study reports are described in detail.Benzyl alcohol is irritating to the eyes and the airways. In a 4‐week inhalation study in rats, microscopic lesions in the airways, especially in the lung, occurred at 1072 mg/m3. The NAEC is estimated to be 300 mg/m3, a concentration at which benzyl alcohol can occur as vapour, corresponding to 67 ml/m3. A MAK value of 5 ml/m3has been derived. As local effects are critical, benzyl alcohol is classified in Peak Limitation Category I with an excursion factor of 2.In developmental toxicity studies with benzyl alcohol in mice, foetotoxic effects occurred at 750 mg/kg body weight and day in the presence of marked maternal toxicity. The NOAEL was 550 mg/kg body weight and day; however, teratogenicity was not examined. Benzoic acid is the main metabolite of benzyl alcohol. Considering the developmental toxicity studies with sodium benzoate, the differences between the NOAEL for rats, mice, rabbits and hamsters scaled to an inhalation concentration at the workplace and the MAK value are considered so large that damage to the embryo or foetus is unlikely when the MAK value is observed. Therefore, benzyl alcohol is classified in Pregnancy Risk Group C.Benzyl alcohol is not regarded to be genotoxic or carcinogenic. Sensitization is not expected as benzyl alcohol was not a contact sensitizer in a local lymph node assay and there were no conclusive positive clinical findings of sensitizing effects on the skin. Skin contact is expected to contribute significantly to the systemic toxicity. Therefore, benzyl alcohol is designated with an “H”.Completed: October 08, 2015
Cyclohexylamine [MAK Value Documentation, 2017]
Authors: Hartwig A. ,   MAK Commission
Published: July 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) for cyclohexylamine.

A 4‐hour inhalation study with volunteers showed clear irritation at 10 ml/m
3
, whereas a time‐weighted average concentration of 2 ml/m
3
with peaks of up to 4 ml/m
3
was without impact on sensory irritation parameters and neurobehavioral measurements. The MAK value of 2 ml/m
3
and classification in Peak Limitation Category I has been retained. No irritation was observed up to 4 ml/m
3
; therefore, the excursion factor 2 has been retained as well. As cyclohexylamine is a strong base and 10 ml/m
3
is clearly irritating, a momentary value of 5 ml/m
3
is set.

Completed: April 20, 2016
Azodicarbonamide [MAK Value Documentation, 2017]
Authors: Hartwig A. ,   MAK Commission
Published: July 2018

AbstractThe German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated azodicarbonamide [123‐77‐3] to derive a maximum concentration at the workplace (MAK value), considering all toxicological endpoints. Available publications and unpublished study reports are described in detail. The critical effect is the occurrence of reactions in the airways in exposed workers. In the view of the Commission, the present inhalation studies in animals are not appropriate for the derivation of a MAK value as human airways are probably more sensitive than rodent airways. The workplace investigations show no clear correlation of exposure and frequency of respiratory symptoms. Nevertheless, from the NOAEC of 36 µg/m3for lung function measurements in a small group of injection‐molding workers in the plastics industry, a MAK value of 20 µg/m3 I is established. Due to the incomplete information on the relevant exposure scenario and the uncertainty regarding first occurrence of workplace related symptoms, this value should be considered as preliminary. As local effects are critical, azodicarbonamide is assigned to Peak Limitation Category I and the default excursion factor of 1 is designated. Since developmental toxicity studies are not available, Pregnancy Risk Group D is assigned. There are no carcinogenicity studies and azodicarbonamide is not regarded as germ cell mutagen. Skin contact is not expected to contribute significantly to systemic toxicity. The metabolism of azodicarbonamide and its reactivity do not point to stable protein binding in vivo and therefore, skin or respiratory sensitization is unlikely. Clear‐cut clinical findings or positive results from animal studies on skin sensitization are not available, but the negative results in experimental animals are difficult to evaluate due to the low solubility of the compound. Although azodicarbonamide affects the respiratory tract in several case reports with positive bronchial provocation tests, sensitization by a known mechanism is not adequately verified. Additionally, it appears questionable whether a mono‐causal relationship of respiratory symptoms and azodicarbonamide exposure can really be assumed. In conclusion, a sensitizing effect of azodicarbonamide is not sufficiently proven.Completed: March 22, 2017
Adipic acid [MAK Value Documentation, 2017]
Authors: Hartwig A. ,   MAK Commission
Published: July 2018

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated adipic acid [
124‐04‐9
] to derive a maximum concentration at the workplace (MAK value), considering all toxicity endpoints.

The critical effect is moderate local irritation as shown with the Draize test in the rabbit eye. Available inhalation studies are limited and not suitable to derive a MAK value. Systemic toxicity only occurs at high doses. In a limited oral 2‐year study the body weight of rats was reduced at 2250 mg/kg body weight/day. The resulting systemic NOAEL is 750 mg/kg body weight/day.

After comparing adipic acid with other solid acids, a MAK value of 2 mg adipic acid/m
3
I has been set in analogy to phosphoric acid, which is considered to be the worst‐case.

As the critical effect is local, adipic acid is assigned to Peak Limitation Category I. In analogy to phosphoric acid, a default excursion factor of 2 is set.
Damage to the embryo or foetus is unlikely when the MAK value is observed; thus, the substance is classified in Pregnancy Risk Group C.
Adipic acid is not genotoxic and not carcinogenic. No contact sensitizing effects have been observed. Skin contact is not expected to contribute significantly to systemic toxicity.
Completed: February 24, 2016
N,N‐Dimethylacetamid [MAK Value Documentation in German language, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: July 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,N‐dimethylacetamide [
127‐19‐5
].

N,N‐Dimethylacetamide causes focal cystic degenerations, peliosis, hemosiderin/lipofuscin accumulation and apoptosis in the liver of rats and male mice after chronic whole body inhalation at 100 ml/m
3
. The NOAEC in both species is 25 ml/m
3
. Elastane fibre workers with exposure to N,N‐dimethylacetamide show hepatocellular injury. The data at the workplace is not adequate to derive a MAK value. The former MAK value of 10 ml/m
3
was derived from the NOAEC of 25 ml/m
3
in rats and mice. The MAK value is now lowered to 5 ml/m
3
which takes into account the increased respiratory volume at the workplace because the blood:air partition coefficient of N,N‐dimethylacetamide is > 5 (see List of MAK‐ and BAT Values chapters I b and I c). Since a systemic effect is critical, Peak Limitation Category II is retained. The default excursion factor of 2 is retained as well, as the mechanism of action and the half‐life in blood are not known.

In rats and rabbits, N,N‐dimethylacetamide induces via inhalation at 450 or 570 ml/m
3
, respectively, and above, specific teratogenic effects, cardiovascular and skeletal malformations. The NOAEC for teratogenicity in rats and rabbits are 300 or 200 ml/m
3
, respectively. The lowest NOAEC for developmental toxicity in rats and rabbits are 100 and 57 ml/m
3
, respectively. Considering the increased respiratory volume at the workplace, the NOAEC for rabbits is only six times the MAK value. However, taking into account that the NOAEC could be higher than 57 ml/m
3
and the observed effects, reduced fetal body weight and increased incidence of skeletal variations, are considered marginal, the difference to the MAK value is sufficient. Therefore, damage to the embryo or foetus is unlikely when the MAK value is observed and N,N‐dimethylacetamide remains assigned to Pregnancy Risk Group C. Skin contact should be avoided as N,N‐dimethylacetamide is designated with an “H”.
4‐
tert
‐Octylphenol [MAK Value Documentation, 2017]
Authors: Hartwig A. ,   MAK Commission
Published: July 2018

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated the developmental toxicity of 4‐tert‐octylphenol. In 2015, the maximum concentration at the workplace (MAK value) for 4‐tert‐octylphenol was set at 0.5 ml /m
3
(4.3 mg/m
3
).

In a screening study in rats with gavage administration, litter size and body weight of the progeny at postnatal day 4 was reduced at 500 mg/kg body weight and day, accompanied by maternal toxicity. A NOAEL for foetotoxicity of 250 mg/kg body weight and day was derived, corresponding to a concentration of 28.5 ml/m
3
at the workplace. In a 2‐generation feeding study in rats, foetotoxicity was not observed until postnatal day 13. At 111–369 mg/kg body weight and day, vaginal opening or preputial separation of the F2 progeny was delayed. A NOAEL of 10.9–32.6 mg/kg body weight and day was derived for postnatal developmental toxicity in rats, corresponding to 1.2–3.7 ml/m
3
. Because adequate studies of prenatal developmental toxicity over the complete period of organogenesis are lacking, data are not sufficient for classification and 4‐tert‐octylphenol is assigned to Pregnancy Risk Group D.

Completed: October 7, 2015
2‐Aminoethanol [MAK Value Documentation, 2016]
Authors: Hartwig A. ,   MAK Commission
Published: July 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 2‐aminoethanol [141‐43‐5], 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.
Completed: March 23, 2015