Propoxur [114-26-1] is used as an insecticide and acaricide. It is no longer approved in the European Union. The previous MAK Value documentation and addendum do not reflect the current data situation of the substance. The MAK Commissiondecided that a new evaluation is not of high priority. The MAK value and the other classifications are therefore suspended and the substance is listed in the Section II c of the List of MAK and BAT Values for substances no longer evaluated.
Carbaryl [63-25-2] is used as an insecticide but is no longer approved in the European Union. The previous MAK value documentation and addendum do not reflect the current data situation of the substance. The MAK Commissiondecided that a new evaluation is not of high priority. The MAK value and the other classifications are therefore suspended and the substance is listed in the Section II c of the List of MAK and BAT Values for substances no longer evaluated.
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) has re-evaluated the occupational exposure limit value (maximum concentration at the workplace, MAK value) of sulfur hexafluoride [2551-62-4] considering all toxicological end points. Relevant studies were identified from a literature search and also unpublished study reports were used. This addendum evaluates only pure sulfur hexafluoride. Reaction products that are highly toxic for humans can form during its use as an insulating gas in high voltage switchgear. Under normal conditions, the reactivity of sulfur hexafluoride gas is comparable to that of helium or nitrogen. Therefore, systemic or local effects were not observed in studies carried out in compliance with OECD test guidelines with exposure of rats to the gas at concentrations up to 20 052 ml/m3 for 13 weeks. Acute exposure to 550 000 ml/m3 (55%) induced sleepiness and analgesia in humans. On the basis of the NOAEC of 20 052 ml/m3, a maximum concentration at the workplace (MAK value) of 5000 ml/m3 has been set. As significant effects were not observed in humans up to 390 000 ml/m3, Peak Limitation Category II and the excursion factor of 8 have been retained. Sulfur hexafluoride showed no genotoxic potential. Carcinogenicity studies have not been carried out. Sulfur hexafluoride was not teratogenic in a developmental toxicity study in concentrations up to 19 100 ml/m3, but led to a transient delay in foetal development. After consideration of all data as well as the fact that sulfur hexafluoride is inert under normal conditions, it has been assigned to Pregnancy Risk Group C. There are no data for the sensitizing potential of sulfur hexafluoride. Skin contact is not expected to contribute significantly to systemic toxicity.
The German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) revised the definition of the peak limitation categories to emphasize that the time required for an effect to develop is decisive for the categorization.
The working group "Analyses in Biological Materials" of the German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area developed and verified the presented biomonitoring method. The aim of this method is the selective and sensitive quantitation of glyphosate (N-phosphonomethylglycine) and its only metabolite, aminomethylphosphonic acid (AMPA), in urine. Samples undergo solid-phase extraction prior to liquid chromatography-tandem mass spectrometry using glyphosate-2-13C,15N and AMPA-13C,15N,D2 as internal standards. Calibration is carried out with urine from persons with no known exposure to glyphosate and AMPA. The procedure has been comprehensively validated and the reliability data have been confirmed by replication and verification of the procedure in a second, independent laboratory. Good precision data with standard deviations of 1.3-9.8% for glyphosate and 1.9-5.4% for AMPA, as well as good accuracy data with mean relative recoveries in the range of 91-102% for glyphosate and 100-106% for AMPA, show that the method provides reliable and accurate analytical results. The method is both selective and sensitive, and the limits of quantitation of 0.1 μg/l for glyphosate and 0.5 μg/l for AMPA are sufficient to determine occupational exposure as well as some of the background exposure in the general population.
The working group "Analyses in Biological Materials" of the German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) developed and verified the presented biomonitoring method. The aim of this method is the selective and sensitive quantitation of deoxynivalenol (DON; free DON plus glucuronides not otherwise specified) and its metabolite deepoxydeoxynivalenol (DOM‑1) in urine. After enzymatic hydrolysis of the urine sample and purification of the analytes on an immunoaffinity column, followed by preconcentration of the eluates under a stream of nitrogen, determination is carried out by high-performance liquid chromatography-tandem mass spectrometry (LC‑MS/MS). Calibration is performed with comparative standards prepared in urine and treated analogously to the samples to be analysed. DON is quantified using an internal standard (ISTD; 13C15‑DON), whereas DOM‑1 is quantified without the use of an ISTD. Good precision data with standard deviations below 9% for DON and below 6% for DOM‑1, as well as good accuracy data with mean relative recoveries in the range of 93-114% for DON and 97-103% for DOM‑1, show that the method provides reliable and accurate analytical results. The method is both selective and sensitive, and has a limit of quantitation of 0.179 μg/l for DON and of 0.26 μg/l for DOM‑1. Due to rapid renal excretion, the method is primarily suitable for analysing acute exposure which occurred only hours prior to sampling.
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) has summarized and re-evaluated the data for 2-mercaptobenzothiazole [149-30-4] considering all toxicological end points. Relevant studies were identified from a literature search and also unpublished study reports were used. The critical effect in humans and animals is sensitization. Data for chronic inhalation exposure are not available. The most sensitive systemic end point observed in a 13-week gavage study in rats was an increase in relative liver weights. The female rat was found to be the most sensitive species. A LOAEL of 188 mg/kg body weight and day was derived, which corresponds to a concentration in the air of 27.5 mg/m3. No conclusions can be drawn for systemic toxicity from a 2-year gavage study in rats because of the high spontaneous incidence of different pathological effects observed in the control group. As there are no data for inhalation exposure to the poorly soluble substance, a particle effect in the lungs cannot be excluded. Additionally, epidemiological and animal data suggest a carcinogenic potential. As a result, the present maximum concentration at the workplace (MAK value) has been suspended. 2-Mercaptobenzothiazole is not mutagenic in bacteria. Mutagenic and clastogenic effects in mammalian cells are observed only at high, mostly cytotoxic concentrations. In vivo data do not provide evidence of genotoxic effects in soma cells or male germ cells, even at concentrations that cause systemic toxicity. Overall, the data from epidemiological studies are not sufficient to draw definite conclusions about whether 2-mercaptobenzothiazole is a human carcinogen. A carcinogenicity study with gavage administration in rats observed adenomas of the pancreas, preputial glands and pituitary gland as well as fibromas and phaeochromocytomas. However, the increased incidence of tumours is neither clear evidence for nor against a carcinogenic potential because of a number of uncertainties inherent in the study. Thus, 2-mercaptobenzothiazole remains classified in Carcinogen Category 3 for suspected carcinogens. Dermal absorption is not expected to contribute significantly to systemic toxicity. 2-Mercaptobenzothiaziole is a known contact allergen. Therefore, the "Sh" designation has been retained. There are no data for respiratory sensitization.
The working group "Air Analyses" of the German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) developed and verified the presented analytical method. It is used to determine the levels of carbon disulfide [75-15-0] that occur in the workplace air. The method covers concentrations in the range from one tenth to twice the current German occupational exposure limit value (OELV) of 30 mg/m3. It is also suitable for monitoring compliance with the MAK value of 16 mg/m3 and the short-term exposure limit (STEL; excursion factor 2). Samples are collected by drawing a defined volume of air through a sampling tube filled with activated charcoal using a flow regulated pump at a maximal volumetric flow rate of 0.333 l/min. Exposure during the shift is measured with a sampling period of 2 hours (up to 8 hours, depending on the volumetric flow) and the short-term exposure with a period of 15 minutes. The carbon disulfide adsorbed to the activated charcoal is extracted with toluene and analysed by headspace gas chromatography with flame photometric detection. The quantitative determination is based on multiple-point calibrations with an internal standard. A relative limit of quantification (LOQ) of 0.5 mg/m3 is obtained for an air sample volume of 40 litres and an application volume of 18 ml. As the relative LOQ for a sample volume of 5 litres is below 5 mg/m3, the STEL can also be measured. The recovery, which has to be considered for the calculation of the results, is approx. 70% and the expanded uncertainty is below 22% for a sampling period of 2 hours and below 23% for a period of 15 minutes.
The working group "Analyses in Biological Materials" of the German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) developed and verified the presented biomonitoring method. The aim of this method is the selective and sensitive quantitation of aflatoxins (aflatoxins B1, B2, G1, G2, M1), ochratoxin A (OTA), free ochratoxin α (OTα), gliotoxin (GT), citrinin (CIT) and dihydrocitrinone (DH‑CIT) in urine. Sample preparation comprises enrichment and purification of the analytes by solid-phase extraction using OASIS HLB cartridges. Calibration is performed with comparative standards prepared in pooled urine and treated analogously to the samples to be analysed. The aflatoxins, OTA, CIT, and DH‑CIT are quantified using isotope-labelled internal standards (ISTDs), whereas OTα and GT are quantified without an ISTD. Determination is carried out by high-performance liquid chromatography-tandem mass spectrometry (LC‑MS/MS). The method provides reliable and accurate analytical results, as shown by the good precision data with standard deviations below 9% for the aflatoxins, OTα, GT and CIT, below 13% for OTA, and below 20% for DH‑CIT. Good accuracy data were obtained with mean relative recoveries in the range of 93-107% for the aflatoxins, OTα, GT and CIT, in the range of 83-103% for OTA, and in the range of 81-108% for DH‑CIT. The method is both selective and sensitive, and has quantitation limits in the range of 0.013-0.022 μg/l for the aflatoxins and OTA and a quantitation limit of 1.0 μg/l for OTα, 1.5 μg/l for GT, 0.0075 μg/l for CIT, and 0.01 μg/l for DH‑CIT.
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re-evaluated the occupational exposure limit value (maximum concentration at the workplace, MAK value) of chloroform [67-66-3] considering all toxicological end points. Relevant studies were identified from a literature search and also unpublished study reports were used. There are no human data to derive a MAK value. In 1999, a NOAEC of 5 ml/m3 was determined in a 13-week inhalation study based on the increased cell proliferation in the kidneys and liver of rats and mice. A MAK value of 0.5 ml/m3 was established on the basis of these findings. This value has now been confirmed also after taking the increased respiratory volume at the workplace into account (see List of MAK and BAT values, Section I b and I c). In a new 2-year inhalation study, respiratory metaplasia of the olfactory epithelium and thickening of the bone in the nasal cavity was observed at the lowest chloroform concentrations tested of 10 ml/m3 in rats and 5 ml/m3 in mice. Toxicity in the olfactory epithelium can be a local as well as a systemic effect. After considering the two possible modes of action and the increased respiratory volume at the workplace, the MAK value derived from effects in the nose would correspond to 1 ml/m3. The present MAK value of 0.5 ml/m3 thus protects also against effects in the nose. As the critical effect is systemic, chloroform remains classified in Peak Limitation Category II with an excursion factor of 2. A developmental toxicity study with inhalation exposure of rats determined a NOAEC of 10 ml/m3. Additionally, malformations in rats observed in another developmental toxicity study at 100 ml/m3 are suggestive of teratogenicity. The NOAEC in this study was 30 ml/m3. Furthermore, the NOAEL for developmental toxicity after gavage administration was 50 mg/kg body weight and day in rats and 35 mg/kg body weight and day in rabbits. Overall, the margins between the concentrations at the workplace calculated to be without effects and the MAK value are sufficient. Therefore, as damage to the embryo or foetus is unlikely to occur if the MAK value is not exceeded, chloro-form remains assigned to Pregnancy Risk Group C. Chloroform causes tumours of the thyroid gland in rats and liver tumours in mice as well as renal tumours in both species. However, chloroform is not expected to induce these tumours via a genotoxic mode of action and has thus been classified in Carcinogen Category 4. There are no data for sensitizing effects in humans and no reliable positive results from animal and in vitro studies. Data for sensitization of the respiratory tract are not available. Uptake via the skin can contribute significantly to systemic toxicity. Therefore, chloroform remains designated with an "H".
The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) has re-evaluated the occupational exposure limit value (maximum concentration at the workplace, MAK value) of synthetic amorphous silica [7631-86-9] considering all toxicological end points. Relevant studies were identified from a literature search and also unpublished study reports were used. The critical effects are the inflammatory effects in the lungs. A NOAEC cannot be established for these effects. In a 90-day study, one form of nanoscale synthetic amorphous silica induced inflammatory effects in the lungs of rats at the lowest concentration tested of 0.5 mg/m3 and above. Based on this LOAEC, a maximum concentration at the workplace (MAK value) of 0.02 mg/m3 has been derived for the respirable fraction and the substance has been classified in Peak Limitation Category II with an excursion factor of 8. The NOAEL for developmental or perinatal toxicity in rats was 1000 mg/kg body weight and day after gavage; this corresponds to concentrations of 1750 or 2450 mg/m3 at the workplace. As the margins between these values and the MAK value are sufficiently large, synthetic amorphous silica has been assigned to Pregnancy Risk Group C. Studies in animals did not show a carcinogenic potential of synthetic amorphous silica, which is relevant for humans. Synthetic colloidal amorphous silica is not mutagenic in vitro or in vivo. The DNA strand breaks and micronuclei that were observed in vitro were not confirmed by the results in vivo. Synthetic colloidal amorphous silica is not absorbed through the skin in toxicologically relevant amounts and there is no evidence that it induces contact sensitization.
The German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) re-evaluated the data for cadmium [7440-43-9] to derive a biological guidance value (BLW) for its systemic non-carcinogenic end points. Relevant studies were identified from a literature search. Exposure to cadmium dust can cause nasal inflammation and anosmia, bronchitis and pneumonia, which are recognised as local effects. Tubular kidney damage was identified as the most sensitive end point of systemic toxicity, which results in excretion of low molecular weight proteins such as α1 and β2-microglobulins and retinol binding protein (RBP) in the urine. Recent studies on workers occupationally exposed to cadmium revealed a NOEL (no observed effect level) and a BMDL5 (benchmark dose lower limit) for tubular proteinuria at approximately 3 to 5 µg cadmium/g creatinine in ever-smokers, whereas this threshold is higher in never-smokers. Therefore, a BLW of 2 µg cadmium/g creatinine is set for cadmium in urine.
The working group "Air Analyses" of the German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) developed and verified the presented analytical method. It is used to determine the levels of L-(+)-tartaric acid [87-69-4] and D-(-)-tartaric acid [147-71-7] (occurring as inhalable particles) individually or as a racemic mixture [133-37-9] that occur in the workplace air. The method covers concentrations in the range from one tenth up to twice the current Occupational Exposure Limit Value (OELV) of 2 mg/m3 (inhalable fraction). The method is also suitable for measuring the short-term exposure limit (STEL; excursion factor 2) for the inhalable fraction. Samples are collected by drawing a defined volume of air through a glass fibre filter, which is inserted in a GSP sampling system, using a flow regulated pump at a volumetric flow rate of 3.5 l/min. Exposure during the shift is measured with a sampling period of 2 hours and the short-term exposure with a period of 15 minutes. Tartaric acid deposited on the glass fibre filter is extracted with the IC eluent and analysed by ion chromatography using conductivity detection. The quantitative determination is based on multiple-point calibrations with external standards. A relative limit of quantification (LOQ) of 0.00043 mg/m3 is obtained for an air sample volume of 420 litres. As the LOQ for a sample volume of 52,5 litres is 0.0034 mg/m3, the STEL can also be measured. The recovery is 100-104% and the expanded uncertainty is 19-21% for a 2-hour sampling and 20-21% for a 15-minute sampling.
The working group "Analyses in Biological Materials" of the German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) developed and verified this biomonitoring method for the measurement of six specific metabolites of the plasticiser tri‑(2‑ethylhexyl) trimellitate (TEHTM) in urine. Specifically, this method determines two monoester isomers as primary hydrolysis products of TEHTM, 1‑mono-(2‑ethylhexyl) trimellitate (1‑MEHTM) and 2‑mono-(2‑ethylhexyl) trimellitate (2‑MEHTM), as well as the oxidatively formed secondary derivatives, namely 1‑mono-(2‑ethyl-5‑hydroxyhexyl) trimellitate (5OH‑1‑MEHTM), 2‑mono-(2‑ethyl-5‑hydroxyhexyl) trimellitate (5OH‑2‑MEHTM), 1‑mono-(2‑ethyl-5‑carboxypentyl) trimellitate (5cx‑1‑MEPTM), and 2‑mono-(2‑ethyl-5‑carboxypentyl) trimellitate (5cx‑2‑MEPTM). Determination is carried out after enzymatic hydrolysis of the urine sample as well as enrichment of the analytes by online SPE. Via integrated, automatic column-switching, the analytes are transferred onto the analytical column in backflush mode, separated by liquid chromatography, and quantified by tandem mass spectrometry. Calibration is performed using calibration standards prepared in pooled urine and processed analogously to the samples to be analysed. The following isotope-labelled substances are added to the urine samples as internal standards: D5‑1‑MEHTM, D5‑2‑MEHTM, D5‑5OH‑1‑MEHTM, D5‑5cx‑1‑MEPTM, and D5‑5cx‑2‑MEPTM. The method provides reliable and accurate analytical results, as shown by the good precision data with standard deviations no greater than 8%. Good accuracy data were obtained with mean relative recoveries in the range of 97-109%. The method is both selective and sensitive, and provides quantitation limits in the range of 0.04-0.12 μg/l.
The working group "Air Analyses" of the German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) developed and verified the presented analytical method. It is used to determine the levels of 4-methyl-3-penten-2-one [141-79-7] that occur in the workplace air. The method covers concentrations in the range from one tenth up to twice the current occupational exposure limit value (OELV) of 8.1 mg/m3. The method is also suitable for verifying the short-term exposure limit (STEL; excursion factor 2). Samples are collected by drawing a defined volume of air through a sampling tube filled with silica gel using a flow regulated pump at a volumetric flow rate of 0.5 l/min. Exposure during the shift is measured with a sampling period of 2 hours and the short-term exposure with a period of 15 minutes. The 4-methyl-3-penten-2-one adsorbed to the silica gel is extracted by liquid extraction with methanol and analysed by high-performance liquid chromatography using diode array detection. The quantitative determination is based on multiple-point calibrations with external standards. A relative limit of quantification (LOQ) of 0.06 mg/m3 is obtained for an air sample volume of 60 litres. As the LOQ for a sample volume of 30 litres is 0.03 mg/m3, the STEL can also be measured. The recovery is approx. 100% and the expanded uncertainty is 14% for a sampling period of 2 hours and below 16% for a period of 15 minutes.
The German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) has re-evaluated the data for benzoic acid [65-85-0] to derive an occupational exposure limit value (maximum concentration at the workplace, MAK value) for the inhalable fraction. The critical effects are severe irritation in the eyes and lung toxicity. For this reason, irritation is assumed to occur also in the upper respiratory tract. Inhalation studies investigating the inhalable fraction of benzoic acid in humans or animals are not available. Therefore, data for similarly strong acids are used for the evaluation of the local effects on the respiratory tract. In analogy to the MAK value derived for phosphoric acid, a MAK value of 2 mg/m3 I (inhalable fraction) has been established. This represents the "worst case" for benzoic acid due to its weaker acidity. Peak Limitation Category I with an excursion factor of 2 has been set in analogy to the classification made for phosphoric acid. There are no valid prenatal developmental studies of benzoic acid available. Benzoates are classified in Pregnancy Risk Group C at the MAK value of 10 mg/m3. As the benzoate anion is responsible for the systemic effects of benzoic acid and the acid has a lower MAK value, Pregnancy Risk Group C is valid also for the inhalable fraction of benzoic acid at the MAK value of 2 mg/m3. Dermal uptake is expected to contribute to systemic toxicity and benzoic acid remains designated with "H" (for substances which can be absorbed through the skin in toxicologically relevant amounts).
