bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addendum to 2‐Butoxyethanol (Ethylene glycol monobutyl ether) [BAT Value Documentation, 2016]
Authors: Göen T. , Rettenmeier A.W. , Drexler H. , Hartwig A. ,   MAK Commission
Published: October 2018

Abstract

In 2015 the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the biological tolerance value at the work place (BAT value) for 2‐butoxyethanol (ethylene glycol monobutyl ether) [CAS No.
111‐76‐2
], considering butoxyacetic acid in urine to characterise the internal exposure. The main systemic adverse effects of 2‐butoxyethanol are on the haematopoietic system (haemolytic effects), followed by possible teratogenic and testicular effects. 2‐Butoxyethanol was classified in category 4 for carcinogenic substances, which enables the evaluation of a health based exposure limit. It can easily pass through the skin, so biological monitoring is necessary for a valid individual risk assessment. A considerable part of the absorbed 2‐butoxyethanol is excreted in form of the glutamine conjugate of butoxyacetic acid,i.e. N‐butoxyacetyl glutamine. The relative amount of this conjugate in the total excretion of butoxyacetic acid varied considerably intra‐ and inter‐individually depending on the exposure levels and possibly on enzyme polymorphisms. On average half of the total butoxyacetic acid is excreted in the form of the glutamine conjugate (factor 2). Various studies indicate that at high exposure levels the capacity of the conjugate reaction is exceeded and lower conjugated amounts appear. Due to the high variability of conjugated amounts of the butoxyacetic acid and the limitation of conjugated amounts at high exposure levels the previous BAT value for free 2‐butoxyacetic acid is converted with a factor of 1.5 to the total amounts of 2‐butoxyacetic acid. Additionally, the impact of diuresis is considered by the relation to the creatinine concentration. Therefore, a BAT value for the total butoxyacetic acid excretion of 150 mg butoxyacetic acid (after hydrolysis)/g creatinine was established. Sampling should be performed at the end of exposure and shift, respectively, after several previous shifts. This BAT value applies also for combined exposure to 2‐butoxyethanol and 2‐butoxyethylacetate.
Addendum to 2‐Butoxyethylacetate (Ethylene glycol monobutyl ether acetate) [BAT Value Documentation, 2016]
Authors: Göen T. , Rettenmeier A.W. , Drexler H. , Hartwig A. ,   MAK Commission
Published: October 2018

Abstract

In 2015 the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the biological tolerance value at the work place (BAT value) for 2‐butoxyethylacetate (ethylene glycol monobutyl ether acetate) [CAS No.
112‐07‐2
], considering butoxyacetic acid in urine to characterise the internal exposure.

Due to the high variability of conjugated amounts of the butoxyacetic acid and the limitation of conjugated amounts at high exposure levels the previous BAT value for free 2‐butoxyacetic acid is converted with a factor of 1.5. Additionally, the impact of diuresis is considered by the relation to the creatinine concentration. Therefore, a BAT value for the total butoxyacetic acid excretion of 150 mg butoxyacetic acid (after hydrolysis)/g creatinine was established. The sampling time is at the end of exposure/shift after several previous shifts.
As the effects of the two glycol ethers 2‐butoxyethyl acetate and 2‐butoxyethanol are largely the same in the human organism, the BAT value applies to both and for combined exposure. The two substances were discussed together in the addendum of 2‐butoxyethanol.
Addendum to Arsenic and Inorganic Arsenic Compounds (with the exception of arsine) [BAT Value Documentation, 2016]
Authors: Ochsmann E. , Göen T. , Michalke B. , Weistenhöfer W. , Klotz K. , Drexler H. , 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 “Biologischer Arbeitsstoff‐Referenzwert” (BAR) as well as the exposure equivalents for carcinogenic substances (EKA) for arsenic and inorganic arsenic compounds (with the exception of arsenic hydride). Available publications are described in detail.The quantification of the various arsenic species is essential to understand the hazardous potential of the arsenic compounds which differ highly in their toxicity. Therefore the BAR for the sum of different arsenic species is no longer valid. Considering published data from occupational not exposed persons, new BAR for the arsenic species of 0.5 µg/l urine for arsenic (+III), 0.5 µg/l urine for arsenic (+V), 2 µg/l urine for monomethylarsonic acid (MMA) and 10 µg/l urine for dimethylarsinic acid (DMA) were evaluated. The differentiation of arsenic species now allows for the estimation of the individual health risks taking into account special influences like seafood consumption. Sampling time is at the end of exposure or the end of the working shift and after long term exposure at the end of the working shift after several shifts.Data of a correlation of arsenic in the air and the sum of the arsenic species in urine were considered for the evaluation of the exposure equivalents for carcinogenic substances. This correlation is in good accordance with the EKA correlation of arsenic trioxide, which is based on former studies in which also the urinary concentrations of the sum of As (+III), As (+V), MMA and DMA were measured. Sampling time is at the end of exposure or the end of the working shift and after long term exposure at the end of the working shift after several shifts.
Addendum to Dichloromethane [BAT Value Documentation, 2016]
Authors: Bolt H.M. , Weistenhöfer W. , Drexler H. , Hartwig A. ,   MAK Commission
Published: October 2018

Abstract

In 2015 the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated dichloromethane [CAS No.
75‐09‐2
], considering dichloromethane in blood to characterize the internal exposure.

In a chamber study, 14 non‐smokers were exposed to different concentrations of dichloromethane. After exposure to the present MAK value of 50 ml dichloromethane/m³ without physical activity, a concentration of 0.3 mg dichloromethane/l blood was measured. Considering an increased intake due to elevated breathing volume during work, the exposure to 50 ml dichloromethane/m³ results in a blood concentration of 0.5 mg/l. Taking into account this study and the EKA correlation of 2001, a BAT value of 500 µg dichloromethane/l blood was evaluated. Sampling time is straight after exposure.
Lead and its compounds – Determination of δ‐aminolevulinic acid in urine by HPLC with fluorescence detection [Biomonitoring Methods, 2018]
Authors: Göen T. , Weißflog L. , Blaszkewicz M. , Baumhoer G. , Schettgen T. , Dewes P. , 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 method described hereinafter permits the determination ofδ‐aminolevulinic acid (ALA) in urine as a biological marker of effect to assess exposure to lead. An indicator of such exposure is the increased urinary excretion of ALA caused by lead‐induced inhibition of the enzymeδ‐aminolevulinic acid dehydratase. The determination of ALA in urine is based on a condensation reaction of ALA with formaldehyde and acetylacetone yielding a pyrrolizine derivate, which can be sensitively detected using fluorescence detection. 6‐Amino‐5‐oxohexanoic acid is used as an internal standard. Calibration standards are prepared in pooled urine and processed in the same way as the samples to be analysed.The method was extensively validated and the reliability data were confirmed by two independent laboratories, which have established and cross‐checked the whole procedure.
Arsenic and arsenic compounds – Determination of arsenic species (As(III), As(V), monomethylarsonic acid, dimethylarsinic acid and arsenobetaine) in urine by HPLC‐ICP‐MS [Biomonitoring Methods, 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.
Ethylbenzene [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 ethylbenzene [
100‐41‐4
].

Critical effect is the liver toxicity, which is observed as centrilobular hypertrophy and liver weight increase resulting from the induction of enzymes and proliferation of hepatocytes, in long‐term studies with rats and mice. In an oral 13‐week study a NOAEL of 75 mg/kg bodyweight and day for rats and a NOAEC of 75 ml/m
3
for liver cell proliferation in mice were established. Based on this data, a MAK value of 20 ml/m
3
had been set. This value is now reaffirmed even considering the increased respiratory volume at the workplace for the cell proliferation study (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 and since it is not clear whether the effects are due to the metabolites or ethylbenzene the default factor of 2 is confirmed.

The NOAEC for developmental toxicity in rats is 500 ml/m³ 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 ethylbenzene remains in Pregnancy Risk Group C.
Crotonaldehyde [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 germ cell mutagenicity and carcinogenicity of crotonaldehyde [
4170‐30‐3
,
123‐73‐9
].

Crotonaldehyde is a highly reactive mutagenic and cytotoxic compound without metabolic activation.
An oral carcinogenicity study in male rats, with the liver as the only organ examined, provides at most only an indication of a carcinogenic potential. Crotonaldehyde remains assigned to Carcinogen Category 3B because of the still limited database.
Despite some methodical deficiencies, new in vivo studies with positive results for bone marrow and spermatocyte chromosomal aberrations as well as dominant lethal mutations in mice lead to a reclassification in Category 3A for Germ Cell Mutagens.
1‐Ethoxy‐2‐propyl acetate [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‐propyl acetate [
54839‐24‐6
].

1‐Ethoxy‐2‐propyl acetate is weakly irritating to the skin and eyes of rabbits. The critical effect is CNS depression after repeated inhalative exposure with a NOAEC of 100 ml/m
3
in a 28‐day study with rats. Based on this, the maximum concentration at the work place (MAK value) for 1‐ethoxy‐2‐propyl acetate is set at 20 ml/m
3
(120 mg/m
3
). This value also protects against possible irritation, as local effects are not observed up to 1200 ml/m
3
in the 28‐day rat inhalation study.

Since the critical effect of 1‐ethoxy‐2‐propyl acetate is systemic, Peak Limitation Category II is retained. There are still no specific toxicokinetic data available, so that the default excursion factor of 2 is also retained.
There are no data on reproduction toxicity with 1‐ethoxy‐2‐propyl acetate available. 1‐Ethoxy‐2‐propyl acetate remains assigned to Pregnancy Risk Group C in analogy to 1‐ethoxy‐2‐propanol. On the basis of data with 1‐ethoxy‐2‐propanol and other glycol ether acetates, skin contact is expected to contribute significantly to systemic toxicity and 1‐ethoxy‐2‐propyl acetate is designated with “H”.
N,N
‐Dimethylethylamine [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 evaluated a momentary value of N,N‐dimethylethylamine [
598‐56‐1
].

Critical effects are vision disturbances and irritation of the eyes and the respiratory tract in exposed workers and volunteers. In a study in a foundry, these effects were caused by peak exposures of about 10 ml/m
3
. By analogy with cyclohexylamine, a momentary value of 5 ml/m
3
which must not be exceeded at any time is also established for N,N‐dimethylethylamine.
Ethanol [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) and the Pregnancy Risk Group of ethanol [
64‐17‐5
].

Ethanol is produced endogenously. Uptake of greater amounts depresses the central nervous system and is carcinogenic especially for the liver. The former MAK value of 500 ml/m
3
was derived from a study in exposed subjects at rest. It was calculated that at 500 ml/m
3
the AUC (product of the blood ethanol concentration and time of exposure) was similar to the standard deviation of the lifetime AUC of endogenous ethanol. At 50 W physical activity, which corresponds to a respiratory volume of 10 m
3
per day, the blood concentration of ethanol is about twice as high as compared with that of subjects in rest. Therefore, taking into account the increased respiratory volume at the workplace (see List of MAK‐ and BAT Values, Sections I b and I c), the MAK value is now lowered to 200 ml/m
3
. Since a systemic effect is critical, Peak Limitation Category II is retained. As irritation was observed at 1900 ml/m
3
, the excursion factor is now set to 4.

After oral uptake, ethanol causes developmental toxicity. The lowest reported concentration of ethanol in the blood in pregnant rats causing effects in the F1‐generation was 300 mg/l with a NOAEC of 70 mg/l. In an inhalation study, the NOAEC for developmental neurotoxicity in rats was 10 000 ml/m
3
which according to a PBPK model corresponds to a concentration of ethanol in the blood of about 65 mg/l. These NOAEC are more than 10 times as high as the ethanol concentration of 1 mg/l in humans exposed to 200 ml/m
3
even considering the increased respiratory volume at the workplace. Therefore, ethanol remains assigned to Pregnancy Risk Group C.
1,3‐Dioxolane [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 1,3‐dioxolane [
646‐06‐0
].

1,3‐Dioxolane causes a reduction in white blood cell count and in relative spleen weight at 1000 ml/m
3
and above in female rats after 13 weeks whole body inhalation. The NOAEC is 298 ml/m
3
. As the percentage of white blood cell count reduction is the same after four and 13 weeks, no decrease of the NOAEC after chronic exposure is expected. The former MAK value of 100 ml/m
3
was derived from the NOAEC. The MAK value is now lowered to 50 ml/m
3
which takes into account the increased respiratory volume at the workplace because the blood:air partition coefficient of 1,3‐dioxolane 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. The default excursion factor of 2 is retained as well, as no half‐life in blood is known.

In a prenatal toxicity study in rats with gavage application, 1,3‐dioxolane results in reduced fetal body weights and gross external, soft tissue and skeletal malformations or variations at 1000 mg/kg body weight and day. The NOAEL for developmental toxicity is 500 mg/kg body weight and day. After toxicokinetic scaling this dose corresponds to a concentration of 875 mg/m
3
(285 ml/m
3
) at the workplace. The difference to the MAK value of 50 ml/m
3
is not sufficient. Therefore, the assignment to Pregnancy Risk Group B, for substances, for which damage to the embryo or foetus must be expected even when the MAK value is observed, is confirmed.
Distillates (petroleum), hydrotreated light [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 hydrotreated light petroleum distillates [
64742‐47‐8
].

Critical effect of the vapour phase of hydrotreated light petroleum distillates is CNS depression in exposed subjects. A MAK value of 50 ml/m
3
had been set taking into account the increased respiratory volume at the workplace as compared with volunteers at rest (see List of MAK and BAT Values, Sections I b and I c). For the aerosol phase the critical effect is considered to be the lung toxicity seen in rats and mice. A MAK value of 5 mg/m
3
had been set as the respirable fraction (R). This value is now reaffirmed even considering the increased respiratory volume at the workplace.

Hydrotreated light petroleum distillates had been classified in Pregnancy Risk Group C because the NOAEC for developmental toxicity in rats is 400 ml/m
3
, the highest concentration tested. There is no new data on developmental toxicity. This classification is retained even considering the increased respiratory volume at the workplace.
Benzoic acid and alkali benzoates [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 benzoic acid and alkali benzoates [65‐85‐0;532‐32‐1;582‐25‐2] to derive a maximum concentration at the workplace (MAK value), considering all toxicity endpoints. Available study reports and publications are described in detail.Based on the NOAEC for lung toxicity of 12.6 mg/m3in a 4‐week inhalation study in rats, a MAK value of 0.5 mg/m3for the strongly irritating benzoic acid has been derived. Alkali benzoates are only slightly irritating. In consideration of the systemic NOAEC of 250 mg/m3in another 4‐week inhalation study in rats exposed to benzoic acid, a MAK value for alkali benzoates of 10 mg/m3(inhalable fraction), calculated as benzoate, has been derived. Benzoic acid and alkali benzoates are assigned to Peak Limitation Category II, because systemic effects are critical, and excursion factors of 2 for alkali benzoates and of 4 for benzoic acid are set.In a developmental toxicity study with sodium benzoate in rats, foetotoxic effects were observed at 1850 mg/kg body weight and day. The NOAEL was 1340 mg/kg body weight and day. In mice, rabbits and hamsters, no developmental toxicity from sodium benzoate was detected in the foetuses of dams treated with up to 175, 250 or 300 mg/kg body weight and day, respectively. 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, benzoic acid and alkali benzoates are classified in Pregnancy Risk Group C.Benzoic acid and alkali benzoates are not regarded as genotoxic. Long‐term studies with sodium benzoate in rats and mice were of limited validity and do not point to a carcinogenic potential. Sensitization is not expected as benzoic acid and alkali benzoates are not contact sensitizers in animal studies. Immediate contact reactions observed in animals and humans are based on a non‐immunologic mechanism. Skin contact is expected to contribute significantly to the systemic toxicity. Therefore, benzoic acid and alkali benzoates are designated with an “H”.
Polyalphaolefins [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 polyalphaolefins [e.g.
68649‐11‐6
].

Polyalphaolefins are synthetic mineral oils. For refined mineral oils, the critical effect is lung toxicity which is observed as microgranulomas in two long‐term studies with rats and dogs at a respirable aerosol concentration of 100 mg/m
3
with a NOAEC of 5 mg/m
3
. With these studies, a MAK value of 5 mg/m
3
had been set as the respirable fraction (R) for polyalphaolefins. This value is now reaffirmed even considering the increased respiratory volume at the workplace (see List of MAK and BAT Values, Sections I b and I c).

Polyalphaolefins had been classified in Pregnancy Risk Group C because of studies with oral and dermal application in rats. Additionally, now an inhalation study with white mineral oil and a NOAEC for developmental toxicity of 1000 mg/m
3
in rats is used to confirm the assignment of polyalphaolefins to Pregnancy Risk Group C even considering the increased respiratory volume at the workplace.