bluuebunny/crossref_metadata_2025 huggingface dataset:
Addendum zu Lindan (γ‐1,2,3,4,5,6‐Hexachlorcyclohexan) [BAT value documentation in German language, 2019]
Authors: Brinkmann B. , Drexler H. , Hartwig A. ,   MAK Commission
Published: November 2019

In 2018, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated lindane. The critical toxic effects of lindane are immunotoxic and immunomodulating effects. After inhalation exposure a NOAEC of 0.6 mg/m
3
(rat) and 1 mg/m
3
(mouse) for histological changes of the spleen, thymus and bone marrow and a NOAEL of 0.45 mg/kg body weight for rats and 2 mg/kg body weight for mice for immunological effects can be derived. Exposure to the MAK value of 0.1 mg/m
3
results in a daily intake of 0.014 mg/kg body weight (100% inhalation absorption, 70 kg body weight and 10 m
3
respiratory volume) for humans excluding skin contact. In this low concentration range, an inhibition of immunological responses is not likely. So the MAK value of 0.1 mg/m
3
was confirmed. No data are available to correlate the concentration of lindane in the air with its concentration in serum. There are no indications that immunotoxic effects occur at a serum concentration of 25 µg lindane/l, therefore, the BAT value of 25 µg lindane/l is confirmed. The NOAEL for developmental toxicity after oral application is 10 mg/kg body weight and day corresponds to 900 µg/L serum concentration. The distance of the NOAEL for developmental toxicity relating to serum concentration in rats is 40‐fold of the BAT‐value. Therefore, lindane is assigned to Pregnancy Risk Group C.
Addendum zu Methanol [BAT value documentation in German language, 2019]
Authors: Kreis P. , Brinkmann B. , Drexler H. , Hartwig A. ,   MAK Commission
Published: November 2019

In 2018, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has lowered the maximum concentration at the workplace (MAK value) to 100 mL methanol/m
3
. The BAT value was correlated to the MAK value. Therefore, the BAT value has to be re‐evaluated.

After 8‐hour exposure of test persons to 100 mL methanol/m
3
with physical activity, a concentration of 15 mg methanol/L urine was measured. This is in line with the results of a field study in which a methanol concentration of approximately 100 mL/m
3
corresponded to around 20 mg methanol/L urine.

Therefore, the BAT value has now been set to 15 mg methanol/L urine. Sampling time is at the end of exposure or the end of the working shift, for long‐term exposure at the end of the shift after several shifts.
Addendum zu Pentachlorphenol [BAT value documentation in German language, 2019]
Authors: Walter D. , Drexler H. , Hartwig A. ,   MAK Commission
Published: November 2019

In 2018, the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the correlation (EKA) between inhalational exposure to pentachlorophenol and urinary pentachlorophenol excretion. The re‐evaluation of the available literature led to the conclusion that the present data are limited and all available studies show limitations regarding to air exposure assessment and characterisation of possible dermal exposure of the workers. Thus, the EKA correlation was withdrawn.
Tabakspezifische Nitrosamine – Bestimmung von
N
‐Nitrosoanabasin,
N
‐Nitrosoanatabin,
N
‐Nitrosonornikotin und 4‐(Methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol in Urin mittels LC‐MS/MS [Biomonitoring methods in German language, 2019]
Authors: Scherer G. , Gilch G. , Köhler D. , Völkel W. , Göen T. , Hartwig A. ,   MAK Commission
Published: November 2019

The working group “Analyses in Biological Materials” of the Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area developed and validated the presented biomonitoring method.

This analytical method permits the determination of tobacco‐specific nitrosamines (TSNA) in urine using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). The parameters in question are
N
‐nitrosoanabasine (NAB),
N
‐nitrosoanatabine (NAT),
N
‐nitrosonornicotine (NNN) and 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol (NNAL). NNAL is a metabolite of 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK). Due to its sensitivity, this method is suitable for the detection of the aforementioned analytes in the urine of smokers. NNAL can also be quantified in the urine of passive smokers.

The analytes NAB, NAT, NNN and NNAL are present in urine in both free and glucuronidated forms. For the determination of the total TSNA level in urine, the glucuronides are cleaved by enzymatic hydrolysis and then the analytes are isolated and concentrated using solid phase extraction (SPE). Two sorbent materials are used for sample preparation via SPE, first a material based on molecularly imprinted polymers and then a mixed‐mode cation exchange polymer. Analysis is performed by LC‐MS/MS. Deuterated internal standards are used for calibration. Calibration standards are prepared in pooled urine obtained from non‐smokers and are processed in the same way as the samples to be analysed.
Fibrous Dusts, inorganic [MAK value documentation, 2017]
Authors: Hartwig A. ,   MAK Commission
Published: November 2019

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated 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 fibres, data derived from studies with asbestos fibres were also considered, in order to obtain some knowledge with regard to the biological effects of the other inorganic fibrous dusts. The formation of tumours 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 fibre 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 fibres themselves, as a result of their own surface reactivity. Fibres can stimulate cell receptors and inflammasomes.

Each fibre 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.
Chlorobenzene [MAK value documentation, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: November 2019

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated chlorobenzene [
108‐90‐7
] to derive a maximum concentration at the workplace (MAK value), considering all toxicity endpoints. Adverse effects are a depression of the central nervous system in humans and histological alterations in liver and kidney in rats. A 2 generation reproduction study with chlorobenzene vapour in Sprague‐Dawley rats resulted in a NOAEC of 50 ml/m
3
. Based on this NOAEC, a MAK value of 5 ml/m
3
is derived. This value is supported by a study with healthy volunteers at rest, who showed no neurotoxic or chemosensory effects at a NAEC of 5.9 ml/m
3
, which takes the increased respiratory volume at the work place into account. As systemic effects are critical, the substance remains assigned to Peak Limitation Category II and the excursion factor of 2 is confirmed. Chlorobenzene caused a statistically significantly increased incidence of neoplastic nodules in the liver of male F344 rats in a carcinogenicity study at the highest dose of 120 mg/kg body weight and day. As chlorobenzene is genotoxic only at high doses given intraperitoneally, and female rats and mice did not show any tumours in this study, it remains regarded neither as a carcinogen nor as a germ cell mutagen. From a synopsis of all data, the classification of chlorobenzene in Pregnancy Risk Group C is maintained. Chlorobenzene did not lead to contact sensitization in mice and guinea pigs.
1‐Octanol [MAK Value Documentation, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: November 2019

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated 1‐octanol [111‐87‐5] to derive a maximum concentration at the workplace (MAK value), considering all toxicity endpoints. Irritation is the critical effect. Neither appropriate data in humans nor inhalation or oral studies of 1‐octanol with animals are available for derivation of a MAK value. An 8‐week feeding study in Wistar rats with the structurally related 1‐dodecanol resulted in a NOAEL of 100 mg/kg body weight and day for systemic toxicity. Additionally, a NOAEL of 125 mg/kg body weight and day for 2‐ethylhexanol was obtained in a 90‐day oral study in rats. Therefore, a NOAEL of approximately 100 mg/kg body weight and day was assumed for 1‐octanol. From this NOAEL, the concentration in workplace air was calculated to be 245 mg 1‐octanol/m3according to the Commission's procedure. However, 1‐octanol can cause irritation. The RD50values of 50 ml/m3and 45 ml/m3for 1‐octanol and 2‐ethylhexanol, respectively, suggest a similar irritating potency. Therefore, the MAK value for 1‐octanol was set at 10 ml/m3by analogy with 2‐ethylhexanol. As local effects are critical, the substance is assigned to Peak Limitation Category I and an excursion factor of 1 has been established by analogy with 2‐ethylhexanol. From a synopsis of all data, 1‐octanol is classified in Pregnancy Risk Group C. 1‐Octanol is not mutagenic in bacteria. There are no long‐term studies with 1‐octanol. Skin absorption does not contribute significantly to systemic toxicity and 1‐octanol is not expected to lead to contact sensitization.
Diisotridecyl phthalate, ditridecyl phthalate [MAK value documentation, 2019]
Authors: Hartwig A. ,   MAK Commission
Published: November 2019

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated diisotridecyl phthalate (a mixture of various isomers) [
27253‐26‐5
] and ditridecyl phthalate [
119‐06‐2
] considering all toxicological endpoints. Available publications and unpublished study reports are described in detail. The critical effect is centrilobular hepatocyte hypertrophy following prolonged oral exposure of rats. There are signs of peroxisome proliferating activity which has also been observed with other phthalates like di(2‐ethylhexyl) phthalate. Diisotridecyl phthalate and ditridecyl phthalate are not genotoxic. No carcinogenicity study has been performed, but due to the similarity to di(2‐ethylhexyl) phthalate, liver carcinogenicity cannot be excluded. Therefore, diisotridecyl phthalate and ditridecyl phthalate are classified in Category 3B for suspected carcinogens.

Both phthalates cause at most minimal irritation to the eyes and skin of rabbits. As no inhalation study has been performed, possible long‐term effects on larynx and nasal goblet cells, the targets of other phthalates, cannot be evaluated. Therefore, no maximum concentration at the workplace (MAK value) can be derived.

Ditridecyl phthalate does not cause developmental toxicity in rats up to an oral dose of 100 mg/kg body weight and day, the highest dose tested. Skin contact is not expected to contribute significantly to systemic toxicity. Limited data show no sensitization.
Tetrachloroethylene [MAK Value Documentation, 2017]
Authors: Hartwig A. ,   MAK Commission
Published: November 2019

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated tetrachloroethylene [
127‐18‐4
] to derive a maximum concentration at the workplace (MAK value), considering all toxicity endpoints. Available study reports and publications are described in detail.

Results from human studies do not point to a genotoxic potential of tetrachloroethylene. In vitro and in vivo studies in mammalian cells do not show a distinct genotoxic potential. From epidemiologic and animal studies there is concern that tetrachloroethylene could be carcinogenic for humans; therefore, tetrachloroethylene has been classified in Carcinogen Category 3B. However, since carcinogenic effects are judged to be not predominantly caused by genotoxic mechanisms, a MAK value can be derived.

Neurotoxicity is considered the most sensitive endpoint for tetrachloroethylene. In volunteers, repeated daily 4‐hour inhalation exposure caused small but significant effects on visual evoked potentials. The NOAEC was 10 ml/m
3
, but as only weak effects were observed at the LOAEC of 50 ml/m
3
, 20 ml/m
3
is regarded as the NAEC. As a doubling of uptake is expected under workplace conditions, a MAK value of 10 ml/m
3
has been set. As the critical effect is systemic, tetrachloroethylene is assigned to Peak Limitation Category II. The default excursion factor of 2 is set as the half‐life in the central nervous system is unknown.

There is limited evidence suggesting that women working in a dry‐cleaner have an increased risk of spontaneous abortion. But the limited validity of the studies is not sufficient to prove a causal relationship. In developmental toxicity studies, NOAECs for developmental toxicity of 65 and 217 ml/m
3
in rats, 500 ml/m
3
in rabbits, and a LOAEC of 217 ml/m
3
in mice were obtained. The NOAEC for behavioural toxicity in the offspring of treated rats was 100 ml/m
3
. The differences between these NOAECs as well as the LOAEC and the MAK value are considered so large that damage to the embryo or foetus is unlikely when the MAK value is observed. Therefore, tetrachloroethylene is classified in Pregnancy Risk Group C.

Sensitization is not expected due to results of animal studies and experience in humans. Skin contact is expected to contribute significantly to the systemic toxicity of tetrachloroethylene. Therefore, designation with an “H” is confirmed.
N,N
‐Dimethylacetamide [MAK Value Documentation, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: November 2019

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, 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 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”.
Ethyl acetate [MAK Value Documentation, 2017]
Authors: Hartwig A. ,   MAK Commission
Published: November 2019

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 acetate [141‐78‐6] of 400 ml/m
3
, considering all toxicological endpoints. Available publications and unpublished study reports are described in detail. The critical effect of ethyl acetate is irritation of eye and nose in humans and of the olfactory mucosa in rats; in addition, neurotoxic effects are observed in animals at high concentrations. In three studies with volunteers exposed to 400 ml ethyl acetate/m
3
, slight irritation in the nose, throat and eye were observed, however the physiological parameters blinking frequency and nasal resistance, both indicators of irritation were not affected. Overall, 400 ml ethyl acetate/m
3
is not an unequivocal NOAEC. Accordingly, the MAK value has been lowered to 200 ml/m
3
. As local effects are critical, the assignment to Peak Limitation Category I and the excursion factor of 2 are confirmed. Taking into consideration the data for the metabolites acetic acid and ethanol, damage to the embryo and fetus is unlikely when the MAK value for ethyl acetate is observed. Therefore, ethyl acetate remains classified in Pregnancy Risk Group C. Ethyl acetate is not genotoxic and there are no carcinogenicity studies. Skin contact is not expected to contribute significantly to systemic toxicity. Skin sensitization is not expected from the limited data. There are no data concerning the potential for respiratory sensitization.
2‐Propoxyethanol (2‐(Propyloxy)ethanol) [MAK Value Documentation, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: November 2019

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated 2‐(propyloxy)ethanol (2‐propoxyethanol) [
2807‐30‐9
] considering all toxicological end points.

2‐(Propyloxy)ethanol is a haemolytic and irritant glycol ether, similar to the homologous 2‐butoxyethanol. The haemolytic activity for both compounds is mediated by the corresponding alkoxy acid and is lower in human erythrocytes than in rat erythrocytes in vitro. The critical effect is the irritation seen in subchronic studies in rats at the lowest concentration tested of 100 ml/m
3
. A NOAEC was not obtained. For 2‐butoxyethanol the NOAEC for nasal effects in rats was 31 ml/m
3
. Therefore, by analogy with the better investigated 2‐butoxyethanol, the maximum concentration at the workplace (MAK value) of 2‐(propyloxy)ethanol is lowered to 10 ml/m
3
. This limit also protects from systemic toxicity. The assignment to Peak Limitation Category I with an excursion factor of 2 is retained.

A prenatal toxicity study in rats was re‐evaluated by the Commission and the NOAEC for developmental toxicity of 400 ml/m
3
was confirmed. In rabbits, the NOAEC for developmental toxicity is 500 ml/m
3
. Even after considering the increased respiratory volume at the workplace the differences of both NOAECs to the MAK value are sufficient. Therefore, damage to the embryo or foetus is unlikely when the MAK value is observed and 2‐(propyloxy)ethanol remains assigned to Pregnancy Risk Group C.

2‐(Propyloxy)ethanol is not genotoxic in vitro. In vivo studies as well as carcinogenicity studies are not available.

Percutaneous absorption can contribute significantly to systemic toxicity and 2‐(propyloxy)ethanol remains designated with an “H” notation. Results in animal studies do not point to a sensitization potential.
trans‐1,3,3,3‐Tetrafluoropropene [MAK Value Documentation, 2019]
Authors: Hartwig A. ,   MAK Commission
Published: November 2019

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 trans‐1,3,3,3‐tetrafluoropropene [
29118‐24‐9
]. As the blood:air partition coefficient of trans‐1,3,3,3‐tetrafluoropropene is < 5, the increased respiratory volume at the workplace (see List of MAK and BAT Values, Sections I b and I c) does not have to be taken into account for the derivation of the MAK value. Even after extrapolation of 6‐hour exposure in the animal experiment to 8‐hour exposure at the workplace, the MAK value for trans‐1,3,3,3‐tetrafluoropropene of 1000 ml/m
3
can be retained.
tert
‐Butyl acetate [MAK Value Documentation, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: November 2019

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 for
tert
‐butyl acetate [
540‐88‐5
].

Critical effects are transient acute neurotoxic symptoms which are observed in a 90‐day‐study with mice with a NOAEC of 100 ml/m
3
. From this concentration the former MAK value of 50 ml/m
3
was derived. It is now lowered to 20 ml/m
3
taking into account the increased respiratory volume at the workplace because the blood:air partition coefficient of
tert
‐butyl acetate is > 5 (see List of MAK and BAT Values, Sections I b and I c). This value also provides protection from irritation. Since a systemic effect is critical, Peak Limitation Category II is retained. The excursion factor of 2 is set in spite of the short half‐life of
tert
‐butyl acetate in blood as it is an acute effect for which an adaptation during subchronic exposure has been noticed. Therefore, peaks of exposure will not enhance the effect at chronic exposure. Furthermore, since the incidences after 90 days at 400 ml/m
3
are low, the true NAEC might have been higher than 100 ml/m
3
.

tert
‐Butyl acetate had been classified in Pregnancy Risk Group C because the NOAEC for fetotoxicity is 1600 ml/m
3
in a screening study in rats and taking into consideration the data for the metabolite
tert
‐butyl alcohol. There is no new data on developmental toxicity. This classification is retained even considering the increased respiratory volume at the workplace.
Isopropyl alcohol [MAK Value Documentation, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: November 2019

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 isopropyl alcohol [
67‐63‐0
].

In carcinogenicity studies no tumours were observed in rats and mice up to 5000 ml/m
3
. From the LOAEC in rats and mice of 2500 ml/m
3
where narcotic effects were observed, a MAK value of 200 ml/m
3
is derived also considering the increased respiratory volume at the workplace because the blood:air partition coefficient of isopropyl alcohol is > 5 (see List of MAK and BAT Values, Sections I b and I c). Therefore, the MAK value of 200 ml/m
3
is confirmed. At this concentration, no irritation is expected in humans based on the limited data in humans and animals.

Since a systemic effect is critical, Peak Limitation Category II is retained for isopropyl alcohol. Due to the half‐life of up to 2 hours in rats, the excursion factor of 2 is confirmed.

In developmental toxicity studies, isopropyl alcohol does not result in teratogenicity but in fetotoxicity at maternally toxic doses in rats and rabbits. According to a PBPK model and considering the increased respiratory volume at the workplace, the NOAEL of 600 mg/kg body weight in rats is scaled to a concentration of 1000 ml/m
3
. There is no PBPK model for rabbits but due to the similar NOAEL for developmental toxicity in rabbits the same concentration is supposed. Because fetotoxicity was only observed at maternally toxic doses, the difference of the NOAEC for fetotoxicity and the MAK value is sufficient so that isopropyl alcohol remains assigned to Pregnancy Risk Group C.
Ethylamine [MAK Value Documentation, 2019]
Authors: Hartwig A. ,   MAK Commission
Published: November 2019

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated ethylamine [
75‐04‐7
], considering all toxicological endpoints.

The critical effect is irritation of the nasal epithelium of rats with a NOAEC of 100 ml/m
3
in a 24‐week inhalation study. The maximum concentration at the workplace (MAK value) for ethylamine is derived by using additional data of the structurally related diethylamine. For diethylamine a MAK value of 2 ml/m
3
was derived based on a two‐year study in rats with a NOAEC of 16 ml/m
3
for irritation of the nasal epithelium and a study in humans with a LOAEC of 10 ml/m
3
for sensory irritation. As the inhalation toxicity of ethylamine is lower than that of diethylamine, the previous MAK value for ethylamine of 5 ml/m
3
is retained. As the local effect is critical, ethylamine remains classified in Peak Limitation Category I. The excursion factor of 2 and the momentary value (concentration which must not be exceeded at any time) of 10 ml/m
3
are retained.

There are no developmental toxicity studies and ethylamine remains assigned to Pregnancy Risk Group D. Ethylamine is not genotoxic in vitro, data on genotoxicity in vivo and carcinogenicity are lacking. There is, however, no corresponding structural alert. There are no data on sensitization. According to skin absorption models, percutaneous absorption does not contribute significantly to systemic toxicity.
2,3,3,3‐Tetrafluoropropene [MAK Value Documentation, 2019]
Authors: Hartwig A. ,   MAK Commission
Published: November 2019

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 2,3,3,3‐tetrafluoropropene [
754‐12‐1
]. As the blood:air partition coefficient of 2,3,3,3‐tetrafluoropropene is < 5, the increased respiratory volume at the workplace (see List of MAK and BAT Values, Sections I b and I c) does not have to be taken into account for the derivation of the MAK value. Moreover, the extrapolation of 6‐hour exposure in the animal experiment to 8‐hour exposure at the workplace does not need to be applied because the effect is much more dependent on the concentration than on time. The MAK value for 2,3,3,3‐tetrafluoropropene of 200 ml/m
3
can therefore be retained.
Benzyl butyl phthalate [MAK Value Documentation, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: November 2019

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated benzyl butyl phthalate [85‐68‐7] to derive a maximum concentration at the workplace (MAK value), considering all toxicological endpoints. Available publications and unpublished study reports are described in detail. Critical effect is the toxicity to kidneys and liver. In higher doses benzyl butyl phthalate acts adversely to male reproductive organs, fertility and fetal development. The NOAEC of 218 mg/m3derived from a 13‐week inhalation study in rats is used to set a MAK value of 20 mg/m3for the respirable fraction (R), the MAK value is supported by the long‐term feeding studies in rats and mice.

Since a systemic effect is critical, Peak Limitation Category II is assigned. The default excursion factor of 2 is set as no half‐life in blood is known.

In prenatal toxicity studies in rats at 450 mg/kg body weight and day and above an increased number of resorptions and at 750 mg/kg body weight and day increased mortality and teratogenicity occurred, with a NOAEL of 350 mg/kg body weight and day. From a 2‐generation study in rats a NOAEL for fetotoxicity of 100 mg/kg body weight and day was derived. In a prenatal study in mice the LOAEL for increased resorptions and malformations was 910 mg/kg body weight and day with a NOAEL of 182 mg/kg body weight and day. The NOAELs can be scaled to concentrations of 613 mg/m3(rat, prenatal), 182 mg/m3(mice, prenatal) and 245 mg/m3(rat, pre‐ and postnatal), respectively, at the workplace. Thus, damage to the embryo or foetus is unlikely when the MAK value is observed, and benzyl butyl phthalate is classified in Pregnancy Risk Group C.

Available in vitro and in vivo data predominantly show no genotoxic effects. A contribution of cytotoxic effects for some positive test results cannot be excluded. A dominant lethal test with subcutaneous administration to rats was negative. Therefore, the substance is not regarded as a germ cell mutagen.

No increased tumour incidence was observed in chronic feeding studies in mice. In F344 rats at high doses an increased incidence of mononuclear cell leukemia is observed, which was within the range of the historical control. Furthermore, in F344 rats incidences of adenomas (pancreas tumours, adrenal phaeochromocytomas, urinary bladder tumours), but not of carcinomas are increased. The adenoma incidences were mainly within the range of historical controls. A carcinogenic effect in humans, therefore, is unlikely.

Skin contact is not expected to contribute significantly to systemic toxicity.

Data in humans and limited data in animals do not show a skin sensitizing potential.
Investigating honesty‐humility and impulsivity as predictors of aggression in children and youth
Authors: MacDonell Elliott T. , Willoughby Teena
Published: November 2019

Among adult and adolescent populations, the personality trait of honesty‐humility (HH) has been linked to aggression. For example, adults low in HH have been found to exhibit higher levels of workplace delinquency and revenge motivation, and adolescent low in HH are more likely to bully others. However, there is a paucity of research examining this relationship in children and youth, and how these relationships develop over time. The current study addressed these gaps in the literature by assessing whether HH and impulsivity are independently associated with aggression in children Grades 3 through 8 (N = 1201). Using data from the two waves of a longitudinal project, autoregressive crossed‐lagged path analysis was used to examine the bidirectional relationships between HH, impulsivity, and aggression over a 1‐year period. Results revealed significant bidirectional relationships between HH and aggression, such that lower scores of HH at Time 1 were associated with higher scores of aggression at Time 2 and vice versa. Similarly, higher scores of impulsivity at Time 1 were associated with higher scores of aggression at Time 2 and vice versa. In addition, these relationships were strongest in boys and at higher ages. Consistent with research in other populations, these results indicate that low HH and high impulsivity are linked to aggression in children and youth. Further, our results demonstrate that HH and impulsivity bidirectionally impact aggression as one age, suggesting a need for early intervention.
Commissioning and performance evaluation of RadCalc for the Elekta unity MRI‐linac
Authors: Graves Stephen A. , Snyder Jeffrey E. , Boczkowski Amanda , St‐Aubin Joël , Wang Dongxu , Yaddanapudi Sridhar , Hyer Daniel E.
Published: November 2019

Recent availability of MRI‐guided linear accelerators has introduced a number of clinical challenges, particularly in the context of online plan adaptation. Paramount among these is verification of plan quality prior to patient treatment. Currently, there are no commercial products available for monitor unit verification that fully support the newly FDA cleared Elekta Unity 1.5 T MRI‐linac. In this work, we investigate the accuracy and precision of RadCalc for this purpose, which is a software package that uses a Clarkson integration algorithm for point dose calculation. To this end, 18 IMRT patient plans (186 individual beams) were created and used for RadCalc point dose calculations. In comparison with the primary treatment planning system (Monaco), mean point dose deviations of 0.0 ± 1.0% (n = 18) and 1.7 ± 12.4% (n = 186) were obtained on a per‐plan and per‐beam basis, respectively. The dose plane comparison functionality within RadCalc was found to be highly inaccurate, however, modest improvements could be made by artificially shifting jaws and multi leaf collimator positions to account for the dosimetric shift due to the magnetic field (67.3% vs 96.5% mean 5%/5 mm gamma pass rate).
Entangled Azobenzene‐Containing Polymers with Photoinduced Reversible Solid‐to‐Liquid Transitions for Healable and Reprocessable Photoactuators
Authors: Chen Mingsen , Yao Bingjian , Kappl Michael , Liu Senyang , Yuan Jinying , Berger Rüdiger , Zhang Faai , Butt Hans‐Jürgen , Liu Yuanli , Wu Si
Published: November 2019

Photoactuators based on liquid crystal elastomers or networks are smart materials that show photoinduced motions. However, their crosslinked networks make their repair or reprocessing difficult. Here, a healable and reprocessable photoactuator is fabricated using entangled high‐molecular‐weight azobenzene‐containing polymers (azopolymers) that are non‐crosslinked. A series of linear liquid crystal azopolymers with different molecular weights are synthesized. The low‐molecular‐weight azopolymers (5–53 kg mol−1) cannot form freestanding photoactuators because their polymer chains lack entanglements, which makes them hard and brittle. In contrast, flexible and stretchable actuators are fabricated using high‐molecular‐weight azopolymers (80–100 kg mol−1) that exhibit good processability because of the polymer chain entanglements. The azopolymer photoactuators show photoinduced bending based on photoinduced trans–cis isomerization of the azopolymers on the irradiated side. The experiments show not only photoinduced phase transitions or changes in the order parameters but also photoinduced solid‐to‐liquid transition of the azopolymers resulting in shape changes and mechanical responses. Thus, photoinduced solid‐to‐liquid transition is a new mechanism for the design of photoactuators. Moreover, the azopolymer photoactuators are healable and reprocessable via solution processing or light irradiation. Healability and reprocessability prolong lifetimes of photoactuators are important for materials reusage and recycling, and represent a new strategy for the preparation of smart materials.
Ternary Polymer Solar Cells Facilitating Improved Efficiency and Stability
Authors: Dong Yingying , Zou Yan , Yuan Jianyu , Yang Hang , Wu Yue , Cui Chaohua , Li Yongfang
Published: November 2019

The use of a ternary active layer offers a promising approach to enhance the power conversion efficiency (PCE) of polymer solar cells (PSCs) via simply incorporating a third component. Here, a ternary PSC with improved efficiency and stability facilitated by a new small molecule IBC‐F is demonstrated. Even though the PBDB‐T:IBC‐F‐based device gives an extremely low PCE of only 0.21%, a remarkable PCE of 15.06% can be realized in the ternary device based on PBDB‐T:IE4F‐S:IBC‐F with 20% IBC‐F, which is ≈10% greater than that (PCE = 13.70%) of the control binary device based on PBDB‐T:IE4F‐S. The improvement in the device performance of the ternary PSC is mainly attributed to the enhancement of fill factor, which is due to the improved charge dissociation and extraction, suppressed bimolecular and trap‐assisted recombination, longer charge‐carrier lifetime, and enhanced intermolecular interactions for preferential face‐on orientation. Additionally, the ternary device with 20% IBC‐F shows better thermal and photoinduced stability over the control binary device. This work provides a new angle to develop the third components for building ternary PSCs with enhanced photovoltaic performance and stability for practical applications.
Superconductivity of Topological Surface States and Strong Proximity Effect in Sn1−xPbxTe–Pb Heterostructures
Authors: Yang Hao , Li Yao‐Yi , Liu Teng‐Teng , Xue Huan‐Yi , Guan Dan‐Dan , Wang Shi‐Yong , Zheng Hao , Liu Can‐Hua , Fu Liang , Jia Jin‐Feng
Published: November 2019

Superconducting topological crystalline insulators are expected to form a new type of topological superconductors to host Majorana zero modes under the protection of lattice symmetries. The bulk superconductivity of topological crystalline insulators can be induced through chemical doping and the proximity effect. However, only conventional full gaps are observed, so the existence of topological superconductivity in topological crystalline insulators is still controversial. Here, the successful fabrication of atomically flat lateral and vertical Sn1−xPbxTe–Pb heterostructures by molecular beam epitaxy is reported. The superconductivity of the Sn1−xPbxTe–Pb heterostructures can be directly investigated by scanning tunneling spectroscopy. Unconventional peak–dip–hump gap features and fourfold symmetric quasiparticle interference patterns taken at the zero energy in the superconducting gap support the presence of the topological superconductivity in superconducting Sn1−xPbxTe. Strong superconducting proximity effect and easy preparation of various constructions between Sn1−xPbxTe and Pb make the heterostructures to be a promising candidate for topological superconducting devices to detect and manipulate Majorana zero modes in the future.
Bright Deep Blue TADF OLEDs: The Role of Triphenylphosphine Oxide in NPB/TPBi:PPh3O Exciplex Emission
Authors: Hippola Chamika , Danilovic Dusan , Bhattacharjee Ujjal , Perez‐Bolivar Cesar , Sachinthani K. A. Niradha , Nelson Toby L. , Anzenbacher Pavel , Petrich Jacob W. , Shinar Ruth , Shinar Joseph
Published: November 2019

Very bright (≈14 000 cd m−2) deep blue exciplex organic light emitting diodes (OLEDs) peaking at ≈435 nm, where the photopic response is ≈0.033, and with CIE color coordinates (0.1525, 0.0820), are described. The OLED properties are interestingly linked to PPh3O (triphenylphosphine oxide) and attributes of the emitting layer (EML) comprising NPB interfacing host:guest TPBi:PPh3O 5:1 weight ratio. A neat PPh3O layer that is central for device performance follows the EML (NPB/TPBi:PPh3O 5:1/PPh3O). The bright electroluminescence originates from NPB/TPBi:PPh3O exciplexes involving triplets via thermally activated delayed fluorescence, as evident from the strong quenching of the photoluminescence (PL) by oxygen and interestingly, the monomolecular emission process. The transient PL decay times of a NPB/TPBi:PPh3O 5:1/PPh3O film are 43 ns in air versus 136, 610, and weak ≈2000 ns in N2. For comparison, the respective PL decay times of films of NPB:TPBi are 16 ns in air versus 131 and 600 ns in N2, and of NPB:PPh3O they are 29 ns in air versus 56, 483, and weak ≈2000 ns in N2. It is suspected that slow emitting states are associated with a PPh3O aggregate interacting with NPB.
Two‐Dimensional GeP‐Based Broad‐Band Optical Switches and Photodetectors
Authors: Yu Tongtong , Nie Hongkun , Wang Shanpeng , Zhang Baitao , Zhao Shuqi , Wang Ziming , Qiao Jie , Han Bing , He Jingliang , Tao Xutang
Published: November 2019

Germanium phosphide (GeP), a typical 2D group IV–V semiconductor, has attracted significant attention due to the advantages of higher thermodynamic stability than black phosphorus (BP), widely tunable bandgap, high carrier mobility, and in‐plane anisotropy. However, its photonic and optoelectronic properties have not been extensively explored so far. Herein, large size and high‐quality GeP single bulk crystal is successfully grown by flux method and stripped into 2D nanosheets with liquid phase exfoliation (LPE) and spin‐coating methods. The broad‐band photonic and optoelectronic properties of 2D GeP nanosheets are systematically investigated. First principles calculations are performed to verify its widely tunable bandgap from 0.43 eV for bulk to 1.58 eV for monolayer. The ultrafast carrier dynamic and non‐linear optical responses are investigated by non‐degenerated pump‐probe and open‐aperture Z‐scan methods, and the results indicate that 2D GeP nanosheets can present excellent broad‐band saturable absorption properties. Furthermore, the 2D GeP nanosheets‐based broad‐band saturable absorbers (SAs) and photodetectors are demonstrated. The results indicate that 2D GeP nanosheets can be used as excellent broad‐band optical modulators and detectors, which will arouse a considerable interest in exploring novel group IV–V 2D materials for broad‐band photonic and optoelectronic applications.
Threshold Switching in Single Metal‐Oxide Nanobelt Devices Emulating an Artificial Nociceptor
Authors: Xiao Ming , Shen Daozhi , Futscher Moritz H. , Ehrler Bruno , Musselman Kevin P. , Duley Walter W. , Zhou Y. Norman
Published: November 2019

Electronic devices that can simulate the dynamics of neurotransmission in the human body are of great interest for the development of artificial intelligence in modern information technology. An artificial nociceptor realized by a single metal‐oxide nanobelt device with a unique capacitive‐coupled threshold switching behavior is demonstrated. Via thermal admittance spectroscopy and temperature‐dependent sweeping study, the properties of the nanobelt devices are determined by Schottky emission at low bias and by defect‐assisted quantum tunneling at high bias subject to a threshold voltage. The low activation energy associated with dynamic electron trapping gives rise to a voltage‐dependent volatile threshold switching behavior. This threshold switching behavior allows the emulation of several characteristic features of a nociceptor, a critical type of sensory neuron in the human body, including “threshold,” “relaxation,” “no adaptation,” “allodynia,” and “hyperalgesia” behaviors, essential for the realization of electronic sensory receptors that detect noxious stimuli and signal rapid warning to the central nervous system. One‐dimensional metal oxide nanobelt devices of this type yield multifunctional nociceptor performance that is fundamental for applications in artificial intelligence systems, representing a key step in the realization of neural integrated devices via a bottom‐up approach.
Regulating Pore Structure of Hierarchical Porous Waste Cork‐Derived Hard Carbon Anode for Enhanced Na Storage Performance
Authors: Li Yuqi , Lu Yaxiang , Meng Qingshi , Jensen Anders C. S. , Zhang Qiangqiang , Zhang Qinghua , Tong Yuxin , Qi Yuruo , Gu Lin , Titirici Maria‐Magdalena , Hu Yong‐Sheng
Published: November 2019

Porous structure design is generally considered to be a reliable strategy to boost ion transport and provide active sites for disordered carbon anodes of Na‐ion batteries (NIBs). Herein, a type of waste cork‐derived hard carbon material (CC) is reported for efficient Na storage via tuning the pore species. Benefiting from the natural holey texture of this renewable precursor, CCs deliver a novel hierarchical porous structure. The effective skeletal density test combined with small angle X‐ray scattering analysis (SAXS) is used to obtain the closed pore information. Based on a detailed correlation analysis between pore information and the electrochemical performance of CCs, improving pyrolysis temperature to reduce open pores (related to initial capacity loss) and increase closed pores (related to plateau capacity) endows an optimal CC with a high specific capacity of ≈360 mAh g−1 in half‐cells and a high energy density of 230 Wh kg−1 in full‐cells with a capacity retention of 71% after 2000 cycles at 2C rate. The bioinspired high temperature pore‐closing strategy and the new insights about the pore structure–performance relationship provide a rational guide for designing porous carbon anode of NIBs with tailored pore species and high Na storage capacity.
Autopolyploidy alters nodule‐level interactions in the legume–rhizobium mutualism
Authors: Forrester Nicole J. , Ashman Tia‐Lynn
Published: November 2019

Premise

Polyploidy is a major genetic driver of ecological and evolutionary processes in plants, yet its effects on plant interactions with mutualistic microbes remain unresolved. The legume–rhizobium symbiosis regulates global nutrient cycles and plays a role in the diversification of legume species. In this mutualism, rhizobia bacteria fix nitrogen in exchange for carbon provided by legume hosts. This exchange occurs inside root nodules, which house bacterial cells and represent the interface of legume–rhizobium interactions. Although polyploidy may directly impact the legume–rhizobium mutualism, no studies have explored how it alters the internal structure of nodules.

Methods

We created synthetic autotetraploids using Medicago sativa subsp. caerulea. Neotetraploid plants and their diploid progenitors were singly inoculated with two strains of rhizobia, Sinorhizobium meliloti and S. medicae. Confocal microscopy was used to quantify internal traits of nodules produced by diploid and neotetraploid plants.

Results

Autotetraploid plants produced larger nodules with larger nitrogen fixation zones than diploids for both strains of rhizobia, although the significance of these differences was limited by power. Neotetraploid M. sativa subsp. caerulea plants also produced symbiosomes that were significantly larger, nearly twice the size, than those present in diploids.

Conclusions

This study sheds light on how polyploidy directly affects a plant–bacterium mutualism and uncovers novel mechanisms. Changes in plant–microbe interactions that directly result from polyploidy likely contribute to the increased ability of polyploid legumes to establish in diverse environments.
Community turnover by composition and climatic affinity across scales in an alpine system
Authors: Smithers Brian V. , Oldfather Meagan F. , Koontz Michael J. , Bishop Jim , Bishop Catie , Nachlinger Jan , Sheth Seema N.
Published: November 2019

Premise

Examining community turnover across climate gradients at multiple scales is vital to understanding biogeographic response to climate change. This approach is especially important for alpine plants in which the relative roles of topographic complexity and nonclimatic or stochastic factors vary across spatial scales.

Methods

We examined the structure of alpine plant communities across elevation gradients in the White Mountains, California. Using community climatic niche means (CCNMs) and measures of community dissimilarity, we explored the relation between community composition and elevation gradients at three scales: the mountain range, individual peaks, and within elevation contours.

Results

At the mountain range scale, community turnover and CCNMs showed strongly significant relations with elevation, with an increase in the abundance of cooler and wetter‐adapted species at higher elevations. At the scale of single peaks, we found weak and inconsistent relations between CCNMs and elevation, but variation in community composition explained by elevation increased. Within the elevation contours, the range of CCNMs was weakly positively correlated with turnover in species identity, likely driven by microclimate and other site‐specific factors.

Conclusions

Our results suggest that there is strong environmental sorting of alpine plant communities at broad scales, but microclimatic and site‐specific, nonclimatic factors together shape community turnover at finer scales. In the context of climate change, our results imply that community–climate relations are scale‐dependent, and predictions of local alpine plant range shifts are limited by a lack of topoclimatic and habitat information.