bluuebunny/crossref_metadata_2025_split huggingface dataset:
Di(2‐ethylhexyl) phthalate (DEHP) [BAT Value Documentation, 2018]
Authors: Rettenmeier A.W. , Drexler H. , Hartwig A. ,   MAK Commission
Published: April 2019

AbstractThe German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area evaluated di(2‐ethylhexyl) phthalate [CAS No.118‐81‐7] in 2017 and derived a biological guidance value at the workplace (BLW) for the combined urinary concentration of the four major DEHP metabolites mono(2‐ethylhexyl) phthalate (MEHP), mono(2‐ethyl‐5‐hydroxyhexyl) phthalate (5‐OH‐MEHP), mono(2‐ethyl‐5‐oxohexyl) phthalate (5‐oxo‐MEHP) and mono(2‐ethyl‐5‐carboxypentyl) phthalate (5‐cx‐MEPP). Available publications are described in detail.Human studies are not available for deriving a quantitative relationship between the internal dose and the critical toxic effects of DEHP (tumour promotion in the liver, respiratory effects, reproductive and developmental toxicity). Therefore, the evaluation of the BLW was based on the relationship between DEHP uptake by inhalation at the level of the MAK value and the urinary excretion rates of MEHP, 5‐OH‐MEHP, 5‐oxo‐MEHP and 5‐cx‐MEPP, using a conversion factor that defines this relationship. In accordance with this conversion factor external exposure to DEHP at the level of the MAK value corresponds to a combined urinary concentration of the four metabolites of approx. 4 mg/g creatinine at steady state. As the conversion factor has been derived from oral DEHP uptake and metabolite excretion data of only one male volunteer, the concentration of 4 mg/g creatinine is considered a BLW. Sampling time is for long‐term exposure at the end of the shift after several shifts.
Addendum zu Blei und seine Verbindungen (außer Bleiarsenat, Bleichromat und Alkylbleiverbindungen) [BAT Value Documentation in German language, 2019]
Authors: Bolt H.M. , Drexler H. , Hartwig A. ,   MAK Commission
Published: April 2019

AbstractIn 2018 the German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area re‐evaluated lead and its compounds and has derived a biological guidance value at the workplace (BLW) for the blood concentration of lead. Available publications are described in detail. The re‐evaluation is entirely based on studies in humans. The following critical health effects were considered: effects on heme synthesis, behavioural toxicity/neurotoxicity, male fertility, developmental toxicity, nephrotoxicity, cardiovascular effects, genotoxicity/carcinogenicity.Effects on neurobehaviour and nephrotoxicity have been described at blood levels around 300 µg Pb/L and higher. Therefore, a BLW of 200 µg Pb/L blood has been deduced. As investigations of lead‐exposed workers show no statistical increase in lymphocyte micronuclei at this blood level, it is reasonably expected that the proposed BLW will also minimize a lead‐induced genotoxic/carcinogenic risk.For women a Biological Reference Value (BAR) of 70 µg Pb/L blood is proposed, based on the 95th percentile of lead blood levels of the general population in Germany.Because of the long persistence of lead in the body, the sampling time is not fixed.
Polyethylenglykole (PEG) (mittlere Molmasse 200–600) [MAK Value Documentation in German language, 2019]
Authors: Hartwig A. ,   MAK Commission
Published: April 2019

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated polyethylene glycols (PEGs) (average molar mass 200–600) [
25322‐68‐3
] considering all toxicological endpoints.

In 13‐week studies in rats, the NOAEC for aerosols of PEG 200 and PEG 400 was the highest concentration tested of 1000 mg/m
3
. Taking into account the increased respiratory volume at the workplace (see List of MAK and BAT Values, Sections I b and I c), the extrapolation of data in animals to humans and the preferred value approach, the maximum concentration at the workplace (MAK value) has now been lowered to 200 mg/m
3
for the inhalable fraction. PEG 300 is composed of PEG 200 and PEG 400. PEG 600 is composed of 50% PEG 400. Therefore, the MAK value also applies to PEG 300 and PEG 600. In a chronic study at 2000 mg PEG 400/kg body weight and day, the body weight gain in rats was diminished. Therefore, the critical effect of PEGs is expected to be systemic and PEGs are classified in Peak Limitation Category II. As the half‐life is between 2 and 4 hours, the excursion factor of 2 is confirmed. Because formation of a mist is possible, exposure should be minimized for reasons of occupational safety and hygiene.

Several studies in rats, mice and rabbits with PEG 200 and PEG 400 show that the margins between the NOAECs for developmental toxicity scaled to a concentration at the workplace and the MAK value of 200 mg/m
3
are sufficient. Therefore, damage to the embryo or foetus is unlikely when the MAK value is not exceeded and PEGs remain classified in Pregnancy Risk Group C. PEGs are not genotoxic and are not suspected to be carcinogenic.

According to skin absorption models, PEGs are not taken up via the skin in toxicologically relevant amounts. A large number of studies in humans show that PEGs are not skin sensitizers, however, it cannot be excluded that autoxidation products of PEG might induce a low number of positive reactions. There are no data on respiratory sensitization.
4‐Methyl‐1,3‐dioxolan‐2‐on [MAK Value Documentation in German language, 2019]
Authors: Hartwig A. ,   MAK Commission
Published: April 2019

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated 4‐methyl‐1,3‐dioxolan‐2‐one [
108‐32‐7
;
51260‐39‐0
;
16606‐55‐6
] considering all toxicological endpoints. Available publications and unpublished study reports are described in detail.

The critical effect of 4‐methyl‐1,3‐dioxolan‐2‐one is eye irritation. Rats did not show systemic effects in a 13‐week inhalation study with whole‐body exposure to aerosols of 4‐methyl‐1,3‐dioxolan‐2‐one up to the highest concentration tested of 1000 mg/m
3
. At 100 mg/m
3
, swollen periocular tissue is observed in male animals. This finding is substantiated by the results of the acute eye irritation studies. Due to the weak effects, a NAEC of 50 mg/m
3
(12 ml/m
3
) is extrapolated. At this concentration, the substance can occur as a vapour; the maximum concentration at the workplace (MAK value) is therefore set in ml/m
3
. By applying the usual extrapolation steps, a MAK value of 2 ml/m
3
is derived.

Since the critical effect of 4‐methyl‐1,3‐dioxolan‐2‐one is local, Peak Limitation Category I is designated. An excursion factor of 1 is set as the critical effect concentration is twice as high as the extrapolated NAEC.
There is an adequate margin between the NOAEC for developmental toxicity and the MAK value. Therefore, damage to the embryo or foetus is unlikely when the MAK value is not exceeded and 4‐methyl‐1,3‐dioxolan‐2‐one is assigned to Pregnancy Risk Group C.
4‐Methyl‐1,3‐dioxolan‐2‐one is not genotoxic and the local tumour incidence was not increased in a chronic dermal study in male mice.
Skin contact is not expected to contribute significantly to systemic toxicity. Limited data show no sensitization.
Dimethoxymethan [MAK Value Documentation in German language, 2019]
Authors: Hartwig A. ,   MAK Commission
Published: April 2019

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 dimethoxymethane [
109‐87‐5
].

The critical effect is depression of the central nervous system, which was observed in a 13‐week study in rats at 9650 ml/m
3
. A MAK value of 500 ml/m
3
is derived from the NOAEC of 1908 ml/m
3
, taking into account the increased respiratory volume at the workplace because the blood:air partition coefficient of dimethoxymethane is > 5 (see List of MAK and BAT Values, Sections I b and I c). Since a systemic effect is critical, classification in Peak Limitation Category II is retained. As the half‐life is somewhat longer than one hour, the excursion factor of 2 is confirmed.

The NOAEC for developmental toxicity in rats is 10 068 ml/m
3
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 not exceeded and dimethoxymethane remains assigned to Pregnancy Risk Group C.

Skin contact is not expected to contribute significantly to systemic toxicity. Limited data show no sensitization.
Titandioxid (alveolengängige Fraktion) [MAK Value Documentation in German language, 2019]
Authors: Hartwig A. ,   MAK Commission
Published: April 2019

AbstractThe German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated titanium dioxide [13463‐67‐1]. Titanium dioxide causes lung tumours in rats at high concentrations. In 2009, titanium dioxide was evaluated and, because a maximum concentration at the workplace (MAK value) could not be established, it was classified in Carcinogen Category 3A. Titanium dioxide is a biopersistent granular dust and, in a later evaluation, inhalation studies with titanium dioxide were used to derive the general threshold limit value for granular biopersistent dusts. Therefore, the respirable fraction of titanium dioxide dust is reclassified in Carcinogen Category 4 and a MAK value of 0.3 mg/m3× material density is established for the respirable fraction according to the general threshold value for biopersistent granular dusts. Reclassification in Carcinogen Category 4 is justified because the lung tumours are regarded as a consequence of the inflammatory mechanism of action, for which a threshold can be defined. Direct genotoxic effects appear to be of subordinate relevance for the carcinogenicity of biopersistent granular dusts. By analogy with the biopersistent granular dusts, Peak Limitation Category II is established for titanium dioxide with an excursion factor of 8. Since titanium dioxide is not systemically distributed and accumulates only locally in the lungs, damage to the embryo or foetus is unlikely when the MAK value is not exceeded. Titanium dioxide is classified accordingly in Pregnancy Risk Group C. Titanium dioxide is not expected to be a sensitizer and is not taken up via the skin in toxicologically relevant amounts.
Polytetrafluorethen [MAK Value Documentation in German language, 2019]
Authors: Hartwig A. ,   MAK Commission
Published: April 2019

AbstractThe German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated polytetrafluoroethene [9002‐84‐0] to derive a maximum concentration at the workplace (MAK value), considering all toxicological endpoints. Available publications are described in detail. As polytetrafluoroethene is an insoluble and chemically inert polymer, showing no systemic toxicity after subchronic oral dosing, polytetrafluoroethene granular dusts are considered to be biopersistent. According to the mechanistic model, chronic inhalative overload of alveolar particle clearance results in particle‐induced inflammation and diverse proliferative tissue changes in lungs. The general threshold limit value and all its classifications for the respirable and inhalable fractions are applied to polytetrafluoroethene:For the respirable fraction, a MAK value of 0.3 mg/m3× density (2.2 g/cm3) is set with Peak Limitation Category II and an excursion factor of 8. It is classified in Carcinogen Category 4 and in Pregnancy Risk Group C. For the inhalable fraction, a MAK value of 4 mg/m3is set. The inhalable fraction is also assigned to Pregnancy Risk Group C because polytetrafluoroethene is an insoluble and inert polymer, which is not systemically toxic after oral dosing.There are no data on genotoxicity, sensitization or dermal absorption. As polytetrafluoroethene is an insoluble polymer, genotoxic and sensitizing effects and a significant contribution of skin absorption to systemic toxicity are not expected.
Benzotriazol [MAK Value Documentation in German language, 2019]
Authors: Hartwig A. ,   MAK Commission
Published: April 2019

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated benzotriazole [
95‐14‐7
], considering all toxicological endpoints. Available publications and unpublished study reports are described in detail. A genotoxic potential is not found in bacterial or mammalian cell systems in vitro and benzotriazole does not induce micronuclei in the bone marrow of mice. In oral carcinogenicity studies in rats and mice, benzotriazole causes tumours in various organs with a low incidence of glioma and oligodendroglioma in the brain of rats. These rarely occur in control animals and are therefore considered to be substance‐induced. For this reason, benzotriazole is suspected of being carcinogenic and is classified in Carcinogen Category 3B. A NOAEL of 12.5 mg/kg body weight and day is obtained for bleeding of mucous membranes at nose and mouth and salivation at 5 mg/kg body weight and day from a subchronic oral toxicity study in rats. As an inhalation study has not been performed, but benzotriazole is irritating to the eye and is therefore expected to be irritating to the respiratory tract, a maximum concentration at the workplace (MAK value) cannot be derived. In a reproductive toxicity study with exposure of rats to benzotriazole, at 300 mg/kg body weight and day the body weight of pups is reduced during lactation. Teratogenicity was not examined. Skin contact is expected to contribute significantly to systemic toxicity. Therefore, benzotriazole is designated with an “H”. Limited data show no sensitization.
2019 American College of Rheumatology/Arthritis Foundation Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Non‐Systemic Polyarthritis, Sacroiliitis, and Enthesitis
Authors: Ringold Sarah , Angeles‐Han Sheila T. , Beukelman Timothy , Lovell Daniel , Cuello Carlos A. , Becker Mara L. , Colbert Robert A. , Feldman Brian M. , Ferguson Polly J. , Gewanter Harry , Guzman Jaime , Horonjeff Jennifer , Nigrovic Peter A. , Ombrello Michael J. , Passo Murray H. , Stoll Matthew L. , Rabinovich C. Egla , Schneider Rayfel , Halyabar Olha , Hays Kimberly , Shah Amit Aakash , Sullivan Nancy , Szymanski Ann Marie , Turgunbaev Marat , Turner Amy , Reston James 
Published: April 2019

ObjectiveTo develop treatment recommendations for children with juvenile idiopathic arthritis manifesting as non‐systemic polyarthritis, sacroiliitis, or enthesitis.MethodsThe Patient/Population, Intervention, Comparison, and Outcomes (PICO) questions were developed and refined by members of the guideline development teams. A systematic review was conducted to compile evidence for the benefits and harms associated with treatments for these conditions. GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to rate the quality of evidence. A group consensus process was conducted among the Voting Panel to generate the final recommendations and grade their strength. A Parent and Patient Panel used a similar consensus approach to provide patient/caregiver preferences for key questions.ResultsThirty‐nine recommendations were developed (8 strong and 31 conditional). The quality of supporting evidence was very low or low for 90% of the recommendations. Recommendations are provided for the use of nonsteroidal antiinflammatory drugs, disease‐modifying antirheumatic drugs, biologics, and intraarticular and oral glucocorticoids. Recommendations for the use of physical and occupational therapy are also provided. Specific recommendations for polyarthritis address general medication use, initial and subsequent treatment, and adjunctive therapies. Good disease control, with therapeutic escalation to achieve low disease activity, was recommended. The sacroiliitis and enthesitis recommendations primarily address initial therapy and adjunctive therapies.ConclusionThis guideline provides direction for clinicians, caregivers, and patients making treatment decisions. Clinicians, caregivers, and patients should use a shared decision‐making process that accounts for patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.
Floral adaptations of two lilies: implications for the evolution and pollination ecology of huge trumpet‐shaped flowers
Authors: Liu Chang‐Qiu , Gao Yun‐Dong , Niu Yang , Xiong Ying‐Ze , Sun Hang 
Published: April 2019

PremiseEvolutionary transitions among floral morphologies, many of which provide evidence for adaptation to novel pollinators, are common. Some trumpet‐shaped flowers are among the largest flowers in angiosperms, occurring in different lineages. Our goal was to investigate the role of pollinators in the evolution of these flowers using Lilium.MethodsWe investigated floral traits and pollinators of L. primulinum var. ochraceum and L. brownii var. viridulum and reviewed reports of visitors to huge trumpet‐shaped flowers. Using a published phylogeny of Lilium, we reconstructed ancestral floral morphological states in Lilium to elucidate the origins of trumpet‐shaped lilies.ResultsBoth lilies are largely self‐incompatible and show floral syndromes indicative of hawkmoth pollination. The short trumpet‐shaped lily can be pollinated by short‐tongued (<40 mm) but not long‐tongued hawkmoths (>65 mm), while the huge trumpet‐shaped lily can be pollinated by both. A literature review including 22 species of trumpet‐shaped flowers suggests that their pollinator guilds commonly include both short‐ and long‐tongued moths. A phylogenetic reconstruction indicates that trumpet‐shaped lilies possibly have multiple origins from tepal‐reflexed ancestors, at least six of which have evolved huge flowers (>50 mm).ConclusionsAdaptation to short‐tongued hawkmoths may have initiated the evolution of trumpet‐shaped lilies. Huge trumpet‐shaped lilies may have evolved as a response to selection by long‐tongued hawkmoths, without excluding the short‐tongued ones. This evolutionary pathway leads to a functionally more generalized pollination system instead of an increasingly specialized one and is not necessarily associated with pollinator shifts.
Weekly carfilzomib, lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: A phase 1b study
Authors: Biran Noa , Siegel David , Berdeja Jesus G. , Raje Noopur , Cornell Robert Frank , Alsina Melissa , Kovacsovics Tibor , Fang Belle , Kimball Amy S. , Landgren Ola 
Published: April 2019

AbstractTwice‐weekly carfilzomib (27 mg/m2) with lenalidomide‐dexamethasone (KRd) is a standard‐of‐care in relapsed or refractory multiple myeloma (RRMM). This phase 1b study evaluated KRd with once‐weekly carfilzomib in RRMM. Patients received carfilzomib (30‐minute infusion; 56 or 70mg/m2) on days 1, 8, and 15; lenalidomide 25 mg on days 1‐21; and dexamethasone 40 mg on days 1, 8, 15, and 22 (day 22 omitted for cycles 9+) of 28‐day cycles. Primary objective was safety/tolerability; efficacy was a secondary objective. Fifty‐six RRMM patients enrolled: 22 during dose evaluation (56‐mg/m2, n = 10; 70‐mg/m2, n = 12) and 34 during dose expansion (all initiated dosing at 70 mg/m2). After 2 fatal adverse events (AEs) during 70‐mg/m2 dose expansion, dosage reduction to 56 mg/m2 was permitted. Results are presented for carfilzomib 56‐mg/m2 (n = 10) and 70‐mg/m2 groups (dose evaluation/expansion; n = 46). Median carfilzomib dose was 53.2 mg/m2 (56‐mg/m2 group) and 62.4 mg/m2 (70‐mg/m2 group). Grade ≥3 AE rates were 70.0% (56 mg/m2) and 69.6% (70 mg/m2). Overall response rates were 90.0% (56 mg/m2) and 89.1% (70 mg/m2); ≥very good partial response rates were 50.0% (56 mg/m2) and 73.9% (70 mg/m2). Once‐weekly KRd was active with acceptable toxicity in RRMM, supporting further evaluation of this regimen.
High‐Resolution Photoelectron Imaging of IrB3−: Observation of a π‐Aromatic B3+ Ring Coordinated to a Transition Metal
Authors: Czekner Joseph , Cheung Ling Fung , Kocheril G. Stephen , Kulichenko Maksim , Boldyrev Alexander I. , Wang Lai‐Sheng 
Published: April 2019

AbstractIn a high‐resolution photoelectron imaging and theoretical study of the IrB3− cluster, two isomers were observed experimentally with electron affinities (EAs) of 1.3147(8) and 1.937(4) eV. Quantum calculations revealed two nearly degenerate isomers competing for the global minimum, both with a B3 ring coordinated with the Ir atom. The isomer with the higher EA consists of a B3 ring with a bridge‐bonded Ir atom (Cs , 2A′), and the second isomer features a tetrahedral structure (C3v , 2A1). The neutral tetrahedral structure was predicted to be considerably more stable than all other isomers. Chemical bonding analysis showed that the neutral C3v isomer involves significant covalent Ir−B bonding and weak ionic bonding with charge transfer from B3 to Ir, and can be viewed as an Ir–(η3‐B3+) complex. This study provides the first example of a boron‐to‐metal charge‐transfer complex and evidence of a π‐aromatic B3+ ring coordinated to a transition metal.
Boron Phosphorus Nitride at Extremes: PN6 Octahedra in the High‐Pressure Polymorph β‐BP3N6
Authors: Vogel Sebastian , Bykov Maxim , Bykova Elena , Wendl Sebastian , Kloß Simon D. , Pakhomova Anna , Chariton Stella , Koemets Egor , Dubrovinskaia Natalia , Dubrovinsky Leonid , Schnick Wolfgang 
Published: April 2019

AbstractThe high‐pressure behavior of non‐metal nitrides is of special interest for inorganic and theoretical chemistry as well as materials science, as these compounds feature intriguing elastic properties. The double nitride α‐BP3N6 was investigated by in situ single‐crystal X‐ray diffraction (XRD) upon cold compression to a maximum pressure of about 42 GPa, and its isothermal bulk modulus at ambient conditions was determined to be 146(6) GPa. At maximum pressure the sample was laser‐heated, which resulted in the formation of an unprecedented high‐pressure polymorph, β‐BP3N6. Its structure was elucidated by single‐crystal XRD, and can be described as a decoration of a distorted hexagonal close packing of N with B in tetrahedral and P in octahedral voids. Hence, β‐BP3N6 is the first nitride to contain PN6 octahedra, representing the much sought‐after proof of principle for sixfold N‐coordinated P that has been predicted for numerous high‐pressure phases of nitrides.
Designing a Perylene Diimide/Fullerene Hybrid as Effective Electron Transporting Material in Inverted Perovskite Solar Cells with Enhanced Efficiency and Stability
Authors: Luo Zhenghui , Wu Fei , Zhang Teng , Zeng Xuan , Xiao Yiqun , Liu Tao , Zhong Cheng , Lu Xinhui , Zhu Linna , Yang Shihe , Yang Chuluo 
Published: April 2019

AbstractElectron transport materials (ETM) play an important role in the improvement of efficiency and stability for inverted perovskite solar cells (PSCs). This work reports an efficient ETM, named PDI‐C60, by the combination of perylene diimide (PDI) and fullerene. Compared to the traditional PCBM, this strategy endows PDI‐C60 with slightly shallower energy level and higher electron mobility. As a result, the device based on PDI‐C60 as electron transport layer (ETL) achieves high power conversion efficiency (PCE) of 18.6 %, which is significantly higher than those of the control devices of PCBM (16.6 %) and PDI (13.8 %). The high PCE of the PDI‐C60‐based device can be attributed to the more matching energy level with the perovskite, more efficient charge extraction, transport, and reduced recombination rate. To the best of our knowledge, the PCE of 18.6 % is the highest value in the PSCs using PDI derivatives as ETLs. Moreover, the device with PDI‐C60 as ETL exhibits better device stability due to the stronger hydrophobic properties of PDI‐C60. The strategy using the PDI/fullerene hybrid provides insights for future molecular design of the efficient ETM for the inverted PSCs.