bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diisotridecyl phthalate, ditridecyl phthalate [MAK value documentation, 2019]
Authors: Hartwig A. ,   MAK Commission
Published: November 2019

Abstract

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 Available publications and unpublished study reports are described in detail.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

Abstract

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

Abstract

The German Commission for the investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the workplace (MAK value) and the Pregnancy Risk Group of
N,N
‐dimethylacetamide [
127‐19‐5
].

N,N
‐Dimethylacetamide causes focal cystic degenerations, peliosis, hemosiderin/lipofuscin accumulation and apoptosis in the liver of rats and male mice after chronic whole body inhalation at 100 ml/m
3
. The NOAEC in both species is 25 ml/m
3
. Elastane fibre workers with exposure to
N,N
‐dimethylacetamide show hepatocellular injury. The data at the workplace is not adequate to derive a MAK value. The former MAK value of 10 ml/m
3
was derived from the NOAEC of 25 ml/m
3
in rats and mice. The MAK value is now lowered to 5 ml/m
3
which takes into account the increased respiratory volume at the workplace because the blood:air partition coefficient of
N,N
‐dimethylacetamide is > 5 (see List of MAK and BAT Values, 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

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) 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

Abstract

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

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) 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

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 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

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 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

Abstract

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

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) 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

AbstractThe 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

AbstractAmong 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

AbstractRecent 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).