HBCD was detected in the adipose tissue of male and female rats treated with 1000 mg/kg/day for up to 90 days. Isomer-specific analysis showed that the relative isomer concentrations in adipose tissue at all time points were alpha>>gamma>beta which is in contrast to the test article composition (gamma>>alpha>beta). Steady state levels were achieved by study day 27. Levels in male and female rats were similar at all time points and declined during the recovery period.
Juvenile rainbow trout (Oncorhynchus mykiss) were exposed to three diastereoisomers (alpha, Beta, gamma) of hexabromocyclododecane (C12H18Br6) via their diet for 56 days followed by 112 days of untreated food to examine bioaccumulation parameters and test the hypothesis of in vivo bioisomerization. Four groups of 70 fish were used in the study. Three groups were exposed to food fortified with known concentrations of an individual diastereoisomer, while a fourth group were fed unfortified food. Bioaccumulation of the gamma-diastereoisomer was linear during the uptake phase, while the alpha- and Beta-diastereoisomers were found to increase exponentially with respective doubling times of 8.2 and 17.1 days. Both the Beta- and the gamma-diastereoisomers followed a first-order depuration kinetics with calculated half-lives of 157 + or - 71 and 144 + or - 60 days (+ or -1 x standard error), respectively. The biomagnification factor (BMF) for the alpha-diastereoisomer (BMF = 9.2) was two times greater than the Beta-diastereoisomer (BMF = 4.3); the large BMF for the alpha-diastereoisomer is consistent with this diastereoisomer dominating higher-trophic-level organisms. Although the BMF of the Beta-diastereoisomer suggests that it will biomagnify, it is rarely detected in environmental samples because it is present in small quantities in commercial mixtures. Results from these studies also provide evidence of bioisomerization of the Beta- and gamma-diastereoisomers. Most importantly, the alpha-diastereoisomer that was recalcitrant to bioisomerization by juvenile rainbow trout in this study and known to be the dominant diastereosiomer in fish was bioformed from both the Beta- and the gamma-diastereoisomers.
A single oral dose (7-9 mg/kg) of 14C-HBCD was administered to male (n=2) and female (n=8) rats. ...Only metabolites were detected in feces and urine -no parent molecule was detected. Thus, the gamma isomer appears to be extensively metabolized prior to excretion. In contrast, only unmetabolized gamma isomer was detected in adipose tissue.
The laboratory trophic transfer of hexabromocyclododecanes (HBCDs) was studied using predatory (oscar) fish and a prey species (tiger barb) exposed to a technical HBCD. Gut absorption, dynamic changes of diastereomer pattern and enantiomer fractions, and potential metabolism of HBCDs were examined. Compared with b- or g-HBCD, a-HBCD showed lower absorption efficiency in the gut of oscar fish. A predominance of g-HBCD was observed in the tiger barb after 5 d HBCD-exposed and oscar feeding on the tiger barb for 16 d. After 20 d of depuration, 41.1% g-HBCD and 42.7% b-HBCD disappeared, and a-HBCD exceeded the initial amount. The transformation from g-HBCD predominance in the food to a-HBCD predominance in the oscar was attributed mainly to the isomerization of g-HBCD (at least 3% and up to 22.7%) to a-HBCD. Selective enrichment of the (+) a- and (-) b-enantiomers and no enantioselective enrichment of g-HBCD were observed in the tiger barbs. No enantioselective uptake of the 3 diasteromers was found in the oscar gut. The enantiomer fractions of a- and g-diastereomers were significantly higher, but that of b-diastereomer were significantly lower in the oscars than in the tiger barbs, indicating enantioselective metabolism of the 3 diastereomers. Two HBCD monohydroxylated metabolites were detected in the 2 fish species, but their composition patterns differed, indicating a species-specific metabolism of HBCD in the studied fish species.
Until now, the bioaccumulation of hexabromocyclododecanes (HBCDs) in aquatic organisms has been studied only via dietary exposure. To better understand the environmental fate of HBCDs, we conducted a bioaccumulation test by exposing mirror carp to three HBCD diastereomers in water during 30d of accumulation and 30d of depuration according to Organization for Economic Co-operation and Development (OECD) Test Guidelines 305 (Bioaccumulation in Fish: Aqueous and Dietary Exposure). We found that the BCFKL values (bioconcentration factor calculated from kinetic data and adjusted to lipid content) of a-HBCD in different tissues of the carp were in the range of (3.07-4.52)x10(4), much higher than those of b-HBCDs (1.03-1.90x10(3)) and g-HBCD (0.95-1.73x10(3)), as was true of t1/2. The order of BCFK for a-, b- and g-HBCD in different tissues was viscera>gill>skin>muscle. b-HBCD and g-HBCD were transformed to a-HBCD, with 50.0-92.9% and 96.2-98.6% bioisomerization efficiencies by the end of the experiment, respectively. No isomerization product from a-HBCD was found. Selective enrichment of the (+) a- and g-HBCD was found, whereas b-HBCD did not show significant enantioselectivity. New metabolites such as tetrabromocyclododecene (TBCDe), tribromocyclododecadiene (TriBCDi) and tribromocyclododecatriene (TriBCDie) were found in mirror carp for the first time under multiple reaction monitoring (MRM) mode.
Thyroid hormone (TH) plays an essential role in growth and differentiation of the central nervous system. Deficiency of TH during perinatal period results in abnormal brain development known as cretinism in human. We recently reported that an environmental chemical 1,2,5,6,9,10-a-hexabromocyclododecane (HBCD) suppressed TH receptor (TR)-mediated transcription. To examine the effect of HBCD on cerebellar granule cells, we used purified rat cerebellar granule cells in reaggregate culture. Low dose HBCD (10(-10)M) significantly suppressed TH-induced neurite extension of granule cell aggregate. To clarify further the mechanisms of such suppression, we added brain-derived neurotrophic factor (BDNF) into culture medium, since BDNF plays a critical role in promoting granule cell development and is regulated by TH. BDNF completely rescued HBCD-induced suppression of granule cell neurite extension in the presence of T3. These results indicate that HBCD may disrupt TH-mediated brain development at least in part due to a disruption of the T3 stimulated increase in BDNF and BDNF may possess ability to ameliorate the effect of HBCD in granule cells.
Hexabromocyclododecane (HBCD), a type of brominated flame retardants (BFR), has become ubiquitous organic contaminants in recent years. However, studies on HBCD toxicity and the related molecular mechanisms are so far limited. The objective of the present study was to investigate the effects of oligomeric proanthocyanidins (OPCs) on cytotoxicity induced by HBCD and the underlying molecular mechanisms. HepG2 cells were treated with HBCD and/or OPCs at different concentrations, and cell viability, cell apoptosis, reactive oxygen species (ROS) production, cellular Ca(2+) level, mitochondrial membrane potential, cytochrome C (Cyt-c) release, and nuclear factor-erythroid 2-related factor 2 (Nrf2) proteins expression were evaluated. Results showed that HBCD induced toxic effects in HepG2 cells in a concentration-dependent manner. HBCD at high concentrations (40 and 60 uM) caused a significant decrease of cell viability and led to elevated cell apoptosis ratio, intracellular Ca(2+) level, cytoplasmic Cyt-c level, and ROS production, together with a loss of /mitochondrial membrane potential/ and mobilization of Nrf2. Pretreatment with OPCs effectively attenuated the cytotoxic effects and ROS production, as well as mitochondrial responses induced by HBCD. Thus, OPCs could alleviate cytotoxicity in HepG2 cells induced by HBCD through regulation on intracellular Ca(2+) level and ROS formation in a mitochondrial pathway.
Proteomic effect screening in zebrafish liver cells was performed to generate hypotheses regarding single and mixed exposure to the BFRs HBCD and TBBPA. Responses at sublethal exposure were analysed by two-dimensional gel electrophoresis followed by MALDI-TOF and FT-ICR protein identification. Mixing of HBCD and TBBPA at sublethal doses of individual substances seemed to increase toxicity. Proteomic analyses revealed distinct exposure-specific and overlapping responses suggesting novel mechanisms with regard to HBCD and TBBPA exposure. While distinct HBCD responses were related to decreased protein metabolism, TBBPA revealed effects related to protein folding and NADPH production. Overlapping responses suggest increased gluconeogenesis (GAPDH and aldolase) while distinct mixture effects suggest a pronounced NADPH production and changes in proteins related to cell cycle control (prohibitin and crk-like oncogene). We conclude that mixtures containing HBCD and TBBPA may result in unexpected effects highlighting proteomics as a sensitive tool for detecting and hypothesis generation of mixture effects.
...Rats administered a single oral dose of 1.93 mg of radiolabeled HBCD eliminated 86% of the dose within 72 hr. (The total dose administered was 7-9 mg/kg body weight.) Absorption from the gastrointestinal tract reportedly occurred rapidly, with a half-life of 2 hr. However, the amount of the absorbed fraction was not reported. HBCD was reported to be rapidly metabolized and eliminated in the feces and urine following absorption, with 70% of the administered radioactivity eliminated in the feces and another 16% eliminated in the urine 72 hr after dosing. A two-compartment model was constructed, with non-adipose tissues in one compartment and adipose tissue in the other. Elimination from the adipose compartment was reported to be slower than elimination from the non-adipose compartment, although elimination half-times were not provided in the review. In another study, ... HBCD was orally administered to male Wistar rats (number not reported) in olive oil at 500 mg/kg/day for 5 days. HBCD was found to be present only in adipose tissue, and in none of the other organs examined (i.e., spleen, pancreas, liver, kidneys, and heart). HBCD was found to be excreted in the feces, with an average of 32-35% of the cumulative administered dose excreted. No HBCD was found in the urine. Although differences in study design, including the test vehicle and the analytic methods used, may account for some of the difference in the results, both studies... suggest that following acute oral doses, HBCD is rapidly absorbed from the gastrointestinal tract, distributed primarily to body fat, and eliminated rapidly, primarily in the feces.
The excretion of HBCD in urine and feces as well as its distribution to various organs was investigated. The test article was "Pyroguard SR-103"... . A fine suspension of SR-103 in olive oil was prepared by mixing well to homogeneity in a mortar. The dose was 500 mg/kg/day for 5 consecutive days (n= 4 male Wistar rats). ...The average daily rate of excretion in the feces was 29-37% of the dose. The cumulative excretion was roughly constant at 32-35% with respect to the cumulative administered amount. Urinary excretion was not observed. No evidence for the presence of metabolites was observed in urine or feces. A separate study with isolated intestinal loop (upper jejunum) indicated about 12% of the dose was detectable in the intestinal tissue and the amount remaining in the lumen loop "small". The test article was detected only in the adipose tissue after dosing for 5 days. The level in adipose tissue was 0.3-0.7 mg/g fat.
A single oral dose (7-9 mg/kg) of 14C-HBCD was administered to male (n=2) and female (n=8) rats. Based on the starting material and the melting point of the final product described in the report, the test article appeared to be composed of the gamma isomer. The rats were sacrificed 8, 24, 48 and 72 hours (females) and 48 hours (males) after dosing. One female rat served as control. Urine and feces were collected daily, blood samples from 4 animals were collected during the first 24 hours. Tissue samples were collected at the time of sacrifice. ... HBCD appeared to be well absorbed from the gastrointestinal tract and extensively metabolized prior to elimination in feces (primary route) and urine. The estimated absorption half-life was 2 hours; peak radioactivity was detected in blood 4 hours post-dosing. The pharmacokinetics of the gamma stereoisomer appeared to follow an open two-compartment model. The central compartment was described as liver, lung, kidney, heart, muscle, gonads, uterus, spleen, and brain; the peripheral compartment was described as adipose tissue. Roughly 80 ->90% of the gamma stereoisomer was eliminated within 3 days following a single oral dose, with an apparent half-life of elimination of 27 hours. Only metabolites were detected in feces and urine -no parent molecule was detected. Thus, the gamma isomer appears to be extensively metabolized prior to excretion. In contrast, only unmetabolized gamma isomer was detected in adipose tissue. In females at 8, 24, 48 and 72 hours post-dosing, the total 14C activity detected in tissues of female rats was about 43, 24, 18 and 17% of the dose, respectively. In male rats at 48 hours post-dosing (the only time point investigated in males), the 14C-activity was about 10% of the dose. Similarly, that detected in feces from female rats was about 4, 65, 54 and 77% at 8, 24, 48 and 72 hr. Urine contained 0.1, 6, 18 and 15% of the dose at the same time intervals. Feces from male rats at 48 hours contained about 94% of the dose while urine from male rats contained about 15%. At 48 hours post-dosing approximately 81% of the dose was detected in feces and urine of female rats. Thus, at 48 hours post-dosing approximately 86% of the dose was recovered in the tissues, feces and urine from female rats whereas 119% was recovered from males. The lower 48 hour recovery from this group of female rats is largely accounted for by the lower fecal content (43%) of radioactivity collected during the 0-24 hours post-dosing. By 48 hours post-dosing, females sacrificed at 24 hours, had a total fecal 14C-content of 65% of the dose, and females sacrificed at 72 hours had a total fecal 14C-content of 62% of the dose. Substituting the average value, 63%, from these two groups for the 43% value used to calculate overall recovery, the total per cent of the dose accounted for at 48 hours becomes feces (74%) urine (17%) and tissues (18%) or 109% of the dose. It appears likely that some unknown factor resulted in the lower 0-24 hour percent recovery from feces, and that percent of dose present in tissues, feces and urine 48 hours post-dosing is similar in male and female rats.
Seven week old Wistar rats were administered HBCDD by gavage for 28 days. The HBCDD was properly dissolved in corn oil ... The composition of diastereomers was 10.3 - 8.72 - 81.0% of alpha, beta, and gamma, respectively ... The doses were 0, 0.3, 1, 3, 10, 30, 100, and 200 mg/kg bw/day ... The chemical analysis showed that nearly no beta-HBCDD was present in the animals. The concentration of alpha-HBCDD and gamma-HBCDD in liver fat increased dose-dependently, but there were signs of a plateau being reached at the highest dose level(s), and perhaps earlier for gamma than for alpha. Accordingly, with increasing dose, more and more of the HBCDD-residues consisted of the alpha diastereomer. Females consistently accumulated more HCBDD in the liver compared to males, but as no absolute concentrations are presented, it is difficult to quantify the difference. At doses up to the levels where the residue levels seem to plateau (30-200 mg/kg/day), the accumulation of alpha seemed to be roughly twice as high as gamma. At doses of 100 mg/kg/day and above, the relative concentration of alpha increased much further compared to gamma. This may be explained by either reduced absorption or increased metabolism of gamma at high doses. The latter is possibly explained by induction of CYP 2B.
来源:Hazardous Substances Data Bank (HSDB)
安全信息
危险等级：
9
安全说明：
S22,S24/25
WGK Germany：
1
文献信息
SULFENAMIDES AS FLAME RETARDANTS
申请人：SONGWON INTERNATIONAL AG
公开号：US20160289566A1
公开（公告）日：2016-10-06
The present invention is in the field of flame retardants and relates to use of sulfenamides as flame retardants, in particular in polymeric substrates.
本发明属于阻燃剂领域，涉及将硫代酰胺用作阻燃剂，特别是在聚合物基材中的使用。
NOVOLAC RESIN AND RESIST FILM
申请人：DIC Corporation
公开号：US20180334523A1
公开（公告）日：2018-11-22
Provided are a novolac resin having developability, heat resistance, and dry etching resistance, and a photosensitive composition, a curable composition, and a resist film. A novolac resin including, as a repeating unit, a structural moiety represented by Structural Formula (1) or (2):
(in the formula, Ar represents an arylene group, R
1
's each independently represent any one of a hydrogen atom, an alkyl group, an alkoxy group, and a halogen atom, m's each independently represent an integer of 1 to 3, and X is any one of a hydrogen atom, a tertiary alkyl group, an alkoxyalkyl group, an acyl group, an alkoxycarbonyl group, a hetero atom-containing cyclic hydrocarbon group, and a trialkylsilyl group) in which at least one of X's present in the resin is any one of a tertiary alkyl group, an alkoxyalkyl group, an acyl group, an alkoxycarbonyl group, a hetero atom-containing cyclic hydrocarbon group, and a trialkylsilyl group.
BITTER TASTE MODIFIERS INCLUDING SUBSTITUTED 1-BENZYL-3-(1-(ISOXAZOL-4-YLMETHYL)-1H-PYRAZOL-4-YL)IMIDAZOLIDINE-2,4-DIONES AND COMPOSITIONS THEREOF
申请人：SENOMYX, INC.
公开号：US20160376263A1
公开（公告）日：2016-12-29
The present invention includes compounds and compositions known to modify the perception of bitter taste, and combinations of said compositions and compounds with additional compositions, compounds, and products. Exemplary compositions comprise one or more of the following: cooling agents; inactive drug ingredients; active pharmaceutical ingredients; food additives or foodstuffs; flavorants, or flavor enhancers; food or beverage products; bitter compounds; sweeteners; bitterants; sour flavorants; salty flavorants; umami flavorants; plant or animal products; compounds known to be used in pet care products; compounds known to be used in personal care products; compounds known to be used in home products; pharmaceutical preparations; topical preparations; cannabis-derived or cannabis-related products; compounds known to be used in oral care products; beverages; scents, perfumes, or odorants; compounds known to be used in consumer products; silicone compounds; abrasives; surfactants; warming agents; smoking articles; fats, oils, or emulsions; and/or probiotic bacteria or supplements.
ASYMMETRIC ORGANIC PEROXIDE, CROSSLINKING AGENT COMPRISING THE SAME, AND METHOD OF CROSSLINKING WITH THE SAME
申请人：NOF CORPORATION
公开号：EP1233014A1
公开（公告）日：2002-08-21
A crosslinking agent comprising an asymmetry organic peroxide having at least one structure unit of (substituted)benzoylcarbonyloxy group represented by the following formula (1) in the molecule thereof.
Environmentally friendly crosslinking agents and crosslinked silicone rubber moldings are provided thereby.
Specifically, useful crosslinking agents and crosslinking processes for silicone rubber are provided.
USE OF PHOSPHOROUS-CONTAINING ORGANIC OXYIMIDES AS FLAME RETARDANTS AND/OR AS STABILIZERS FOR PLASTICS, FLAME-RETARDANT AND/OR STABILIZED PLASTIC COMPOSITIONS, METHOD FOR THE PRODUCTION THEREOF, MOULDED PART, PAINT AND COATINGS
申请人：FRAUNHOFER-GESELLSCHAFT ZUR FÖRDERUNG DER ANGEWANDTEN FORSCHUNG E.V.
公开号：US20170260366A1
公开（公告）日：2017-09-14
The present invention relates to the use of phosphorous-containing organic oxyimides according to the general formula (I) as flame retardant for plastic materials, as radical generators in plastic materials and/or stabilisers for plastics. In addition, the present invention relates to a flame-retardant plastic material moulding compound in which the previously described phosphorous-containing organic oxyimides are integrated, and also to a method for the production of the previously mentioned plastic material composition. Furthermore, the present invention relates to a moulded article, a paint or a coating from the previously mentioned flame-retardant plastic material composition.
