Source: http://www.science.gov/topicpages/a/act+tsca+chemical.html
Timestamp: 2016-10-24 21:55:49
Document Index: 96970179

Matched Legal Cases: ['art 790', 'art 2', 'art 2', 'art 1', 'art 2', 'art 1', 'art 2', '§ 710', '§ 710', '§ 710', '§ 710', '§ 711', '§ 711', '§ 710', '§ 710', '§ 710', '§ 710', '§ 710', '§ 766', '§ 766', '§ 766', '§ 766']

act tsca chemical: Topics by Science.gov
Sample records for act tsca chemical
75 FR 57770 - Certain New Chemicals; Receipt and Status Information
...Section 5 of the Toxic Substances Control Act (TSCA) requires any person who intends to manufacture (defined by statute to include import) a new chemical (i.e., a chemical not on the TSCA Inventory) to notify EPA and comply with the statutory provisions pertaining to the manufacture of new chemicals. Under sections 5(d)(2) and 5(d)(3) of TSCA, EPA is required to publish a notice of receipt of......
75 FR 60444 - Certain New Chemicals; Receipt and Status Information
75 FR 39520 - Certain New Chemicals; Receipt and Status Information
75 FR 11414 - Certain New Chemicals; Receipt and Status Information
75 FR 11403 - Certain New Chemicals; Receipt and Status Information
75 FR 32754 - Certain New Chemicals; Receipt and Status Information
77 FR 48858 - Significant New Use Rules on Certain Chemical Substances
...EPA is promulgating significant new use rules (SNURs) under the Toxic Substances Control Act (TSCA) for 25 chemical substances which were the subject of premanufacture notices (PMNs). Fourteen of these chemical substances are subject to TSCA section 5(e) consent orders issued by EPA. This action requires persons who intend to manufacture, import, or process any of these 25 chemical substances......
77 FR 58665 - Significant New Use Rules on Certain Chemical Substances
...EPA is promulgating significant new use rules (SNURs) under the Toxic Substances Control Act (TSCA) for 107 chemical substances which were the subject of premanufacture notices (PMNs). Eight of these chemical substances are subject to TSCA consent orders issued by EPA. This action requires persons who intend to manufacture, import, or process any of these 107 chemical substances for an......
78 FR 27860 - Revocation of TSCA Section 4 Testing Requirements for One High Production Volume Chemical Substance
... Certain High Production Volume Chemicals; Final Rule. Federal Register (71 FR 13708, March 16, 2006) (FRL... Requirements Certain High Production Volume Chemical Substances; Direct Final Rule. Federal Register (77 FR... Substance; Final Rule. Federal Register (77 FR 28281, May 14, 2012) (FRL-9350- 2). Document ID number...
CHEMICAL CATEGORIES IN EPA'S NEW CHEMICALS PROGRAM
Under section 5 of the Toxic Substances Control Act (TSCA),any person who intends to manufacture or import a new chemical substance, or mixture containing such a substance, in the United States for commercial purposes must submit a premanufacture notice (PMN) to the Environmental...
78 FR 41768 - Chemical Substances and Mixtures Used in Oil and Gas Exploration or Production; TSCA Section 21...
... Significant Human Exposure; Final Statement of Policy. Federal Register (58 FR 28736, May 14, 1993) (FRL-4059... AGENCY 40 CFR Chapter I Chemical Substances and Mixtures Used in Oil and Gas Exploration or Production...(a) to require manufacturers and processors of oil and gas exploration and production (E&P)...
77 FR 28340 - Revocation of TSCA Section 4 Testing Requirements for One High Production Volume Chemical Substance
... High Production Volume Chemicals; Final Rule. Federal Register (71 FR 13708, March 16, 2006) (FRL-7335... significant regulatory action under Executive Order 12866, entitled ``Regulatory Planning and Review'' (58 FR... Environmental Health Risks and Safety Risks'' (62 FR 19885, April 23, 1997), and Executive Order 13211,...
76 FR 1067 - Testing of Certain High Production Volume Chemicals; Second Group of Chemicals
...EPA is promulgating a final rule under section 4(a)(1)(B) of the Toxic Substances Control Act (TSCA) to require manufacturers, importers, and processors of certain high production volume (HPV) chemical substances to conduct testing to obtain screening level data for health and environmental effects and chemical...
77 FR 21769 - Certain New Chemicals; Receipt and Status Information
... intends to manufacture (defined by statute to include import) a new chemical (i.e., a chemical not on the TSCA Chemical Substances Inventory (TSCA Inventory)) to notify EPA and comply with the statutory... manufacture a new chemical that the Agency has received under TSCA section 5 during this time period....
77 FR 5100 - Certain New Chemicals; Receipt and Status Information
... intends to manufacture (defined by statute to include import) a new chemical (i.e., a chemical not on the TSCA Chemical Substances Inventory (TSCA Inventory)) to notify EPA and comply with the statutory... the NOC to manufacture a new chemical that the Agency has received under TSCA section 5 during...
77 FR 48976 - Certain New Chemicals; Receipt and Status Information
78 FR 27048 - Significant New Use Rules on Certain Chemical Substances
...EPA is promulgating significant new use rules (SNURs) under the Toxic Substances Control Act (TSCA) for 15 chemical substances which were the subject of premanufacture notices (PMNs). This action requires persons who intend to manufacture, import, or process any of these 15 chemical substances for an activity that is designated as a significant new use by this rule to notify EPA at least 90......
77 FR 3725 - Proposed Significant New Use Rules on Certain Chemical Substances; Extension of Comment Period
... 28, 2011 (76 FR 81441) (FRL-9329-4). In that document, EPA proposed SNURs under section 5(a)(2) of... Substances Control Act (TSCA) for the chemical substances rutile, tin zinc, calcium-doped (CAS No. 389623-01- 2) and rutile, tin zinc, sodium-doped (CAS No. 389623-07-8) which were the subject of...
76 FR 65385 - Testing of Certain High Production Volume Chemicals; Third Group of Chemicals
...EPA is promulgating this final rule under section 4(a)(1)(B) of the Toxic Substances Control Act (TSCA) to require manufacturers, importers, and processors to conduct testing to obtain screening level data for health and environmental effects and chemical fate for 15 high production volume (HPV) chemical substances listed in this final rule. This test data is needed in order to help EPA to......
...Under the Toxic Substances Control Act (TSCA), EPA is proposing: To add nine benzidine-based chemical substances to the Significant New Use Rule (SNUR) on benzidine-based chemical substances; a SNUR for di-n-pentyl phthalate (DnPP) (1,2-benzenedicarboxylic acid, 1,2-dipentyl ester) (CAS No. 131-18-0); and a SNUR for alkanes, C12-13, chloro (CAS No. 71011-12-6). In the case of the......
75 FR 71688 - Certain New Chemicals; Receipt and Status Information
...Under sections 5(d)(2) and 5(d)(3) of the Toxic Substances Control Act (TSCA), EPA is required to publish in the Federal Register a notice of receipt of a premanufacture notice (PMN) or an application for a test marketing exemption (TME), and to publish in the Federal Register periodic status reports on the new chemicals under review and the receipt of notices of commencement (NOC) to begin......
Woo, Y T; Lai, D Y; Argus, M F; Arcos, J C
Since the inception of Section 5 (Premanufacturing/Premarketing Notification, PMN) of the Toxic Substances Control Act (TSCA), structure-activity relationship (SAR) analysis has been effectively used by U.S. Environmental Protection Agency's (EPA) Structure Activity Team (SAT) in the assessment of potential carcinogenic hazard of new chemicals for which test data are not available. To capture, systematize and codify the Agency's predictive expertise in order to make it more widely available to assessors outside the TSCA program, a cooperative project was initiated to develop a knowledge rule-based expert system to mimic the thinking and reasoning of the SAT. In this communication, we describe the overall structure of this expert system, discuss the scientific bases and principles of SAR analysis of chemical carcinogens used in the development of SAR knowledge rules, and delineate the major factors/rules useful for assessing the carcinogenic potential of fibers, polymers, metals/metalloids and several major classes of organic chemicals. An integrative approach using available short-term predictive tests and non-cancer toxicological data to supplement SAR analysis has also been described. PMID:7570659
[Physico-chemical profiling of centrally acting molecules for prediction of pharmacokinetic properties].
Physico-chemical profiling is a fundamental tool at the early stage of drug discovery in screening drug-like candidates. Complex physico-chemical profiling, including molecular properties such as solubility, ionization, lipophilicity and permeability, has been found to be of predictive power in ADME (absorption, distribution, metabolism, elimination). In the present thesis work, the physico-chemical properties of centrally acting compounds were investigated. We determined the protonation constants (K), the partition coeffitient in octanol/water (Poct) and cyclohexane/water (Pch) systems of antidepressive sertraline and 15 antipsychotic piperidine and piperazine derivatives and calculated the delta logP (logPoct-logPch) values of the molecules. Due to the poor water solubility of the compounds potentiometry using the "co-solvent" technique was applied for the determination of the protonation constants. The logP values were measured by the dual-phase potentiometric titration in octanol/water system and the traditional shake-flask method was used in cyclohexane/water system. Highly precise physico-chemical data were obtained by these validated methods. The relationship between the structure of the molecules and the physico-chemical data was investigated. The pharmacokinetic properties of the compounds were predicted by the physico-chemical parameters. Linear relationship has been found between the brain penetration characterized by the logBB values and the delta logP values. The validity of the equation was controlled by the delta logP and the logBB values of sertraline. PMID:18986088
Advances in Exposure Science (Washington, DC Modernized TSCA meeting)
I am describing current research from the Chemical Safety for Sustainability research program's Rapid Exposure and Dosimetry project that relates to predicting human exposure to environmental chemicals for thousands of chemicals.
Request for interim approval to operate Trench 94 of the 218-E-12B Burial Ground as a chemical waste landfill for disposal of polychlorinated biphenyl waste in submarine reactor compartments. Revision 2
This request is submitted to seek interim approval to operate a Toxic Substances Control Act (TSCA) of 1976 chemical waste landfill for the disposal of polychlorinated biphenyl (PCB) waste. Operation of a chemical waste landfill for disposal of PCB waste is subject to the TSCA regulations of 40 CFR 761. Interim approval is requested for a period not to exceed 5 years from the date of approval. This request covers only the disposal of small 10 quantities of solid PCB waste contained in decommissioned, defueled submarine reactor compartments (SRC). In addition, the request applies only to disposal 12 of this waste in Trench 94 of the 218-E-12B Burial Ground (Trench 94) in the 13 200 East Area of the US Department of Energy`s (DOE) Hanford Facility. Disposal of this waste will be conducted in accordance with the Compliance 15 Agreement (Appendix H) between the DOE Richland Operations Office (DOE-RL) and 16 the US Environmental Protection Agency (EPA), Region 10. During the 5-year interim approval period, the DOE-RL will submit an application seeking final 18 approval for operation of Trench 94 as a chemical waste landfill, including 19 any necessary waivers, and also will seek a final dangerous waste permit from 20 the Washington State Department of Ecology (Ecology) for disposal of lead 21 shielding contained in the SRCS.
... chemical classes that include short chain aliphatic nitrosamines, divalent metals, aldehydes, azo-dyes and... solvent/vehicle should not be suspected of chemical reaction with the test substance and shall...
40 CFR 711.6 - Chemical substances for which information is not required.
...) developed under the procedures of 40 CFR part 790, or is the subject of an order issued under TSCA section 5... living organism, and that meets the definition of microorganism at 40 CFR 725.3. Any chemical substance... occurring chemical substances. Any naturally occurring chemical substance, as described in 40 CFR...
A toxicokinetic study of specifically acting and reactive organic chemicals for the prediction of internal effect concentrations in Scenedesmus vacuolatus.
The toxic potency of chemicals is determined by using the internal effect concentration by accounting for differences in toxicokinetic processes and mechanisms of toxic action. The present study examines toxicokinetics of specifically acting and reactive chemicals in the green algae Scenedesmus vacuolatus by using an indirect method. Concentration depletion in the exposure medium was measured for chemicals of lower (log KOW < 3: isoproturon, metazachlor, paraquat) and moderate (log KOW 4-5: irgarol, triclosan, N-phenyl-2-naphthylamine) hydrophobicity at 7 to 8 time points over 240 min or 360 min. Uptake and overall elimination rates were estimated by fitting a toxicokinetic model to the observed concentration depletions. The equilibrium of exposure concentrations was reached within minutes to hours or was even not observed within the exposure time. The kinetics of bioconcentration cannot be explained by the chemical's hydrophobicity only, but influential factors such as ionization of chemicals, the ion trapping mechanism, or the potential susceptibility for biotransformation are discussed. Internal effect concentrations associated with 50% inhibition of S. vacuolatus reproduction were predicted by linking the bioconcentration kinetics to the effect concentrations and ranged from 0.0480 mmol/kg wet weight to 7.61 mmol/kg wet weight for specifically acting and reactive chemicals. Knowing the time-course of the internal effect concentration may promote an understanding of toxicity processes such as delayed toxicity, carry-over toxicity, or mixture toxicity in future studies. PMID:25263251
75 FR 57169 - Significant New Use Rules on Certain Chemical Substances
... Register of April 24, 1990 (55 FR 17376). Consult that preamble for further information on the objectives.../chemical properties of the PMN substance, as described in the New Chemical Program's PBT category (64 FR... includes one PMN substance (P-04-269) that is subject to a ``risk-based'' consent order under TSCA...
Two listed toxic chemicals were used at the Hanford Site above established activity thresholds: phosphoric acid and chlorine. Because total combined quantities of chlorine released, disposed, treated, recovered through recycle operations, co-combusted for energy recovery, and transferred to off-site locations for the purpose of recycle, energy recovery, treatment, and/or disposal, amounted to less than 500 pounds, the Hanford Site qualified for the alternate one million pound threshold for chlorine. Accordingly, this Toxic Chemical Release Inventory includes a Form A for chlorine, and a Form B for phosphoric acid.
...This final rule requires manufacturers (including importers) of cadmium or cadmium compounds, including as part of an article, that have been, or are reasonably likely to be, incorporated into consumer products to report certain unpublished health and safety studies to EPA. The Interagency Testing Committee (ITC), established under section 4(e) of the Toxic Substances Control Act (TSCA) to......
75 FR 3462 - Claims of Confidentiality of Certain Chemical Identities Submitted under Section 8(e) of the...
... AGENCY Claims of Confidentiality of Certain Chemical Identities Submitted under Section 8(e) of the Toxic... announcing a new general practice of reviewing submissions under section 8(e) of the Toxic Substances Control... section 8(e) of TSCA involves a chemical identity that is already listed on the public portion of the...
77 FR 15609 - Revocation of TSCA Section 4 Testing Requirements for Certain High Production Volume Chemical...
... Register (71 FR 13708, March 16, 2006) (FRL-7335-2). (Document ID number EPA-HQ-OPPT-2005-0033-0001). 2..., Substantial Release, and Substantial or Significant Human Exposure; Notice. Federal Register (58 FR 28736, May... regulatory action'' under Executive Order 12866, entitled ``Regulatory Planning and Review'' (58 FR...
40 CFR 749.68 - Hexavalent chromium-based water treatment chemicals in cooling systems.
... claim of confidentiality only to the extent permitted by section 14 of TSCA and 40 CFR part 2, subpart B... water treatment chemicals to prevent unreasonable risks associated with human exposure to air emissions... chromium air emissions increases the risk of lung cancer. Federal Law prohibits use of this substance...
77 FR 4947 - Proposed Significant New Use Rules on Certain Chemical Substances; Reopening of Comment Period
... in the Federal Register of December 28, 2011 (76 FR 81447) (FRL-9326-2). In that document, EPA...: Kenneth Moss, Chemical Control Division (7405M), Office of Pollution Prevention and Toxics, Environmental...; email address: moss.kenneth@epa.gov . For general information contact: The TSCA-Hotline,...
... water treatment chemicals to prevent unreasonable risks associated with human exposure to air emissions... municipality; any interstate body; and any department, agency, or instrumentality of the Federal Government... claim of confidentiality only to the extent permitted by section 14 of TSCA and 40 CFR part 2, subpart...
Background In mammals, ABCB1 constitutes a cellular “first line of defense” against a wide array of chemicals and drugs conferring cellular multidrug or multixenobiotic resistance (MDR/MXR). We tested the hypothesis that an ABCB1 ortholog serves as protection for the sensitive developmental processes in zebrafish embryos against adverse compounds dissolved in the water. Results Indication for ABCB1-type efflux counteracting the accumulation of chemicals in zebrafish embryos comes from experiments with fluorescent and toxic transporter substrates and inhibitors. With inhibitors present, levels of fluorescent dyes in embryo tissue and sensitivity of embryos to toxic substrates were generally elevated. We verified two predicted sequences from zebrafish, previously annotated as abcb1, by cloning; our synteny analyses, however, identified them as abcb4 and abcb5, respectively. The abcb1 gene is absent in the zebrafish genome and we explored whether instead Abcb4 and/or Abcb5 show toxicant defense properties. Quantitative real-time polymerase chain reaction (qPCR) analyses showed the presence of transcripts of both genes throughout the first 48 hours of zebrafish development. Similar to transporter inhibitors, morpholino knock-down of Abcb4 increased accumulation of fluorescent substrates in embryo tissue and sensitivity of embryos toward toxic compounds. In contrast, morpholino knock-down of Abcb5 did not exert this effect. ATPase assays with recombinant protein obtained with the baculovirus expression system confirmed that dye and toxic compounds act as substrates of zebrafish Abcb4 and inhibitors block its function. The compounds tested comprised model substrates of human ABCB1, namely the fluorescent dyes rhodamine B and calcein-am and the toxic compounds vinblastine, vincristine and doxorubicin; cyclosporin A, PSC833, MK571 and verapamil were applied as inhibitors. Additionally, tests were performed with ecotoxicologically relevant compounds: phenanthrene (a
02/04/2014 Committee on Environment and Public Works Subcommittee on Water and Wildlife. Hearings held. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:
Results of Hazardous and Mixed Waste Excavation from the Chemical Waste Landfill
Young, S. G.; Schofield, D. P.; Kwiecinski, D.; Edgmon, C. L.; Methvin, R.
77 FR 69824 - Certain New Chemicals; Receipt and Status Information
... required by TSCA section 5 to provide EPA with a PMN, before initiating the activity. Section 5(h)(1) of............ (S) Fragrance (S) 2- ingredient. octenenitrile,3,5,7- trimethyl-. P-13-0013 10/5/2012 1/2/2013 Dow Chemical (G) Open-non dispersive (G) Polyurethane Company. use. polymer. P-13-0014 10/8/2012 1/5/2013...
Cheminformatics and Computational Chemistry: A Powerful Combination for the Encoding of Process Science
The registration of new chemicals under the Toxicological Substances Control Act (TSCA) and new pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) requires knowledge of the process science underlying the transformation of organic chemicals in natural...
Cheminformatics Applications and Physicochemical Property Calculators: A Powerful Combination for the Encoding of Process Science
The registration of new chemicals under the Toxic Substances Control Act (TSCA) and new pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) requires knowledge of the process science underlying the transport and transformation of organic chemicals in n...
Use of QSAR validation principles to enhance predictive approaches in the US EPA ECOSAR model
The US EPA Office of Pollution Prevention and Toxics (OPPT) is responsible for implementing the Toxic Substances Control Act (TSCA). TSCA is the US law that regulates industrial chemicals in the US and OPPT evaluates both new chemicals entering commerce, as well as those chemica...
McRobb, Fiona M; Kufareva, Irina; Abagyan, Ruben
Endocrine disrupting chemicals (EDCs) pose a significant threat to human health, society, and the environment. Many EDCs elicit their toxic effects through nuclear hormone receptors, like the estrogen receptor α (ERα). In silico models can be used to prioritize chemicals for toxicological evaluation to reduce the amount of costly pharmacological testing and enable early alerts for newly designed compounds. However, many of the current computational models are overly dependent on the chemistry of known modulators and perform poorly for novel chemical scaffolds. Herein we describe the development of computational, three-dimensional multi-conformational pocket-field docking, and chemical-field docking models for the identification of novel EDCs that act via the ligand-binding domain of ERα. These models were highly accurate in the retrospective task of distinguishing known high-affinity ERα modulators from inactive or decoy molecules, with minimal training. To illustrate the utility of the models in prospective in silico compound screening, we screened a database of over 6000 environmental chemicals and evaluated the 24 top-ranked hits in an ERα transcriptional activation assay and a differential scanning fluorimetry-based ERα binding assay. Promisingly, six chemicals displayed ERα agonist activity (32nM-3.98μM) and two chemicals had moderately stabilizing effects on ERα. Two newly identified active compounds were chemically related β-adrenergic receptor (βAR) agonists, dobutamine, and ractopamine (a feed additive that promotes leanness in cattle and poultry), which are the first βAR agonists identified as activators of ERα-mediated gene transcription. This approach can be applied to other receptors implicated in endocrine disruption. PMID:24928891
In Silico Identification and Pharmacological Evaluation of Novel Endocrine Disrupting Chemicals That Act via the Ligand-Binding Domain of the Estrogen Receptor α
Kufareva, Irina; Abagyan, Ruben
Endocrine disrupting chemicals (EDCs) pose a significant threat to human health, society, and the environment. Many EDCs elicit their toxic effects through nuclear hormone receptors, like the estrogen receptor α (ERα). In silico models can be used to prioritize chemicals for toxicological evaluation to reduce the amount of costly pharmacological testing and enable early alerts for newly designed compounds. However, many of the current computational models are overly dependent on the chemistry of known modulators and perform poorly for novel chemical scaffolds. Herein we describe the development of computational, three-dimensional multi-conformational pocket-field docking, and chemical-field docking models for the identification of novel EDCs that act via the ligand-binding domain of ERα. These models were highly accurate in the retrospective task of distinguishing known high-affinity ERα modulators from inactive or decoy molecules, with minimal training. To illustrate the utility of the models in prospective in silico compound screening, we screened a database of over 6000 environmental chemicals and evaluated the 24 top-ranked hits in an ERα transcriptional activation assay and a differential scanning fluorimetry-based ERα binding assay. Promisingly, six chemicals displayed ERα agonist activity (32nM–3.98μM) and two chemicals had moderately stabilizing effects on ERα. Two newly identified active compounds were chemically related β-adrenergic receptor (βAR) agonists, dobutamine, and ractopamine (a feed additive that promotes leanness in cattle and poultry), which are the first βAR agonists identified as activators of ERα-mediated gene transcription. This approach can be applied to other receptors implicated in endocrine disruption. PMID:24928891
Chen, Haojun; Wang, Guohao; Lang, Lixin; Jacobson, Orit; Kiesewetter, Dale O.; Liu, Yi; Ma, Ying; Zhang, Xianzhong; Wu, Hua; Zhu, Lei; Niu, Gang; Chen, Xiaoyuan
The efficacy of therapeutic drugs is highly dependent on their optimal in vivo pharmacokinetics. Albumin conjugation is considered to be one of the most effective means of protracting the short lifespan of peptides and proteins. In this study, we proposed a novel platform for developing long lasting therapeutics by conjugating a small molecular albumin binding moiety, truncated Evans blue, to either peptides or proteins. Using the anti-diabetic peptide drug Exendin-4 as a model peptide, we synthesized a new long-acting Exendin-4 derivative (denoted as Abextide). Through complexation with albumin in situ, the biological half-life of Abextide was significantly extended. The hypoglycemic effect of Abextide was also improved remarkably over Exendin-4. Thus, Abextide has considerable potential to treat type 2 diabetes. This strategy as a general technology platform can be applied to other small molecules and biologics for the development of long-acting therapeutic drugs. PMID:26877782
The glossary contains chemical names and their synonyms for substances covered by the reporting requirements of SARA Title III, section 313. The glossary was developed to aid in determining whether a facility manufactures, processes, or otherwise uses a chemical subject to section 313 reporting. These synonyms are available to the EPA through the public literature, primarily CAS Online. The glossary is divided into two parts. Part 1 is a listing by CAS registry number. Part 2 contains names and synonyms in an alphabetical listing.
Common synonyms: For chemicals listed under Section 313 of the Emergency Planning and Community Right-To-Know act
This glossary contains chemical names and their synonyms for substances covered by the reporting requirements of SARA Title III, section 313. The glossary was developed to aid in determining whether a facility manufactures, processes, or otherwise uses a chemical subject to section 313 reporting. These synonyms are available to the EPA through the public literature, primarily CAS Online. The glossary is divided into two parts. Part 1 is a listing by CAS registry number. Part 2 contains names and synonyms in an alphabetical listing.
The creation of effective bioscavengers as a pretreatment for exposure to nerve agents is a challenging medical objective. We report a recombinant method using chemical polysialylation to generate bioscavengers stable in the bloodstream. Development of a CHO-based expression system using genes encoding human butyrylcholinesterase and a proline-rich peptide under elongation factor promoter control resulted in self-assembling, active enzyme multimers. Polysialylation gives bioscavengers with enhanced pharmacokinetics which protect mice against 4.2 LD50 of S-(2-(diethylamino)ethyl) O-isobutyl methanephosphonothioate without perturbation of long-term behavior. PMID:23297221
Elucidation of Pseurotin Biosynthetic Pathway Points to Trans-Acting C-Methyltransferase and Source of Chemical Diversity Generation**
Tsunematsu, Yuta; Fukutomi, Manami; Saruwatari, Takayoshi; Noguchi, Hiroshi; Watanabe, Kenji; Hotta, Kinya; Tang, Yi
Pseurotins comprise a family of structurally related Aspergillal natural products having interesting bioactivity. However, little is known about the biosynthetic steps involved in the formation of their complex chemical features. Here, we systematically deleted the pseurotin biosynthetic genes in A. fumigatus and performed in vivo and in vitro characterization of the tailoring enzymes to determine the biosynthetic intermediates and the gene products responsible for the formation of each intermediate. This allowed us to elucidate the main biosynthetic steps leading to the formation of pseurotin A from the predominant precursor, azaspirene. The study revealed the combinatorial nature of the biosynthesis of the pseurotin family of compounds and the intermediates. Most interestingly, we report the first identification of an epoxidase–C-methyltransferase bifunctional fusion protein PsoF that appears to methylate the nascent polyketide backbone carbon atom in trans. PMID:24939566
77 FR 34777 - Seventieth Report of the TSCA Interagency Testing Committee to the Administrator of the...
... dermal absorption rate data, and 164 High Production Volume (HPV) Challenge Program orphan chemicals; a...-(1,1,3,3- Recommended. tetramethylbutyl)-. 55 December 2004...... 161 High Production Volume (HPV) Recommended. Challenge Program orphan chemicals. 56 August 2005........ 3 HPV Challenge Program...
... chemical substances. Suitable cell lines include L5178Y mouse lymphoma cells, the CHO, AS52 and V79 lines.... Differential Mutant Quantitation at the Mouse Lymphoma TK and CHO HGPRT Loci. Mutagenesis. 4, 394-403 (1989...., Batson, A.G., and Clive, D. Eds. Kilbey, B.J. et al. Procedures for the L5178Y/TK=/− > TK=/−...
75 FR 80665 - Sixty-Seventh Report of the TSCA Interagency Testing Committee to the Administrator of the...
... chemicals with insufficient dermal absorption rate data, and 207 High Production Volume (HPV) Challenge... (HPV) Recommended. Challenge Program orphan chemicals. 56 August 2005 4 HPV Challenge Program...
Bruderer, Shirin; Hurst, Noémie; de Kanter, Ruben; Miraval, Tommaso; Pfeifer, Thomas; Donazzolo, Yves; Dingemanse, Jasper
Emerging resistance to antimalarial agents raises the need for new drugs. ACT-451840 is a new compound with potent activity against sensitive and resistant Plasmodium falciparum strains. This was a first-in-humans single-ascending-dose study to investigate the safety, tolerability, and pharmacokinetics of ACT-451840 across doses of 10, 50, 200, and 500 mg in healthy male subjects. In the 200- and 500-mg dose groups, the effect of food was investigated, and antimalarial activity was assessed using an ex vivo bioassay with P. falciparum. No (serious) adverse events leading to discontinuation were reported. At the highest dose level, the peak drug concentration (Cmax) and the area under the plasma concentration-time curve from zero to infinity of ACT-451840 under fasted conditions reached 11.9 ng/ml and 100.6 ng·h/ml, respectively, and these were approximately 13-fold higher under fed conditions. Food did not affect the half-life (approximately 34 h) of the drug, while the Cmax was attained 2.0 and 3.5 h postdose under fasted and fed conditions, respectively. The plasma concentrations estimated by the bioassay were approximately 4-fold higher than those measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Several potentially active metabolites were also identified. ACT-451840 was well tolerated across all doses. Exposure to ACT-451840 significantly increased with food. The bioassay indicated the presence of circulating active metabolites. (This study has been registered at ClinicalTrials.gov under registration no. NCT02186002.). PMID:25421475
Bruderer, Shirin; Hurst, Noémie; de Kanter, Ruben; Miraval, Tommaso; Pfeifer, Thomas; Donazzolo, Yves
Emerging resistance to antimalarial agents raises the need for new drugs. ACT-451840 is a new compound with potent activity against sensitive and resistant Plasmodium falciparum strains. This was a first-in-humans single-ascending-dose study to investigate the safety, tolerability, and pharmacokinetics of ACT-451840 across doses of 10, 50, 200, and 500 mg in healthy male subjects. In the 200- and 500-mg dose groups, the effect of food was investigated, and antimalarial activity was assessed using an ex vivo bioassay with P. falciparum. No (serious) adverse events leading to discontinuation were reported. At the highest dose level, the peak drug concentration (Cmax) and the area under the plasma concentration-time curve from zero to infinity of ACT-451840 under fasted conditions reached 11.9 ng/ml and 100.6 ng · h/ml, respectively, and these were approximately 13-fold higher under fed conditions. Food did not affect the half-life (approximately 34 h) of the drug, while the Cmax was attained 2.0 and 3.5 h postdose under fasted and fed conditions, respectively. The plasma concentrations estimated by the bioassay were approximately 4-fold higher than those measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Several potentially active metabolites were also identified. ACT-451840 was well tolerated across all doses. Exposure to ACT-451840 significantly increased with food. The bioassay indicated the presence of circulating active metabolites. (This study has been registered at ClinicalTrials.gov under registration no. NCT02186002.) PMID:25421475
75 FR 5405 - Sixty-Fifth Report of the TSCA Interagency Testing Committee to the Administrator of the...
... Register issue of January 28, 2008 (73 FR 4861) (FRL-8344-5) available on-line at http://www.epa.gov... alkylphenols, 12 lead compounds, 16 chemicals with insufficient dermal absorption rate data, and 207 HPV... Volume (HPV) Challenge Program orphan chemicals 56 August 2005 4 HPV Challenge Program Recommended...
... address set forth in § 710.39. (3) The specific chemical name and Chemical Abstracts Service (CAS... CONTROL ACT TSCA CHEMICAL INVENTORY REGULATIONS 2002 Inventory Update Reporting § 710.32 Reporting... section for each chemical substance described in § 710.25 that the person manufactured for...
Curcumin, or diferuloylmethane, a polyphenolic molecule isolated from the rhizome of Curcuma longa, is reported to modulate multiple molecular targets involved in cancer and inflammatory processes. On the basis of its pan-inhibitory characteristics, here we show that simple chemical modifications of the curcumin scaffold can regulate its biological selectivity. In particular, the curcumin scaffold was modified with three types of substituents at positions C-1, C-8, and/or C-8' [C5 (isopentenyl, 5-8), C10 (geranyl, 9-12), and C15 (farnesyl, 13, 14)] in order to make these molecules more selective than the parent compound toward two specific targets: histone deacetylase (HDAC) and microsomal prostaglandin E2 synthase-1 (mPGES-1). From combined in silico and in vitro analyses, three selective inhibitors by proper substitution at position 8 were revealed. Compound 13 has improved HDAC inhibitory activity and selectivity with respect to the parent compound, while 5 and 9 block the mPGES-1 enzyme. We hypothesize about the covalent interaction of curcumin, 5, and 9 with the mPGES-1 binding site. PMID:26588603
77 FR 20354 - Meetings; Sunshine Act
... From the Federal Register Online via the Government Publishing Office CHEMICAL SAFETY AND HAZARD INVESTIGATION BOARD Meetings; Sunshine Act The U.S. Chemical Safety and Hazard Investigation Board (CSB... Nemours and Co. Inc. chemical plant in Buffalo, New York. The incident involved a contract welder...
PEER REVIEW OF THE PERSISTENT, BIOACCUMULATIVE, AND TOXIC (PBT) PROFILER
The U.S. EPA is required, under Sections 4, 5, and 6 of the Toxic Substances Control Act (TSCA), to screen chemicals for potential risk to humans and the environment. OPPT has developed computerized methods designed to support screening-level assessment of chemicals in the absen...
77 FR 19861 - Certain Polybrominated Diphenylethers; Significant New Use Rule and Test Rule
...The Agency is proposing to amend the Toxic Substances Control Act (TSCA) section 5(a) Significant New Use Rule (SNUR), for certain polybrominated diphenylethers (PBDEs) by: Designating processing of six PBDEs, or any combination of these chemical substances resulting from a chemical reaction, as a significant new use; designating manufacturing, importing, and processing of a seventh PBDE,......
40 CFR 710.4 - Scope of the inventory.
... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Scope of the inventory. 710.4 Section 710.4 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT COMPILATION OF THE TSCA CHEMICAL SUBSTANCE INVENTORY § 710.4 Scope of the inventory. (a) Chemical substances subject to these regulations....
77 FR 17386 - Significant New Use Rule for Hexabromocyclododecane and 1,2,5,6,9,10-Hexabromocyclododecane
...EPA is proposing a significant new use rule (SNUR) under section 5(a)(2) of the Toxic Substances Control Act (TSCA) for two chemical substances: Hexabromocyclododecane (Chemical Abstracts Service Registry Number (CASRN) 25637-99-4) and 1,2,5,6,9,10- hexabromocyclododecane (CASRN 3194-55-6), hereinafter collectively referred to as HBCD. This proposed rule would designate ``use in consumer......
Microorganisms and Chemical Pollution
Discusses the importance of microorganisms in chemical pollution and pollution abatement. Selected chemical pollutants are chosen to illustrate that microorganisms synthesize hazardous substances from reasonably innocuous precursors, while others act as excellent environmental decontaminating agents by removing undesirable natural and synthetic…
... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Electronic filing. 711.35 Section 711.35 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT TSCA CHEMICAL DATA REPORTING REQUIREMENTS § 711.35 Electronic filing. (a) You must use e-CDRweb...
... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Electronic filing. 711.35 Section 711.35 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT TSCA CHEMICAL DATA REPORTING REQUIREMENTS § 711.35 Electronic filing. (a) You must use e-CDRweb...
40 CFR 710.58 - Confidentiality.
... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT TSCA CHEMICAL INVENTORY REGULATIONS Inventory Update Reporting for 2006 and Beyond § 710.58 Confidentiality. (a... Inventory File as of the time the report is submitted for that substance under this subpart. The...
76 FR 77224 - Access to Confidential Business Information by Primus Solutions, Inc.
... Toxic Substances Control Act (TSCA). Some of the information may be claimed or determined to be... interest to all who manufacture, process, or distribute industrial chemicals. Since other entities may also... information is not publicly available, e.g., CBI or other information whose disclosure is restricted...
77 FR 29635 - Access to Confidential Business Information by Several Student Services Contractors
... Control Act (TSCA). Some of the information may be claimed or determined to be Confidential Business... interest to all who manufacture, process, or distribute industrial chemicals. Since other entities may also... information is not publicly available, e.g., CBI or other information whose disclosure is restricted...
78 FR 67139 - Access to Confidential Business Information by Eastern Research Group and Its Identified...
... sections of the Toxic Substances Control Act (TSCA). Some of the information may be claimed or determined... interest to all who manufacture, process, or distribute industrial chemicals. Since other entities may also... information is not publicly available, e.g., CBI or other information whose disclosure is restricted...
... has been submitted to EPA under all sections of the Toxic Substances Control Act (TSCA). Some of the... manufacture, process or distribute industrial chemicals. Since other entities may also be interested, the... available, e.g., CBI or other information whose disclosure is restricted by statute. Certain other...
40 CFR 710.50 - Activities for which reporting is not required.
... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Activities for which reporting is not... SUBSTANCES CONTROL ACT TSCA CHEMICAL INVENTORY REGULATIONS Inventory Update Reporting for 2006 and Beyond § 710.50 Activities for which reporting is not required. A person described in § 710.48 is not...
40 CFR 710.30 - Activities for which reporting is not required.
... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Activities for which reporting is not... SUBSTANCES CONTROL ACT TSCA CHEMICAL INVENTORY REGULATIONS 2002 Inventory Update Reporting § 710.30 Activities for which reporting is not required. A person described in § 710.28 is not subject to...
SAMPLING FOR ORGANIC CHEMICALS IN AIR
Organic chemicals by far account for the majority of pollutants found in air. ore than 90% of the 75,000 chemicals listed in EPA's Toxic Substances Control Act Chemical Substance Inventory and 88% of the 189 Hazardous Air Pollutants (HAPS) named in the Clean Air Act Amendments of...
BINDING OF CHEMICAL CARCINOGENS AND MUTAGENS TO RAT HEMOGLOBIN
The alkylation of hemoglobin is a proposed dose monitor for chemical carcinogens and mutagens. The binding of fifteen chemical carcinogens and mutagens to rat hemoglobin was determined. Direct acting carcinogens and indirect acting carcinogens including aromatic amines, halogenat...
The CounterACT Research Network
Jett, David A.; Yeung, David T.
The National Institutes of Health has developed a comprehensive research program that includes research centers of excellence, individual research projects, small business projects, contracts, and interagency agreements to conduct basic, translational, and clinical research aimed at the discovery and/or identification of better medical countermeasures against chemical threat agents. Chemical threats include chemical warfare agents, toxic industrial and agricultural chemicals, and toxins and other chemicals that could be used intentionally as an act of terror or by large-scale accidents or natural disasters. The overarching goal of this research program is to enhance our medical response capabilities during an emergency. The program is named Countermeasures Against Chemical Threats (CounterACT). It supports translational research, applying ideas, insights, and discoveries generated through basic scientific inquiry to the treatment or prevention of mortality and morbidity caused by chemical threat agents. The categories of research supported under this program include creation and development of screening assays and animal models for therapy development, identification of candidate therapeutics, obtaining preliminary proof-of-principle data on the efficacy of candidate therapeutics, advanced efficacy and preclinical safety studies with appropriate animal models using Good Laboratory Practices (GLP), and clinical studies, including clinical trials with new drugs. Special consideration is given to research relevant to people who are particularly vulnerable, including the young, the elderly, and individuals with pre-existing medical conditions. PMID:20601628
... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Chemical substances for testing. 766... SUBSTANCES CONTROL ACT DIBENZO-PARA-DIOXINS/DIBENZOFURANS Specific Chemical Testing/Reporting Requirements § 766.25 Chemical substances for testing. (a) Listing of chemical substances. Chemical...
... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Chemical substances for testing. 766... SUBSTANCES CONTROL ACT DIBENZO-PARA-DIOXINS/DIBENZOFURANS Specific Chemical Testing/Reporting Requirements § 766.25 Chemical substances for testing. (a) Listing of chemical substances. Chemical...
... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Chemical substances for testing. 766... SUBSTANCES CONTROL ACT DIBENZO-PARA-DIOXINS/DIBENZOFURANS Specific Chemical Testing/Reporting Requirements § 766.25 Chemical substances for testing. (a) Listing of chemical substances. Chemical...
... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Chemical substances for testing. 766... SUBSTANCES CONTROL ACT DIBENZO-PARA-DIOXINS/DIBENZOFURANS Specific Chemical Testing/Reporting Requirements § 766.25 Chemical substances for testing. (a) Listing of chemical substances. Chemical...