scholarly journals Development of a New Threshold of Toxicological Concern Database of Non-cancer Toxicity Endpoints for Industrial Chemicals

2021 ◽  
Vol 3 ◽  
Author(s):  
Takashi Yamada ◽  
Masayuki Kurimoto ◽  
Akihiko Hirose ◽  
Chihae Yang ◽  
James F. Rathman
Keyword(s):  
Daily Intake ◽  
Hazard Evaluation ◽  
Industrial Chemicals ◽  
Subchronic Toxicity ◽  
Chemical Structures ◽  
Class A ◽  
Repeated Dose Toxicity ◽  
Threshold Of Toxicological Concern ◽  
Point Of Departure ◽  
Unique Chemical

In cases where chemical-specific toxicity data are absent or limited, the threshold of toxicological concern (TTC) offers an alternative to assess human exposure below which “there would be no appreciable risk to human health.” The application of TTC to non-cancer systemic endpoints has been pursued for decades using a chemical classification and Point of Departure (POD). This study presents a new POD dataset of oral subacute/subchronic toxicity studies in rats for 656 industrial chemicals retrieved from the Hazard Evaluation Support System (HESS) Integrated Platform, which contains hundreds of reliable repeated-dose toxicity test data of industrial chemicals under the Chemical Substances of Control Law in Japan. The HESS TTC dataset was found to have less duplication with substances in other reported TTC datasets. Each chemical was classified into a Cramer Class, with 68, 3, and 29% of these 656 chemicals distributed in Classes III, II, and I, respectively. For each Cramer Class, a provisional Tolerable Daily Intake (TDI) was derived from the 5th percentile of the lognormal distribution of PODs. The TDIs were 1.9 and 30 μg/kg bw/day for Classes III and I, respectively. The TDI for Cramer Class II could not be determined due to insufficient sample size. This work complements previous studies of the TTC approach and increases the confidence of the thresholds for non-cancer endpoints by including unique chemical structures. This new TTC dataset is publicly available and can be merged with existing databases to improve the TTC approach.

Chitosan in Biomedical Engineering: A Critical Review

2019 ◽  
Vol 14 (2) ◽  
pp. 93-116 ◽  
Author(s):  
Shabnam Mohebbi ◽  
Mojtaba Nasiri Nezhad ◽  
Payam Zarrintaj ◽  
Seyed Hassan Jafari ◽  
Saman Seyed Gholizadeh ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Biomedical Engineering ◽  
Biological Properties ◽  
Advanced Materials ◽  
Comprehensive Overview ◽  
Chemical Structures ◽  
Bio Imaging ◽  
Significant Attention ◽  
Unique Chemical

Biomedical engineering seeks to enhance the quality of life by developing advanced materials and technologies. Chitosan-based biomaterials have attracted significant attention because of having unique chemical structures with desired biocompatibility and biodegradability, which play different roles in membranes, sponges and scaffolds, along with promising biological properties such as biocompatibility, biodegradability and non-toxicity. Therefore, chitosan derivatives have been widely used in a vast variety of uses, chiefly pharmaceuticals and biomedical engineering. It is attempted here to draw a comprehensive overview of chitosan emerging applications in medicine, tissue engineering, drug delivery, gene therapy, cancer therapy, ophthalmology, dentistry, bio-imaging, bio-sensing and diagnosis. The use of Stem Cells (SCs) has given an interesting feature to the use of chitosan so that regenerative medicine and therapeutic methods have benefited from chitosan-based platforms. Plenty of the most recent discussions with stimulating ideas in this field are covered that could hopefully serve as hints for more developed works in biomedical engineering.

Management of Sludge Use on Land

1978 ◽  
Vol 41 (6) ◽  
pp. 476-480 ◽  
Author(s):  
CHARLES F. JELINEK ◽  
GEORGE L. BRAUDE
Keyword(s):  
Environmental Protection Agency ◽  
Daily Intake ◽  
Industrial Chemicals ◽  
Lead And Cadmium ◽  
Federal Water Pollution Control ◽  
Food And Feed ◽  
Special Concern ◽  
Cadmium Lead ◽  
Daily Intakes ◽  
Persistent Pesticides

Passage of the Federal Water Pollution Control Act in 1972 has caused a huge increase in the amount of sewage sludge for disposal. The Food and Drug Administration has worked with the Environmental Protection Agency and other agencies to recommend proper management of the application of sludges to food and feed crops to ensure the safety and wholesomeness of the food supply. FDA's concerns about contamination of food by pathogenic microorganisms, heavy metals, persistent pesticides and industrial chemicals such as polychlorinated biphenyls (PCBs) are described. The reasons for special concern about direct application of sludge onto growing food and feed crops are discussed. The estimated daily intake of lead and cadmium, as compared to the proposed tolerable daily intakes, is presented, together with FDA's program to develop sufficient data on the natural background levels of these metals in raw agricultural products. Limitations recommended to prevent hazardous cadmium, lead, PCB and pathogen contaminations of food and feeds by sludge are presented.

Pesticides, Selected Elements, and Other Chemicals in Adult Total Diet Samples, October 1978-September 1979

1985 ◽  
Vol 68 (5) ◽  
pp. 862-875 ◽  
Author(s):  
Marcia J Gartrell ◽  
John C Craun ◽  
David S Podrebarac ◽  
Ellis L Gunderson
Keyword(s):  
Daily Intake ◽  
Food Group ◽  
Average Concentration ◽  
Food Groups ◽  
Industrial Chemicals ◽  
Food Items ◽  
Total Diet ◽  
The Individual ◽  
Daily Intakes ◽  
Calculated Average

Abstract The U.S. Food and Drug Administration (FDA) conducts Total Diet Studies to determine the dietary intake of selected pesticides, industrial chemicals, and elements (including radionuclides). These studies involve the retail purchase and analysis of foods representative of the diets of infants, toddlers, and adults. The individual food items are separated into a number of food groups, each of which is analyzed as a composite. This report summarizes the results for adult Total Diet samples collected in 20 cities between October 1978 and September 1979. The average concentration, range of concentrations, and calculated average daily intake of each chemical found are presented by food group. The average daily intakes of the chemicals are similar to those found in the several preceding years and are within acceptable limits. The results for samples collected during the same period that represent the diets of infants and toddlers are reported separately.

Pesticides, Selected Elements, and Other Chemicals in Infant and Toddler Total Diet Samples, October 1979-September 1980

1985 ◽  
Vol 68 (6) ◽  
pp. 1184-1197
Author(s):  
Marcia J Gartrell ◽  
John C Craun ◽  
David S Podrebarac ◽  
Ellis L Gunderson
Keyword(s):  
Daily Intake ◽  
Food Group ◽  
Average Concentration ◽  
Food Groups ◽  
Industrial Chemicals ◽  
Total Diet ◽  
The Individual ◽  
Daily Intakes ◽  
Adult Diet ◽  
Calculated Average

Abstract The U.S. Food and Drug Administration (FDA) conducts Total Diet Studies to determine the dietary intake of selected pesticides, industrial chemicals, and elements (including radionuclides). These studies involve the retail purchase and analysis of foods representative of the diets of infants, toddlers, and adults. The individual food items are separated into a number of food groups, each of which is analyzed as a composite. This report summarizes the results for infant and toddler Total Diet samples collected in 10 cities between October 1979 and September 1980. The average concentration, range of concentrations, and calculated average daily intake of each chemical found are presented by food group. The average daily intakes of the chemicals are similar to those found in the several preceding years and generally are within acceptable limits. The results for samples collected during the same period that represent the adult diet are reported separately.

scholarly journals Risk Assessment Paradigm for Glutamate

2018 ◽  
Vol 73 (Suppl. 5) ◽  
pp. 53-64 ◽  
Author(s):  
Ashley Roberts ◽  
Barry Lynch ◽  
Ivonne M.C.M. Rietjens
Keyword(s):  
Safety Assessment ◽  
Developmental Toxicity ◽  
Reproductive Toxicity ◽  
Daily Intake ◽  
Toxicity Study ◽  
Acceptable Daily Intake ◽  
Uncertainty Factor ◽  
Point Of Departure ◽  
Breast Fed ◽  
Toxicokinetic Data

Background: Re-evaluation of the use of glutamic acid and glutamate salts (referred to as glutamate hereafter) by the European Food Safety Authority (EFSA) proposed a group acceptable daily intake (ADI) of 30 mg/kg body weight (bw)/day. Summary: This ADI is below the normal dietary intake, while even intake of free glutamate by breast-fed babies can be above this ADI. In addition, the pre-natal developmental toxicity study selected by EFSA, has never been used by regulatory authorities worldwide for the safety assessment of glutamate despite it being available for nearly 40 years. Also, the EFSA ignored that toxicokinetic data provide support for eliminating the use of an uncertainty factor for interspecies differences in kinetics. Key Messages: A 3-generation reproductive toxicity study in mice that includes extensive brain histopathology, provides a better point of departure showing no effects up to the highest dose tested of 6,000 mg/kg bw/day. Furthermore, kinetic data support use of a compound-specific uncertainty factor of 25 instead of 100. Thus, an ADI of at least 240 mg/kg bw/day would be indicated. In fact, there is no compelling evidence to indicate that the previous ADI of “not specified” warrants any change.

Hepatocarcinogenesis: How Do Peroxisome Proliferators Relate?

1992 ◽  
Vol 11 (3) ◽  
pp. 363-367 ◽  
Author(s):  
Emmanuel Farber
Keyword(s):  
Cell Cancer ◽  
Peroxisome Proliferation ◽  
Peroxisome Proliferators ◽  
Industrial Chemicals ◽  
Carcinogenic Activity ◽  
Chemical Structures ◽  
Reductase Inhibitors ◽  
Hmg Coa Reductase Inhibitors ◽  
Hepatic Lesions ◽  
Coa Reductase

There is an increasing awareness that many peroxisome proliferators are being introduced into our environment and many of these have shown carcinogenic activity in some rodent species. The agents involved include drugs (e.g., hypolipdemic agents of several chemical structures including HMG CoA reductase inhibitors) and industrial chemicals. The neoplasms seen are mainly in the liver with a variable incidence in the pancreas. The association between peroxisome proliferation and neoplasms is impressive. Yet, there are several seemingly fundamental differences between carcinogenic peroxisome proliferators and mutagenic or genotoxic chemical carcinogens. Peroxisome proliferators in general are neither mutagenic nor genotoxic and do not induce precancerous hepatic lesions and liver cell cancer until they have reached the late stage. With many agents, it appears that a considerable degree of peroxisome proliferation must take place for them to be carcinogenic. One poorly documented speculation is that peroxisome proliferators induce cancer by acting mainly as promoters, presupposing that the animals being tested are “preinitiated,” a conclusion that is scientifically indefensible. This presentation covers a comparison between the key requirements for cancer development with genotoxic agents and those seen with peroxisome proliferators, and discusses the methylation of genes for selective enzymes of the resistance phenotype induced by mutagenic carcinogens.

scholarly journals Natural Indole Alkaloids from Marine Fungi: Chemical Diversity and Biological Activities

2021 ◽  
Author(s):  
Jiao Li ◽  
Chun-Lin Zhuang
Keyword(s):  
Marine Fungi ◽  
Biological Activities ◽  
Indole Alkaloids ◽  
Structural Diversity ◽  
Heterocyclic Ring ◽  
Chemical Diversity ◽  
Pharmaceutical Development ◽  
Chemical Structures ◽  
Clinical Drugs ◽  
Unique Chemical

The indole scaffold is one of the most important heterocyclic ring systems for pharmaceutical development, and serves as an active moiety in several clinical drugs. Fungi derived from marine origin are more liable to produce novel indole-containing natural products due to their extreme living environments. The indole alkaloids from marine fungi have drawn considerable attention for their unique chemical structures and significant biological activities. This review attempts to provide a summary of the structural diversity of marine fungal indole alkaloids including prenylated indoles, diketopiperazine indoles, bisindoles or trisindoles, quinazoline-containing indoles, indole-diterpenoids, and other indoles, as well as their known biological activities, mainly focusing on cytotoxic, kinase inhibitory, antiinflammatory, antimicrobial, anti-insecticidal, and brine shrimp lethal effects. A total of 306 indole alkaloids from marine fungi have been summarized, covering the references published from 1995 to early 2021, expecting to be beneficial for drug discovery in the future.

scholarly journals Whole genome sequence of Peribacillus sp. MUM 13 derived from mangrove forest in Malaysia

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hooi-Leng Ser ◽  
Jodi Woan-Fei Law ◽  
Wen-Si Tan ◽  
Wai-Fong Yin ◽  
Kok-Gan Chan ◽  
...  
Keyword(s):  
Genome Analysis ◽  
Mangrove Forest ◽  
Screening Program ◽  
Gene Clusters ◽  
Bioinformatic Analysis ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Chemical Structures ◽  
Pathogenic Microbes ◽  
Unique Chemical

Acting like mini-factories, microorganisms are a valuable source of naturalbioactive compounds of unique chemical structures. Peribacillus sp. MUM 13 was recoveredfrom the mangrove forest in Malaysia during a screening program for bioactive microbes.Whole genome analysis revealed that the genome size of MUM 13 as 4,649,225 bp (with G+ C content of 40.8 %). Bioinformatic analysis predicted the presence of lassopeptidebiosynthetic gene clusters within the genome of MUM 13, which indicates the bioactivepotential of the strain and calls for further experiments to explore the strain characteristics,particularly in combatting against pathogenic microbes.

scholarly journals Uncovering Novel Peptide Chemistry from Bacterial Natural Products

2021 ◽  
Vol 75 (6) ◽  
pp. 543-547
Author(s):  
Florian Hubrich ◽  
Alessandro Lotti ◽  
Thomas A. Scott ◽  
Jörn Piel
Keyword(s):  
Natural Products ◽  
Bioactive Peptides ◽  
Biological Activities ◽  
Biological Properties ◽  
Post Translational Modifications ◽  
Peptide Chemistry ◽  
Chemical Structures ◽  
Therapeutic Value ◽  
Modified Peptides ◽  
Unique Chemical

Nature has evolved a remarkable array of biosynthetic enzymes that install diverse chemistries into natural products (NPs), bestowing them with a range of important biological properties that are of considerable therapeutic value. This is epitomized by the ribosomally synthesized and post-translationally modified peptides (RiPPs), a class of peptide natural products that undergo extensive post-translational modifications to produce structurally diverse bioactive peptides. In this review, we provide an overview of our research into the proteusin RiPP family, describing characterized members and the maturation enzymes responsible for their unique chemical structures and biological activities. The diverse enzymology identified in the first two proteusin pathways highlights the enormous potential of the RiPP class for new lead structures and novel pharmacophore-installing maturases as biocatalytic tools for drug discovery efforts.

scholarly journals Detoxification of the Fumonisin Mycotoxins in Maize: An Enzymatic Approach

Toxins ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 523 ◽  
Author(s):  
Johanna Alberts ◽  
Gerd Schatzmayr ◽  
Wulf-Dieter Moll ◽  
Ibtisaam Davids ◽  
John Rheeder ◽  
...  
Keyword(s):  
Kinetic Parameters ◽  
Reduction Method ◽  
Daily Intake ◽  
Aqueous Environment ◽  
Relative Distribution ◽  
Enzyme Kinetic ◽  
Chemical Structures ◽  
Enzymatic Reduction ◽  
Maize Kernels ◽  
Enzymatic Detoxification

Enzymatic detoxification has become a promising approach for control of mycotoxins postharvest in grains through modification of chemical structures determining their toxicity. In the present study fumonisin esterase FumD (EC 3.1.1.87) (FUMzyme®; BIOMIN, Tulln, Austria), hydrolysing fumonisin (FB) mycotoxins by de-esterification, was utilised to develop an enzymatic reduction method in a maize kernel enzyme incubation mixture. Efficacy of the FumD FB reduction method in “low” and “high” FB contaminated home-grown maize was compared by monitoring FB1 hydrolysis to the hydrolysed FB1 (HFB1) product utilising a validated LC-MS/MS analytical method. The method was further evaluated in terms of enzyme activity and treatment duration by assessing enzyme kinetic parameters and the relative distribution of HFB1 between maize kernels and the residual aqueous environment. FumD treatments resulted in significant reduction (≥80%) in “low” (≥1000 U/L, p < 0.05) and “high” (100 U/L, p < 0.05; ≥1000 U/L, p < 0.0001) FB contaminated maize after 1 h respectively, with an approximate 1:1 µmol conversion ratio of FB1 into the formation of HFB1. Enzyme kinetic parameters indicated that, depending on the activity of FumD utilised, a significantly (p < 0.05) higher FB1 conversion rate was noticed in “high” FB contaminated maize. The FumD FB reduction method in maize could find application in commercial maize-based practices as well as in communities utilising home-grown maize as a main dietary staple and known to be exposed above the tolerable daily intake levels.

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