Toxicology

In my thought carring test for more concentrations involving the concentration leading to 100%mortality is necessary to obtain LC50 value. 

Acetogenins which contain acetylene functionalities are present in  Liagora farinos.These compounds are lethal at 5–8 μg/ml range and your selected doses may have high concentration which is responsible for mortality.

Dear Dr

Only abstract is in English.

https://www.researchgate.net/publication/282862656_Investigate_health_hazardous_of_nanotechnology_and_Nano-particles_application

Regards

Please read this paper

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC91802/

It seems that this  subject is still not settled and no full consensus on the matter had  been established. Some try to adopt the duration of disease or toxicity on drug administration. Even some information are realy confusing. The clear-cut answere which I think practical is: Acute- single or multiple administration and observation for one day;

Subacute -two days-several days or weeks (up to 29 days); Subchronic-30- 90 days; 

Chronic: Above 90 days. 

 ARTICLE published,  environmental science, water quality improving.
http://5bio5.blogspot.ru/2017/06/3006unioexplanation-of-novelty.html;

Freshwater mussel, Unio tumidus  (the swollen river mussel);

https://www.researchgate.net/publication/10614386 ; 
Reference;
Ostroumov S.A. Responses of Unio tumidus to mixed chemical preparations and the hazard of synecological summation of anthropogenic effects. - Doklady Biological Science (Dokl. Biol. Sci.), 2001, 380: 492-495. 

Responses of Unio tumidus to mixed chemical preparations and the hazard of synecological summation of anthropogenic effects. https://www.researchgate.net/publication/10614386; [discovery of toxic effects of detergents on freshwater mussels];. Available from: https://www.researchgate.net/publication/10614386_Responses_of_Unio_tumidus_to_mixed_chemical_preparations_and_the_hazard_of_synecological_summation_of_anthropogenic_effects_httpswwwresearchgatenetpublication10614386_discovery_of_toxic_effects_of_det [accessed Jun 30, 2017].

EXPLANATION OF SOME OF NEW FACTS DISCOVERED IN THIS ARTICLE:
Unio tumidus, freshwater mussel (the swollen river mussel) , is a common species of  molluscs (mollusks) in freshwaters (e.g., streams, rivers). These molluscs filter water. By doing so, they contribute to improving water quality (water self-purification). In this publication, the author reports his new experiments, which discovered toxicity of detergents to freshwater mussel. As a result, the filtration activity of the mollusc slows down, with bad and catastrophic consequenses to water quality.

EXPLANATION/COMMENT ABOUT NEW IDEAS, NEW FUNDAMENTAL CONCEPTS IN THIS ARTICLE:

in this paper, the author formulated a new idea that is presented in a concise form as a new term coined by the author, namely, 'synecological summation of anthropogenic effects'. One of the anthropogenic effects under consideration in this article is the toxic effect of detergents on the freshwater mussel, namely, a decrease in water filtration by the mollusc. Another anthropogenic effect considered is the effect of phosphorus load on algae. You need to read the publication to learn more on this new concept of 
'synecological summation of anthropogenic effects'. 

Thanks

Dear sayed

Thank your for valuable answer.

Then i want one more clarification. There is Integrated bio marker response is used as a measurement of different bio markers. Then how to use this calculation for the measurement of all the bio-markers. what is the equation for use this integrated bio marker response? how to use the equation? what is the purpose of this calculation?

DMSO is toxic in high concentration- you must dilute it 1000 fold for drug solvent.

Dear Dr.Uthpala Jayawardena because of its high dissociation value toxicity of lead acetate is higher  lead sulfate.  

If severe bleeding, more hands may be needed. Universal energy does activate yang qi.

Does the Anesthetic Urethane Influence the Pharmacokinetics of Drugs?

https://www.ncbi.nlm.nih.gov/pubmed/22225247

Check the following

http://file.scirp.org/pdf/AiM_2014011315223073.pdf

www.nrcmushroom.org/book-cultivation-merged.pdf

www.cals.uidaho.edu/edcomm/pdf/cis/cis1077.pdf

https://www.usitc.gov/publications/332/ITS_7.pdf

https://www.mushroomcompany.com/resources/background/attramushroom.pdf

Thank you sir. I found that in case of fluoranthene and phenanthrene the RPV of PHEN is 0. But it makes me wonder what I should do with other combined peaks like 

1) BaA + Chry

2) Ind + BghiP

3) FLU + ACP

Should i consider that complete peak of the compound with high RPF or TEF? Though i will mention the assumptions made for risk assessments in my work as suggested by you. Sir, I would also like to know how  RPF differs from TEF? Please provide me some notes which could help me understand and clarify these doubts. I would be very much thankful to you.

Dear Dr Azari i really appreciate your concern 

The presence of soots generated from the burning of hydrocarbons and waste from Petrol

Hi,

It appears to me that the “seeds” of the strawberry are germinating green shoots. This could be vivipary, which occurs frequently in some plants, but less commonly in others, like the strawberry. Viviparous plants produce seeds that germinate immediately while still attached to the plant. This is often related to endogenous hormones especially, abscisic acid (ABA). The growing conditions of your cultivar could have caused this.

Good luck!

it is mean Conversion into melanin, or an increase in the concentration of melanin within (a tissue or organism)

Very curious question correct and very professional answers from which I learned a lot!

Use Benchmark Dose Software (BMDS) from US EPA

https://www.epa.gov/bmds

(The Benchmark Dose is the preferred regulatory method for dose-response analysis.)

hatch brine shrimps in artificial see water after 24 hours they will convert it into active naupili (tiny shrimps), take out ten in each tes tube with concentration of drug ( in tripicate) count mortality of naupili  (non active naupili is dead) of naupili against black and white background sepateley calculate IC50

Due to the volatility of the solvent, shorter storage length, I think is required to maintain the efficacy of the extract.

Dear Dr. Nasreen ,

Many thanks for your attachments. 

 Dear Dr. Ketil Haarstad,

A lot of thanks.

kind regards

Dear Dr. Barbeau

Along with chemical characterization of the product and estimation of the yield of toxicants from the product in use, measurement of biomarkers of exposure to tobacco toxicants will play an important role in the evaluation of any new types of tobacco product aimed at reducing smokers’ exposure to toxicants.

polycyclic aromatic hydrocarbons (PAH) and tobacco-specific nitrosamines, typified by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are widely considered to be among the most important causative agents for lung cancer.

Hi!

I would recommend to set up your normalization and later analysis using a couple of tool compounds as positive and negative controls. I.e., a regular cell  inhibitor which mechanism of action is not involved with your overexpression target would not be likely shifting your EC50 values neither the curve slope; the other way round, using a pan-killer of your desired target would give you the expected shift.

Once you have established the proper way to analyze your data, then you can proceed your analysis with confidence.

All the best!

EW is better solution or EC formulation?

1. You should discuss these questions with the author :)

2. Some data: 100 micro mole silver are 10.8 mg nano-silver particles. According to (Silver Nanotechnology Working Group. Re: Silver Nanoparticles (AgNPs); Information and Common Request. CDC-2012-0014; NIOSH-260. Comments of the Silver Nanotechnology Working Group for review by the National Institute for Occupational Safety and Health (NIOSH). February 2013), ORAL NOAEL in rats is 30 mg nano-silver/kg/day. Considering 250 g per adult rat, this is 7.5 mg nano-silver /kg/day, which caused no observational effects after oral intake. However, I do not know the relevance for intraperitoneal application.

Thank you Thang!!!

Thank you everyone

Thank you

In Europe, OECD methods are translated into "EU test methods". Upon adoption they are included in annexes to Regulation (EC) 440/2008 (latest consolidated version: http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:02008R0440-20160304). You will find ample guidance on selection and interpretation of appropriate tests in the REACH guidance documents, specifically here: https://echa.europa.eu/guidance-documents/guidance-on-information-requirements-and-chemical-safety-assessment.

I think in addition to the literature, you could use antibodies to check for Cre expression, so you would know 1. how long does the expression last for and 2. how many cells express Cre vs how many cells express your transgene.

Hope this helps!

You may consult Central Food technology Research Institute, Mysore India and Tea Board.

Recommend everyone who runs aquatic toxicity bioassays to include the TRAP program.   It is free and will provide both good insights as to goodness-of-fit about your data as well as LC50s, etc.  It can be downloaded here: https://archive.epa.gov/med/med_archive_03/web/html/trap.html

Check out this link it might answer your question: http://www.cyto.purdue.edu/archive/flowcyt/research/cytotech/apopto/data/chap9.htm

Dear Dr Kaushal 

I think the calculation of dose is a challenging task in the ethomedicinal practice and needs a proper scientific standardization. The traditional healers generally provide a randomized dose depends upon the situation. In my opinion, It is better to find out the dose by some safety and toxicity studies (LD50, ED 50 etc), and if the botanical preparation is well established then you can go for the calculation of the ratio by the proven established dose and the dose given by a folk practitioner, but the chances of errors may be there.  

Hi Iwona,

Telling it shortly - 4 to 6 passages.

In more details - the base medium for this cell line is ATCC-formulated F-12K Medium. To make the complete growth medium, add the following components to the base medium: fetal bovine serum to a final concentration of 10%. Subculturing Volumes used in this protocol are for 75 cm2 flask; proportionally reduce or increase amount of dissociation medium for culture vessels of other sizes. How to remove and discard culture medium: briefly rinse the cell layer with 0.25% (w/v) Trypsin-0.53 mM EDTA solution to remove all traces of serum that contains trypsin inhibitor. Add 2.0 to 3.0 mL of Trypsin-EDTA solution to flask and observe cells under an inverted microscope until cell layer is dispersed (usually within 5 to 15 minutes). Note: To avoid clumping do not agitate the cells by hitting or shaking the flask while waiting for the cells to detach. Cells that are difficult to detach may be placed at 37°C to facilitate dispersal. Add 6.0 to 8.0 mL of complete growth medium and aspirate cells by gently pipetting. Add appropriate aliquots of the cell suspension to new culture vessels. Incubate cultures at 37°C. Medium Renewal: 2 to 3 times a week. About cryopreservation: Freeze culture medium, 95%; DMSO, 5%. Storage temperature: liquid nitrogen vapor phase. And finally, culture conditions: Atmosphere: air, 95%; carbon dioxide (CO2), 5%. Temperature: 37°C.

Best wishes,

Ilya

and http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2013.3143/pdf

There is one example in the veterinary literature, I do not know how generalizable you might find it to your issue

Journal of the American Association for Laboratory Animal Science

Assessment of Sterility in Fluid Bags Maintained for Chronic Use

Vol 50, No 5 September 2011 Pages 708–712

Kristin A Matthews1,* and Douglas K Taylor1,2

Good luck!

Rich

Depending on the type of enzyme you are looking at, these are some of the biochemical processes/methods;

Biochemical analysis

At the end of the exposure period, fish will be sacrificed by medullar transaction (Luckey, 1977) and dissected within 3 min on ice. Liver will be washed in ice cold 1.15% kcl solution, blotted dry and weighed separately. Total protein will be estimated  according to Lowry method (1951) using bovine serum albumin as a standard.

Superoxide Dismutase (SOD) Assay: Superoxide Dismutase (SOD) activity will be determined by measuring the inhibition of autoxidation of epinephrine at pH 10.2 (30 °C) as described by Magwere et al. (1997).

Catase (CAT) Assay: Catalase activity (CAT) will be determined according to the procedure of Clairborne (1995) following the absorbance of hydrogen peroxide at 240nm, pH 7.0 and 25 °C.

Reduced Glutathione (GSH) Assay: Reduced glutathione (GSH) will be determined in the 10,000 g supernatant fraction of the liver of C. gariepinus according to methods described by Jollow et al. (1974), using 5,5’-dithio-bis-2-nitrobenzoic acid (DTNB) and Tris-EDTA buffer with the absorbance being read at 412nm.

Glutathione S-Transferase (GST) Assay: Glutathione S-transferase (GST) activity will be determined by the method of Habig et al. (1974) using 1 chloro 2,4 dinitrobenzene as substrate. The reaction mixture (3 ml) contained 1.7 ml of 100 mM phosphate buffer (pH 6.5), 0.1 ml of 30 mM CDNB. After preincubating the reaction mixture at 37°C for 5 min, the reaction was started by the addition of 0.1 ml diluted sample and the absorbance was followed for 5 min at 340 nm. Reaction mixture without the enzyme was used as blank. The specific activity of glutathione S-transferase is expressed as nmoles of GSH-CDNB conjugate formed/min/mg protein using an extinction coefficient of 9.6 mM-1cm-1.

Malondialdehyde Formation (MDA) Assay: Lipid peroxidation will be determined by measuring the Thiobarbituric Acid Reacting Substances (TBARS) as described by Farombi et al. (2000). Malondialdehyde (MDA) will be quantitated by using extinction co-efficient of Σ = 1.56 × 105 M-1 cm-1 (Buege and Aust, 1978).

Liver enzymatic Assays

Alkaline Phosphatase (ALP) Assay: The activity of Alkaline phosphatase (ALP) will be measured at 410 nm in a spectrophotometer according to the method described by Alkahem  Al-Balawi et al. (2011).

Aspartate Aminotransferase (AST): AST will be determined in the 10000 g supernatant fraction using 2,4 dinitrophenyl hydrazine with the absorbance being read at 412 nm as described by (Abei, 2004).

Alanine Aminotransferase (ALT): The level of Alanine aminotransferase (ALT) will be at 413 nm using spectrophotometer as described Bergmeyer et al. (1978).

Thanks Deepkamal.

Liquid-liquid extraction and analyzed by GC MS system.
Very simple. I use currently.
Good luck with that.

Mihai Ionicã

Hi Fiona and Robert, 

Thank you both!

Alex

The best way to store animal venoms by lyophilize it or store it in the same shape after extraction at -80°C.

hello , I have a question, how  is formaldehyde cause tissue stabilization?how happen is doing? thanks.

Pros: fairly easy, reproducible, can assay thousands of endpoints at once, tells a snapshot of a specific time period in the cell/tissue/organism. GO/KEGG is advancing so there is more identity than there used to be, very sensitive, also specific.

Cons: still just RNA, not protein, not metabolites (although there was that one paper that showed transcripts correlate well with ultimate outcome.. what paper was that..), downstream data analyses can be different and find different results, that amount of data generated can be overwhelming, requires a lot of storage space and someone who can manage/analyze it. Maybe too sensitive -- what is the biological meaning of a differentially expressed gene?

a poison is a substance that, in substantial amount, produces adverse health effects by causing injury, illness, or death, when ingested, inhaled, absorbed or injected into the body of the organism. poisons may be environmental pollutants, household products, pesticides, industrial chemicals, food additives, drugs or natural toxins. 

on the other hand, a toxin, a more specific term, is any of various poisonous substances that are specific products of metabolic activities of the living organisms. the terms poisonous and toxic, although are quite unique, a distinction between them is not always observed and are regarded as synonyms.

Thank u Mr Punit R Bhatt for help. Best luck to u too.

Poisonous plants are part of our ecosystems and as you have said have various means to protect themselves. Poisonous plants are not always harmful, but a quite number have positive physiological effects (medicinal) not only for human beings but also for livestock. please follow my profile to review my various contributions in this respect. Regards. 

There is also a new package RxODE, https://cran.r-project.org/web/packages/RxODE/vignettes/RxODE-intro.html, that looks promising!

Hello!

Quite honestly, I've never stored my emulsions. I typically use mine within hours of making it. If the emulsion sits for too long it will eventually come out of solution. Plus I would seriously begin to question the disease inducing ability of the emulsion if it was stored for more than a few hours. I would recommend making up what you need for that day's injection (plus a little extra), and using that emulsion up that same day. Then when you need the emulsion again, you make it fresh. 

Abstract
Experiments involving neonates should follow the same basic principles as most other experiments. They should be unbiased, be powerful, have a good range of applicability, not be excessively complex, and be statistically analyzable to show the range of uncertainty in the conclusions. However, investigation of growth and development in neonatal multiparous animals poses special problems associated with the choice of “experimental unit” and differences between litters: the “litter effect.” Two main types of experiments are described, with recommendations regarding their design and statistical analysis: First, the “between litter design” is used when females or whole litters are assigned to a treatment group. In this case the litter, rather than the individuals within a litter, is the experimental unit and should be the unit for the statistical analysis. Measurements made on individual neonatal animals need to be combined within each litter. Counting each neonate as a separate observation may lead to incorrect conclusions. The number of observations for each outcome (“n”) is based on the number of treated females or whole litters. Where litter sizes vary, it may be necessary to use a weighted statistical analysis because means based on more observations are more reliable than those based on a few observations. Second, the more powerful “within-litter design” is used when neonates can be  individually assigned to treatment groups so that individuals within a litter can have different treatments. In this case, the individual neonate is the experimental unit, and “n” is based on the number of individual pups, not on the number of whole litters. However, variation in litter size means that it may be difficult to perform balanced experiments with equal numbers of animals in each treatment group within each litter. This increases the complexity of the statistical analysis. A numerical example using a general linear model analysis of variance is provided in the Appendix. The use of isogenic strains should be considered in neonatal research. These strains are like immortal clones of genetically identical individuals (i.e., they are uniform, stable, and repeatable), and their use should result in more powerful experiments. Inbred females mated to males of a different inbred strain will produce F1 hybrid offspring that will be uniform, vigorous, and genetically identical. Different strains may develop at different rates and respond differently to experimental treatments.

Silica is used as a 'normal phase' stationary phase and has no significant UV-Vis spectrum.  Use the AOAC colormetric method for Silicon which if I recall uses Antimony.

DMSO is highy toxic ultimately it will show toxic effect on cells. In order to to solubulize your test compound first dissolve the test compound in little quantity( known volume) of 100% DMSO and finally make the volume to the required conc. in your case 0.25mg/ml with with distill water in such away that final you should be able to get 1ml of 0.1% DMSO containing 0.25mg  of your test item

OK thank you very much for your answer. I already bought a new one. But I will test the old one at the same time before throwing it. away

Quentin 

Heterogeneity of the baseline phenotypic and genomic state of patients T cells and dendritic cells is the general answer. I believe that what you're seeing is normal variance. The age of the cells (older tends to be less responsive), the immune status of the patient (how many T-cells), concentration and other unknown factors. The cells also respond differently to different enhancers such as GM-CSF, IL-15, p38, etc. and the responses are different/variable among patients. When a patient is sampled and prepared for DC-T antigen targeting, there is a range of responses in the population compared to other patients - we aim to get their counts up to ca. 10^8 for administration. 

I agree with Irina. You can perform targeted sequencing using the DNA extracted from FFPE samples. There are different kits available in the market to extract DNA from FFPE. Depends on the tissue size, the DNA yield will vary. De-paraffinization is an important step as well, you can use Hemo-De instead of Zylene. Assessing your DNA conc using fluorometer instead of normal spectrophotometer will be helpful in getting the DS-DNA conc. 

Dear Gaurav,

You welcome. I wish you good luck

To Sarah, You should use acidic medium to prepare lead acetate may be by adding few drops from acetic acid and prepare the mixture freshly every day.

No. However I have put that work on hold for now. The last time I used T. castaneum was in '96. I got my "seed" organisms from a lab. at the University of Vermont.  I don't believe they are currently working with them.  If you are doing genetics work, try the Brown Lab (Susan Brown) at Kansas State University.

Thank you so much Ghosh Sir.

Yes very true Sir. After posting this question, I also went through literature and that also suggested the same.

ya I feel your answer makes sense

Thank you Dr. Macherey

hi.

I have a packing material of lead poisoning

Hello,

You may find the following abstract to be of  interest.

Chevret, S. 2008. Maximum Tolerable Dose (MTD). Wiley Encyclopedia of Clinical Trials. 1–5.  http://onlinelibrary.wiley.com/doi/10.1002/9780471462422.eoct627/abstract

Hopefully the reference list to the full article will include some of the earlier studies you are looking for.  The abstract also refers to other methods that are alternatives to MTD, which may help support your efforts.

See also. 

Takimoto CH. Maximum tolerated dose: clinical endpoint for a bygone era?
Target Oncol. 2009 Apr;4(2):143-7.  http://www.ncbi.nlm.nih.gov/pubmed/19377851

Regards

 Thank you Dr. Keizer, Dr. Zuluaga and Ilika for your valuable information. 

Your attached files are going to help me for further planning of experiment. 

Regards,

Harsha

bee venom can be affected by heat or storage conditions this return to the nature of bee venom component , so it should be kept away from these conditions

ok i got the point

Normal healthy animals are used  to avoid the variations and baseline or historical data of the test facility would also help in better interpretation on the outcome of toxicity profile, if observed. 

 But what about that point related to the amperage? Does using 240 mA instead of 300 make a significant difference?

Yes. It makes a lot of difference. so if you do not have 300mA powerpack get one.

you will not get proper comet with 240mA

There are some publishers in India which published books with low quality and suitable price.

What I understand: if you prepare a solution with the correct concentration for administration at 1 ml / 100 g bw, then the solution is too viscous. So you want do divide the concentration by 2 and then split the administration of 2 ml / 100 g bw. Is that right ?

Are you sure about the stress induced by a single administration of somewhat very viscous vs the stress induced by 2 administrations of somewhat less viscous ? For gavage, we used corn oil or carboxymethylcellulose (2% in my remaining) and this was sometimes really viscous. But fasting and gavage may also be stress inducing...

(Off for Patrick: you make the toxicology matter so poetic when you find a P450 induction "very nice" :-)  )

Here are two references with human drug information that might be useful.  Both are free downloads.  Note that the second reference is from 2003 so won't have information on new drugs.  

Benet, Leslie Z., Fabio Broccatelli, and Tudor I. Oprea. "BDDCS applied to over 900 drugs." The AAPS journal 13.4 (2011): 519-547.
 

Schulz, M., and A. Schmoldt. "Therapeutic and toxic blood concentrations of more than 800 drugs and other xenobiotics." Die Pharmazie-An International Journal of Pharmaceutical Sciences 58.7 (2003): 447-474.

Tell me about the dose and exposure scenario; I'll tell you about the consequences. 

In our newest paper we discussed different activity of two compounds on cell function estimated using MTT and NR.

Please see links for comparative studies on different species of Daphnia for toxicity assessment.

1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792065/

2. http://webcache.googleusercontent.com/search?q=cache:D26ZG6cwzr4J:www.reach-info.de/dokumente/sensitivity_endbericht_final.pdf+&cd=2&hl=en&ct=clnk&gl=in

3. http://webcache.googleusercontent.com/search?q=cache:HPt-kKtqnecJ:www.scielo.br/scielo.php%3Fscript%3Dsci_arttext%26pid%3DS2179-975X2014000100002+&cd=3&hl=en&ct=clnk&gl=in

4. http://webcache.googleusercontent.com/search?q=cache:vC4wzsPv5AEJ:etheses.bham.ac.uk/3814/1/barnett_12_MRes.pdf+&cd=9&hl=en&ct=clnk&gl=in

Hope it help!

BSL II can be used to handle toxins. PFA related to Toxins of Biological Origin
Safe Work Practices which is prepared by University of Washington (Environmental Health and Safety). 

I work on preclinical toxicity (in vitro and in vivo). For me, biomarkers are important in Toxicology.

thanks!

After extraction in aq. phase, you should have just used the HPLC with C18 column to detect NMDA using a suitable primary standard.

Hi everyone,Thank you very much for support anf informations

regards susan verghese P