Carcinogenicity Tests
Carcinogens
Neoplasms, Experimental
Mutagenicity Tests
Rats, Inbred F344
Mutagens
Toxicity Tests, Chronic
Evaluation of the chronic toxicity and oncogenicity of N,N-diethyl-m-toluamide (DEET). (1/865)
Chronic toxicity and/or oncogenicity studies were conducted in rats, mice, and dogs with the insect repellent DEET. DEET was mixed in the diet and administered to CD rats for two years at concentrations that corresponded to dosage levels of 10, 30 or 100 mg/kg/day for males and 30, 100, or 400 mg/kg/day for females; to CD-1 mice for 18 months at dosage levels of 250, 500, or 1000 mg/kg/day; and to dogs for one year, via gelatin capsules, at dosage levels of 30, 100, or 400 mg/kg/day. In the rodent studies, each group consisted of 60 animals of each sex, and two concurrent independent control groups, each containing 60 animals/sex were included in each study. Each group in the dog study consisted of four male and four female dogs and one control group was included in the study. Treatment-related effects were observed at the highest dose level in all three studies. For rats, the effects included decreases in body weight and food consumption and an increase in serum cholesterol in females only. In mice, the effects observed were decreases in body weight and food consumption in both sexes. The effects observed in dogs included increased incidences of emesis and ptyalism, and levels of transient reduction in hemoglobin and hematocrit, increased alkaline phosphatase (males only), decreased cholesterol, and increased potassium. One male dog in the high-dose group also exhibited ataxia, tremors, abnormal head movements, and/or convulsions on several occasions during the study. The highest no-observed-effect levels (NO-ELs) for rats, mice and dogs were determined to be 100, 500, and 100 mg/kg/day, respectively. No specific target organ toxicity or oncogenicity was observed in any of the studies. (+info)Administration of an unconjugated bile acid increases duodenal tumors in a murine model of familial adenomatous polyposis. (2/865)
Intestinal carcinogenesis involves the successive accumulation of multiple genetic defects until cellular transformation to an invasive phenotype occurs. This process is modulated by many epigenetic factors. Unconjugated bile acids are tumor promoters whose presence in intestinal tissues is regulated by dietary factors. We studied the role of the unconjugated bile acid, chenodeoxycholate, in an animal model of familial adenomatous polyposis. Mice susceptible to intestinal tumors as a result of a germline mutation in Apc (Min/+ mice) were given a 10 week dietary treatment with 0.5% chenodeoxycholate. Following this, the mice were examined to determine tumor number, enterocyte proliferation, apoptosis and beta-catenin expression. Intestinal tissue prostaglandin E2 (PGE2) levels were also assessed. Administration of chenodeoxycholate in the diet increased duodenal tumor number in Min/+ mice. Promotion of duodenal tumor formation was accompanied by increased beta-catenin expression in duodenal cells, as well as increased PGE2 in duodenal tissue. These data suggest that unconjugated bile acids contribute to periampullary tumor formation in the setting of an Apc mutation. (+info)Malignant transformation of p53-deficient astrocytes is modulated by environmental cues in vitro. (3/865)
The early incidence of p53 mutation in astrocytomas suggests that it plays an important role in astrocyte transformation. Astrocytes isolated from homozygous p53 knockout mice grow rapidly, lack contact inhibition, and are immortal. Here we tested whether the loss of p53 is sufficient for progression to tumorigenicity of astrocytes. We grew primary astrocytes under three conditions for over 120 population doublings and assessed their antigenic phenotype, chromosome number, and expression of glioma-associated genes as well as their ability to form colonies in soft agarose and tumors s.c. and intracranially in nude mice. Under two conditions (10% FCS and 0.5% FCS plus 20 ng/ml EGF), cells acquired the ability to form colonies in soft agarose and tumors in nude mice, and this was accompanied by the expression of genes, including epidermal growth factor receptor, platelet-derived growth factor receptor alpha and beta, protein kinase Cdelta, and vascular endothelial growth factor, which are known to be aberrantly regulated in human astrocytomas. Under the third condition (0.5% FCS plus 10 ng/ml basic fibroblast growth factor), astrocytes gained the ability to form colonies in soft agarose and had abnormal chromosome numbers similar to cells in the first two conditions but did not form tumors in nude mice or overexpress glioma-associated genes. These data provide experimental evidence for the idea that the malignant progression initiated by the loss of p53 may be subject to modulation by extracellular environmental influences. (+info)Expression of AML1-d, a short human AML1 isoform, in embryonic stem cells suppresses in vivo tumor growth and differentiation. (4/865)
The human AML1 gene encodes a heterodimeric transcription factor which plays an important role in mammalian hematopoiesis. Several alternatively spliced AML1 mRNA species were identified, some of which encode short protein products that lack the transactivation domain. When transfected into cells these short isoforms dominantly suppress transactivation mediated by the full length AML1 protein. However, their biological function remains obscure. To investigate the role of these short species in cell proliferation and differentiation we generated embryonic stem (ES) cells overexpressing one of the short isoforms, AML1-d, as well as cells expressing the full length isoforms AML1-b and AML2. The in vitro growth rate and differentiation of the transfected ES cells were unchanged. However, overexpression of AML1-d significantly affected the ES cells' ability to form teratocarcinomas in vivo in syngeneic mice, while a similar overexpression of AML1-b and AML2 had no effect on tumor formation. Histological analysis revealed that the AML1-d derived tumors were poorly differentiated and contained numerous apoptotic cells. These data highlight the pleiotropic effects of AML1 gene products and demonstrate for the first time an in vivo growth regulation function for the short isoform AML1-d. (+info)Marriage of a medium-term liver model to surrogate markers--a practical approach for risk and benefit assessment. (5/865)
The need for a reliable medium-term alternative to traditional long-term rodent test protocols for carcinogen risk assessment is pressing given the immense variety of compounds being developed for introduction into the human environment. The established lack of a complete correlation between mutagenicity and carcinogenicity means that recourse must be made to an in vivo model. Optimally, this model should be able to detect not only complete carcinogenic or promoting potential but also any ability to inhibit neoplasia. In order to be effective, it must take into account the available detailed knowledge on mechanisms of action of carcinogens and modulating agents. The Ito model, for which a uniquely comprehensive set of background data has already been accumulated, has a solid scientific basis; this model utilizes quantitative data for glutathione S transferase-positive foci as the preneoplasia-based surrogate end point (PSE). A very practical candidate for routine application, its predictive power, its flexibility, and its capacity to incorporate a range of mechanism-based surrogate end points (MSEs) provide a powerful tool for attainment of the twin goals of detecting carcinogenic agents and identifying promising chemopreventors. (+info)Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 in inducing cell cycle arrest, apoptosis and inhibition of tumorigenicity. (6/865)
Cell cycle regulatory proteins are important candidates for therapeutic tumour suppressors. Adenovirus vectors were constructed to overexpress cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 under the control of the murine cytomegalovirus immediate early gene promoter. These vectors directed the efficient expression of each of the cyclin kinase inhibitors and induced growth arrest, inhibited DNA synthesis, and prevented phosphorylation of the retinoblastoma protein (pRb) in cell lines expressing functional pRb. In pRb-deficient cells, expression of the cyclin kinase inhibitors was not effective in inhibiting DNA replication or growth arrest. Interestingly, three of the cyclin kinase inhibitors, p16, p18 and p27 were found to induce apoptotic death in transduced HeLa and A549 cells. When the vectors were tested for their ability to inhibit tumorigenicity in a polyomavirus middle T antigen model of murine breast carcinoma, expression of the cyclin kinase inhibitors resulted in a delay in tumour formation that varied from several weeks for the p19 expressing vector to greater than 25 weeks for the p27 expressing vector. When tumours were injected directly with the adenovirus vectors expressing the cyclin kinase inhibitors, only treatment with the vector expressing p16 resulted in a delay in tumour growth. (+info)Tumorigenic conversion resulting from inhibition of apoptosis in a nontumorigenic HeLa-derived hybrid cell line. (7/865)
Although tumorigenicity in nude mice is one of the most important transformed phenotypes, its mechanism has been little analyzed. To understand the molecular basis of tumorigenicity, we characterized nontumorigenic CGL1 and tumorigenic CGL4 cell lines, both of which were originated from a common ancestral HeLa-human diploid fibroblast hybrid cell clone and retained a malignant state except tumorigenicity. When injected into nude mice, nontumorigenic CGL1 cells underwent apoptosis, but tumorigenic CGL4 cells did not. In vitro, CGL1 was also less resistant to various apoptotic stimuli than CGL4. These results suggested that inhibition of apoptosis may lead to tumorigenicity. To examine this hypothesis, we introduced antiapoptotic genes into the CGL1 cell line and injected the resulting clones into nude mice. The results showed that the ectopic expression of Bcl-2 or E1B19k, but not of crmA, converted CGL1 cells to tumorigenicity, suggesting strongly that this phenotype may be conferred by evasion of apoptosis. (+info)Increased oncogenicity of subclones of SV40 large T-induced neuroectodermal tumor cell lines after loss of large T expression and concomitant mutation in p53. (8/865)
A model for medulloblastoma-like primitive neuroectodermal tumors was established in rat using retrovirally transduced SV40 large T antigen (LT) as an inducing agent (O. D. Wiestler et al., Brain Pathol., 2: 47-59, 1992). A cell line isolated from such a tumor and clonal derivatives thereof were biologically and molecularly characterized. In the parental tumor cell line, TZ870, which had been selected for G418 resistance, virtually all cells expressed LT and wild-type p53, which were complexed to each other. When plated in soft agar, these cells grew relatively slowly and formed disperse colonies. However, when grown without selection pressure, these cells reproducibly gave rise to LT-negative and G418-sensitive derivatives, LT-0 cells. Surprisingly, these latter cells exhibited a higher degree of malignancy both in vitro, growing readily to large colonies in soft agar, and in vivo, where they gave rise to a rapidly growing malignant tumor. Clonal selection from TZ870 cells revealed two types of clones: in one type, LT expression was stably maintained, even without selection pressure, whereas the other type lost the LT coding sequences. All LT-negative clones exhibited the same phenotype as the LT-0 cells. Reexpression of LT had no effect. However, LT no longer formed complexes with p53, and p53 was metabolically stable, suggesting that it had been mutated. Sequence analyses and diagnostic restriction digests of the p53 gene revealed that (a) both the parental LT-transformed cells and their derivatives contained only one complete p53 allele and (b) all LT-positive clones expressed wild-type p53, whereas all LT-negative clones expressed a mutant allele with a common mutation at Cys-174-->Tyr, indicating their clonal origin. We assume that the loss of LT coding sequences is the consequence of the p53 mutation, perhaps by inducing genomic instability, and that both the p53 mutation and additional genetic alterations that accompany the loss of LT coding sequences might contribute to enhanced malignancy. (+info)Carcinogenicity tests are a type of toxicity test used to determine the potential of a chemical or physical agent to cause cancer. These tests are typically conducted on animals, such as rats or mice, and involve exposing the animals to the agent over a long period of time, often for the majority of their lifespan. The animals are then closely monitored for any signs of tumor development or other indicators of cancer.
The results of carcinogenicity tests can be used by regulatory agencies, such as the U.S. Environmental Protection Agency (EPA) and the Food and Drug Administration (FDA), to help determine safe exposure levels for chemicals and other agents. The tests are also used by industry to assess the potential health risks associated with their products and to develop safer alternatives.
It is important to note that carcinogenicity tests have limitations, including the use of animals, which may not always accurately predict the effects of a chemical on humans. Additionally, these tests can be time-consuming and expensive, which has led to the development of alternative test methods, such as in vitro (test tube) assays and computational models, that aim to provide more efficient and ethical alternatives for carcinogenicity testing.
Carcinogens are agents (substances or mixtures of substances) that can cause cancer. They may be naturally occurring or man-made. Carcinogens can increase the risk of cancer by altering cellular DNA, disrupting cellular function, or promoting cell growth. Examples of carcinogens include certain chemicals found in tobacco smoke, asbestos, UV radiation from the sun, and some viruses.
It's important to note that not all exposures to carcinogens will result in cancer, and the risk typically depends on factors such as the level and duration of exposure, individual genetic susceptibility, and lifestyle choices. The International Agency for Research on Cancer (IARC) classifies carcinogens into different groups based on the strength of evidence linking them to cancer:
Group 1: Carcinogenic to humans
Group 2A: Probably carcinogenic to humans
Group 2B: Possibly carcinogenic to humans
Group 3: Not classifiable as to its carcinogenicity to humans
Group 4: Probably not carcinogenic to humans
This information is based on medical research and may be subject to change as new studies become available. Always consult a healthcare professional for medical advice.
Experimental neoplasms refer to abnormal growths or tumors that are induced and studied in a controlled laboratory setting, typically in animals or cell cultures. These studies are conducted to understand the fundamental mechanisms of cancer development, progression, and potential treatment strategies. By manipulating various factors such as genetic mutations, environmental exposures, and pharmacological interventions, researchers can gain valuable insights into the complex processes underlying neoplasm formation and identify novel targets for cancer therapy. It is important to note that experimental neoplasms may not always accurately represent human cancers, and further research is needed to translate these findings into clinically relevant applications.
Carcinogens are agents that can cause cancer. According to the National Institute of Environmental Health Sciences (NIEHS), environmental carcinogens refer to "cancer-causing agents that people encounter in their daily lives, including substances or exposures in air, water, food, and in the workplace." These carcinogens can increase the risk of cancer by damaging DNA or interfering with cellular processes that control growth.
Examples of environmental carcinogens include:
* Air pollution: Certain pollutants in the air, such as diesel exhaust particles and secondhand smoke, have been linked to an increased risk of lung cancer.
* Radon: A naturally occurring radioactive gas that can accumulate in homes and other buildings, radon is the second leading cause of lung cancer in the United States.
* UV radiation: Exposure to ultraviolet (UV) radiation from the sun or tanning beds can lead to skin cancer.
* Certain chemicals: Some chemicals found in the workplace or in consumer products, such as asbestos, benzene, and vinyl chloride, have been linked to an increased risk of cancer.
* Infectious agents: Certain viruses, bacteria, and parasites can increase the risk of cancer. For example, human papillomavirus (HPV) is a major cause of cervical cancer, and hepatitis B and C viruses are leading causes of liver cancer.
It's important to note that exposure to environmental carcinogens does not guarantee that a person will develop cancer. The risk depends on many factors, including the level and duration of exposure, as well as individual susceptibility. However, reducing exposure to these agents can help reduce the overall risk of cancer.
Mutagenicity tests are a type of laboratory assays used to identify agents that can cause genetic mutations. These tests detect changes in the DNA of organisms, such as bacteria, yeast, or mammalian cells, after exposure to potential mutagens. The most commonly used mutagenicity test is the Ames test, which uses a strain of Salmonella bacteria that is sensitive to mutagens. If a chemical causes an increase in the number of revertants (reversion to the wild type) in the bacterial population, it is considered to be a mutagen. Other tests include the mouse lymphoma assay and the chromosomal aberration test. These tests are used to evaluate the potential genotoxicity of chemicals and are an important part of the safety evaluation process for new drugs, chemicals, and other substances.
F344 is a strain code used to designate an outbred stock of rats that has been inbreeded for over 100 generations. The F344 rats, also known as Fischer 344 rats, were originally developed at the National Institutes of Health (NIH) and are now widely used in biomedical research due to their consistent and reliable genetic background.
Inbred strains, like the F344, are created by mating genetically identical individuals (siblings or parents and offspring) for many generations until a state of complete homozygosity is reached, meaning that all members of the strain have identical genomes. This genetic uniformity makes inbred strains ideal for use in studies where consistent and reproducible results are important.
F344 rats are known for their longevity, with a median lifespan of around 27-31 months, making them useful for aging research. They also have a relatively low incidence of spontaneous tumors compared to other rat strains. However, they may be more susceptible to certain types of cancer and other diseases due to their inbred status.
It's important to note that while F344 rats are often used as a standard laboratory rat strain, there can still be some genetic variation between individual animals within the same strain, particularly if they come from different suppliers or breeding colonies. Therefore, it's always important to consider the source and history of any animal model when designing experiments and interpreting results.
Mutagens are physical or chemical agents that can cause permanent changes in the structure of genetic material, including DNA and chromosomes, leading to mutations. These mutations can be passed down to future generations and may increase the risk of cancer and other diseases. Examples of mutagens include ultraviolet (UV) radiation, tobacco smoke, and certain chemicals found in industrial settings. It is important to note that not all mutations are harmful, but some can have negative effects on health and development.
Chronic toxicity tests are a type of experimental procedure in toxicology that are conducted over an extended period to evaluate the potential adverse health effects resulting from repeated exposure to low levels of chemical substances or physical agents. These tests are designed to assess the long-term effects of these agents on living organisms, including humans, and typically span a significant portion of the lifespan of the test species.
The primary objective of chronic toxicity testing is to identify potential health hazards associated with prolonged exposure to chemicals or physical agents, such as heavy metals, pesticides, pharmaceuticals, nanomaterials, and ionizing radiation. The tests provide information on the nature and severity of toxic effects, including cancer, reproductive and developmental toxicity, neurological damage, and other chronic health issues.
Standardized protocols for conducting chronic toxicity tests are established by regulatory agencies such as the US Environmental Protection Agency (EPA), the European Chemicals Agency (ECHA), and the Organisation for Economic Cooperation and Development (OECD). These guidelines typically involve testing on two or more species, often including rodents and non-rodents, to ensure the results are applicable across different taxonomic groups.
The data generated from chronic toxicity tests contribute significantly to risk assessment and help regulatory agencies establish safe exposure limits for chemical substances and physical agents in various settings, such as occupational, consumer, and environmental contexts.
Toxicology is a branch of medical science that deals with the study of the adverse effects of chemicals or toxins on living organisms and the environment, including their detection, evaluation, prevention, and treatment. It involves understanding how various substances can cause harm, the doses at which they become toxic, and the factors that influence their toxicity. This field is crucial in areas such as public health, medicine, pharmacology, environmental science, and forensic investigations.
Umu Chromotest
Chlornaphazine
SOS chromotest
Sudan I
2,4-DB
Liquid Paper
Mirex
4-Chloro-o-toluidine
Prallethrin
Bioassay
2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
Mineral wool
Intratracheal instillation
Furylfuramide
Louise M. Ryan
Dimethyl tetrachloroterephthalate
Ethylbenzene
Genotoxicity
HMX
Safe Drinking Water Act
Animals and tobacco smoke
Benzoyl peroxide
Séralini affair
Naphthalene poisoning
Nickel(II) sulfate
Mifepristone
2-Butoxyethanol
Chlormadinone acetate
Electromagnetic radiation and health
Central Institute for Experimental Animals
FDA's Final Guidance on Carcinogenicity Testing of Pharmaceuticals | FDA
Quality and Study Design Considerations for Carcinogenicity Testing with the rasH2™ Mouse | Taconic Biosciences
Liver toxicity and carcinogenicity in F344/N rats and B6C3F1 mice exposed to Kava Kava
IARC Publications Website - Information Bulletin on the Survey of Chemicals Being Tested for Carcinogenicity No. 1
IARC Publications Website - Directories of Agents Being Tested for Carcinogenicity
Results of search for 'su:{Carcinogenicity tests.}' › WHO HQ Library catalog
FDA Amends Standard of Identity for Yogurt | Food Engineering
DailyMed - busulfex- Busulfan injection
Dulcin (IARC Summary & Evaluation, Volume 12, 1976)
RX List database - use generic or medication brand name - GlobalRPH
Umu Chromotest - Wikipedia
CCOHS: Benzene
ICH S1 Addendum to Carcinogenicity Provides Opportunity to Reduce Testing on Animals - PETA Science Consortium International e...
Replacement of the Year 2020: Animal experiments to Investigate the Risk of Cancer (Carcinogenicity)
Registration Dossier - ECHA
Multiple-endpoint in vitro carcinogenicity test in human cell line TK6 distinguishes carcinogens from non-carcinogens and...
Testosterone (IARC Summary & Evaluation, Volume 6, 1974)
Toxic Neuropathy: Practice Essentials, Background, Pathophysiology
Chlordane | Medical Management Guidelines | Toxic Substance Portal | ATSDR
NIOSHTIC-2 Search Results - Full View
Regulatory Toxicology | SpringerLink
Halaven: Package Insert - Drugs.com
Testing - American Anti-Vivisection Society
Current Topics in Nonclinical Drug Development - - eBooks en anglais | Ex Libris
Vahle J[au] - Search Results - PubMed
Presentations at 11th World Congress on Alternatives and Animal Use
The Journal of Toxicological Sciences
Genotoxicity5
- 10 As a consequence, they cannot be detected using genotoxicity tests. (invitrojobs.com)
- For genotoxicity effects, we look at in vivo testing over in vitro testing. (cdc.gov)
- Although, genotoxicity tests for these ingredients were mostly negative, there were some assays that were positive. (cosmeticsinfo.org)
- There was no evidence that isofetamid was carcinogenic in mice and rats, and isofetamid was tested for genotoxicity in an adequate range of in vitro and in vivo assays and was negative. (tga.gov.au)
- Genotoxicity/mutagenicity/carcinogenicity and microbial effects are the other parameters that characterize biocompatibility 8 . (bvsalud.org)
Mutagenicity3
- The high correlation between the Umu Chromotest and traditional Ames test for mutagenicity supports it as a reasonable alternative for early-stage testing of the thousands of new pharmaceutical, agricultural and industrial chemicals synthesized every year. (wikipedia.org)
- In evaluating mutagenicity for potentially hazardous drugs, responses from multiple test systems are needed before precautions can be required for handling such agents. (cdc.gov)
- 2002. Modulation of heterocyclic amine-induced mutagenicity and carcinogenicity: an 'A-to-Z' guide to chemopreventive agents, promoters, and transgenic models. . (oregonstate.edu)
Genotoxic4
- Speakers included Koji Urano from the Central Institute of Experimental Animals in Japan (CIEA) and Marie McKeon of BioReliance Inc . Both speakers highlighted the increased utility of this model and how faster, more accurate nongenotoxic and genotoxic carcinogenicity testing helps pharmaceutical companies with strategic decision making in their drug development pipeline. (taconic.com)
- Salmonella typhimurium TA 1535 [pSK 1002] bacteria are exposed to potentially genotoxic test compounds in a 96-well microplate. (wikipedia.org)
- The intensity of the colour correlates with the amount of the induced protein and thus genotoxic potency of the test sample. (wikipedia.org)
- A novel, integrated in vitro carcinogenicity test to identify genotoxic and non-genotoxic carcinogens using human lymphoblastoid cells by: Katherine Chapman, et al. (swan.ac.uk)
Mice4
- The Addendum provides guidance for using a weight-of-evidence approach that will shift resources to generating more mechanism-based carcinogenicity assessments and reduce lifetime testing on rats and mice. (thepsci.eu)
- Testosterone was tested by subcutaneous injection and/or implantation in mice, rats and hamsters. (inchem.org)
- Results from a separate, non-clinical 6-month carcinogenicity study in mice demonstrated that LAGEVRIO was not carcinogenic. (merck.com)
- Additionally, Merck is reporting results from a recent carcinogenicity study in transgenic mice, which demonstrated that LAGEVRIO was not carcinogenic at any dose tested. (merck.com)
Carcinogens1
- PFOS is possibly carcinogenic to humans (Group 2B), on the basis of strong mechanistic evidence across test systems, including in exposed humans (for epigenetic alterations and immunosuppression, as well as several other key characteristics of carcinogens). (who.int)
Toxicological1
- All available (eco)toxicological data from standardized or non-standardized tests. (oecd.org)
Toxicology1
- Dr. Williams specializes in developmental and reproductive toxicology, endocrine disruption, carcinogenicity mode-of-action assessments, and general toxicology related to exposure to chemical substances and physical agents. (exponent.com)
Rats2
- Dulcin has been tested only in rats in oral administration. (inchem.org)
- A medium-term liver bioassay system for rapid detection of carcinogenic agents using male F344 rats has been developed, in order to bridge the gap between long-term carcinogenity tests and short-term screening assays. (go.jp)
Dose8
- Marie McKeon focused on key study design considerations when using transgenic mouse models, particularly dose-range finding studies (usually conducted with the wild-type rasH2™ mouse) and twenty-six week carcinogenicity studies. (taconic.com)
- For decades, acute toxicity testing meant poisoning large numbers of animals in Lethal Dose 50 (LD50) tests, which are conducted until at least one half of the test animals die. (aavs.org)
- There was no indication of carcinogenicity at any dose level. (europa.eu)
- However, we take into account the dose for animal testing for reproductive and developmental toxicity and carcinogenicity testing. (cdc.gov)
- In addition to dose, for carcinogenicity testing we look for tumors in more than one species and sex. (cdc.gov)
- One international study that examined the results of rat and mouse LD50 (Lethal Dose 50%) tests for 50 chemicals found that these tests were able to predict toxicity in humans with only 65% accuracy. (choosecrueltyfree.org.au)
- Most standard animal tests were developed decades ago and have either never been validated, or have actually failed retrospective validation (for example, the Draize eye test, the Lethal Dose 50% test and carcinogenicity). (choosecrueltyfree.org.au)
- The lowest tested dose or concentration of a substance which resulted in an observed adverse effect in exposed test organisms when all higher doses or concentrations resulted in the same or more severe effects. (cornell.edu)
Endocrine disruption3
- The OECD releases the Revised Guidance Document 150 on Standardised Test Guidelines for Evaluating Chemicals for Endocrine Disruption originally published in 2012 and updated in 2018 to reflect new and updated OECD test guidelines, as well as reflect on scientific advances in the use of test methods and assessment of the endocrine activity of chemicals. (oecd.org)
- Specific objectives include providing a description of the OECD conceptual framework for evaluating chemicals for endocrine disruption, background on the standardised test methods used, and guidance for interpreting the outcome of individual tests. (oecd.org)
- The OECD Conceptual Framework for Testing and Assessment of Endocrine Disrupters (as revised in 2012) lists the OECD Test Guidelines and standardized test methods available, under development or proposed that can be used to evaluate chemicals for endocrine disruption. (oecd.org)
Carcinogenic risk3
- To provide some background, the ICH S1 guidances (safety guidances on carcinogenicity studies) were issued in 1995 and 1997 that described a strategy to assess carcinogenic risk of new pharmaceuticals. (fda.gov)
- Under the ICH umbrella, we participated in an expert working group that examined the retrospective analyses and conducted a prospective study to see if an alternative to the standard two-year rat carcinogenicity study would still adequately assess the carcinogenic risk of a pharmaceutical. (fda.gov)
- 75% of mouse carcinogenicity studies submitted to the FDA utilize the rasH2™ mouse model (Tg.rasH2), a model accepted by the FDA as an alternative to the two-year in vivo bioassay for predicting human carcinogenic risk. (taconic.com)
Assessments2
- At FDA and in CDER, we are looking toward ways to improve safety assessments and reduce animal testing, where it makes sense, without sacrificing the safety of human patients who will eventually use these medications. (fda.gov)
- No health risks, including no carcinogenicity, were found for the GM maize tested, reaffirming the conclusions of previous risk assessments. (idw-online.de)
IARC3
- The evaluations of IARC working groups are scientific, qualitative judgements about the evidence for or against carcinogenicity provided by the available data. (who.int)
- The IARC Monographs are recognized as an authoritative source of information on the carcinogenicity of a wide range of human exposures. (who.int)
- The International Agency for Research on Cancer (IARC), the cancer agency of the World Health Organization (WHO), has evaluated the carcinogenicity of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS). (who.int)
Addendum1
- The US Food and Drug Administration will now consider data submitted using the Addendum to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) on carcinogenicity testing of pharmaceuticals. (thepsci.eu)
Irritation1
- John H. Draize, Ph.D., a scientist at the United States Food and Drug Administration (FDA), developed the Draize eye test in 1944 to assess eye irritation caused by various chemicals. (aavs.org)
Chemical7
- Most large chemical manufacturers have the ability to screen 100 or more synthetic chemicals per year with the traditional Ames test, which requires the use of several Salmonella strains. (wikipedia.org)
- However, this test only works if you were exposed to the chemical within the last 12 to 15 hours. (cdc.gov)
- Acute toxicity testing is used to determine the danger of exposure to a chemical by mouth, skin, or inhalation. (aavs.org)
- The system is fundamentally based on the two-stage hypothesis of oarcinogenesis : intiation with diethylnitrosamine (200 mg/kg bw, ip) is follwed by test chemical administration during the second, in combination with 2/3 partial hepatectomy. (go.jp)
- Chemical toxicity (poisoning) testing on animals involves subjecting animals to different levels of potentially toxic substances via different routes of exposure in order to assess how and in which way they are affected.Many products are tested to see if they will cause damage to the skin or eyes. (choosecrueltyfree.org.au)
- This approach to chemical testing, which uses animals and is mainly observational, subjective and descriptive, is extremely crude. (choosecrueltyfree.org.au)
- The document is intended to provide guidance for evaluating chemical using standardised test guidelines. (oecd.org)
Bioassay1
- 2017. A miRNA signature for an environmental heterocyclic amine defined by a multi-organ carcinogenicity bioassay in the rat. . (oregonstate.edu)
Monographs2
- The objective of the programme is to prepare, with the help of international working groups of experts, and to publish in the form of monographs, critical reviews and evaluations of evidence on the carcinogenicity of a wide range of human exposures. (who.int)
- The aim of the Monographs has been, from their inception, to evaluate evidence of carcinogenicity at any stage in the carcinogenesis process, independently of the underlying mechanisms. (who.int)
Evaluate2
- Could it be that since the FDA failed to require the manufacturer to test for, evaluate and quantify the risks of residual recombinant HPV DNA in Gardasil™ before granting approval for marketing the vaccine, they just decided to take their toys and go home? (sanevax.org)
- Cytotoxicity assays are the initial screening tests used to evaluate the biocompatibility of materials 7 . (bvsalud.org)
Assays1
- The general approach taken by the document is primarily to provide guidance on how test results might be interpreted based on the outcome of standardised assays. (oecd.org)
Cancer4
- Here, we provide information about carcinogenicity tests - tests to determine whether a substance can cause cancer or not. (invitrojobs.com)
- For some time, regulatory authorities, the Industry and academia agreed, that animal testing should be no longer mandatory - primarily because at the time of the beginning of such tests there is already sufficient information available from animal experiments to estimate a possible risk of cancer in humans. (invitrojobs.com)
- For approval, these substances have to be tested first for its potential to cause cancer (carcinogenicity). (invitrojobs.com)
- The Department of Health and Human Services, the International Agency for Research on Cancer, and the Environmental Protection Agency (EPA) have not classified hexamethylene diisocyanate as to its human carcinogenicity. (cdc.gov)
Human6
- A greater understanding of the mechanisms of carcinogenicity, the publication of several retrospective analyses indicating that two-year rat carcinogenicity studies might not add value to human risk assessment in some cases, and our commitment to patient safety, expediting drug development, and animal welfare, led us to consider how to amend the original S1B guidance. (fda.gov)
- Recommendations, evaluation and validation of a semi-automated, fluorescent-based scoring protocol for micronucleus testing in human cells by: Gareth Jenkins, et al. (swan.ac.uk)
- As a result, animal-based testing methods continue to fail legitimate human needs, while new discoveries in the field of alternatives have led to new and improved techniques that do not involve live animals. (aavs.org)
- Human cell culture tests have been found to predict toxicity in humans with much greater accuracy than animal tests. (choosecrueltyfree.org.au)
- The U.S. Environmental Protection Agency (EPA) considered chlorobenzene to be not classifiable as to human carcinogenicity. (cdc.gov)
- Topics are selected on the basis of two main criteria: (a) there is evidence of human exposure, and (b) there is some evidence or suspicion of carcinogenicity. (who.int)
Assessment4
- Her presentation concluded with suggestions for using the rasH2™ mouse model as part of the Weight of Evidence (WOE) when submitting a Carcinogenicity Assessment Document (CAD) and requesting a waiver of the two-year rat study from drug regulatory agencies. (taconic.com)
- She managed expert committees examining alternatives to carcinogenicity testing, immunotoxicology, the evaluation of epidemiology studies, and the development of biomarkers for safety assessment. (exponent.com)
- The OECD Test Guidelines Programme develop Test Guidelines and other tools to support countries' needs related to testing and assessment of chemicals for endocrine disrupters. (oecd.org)
- The Conceptual Framework is intended to provide a guide to the tests available which can provide information for endocrine disrupters' assessment but is not intended to be a testing strategy. (oecd.org)
Toxicity Tests1
- Animal toxicity tests are crude, subjectively assessed and the results can vary depending upon the species, age, sex and condition of individual animals. (choosecrueltyfree.org.au)
Pharmaceuticals1
- With this in mind, we have worked to amend the safety guidance on testing for carcinogenicity of pharmaceuticals through collaboration with our partners at ICH and other stakeholders. (fda.gov)
Liver1
- Standard liver function tests were applied to blood samples from 25 nickel-plating workers in Damietta, Egypt and 30 administrative workers as a reference group. (who.int)
Data4
- Reactions to the exposure of these products vary among species, making it difficult to extract data from animal tests and apply them to situations in which humans are exposed. (aavs.org)
- There are sufficient existing safety data as well as in vitro alternatives to make animal testing for cosmetic and household products obsolete. (aavs.org)
- The document is not proscriptive but provides suggestions for possible next steps in testing (if any) which might be appropriate for a regulatory authority to take, given the various data scenarios. (oecd.org)
- However, no historical control data was provided, though obtained data on the background incidence of left-sided umbilical artery in rat foetuses in four other testing laboratories indicated they were likely incidental to treatment. (tga.gov.au)
Alternatives1
- While no non-animal alternative has yet been approved as a replacement for the Draize eye test, two alternatives have been created to allow for partial replacement of animal tests in a tiered testing scheme. (aavs.org)
Draize2
Animal13
- Also in the intervening years, there has been a concerted effort to reduce the use of animal testing in drug development studies. (fda.gov)
- If you wish to obtain legal advice about avoiding animal testing under REACH or any other law or regulation, please seek your own, independent legal counsel. (thepsci.eu)
- However, the corresponding regulation is still not deleted and these tests, which are to a large extent highly stressful for the animal, are continued. (invitrojobs.com)
- For years, the U.S. has lagged behind the European Union, which passed a law in 2004 that phased out the use of animals to test cosmetic products and ingredients, as well as the sale of products containing ingredients subjected to new animal tests. (aavs.org)
- China has recently announced plans to limit mandatory animal testing for some cosmetic products. (aavs.org)
- It would also ban the use animals testing cosmetics and their ingredients, as well as phase out the sale of cosmetic products containing animal tested ingredients. (aavs.org)
- However, neither agency requires companies to use animal tests to access safety of their products. (aavs.org)
- Unfortunately, many companies remain resistant to changing their testing techniques and U.S. agencies, like the FDA, continue to endorse animal testing methods as the gold standard. (aavs.org)
- It is hardly surprising then to learn that results from animal tests are often difficult to apply to humans. (choosecrueltyfree.org.au)
- Animal tests were crudely developed as long ago as the 1920s and became commonplace in the 1940s. (choosecrueltyfree.org.au)
- Animal testing is designed to protect a manufacturer against legal claims by consumers. (choosecrueltyfree.org.au)
- There is no actual legal requirement for animal testing. (choosecrueltyfree.org.au)
- Animal tests tell us little about why a substance is toxic, as the results tend to demonstrate effects rather than causes of toxicity. (choosecrueltyfree.org.au)
Vitro tests2
- However, adverse outcomes in several in vitro tests may be considered in our evaluation. (cdc.gov)
- In spite of the advantages of the in vitro tests, they are not able to mimic the orchestrated role of cells present inperiradicular region and the long-term cytotoxicity presented by the sealers. (bvsalud.org)
Substance2
- In the test, a substance is placed in one eye, with the other eye serving as a control. (aavs.org)
- The irony is that the defence "we have safety-tested our products on animals" only becomes relevant when that testing fails to detect a potentially dangerous substance and a consumer is injured. (choosecrueltyfree.org.au)
Investigate1
- Based on scientific works and research efforts, OECD started to investigate test methods that could be standardised and used in chemicals regulations to detect and characterise hazards posed by endocrine disrupting chemicals. (oecd.org)
Evaluation1
- No evaluation of the carcinogenicity of dulcin can be made. (inchem.org)
Organ1
- They do not trigger any short-term mutations in eukaryotic and prokaryotic mutation tests and do not induce any direct DNA damage in the target organ. (invitrojobs.com)
Animals5
- A 2011 survey found that 67% of Americans believe that companies should not test products like cosmetics and dish soap on animals, and 60% are more likely to buy products that have not been testing on animals. (aavs.org)
- Other tests include the acute toxic class method and the up-and-down procedure, which typically involve the use of a smaller number of animals. (aavs.org)
- Many substances tested safely on animals have proven to be dangerous to humans and vice versa. (choosecrueltyfree.org.au)
- Companies continue to test on animals for legal protection. (choosecrueltyfree.org.au)
- 4. Streamlining future testing regimes according to the established evidence base brings important advantages for the EU in expediting innovation and in reducing the unnecessary use of experimental animals according to the agreed principles of Replacement, Reduction and Refinement. (idw-online.de)
Carcinogenesis1
- Structural correlates of carcinogenesis and mutagenesis : a guide to testing priorities? (who.int)
Pesticides1
- WHO is not responsible, and does not accept any liability, for the testing of pesticides for compliance with the specifications, nor for any methods recommended and/or used for testing compliance. (who.int)
Exposure2
- The test results are difficult to extrapolate from laboratory conditions to real life exposure of humans. (choosecrueltyfree.org.au)
- Because chlorobenzene leaves the body quickly, these tests have to be taken within a few days after exposure. (cdc.gov)
Search1
- Results of search for 'su:{Carcinogenicity tests. (who.int)
LD501
- The LD50 test is conducted infrequently now as it is being replaced by several new, but still lethal, options. (aavs.org)
Standard1
- The vinyl chloride standard controls the labeling that polyvinyl chloride must bear with respect to information on carcinogenicity . (ilpi.com)
Chemicals1
- The umu test, using only a single Salmonella strain, could potentially test a greater range of new chemicals with the same resources. (wikipedia.org)
Vivo1
- The EPA evaluations include the type of cells affected and in vitro versus in vivo testing [51 Fed. (cdc.gov)
Safety1
- Title : Ethylene oxide (EtO) : evidence of carcinogenicity Corporate Authors(s) : National Institute for Occupational Safety and Health. (cdc.gov)
Evidence1
- In aggregate, this provides a significant contribution to clarifying and augmenting the evidence base on testing procedures. (idw-online.de)
Results2
- Blood tests may show abnormal results. (ccohs.ca)
- The response pattern varied depending on time and type of cell line used for analysis, although the results indicate a higher cytotoxicity for EPH in short-term tests. (bvsalud.org)