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In recent years, nitrosamine impurities in pharmaceuticals have been subject to intense regulatory scrutiny, with nitrosamine drug substance-related impurities (NDSRIs) treated as cohort of concern impurities, regardless of predicted mutagenic potential. Here, we describe a case study of the NDSRI N-nitroso-hydrochlorothiazide (NO-HCTZ), which was positive in the bacterial reverse mutation (Ames) test but is unstable under the test conditions, generating formaldehyde among other products. The mutagenic profile of NO-HCTZ was inconsistent with that expected of a mutagenic nitrosamine, exhibiting mutagenicity in the absence of metabolic activation, and instead aligned well with that of formaldehyde. To assess further, a modified Ames system including glutathione (3.3 mg/plate) to remove formaldehyde was developed. Strains used were S. typhimurium TA98, TA100, TA1535, and TA1537, and E. coli WP2 uvrA/pKM101. In this system, formaldehyde levels were considerably lower, with a concomitant increase in levels of S-(hydroxymethyl)glutathione (the adduct formed between glutathione and formaldehyde). Upon retesting NO-HCTZ in the modified system (1.6–5000 µg/plate), a clear decrease in the mutagenic response was observed in the strains in which NO-HCTZ was mutagenic in the original system (TA98, TA100, and WP2 uvrA/pKM101), indicating that formaldehyde drives the response, not NO-HCTZ. In strain TA1535, an increase in revertant colonies was observed in the modified system, likely due to a thiatriazine degradation product formed from NO-HCTZ under Ames test conditions. Overall, these data support a non-mutagenic designation for NO-HCTZ and demonstrate the value of further investigation when a positive Ames result does not align with the expected profile. [ABSTRACT FROM AUTHOR]

Contamination of drug products and substances containing impurities is a significant concern in the pharmaceutical industry because it may impact the quality and safety of medicinal products. Special attention is required when mutagenic impurities are present in pharmaceuticals, as they may pose a risk of carcinogenicity to humans. Therefore, controlling potential mutagenic impurities in active pharmaceutical ingredients to an acceptable safety limit is mandatory to ensure patient safety. As per the International Council for Harmonization (ICH) M7 (R2)3 Guideline, mutagenic impurities are those compounds or materials that induce point mutations. In 2018, the sartan class of drugs was recalled due to the presence of N-nitrosamine impurities, which are potential mutagens. In addition to the primary impurities being detected, this class of products, especially losartan, irbesartan and valsartan, have been identified as having organic azido contaminants, which are again highly reactive toward DNA, leading to an increased risk of cancer. These azido impurities form during the preparation of the tetrazole moiety via the reaction of a nitrile intermediate with sodium azide. Given that this is a newly raised issue in the pharmaceutical world, it should be noteworthy to review the related literature. Thus, this review article critically accounts for (i) the toxicity of azido impurities and the proposed mechanism of mutagenicity, (ii) the regulatory perspective, and (iii) the sources and control strategies used during the preparation of drug substances and (iv) future perspectives. [ABSTRACT FROM AUTHOR]

Glyphosate is a chemical compound derived from glycine, marketed as a broadspectrum herbicide, and represents one of the most widely used pesticides in the world. For a long time, it was assumed that glyphosate was harmless, either due to its selective enzymatic acting method on plants, and because commercial formulations were believed to contain only inert chemicals. Glyphosate is widely spread in the environment, the general population is daily exposed to it via different routes, including the consumption of both plant, and non-plant based foods. Glyphosate has been detected in high amounts in workers' urine, but has been detected likewise in bodily fluids, such as blood and maternal milk, and also in 60%-80% of general population, including children. Considering its massive presence, daily exposure to glyphosate could be considered a health risk for humans. Indeed, in 2015, the IARC (International Agency for Research on Cancer) classified glyphosate and its derivatives in Group 2A, as probable human carcinogens. In 2022, nevertheless, EFSA (European Food Safety Authority) stated that the available data did not provide sufficient evidence to prove the mutagenic/carcinogenic effects of glyphosate. Therefore, the European Commission (EC) decided to renew the approval of glyphosate for another 10 years. The purpose of this review is to examine the scientific literature, focusing on potential risks to human health arising from exposure to glyphosate, its metabolites and its commercial products (e.g., Roundup®), with particular regard to its mutagenic and carcinogenic potential and its effects as endocrine disrupter (ED) especially in the human reproductive system. [ABSTRACT FROM AUTHOR]

Interest in microalgae products for use in food is increasing, as demands for sustainable and cost‐effective food choices grow due to the escalating global population and increase in climate‐related struggles with agriculture. Toxicological assessments of some species of microalgae have been conducted, but there were little data available for the oral consumption of the red microalgae Porphyridium purpureum and no data on genotoxicity. This article articulates a genotoxicity assessment and a 90‐day repeated dose oral toxicity study in rats performed according to OECD guidelines. Under the experimental conditions applied, the test item did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used in the bacterial reverse mutation test. Similarly, the test item did not induce structural chromosomal aberrations in V79 hamster lung cells. The test item also did not cause chromosomal damage in bone marrow of mice in the mammalian micronucleus test. The no observed adverse effect level (NOAEL) of the 90‐day repeated dose oral toxicity study in rats was determined to be the highest dose tested, 3000 mg/kg bw/day. These data add to the body of evidence regarding the safety of P. purpureum for human consumption. There is interest in the use of microalgae in food. Many species have been studied and are currently used in food products sold around the world, but little safety data are available for Porphyridium purpureum. This species was used as a test item in a 90‐day repeated dose oral toxicity study in rats as well as a genotoxicity assessment. The no observed adverse effect level was the highest dose tested, 3000 mg/kg bw/day, and it did not induce genotoxic changes. [ABSTRACT FROM AUTHOR]

Glyphosate is a chemical compound derived from glycine, marketed as a broad-spectrum herbicide, and represents one of the most widely used pesticides in the world. For a long time, it was assumed that glyphosate was harmless, either due to its selective enzymatic acting method on plants, and because commercial formulations were believed to contain only inert chemicals. Glyphosate is widely spread in the environment, the general population is daily exposed to it via different routes, including the consumption of both plant, and non-plant based foods. Glyphosate has been detected in high amounts in workers’ urine, but has been detected likewise in bodily fluids, such as blood and maternal milk, and also in 60%–80% of general population, including children. Considering its massive presence, daily exposure to glyphosate could be considered a health risk for humans. Indeed, in 2015, the IARC (International Agency for Research on Cancer) classified glyphosate and its derivatives in Group 2A, as probable human carcinogens. In 2022, nevertheless, EFSA (European Food Safety Authority) stated that the available data did not provide sufficient evidence to prove the mutagenic/carcinogenic effects of glyphosate. Therefore, the European Commission (EC) decided to renew the approval of glyphosate for another 10 years. The purpose of this review is to examine the scientific literature, focusing on potential risks to human health arising from exposure to glyphosate, its metabolites and its commercial products (e.g., Roundup®), with particular regard to its mutagenic and carcinogenic potential and its effects as endocrine disrupter (ED) especially in the human reproductive system.

Drug impurity profile studies have changed significantly during the past ten years, as demonstrated by pharmacopeia and regulatory standards. This review article aims to give viewers a thorough understanding of the numerous facts of impurity profiling in relation to regulatory criteria. Comprehensive information on residual solvents, water impurities, elemental impurities, carcinogenicity and an overview of the most critical components of genotoxic contaminants. To ensure the drug products fulfill the minimal acceptable quality standards and a number of pharmacopoeias have created monographs. ICH, EMEA, USFDA and European Pharmacopeia recommendations are just a few of the regulatory bodies that offer rules to reduce the amount of contaminants in medications. In order to prevent impurities, industry, research and development sectors widely employ different spectrum analyses including HPLC, LC/MS and GC/MS. It involves the recall of medications because of these contaminants. The significance of understanding genotoxic impurities as a crucial element of the impurity profile in medications is emphasized in this abstract. [ABSTRACT FROM AUTHOR]

Background: Zingiber zerumbet (L.) Smith (lempoyang) has a traditional application in the treatment of indigestion, worm infestation, loss of appetite, and postpartum conditions. Objectives: Extracts of Z. zerumbet (methanol, hexane, and ethyl acetate) were utilized to investigate the mutagenic, anti-mutagenic, and cytotoxic properties. Materials and Methods: Initially, a mutagenicity test (Ames test) was conducted, followed by an anti-mutagenicity test, to assess the potential of Z. zerumbet extracts in inhibiting mutagenicity induced by sodium azide and 9-aminoacridine. Furthermore, the cytotoxic ability of the extracts was evaluated using the methyl thiazolyl tetrazolium (MTT) assay. Results: The mutagenicity assessment revealed that the methanol extract of Z. zerumbet exhibited a twofold increase in the number of revertants in Salmonella typhimurium strain TA 1537. Similar results were observed for the hexane extract, except at a concentration of 6.25 mg/mL, where no significant increase in revertants was observed. On the other hand, the ethyl acetate extract demonstrated a twofold increase in revertants in S. typhimurium strain TA 1535. Notably, the ethyl acetate extract displayed remarkable anti-mutagenic activity against 9-aminoacridine, while the hexane extract exhibited strong anti-mutagenic activity against sodium azide. Regarding cytotoxicity assessment using the MTT assay, the methanol extract of Z. zerumbet exhibited the highest cytotoxicity with an IC50 value estimated at 388.50 ± 135.75 µg/mL. The hexane and ethyl acetate extracts showed IC50 values of 514.17 ± 135.75 and 589.67 ± 241.67 µg/mL, respectively. Conclusion: The extracts displayed both mutagenic and cytotoxic activities. However, they also exhibited promising anti-mutagenic potential, which could be harnessed for cancer prevention purposes. [ABSTRACT FROM AUTHOR]

Abstract The objective of this work was to characterize chilling tolerance in rice mutant families of the M4 generation, at the seedling stage. Two experiments were carried out: chilling tolerance was evaluated in 43 mutant families, in the 'BRS Querência' original genotype, and in 19 commercial genotypes. In Experiment II, 8 mutant families from Experiment I, 'BRS Querência', and a mutant of the M5 generation were tested. In both experiments, seedlings were evaluated under two conditions: 10°C for seven days and 25°C for seven days. In Experiment I, the induced mutations in rice led to varied responses in chilling tolerance traits, with some M4 mutant families outperforming the original genotype. Experiment II highlighted the impact of mutations on chilling-tolerance, particularly in terms of leaf discoloration and plant recovery. Mutant families of the M4 generation differ from the original genotype 'BRS Querência' in chilling tolerance at the seedling stage. The mutant families M36, M54, and M56 and 'BRS Querência' show genetic similarity, indicating a lack of chilling tolerance during the seedling stage. The mutant families M17, M21, M22, and M26 are promising for rice breeding programs because they present chilling tolerance. The M30 mutant family exhibits the best performance for all analyzed traits, indicating chilling tolerance at the seedling stage.

Polynuclear aromatic hydrocarbons (PAHs), are known as persistent organic pollutants (POP) which exist in different media as contaminants in parts of the environment's atmosphere, seawater, sediments, soils, and vegetation. PAHs have been known for their mutagenic, carcinogenic, and toxic properties to humans through the food chain. This study is aimed to characterize and investigate the distribution of PAHs in wet precipitations, surface waters, and soils from Ikot Abasi, Ibeno, and Eastern Obolo Local Government Areas of Akwa Ibom State, Nigeria. PAHs were determined in the environmental components by gas chromatography-mass spectrometry technique. Two soil and two surface water samples were taken from selected locations and wet precipitation samples were harvested on event basis from the study areas. The results reveal the presence of the following priority PAHs at different concentrations: naphthalene, (0.02-0.09 mg/L);benzo[k]fluoranthrene (0.001 -0.09 mg/L); benzo[e]pyrene (0.001-0.08 mg/L); benzo[a]pyrene (0.001 -0.09 mg/L); 3-methylcholanthrene (1.27-7.21 mg/L) during the rainy and dry seasons in Ikot Abasi. The concentrations of naphthalene ranges (0.02-0.06 mg/L), 3-methylcholanthrene ranges (2.40-3.65 mg/L), while other PAHs levels were below detection limits in rainwater from Ibeno in both seasons. The concentrations of naphthalene ranges (0.02-0.05 mg/L); 3-methylcholanthrene (2.30 - 5.65 mg/L), while other PAHs levels were below detection limits in rainwater from Eastern Obolo in both seasons The PAHs levels indicated were higher than the World Health Organization (WHO) acceptable limit of PAHs (0.0007 mg/L) in drinking water. The PAHs detected in the surface waters were in the order: Ikot Abasi (11.09 ±0.02 mg/L) > Eastern Obolo (3.87± 0.002 mg/L) > Ibeno (1.94 ± 0.004 mg/L), during the rainy season, while the PAHs detected in the surface waters were in the order: Ikot Abasi (13.79 ± 0.03 mg/L) > Eastern Obolo (3.95± 0.008 mg/L) > Ibeno (2.45±0.011 mg/L), during the dry season. The PAHs obtained for the soils in the three study areas during the rainy season were in the order: Eastern Obolo (776 ± 5.92 ug/kg) > Ibeno (732 ± 8.33 ug/kg) > Ikot Abasi (8 ± 0.07 ug/kg), while, during the dry season, the results were in the order: Ibeno (872±11.05 ug/kg) > Eastern Obolo (105±9.03 ug/kg) > Ikot Abasi (20 ± 1.95 ug/kg). Soils from Eastern Obolo and Ibeno have PAHs levels greater than 700 ug/kg, which is categorized as slightly polluted, with toxic equivalent concentrations (TEQ) higher than permissible limit (33 ug/kg). This may cause ecological risk and raises public health concern that should attract more attention. Molecular diagnostic ratio analyses show that the sources of PAHs in the three study area are mainly pyrogenic. [ABSTRACT FROM AUTHOR]

The goal of this paper is to assess the mutagenic and genotoxic potentials of avocado oil made from the fruit pulp of Persea Americana, a member of the Lauraceae family. Michigan Cancer Foundation-7 (MCF-7) cells are used in the 3-4,5 dimethylthiazol-2yl-2,5-diphenyl tetrazolium bromide (MTT) test to examine the possible antiproliferative and cytostatic qualities of different doses of avocado oil, and MCF-7 cells are used in the comet assay to examine the potential cytostatic effects of avocado oil extracted from the avocado fruit. DNA in human breast cancer cells is partially damaged by avocado oil. However, DNA damage at low, medium, and high levels was discovered in the positive control. Without positive control, the DNA damage level falls in the low, middle, and high ranges. The MTT assay shows that avocado oil exerts a dose-dependent cytostatic impact on human breast cancer MCF-7 cells with an IC50 value of 379.2 µg/mL, which is the IC50 value that causes genotoxicity in the comet assay. [ABSTRACT FROM AUTHOR]

N -Nitrosamines (also referred to as nitrosamines) are a class of substances, many of which are highly potent mutagenic agents which have been classified as probable human carcinogens. Nitrosamine impurities have been a concern within the pharmaceutical industry and by regulatory authorities worldwide since June 2018, when regulators were informed of the presence of N -nitrosodimethylamine (NDMA) in the angiotensin-II receptor blocker (ARB) medicine, valsartan. Since that time, regulatory authorities have collaborated to share information and knowledge on issues related to nitrosamines with a goal of promoting convergence on technical issues and reducing and mitigating patient exposure to harmful nitrosamine impurities in human drug products. This paper shares current scientific information from a quality perspective on risk factors and potential root causes for nitrosamine impurities, as well as recommendations for risk mitigation and control strategies. [Display omitted] [ABSTRACT FROM AUTHOR]

Cordyceps militaris , a traditional medicinal fungus, parasitizes the intestines of lepidopteron pupae or larvae, predominantly during the winter, and undergoes fruiting in the summer or autumn. Compounds extracted from C. militaris have demonstrated a broad spectrum of pharmacological effects, including antioxidant, anti-tumor, anti-metastatic, anti-inflammatory, antiviral, anti-diabetic, and various others. Herein, our study aimed at elucidating the acute, sub-acute toxicity, and genotoxicity profiles of C. militaris methanolic extract following oral administration in Swiss albino mice, representing the inaugural comprehensive exploration of the toxicological and safety profiles of C. militaris. Prior studies have predominantly focused on its biological activities rather than its toxicity. Acute oral toxicity study was conducted at 500, 1000, and 2000 mg/Kg B.W. doses of C. militaris over a 14-day period. For sub-acute toxicity study, three groups of mice were administered 100, 300, and 600 mg/Kg B.W. of C. militaris extract for 28 consecutive days; one group served as a control. Mice were monitored for their body weight and behavioural changes once daily. Hematological, serum biochemical, histopathological, histomorphometric, seminal parameters, and mutagenic investigations were performed post-treatment period. Acute oral toxicity study at 2000 mg/Kg revealed no signs of toxicity, with an LD 50 value surpassing 2000 mg/Kg. No occurrences of mortality observed, and no significant changes were noted in body weight, organ weight, or behaviour. Hematological analysis illustrated a marked upsurge in RBC, Hb, HCT, PLT, MPV, and PCT, alongside minor variations in differential leucocyte count post 28-day treatment. Liver enzyme tests indicated slight elevation in ALP, while renal enzyme tests showed alterations in CRE and BUN levels. Genotoxicity profile and histopathological assessments of the liver, spleen, testis, and ovary manifested no remarkable irregularities, except for mild renal toxicity. Seminal parameters including sperm concentration, motility and testosterone levels demonstrated a noteworthy increase. The study sheds light on the potential risks and safety considerations associated with C. militaris -based medicinal products. These findings establish a foundation for further investigations and the refinement of dosage optimization in the application of C. militaris, with the aim of mitigating any potential adverse effects. [Display omitted] • C. militaris , a traditional Chinese medicine with diverse therapeutic applications, has limited reports on toxicity. • OECD guidelines for acute (423) and sub-acute (407) toxicity studies were followed. • LD 50 greater than 2000 mg/Kg B.W. • Methanolic C. militaris triggered mild nephrotoxicity following sub-acute treatment. • C. militaris enhanced testicular functions. [ABSTRACT FROM AUTHOR]

Background: Chemotherapeutic agents are associated with different unwanted effects; the dangerous are mutagenic actions. Researchers do their best to ameliorate such effects by different supportive agents. Objective: The study designed to demonstrate the mutagenicity of the chemotherapeutic drugs especially cyclophosphamide [CP] and possible protective effects of Zinc Chloride [Zn Cl]Materials and Methods: The experiment was designed as 4 groups each group contain 12 animals, the first group [control group] was injected intraperitoneal normal saline [1 ml/kg] every other day for 20 days, the second group was given intraperitoneal Zn Cl [4 mg/kg] every other day for 20 days. The third group [Test group] injected by intraperitoneal cyclophosphamide [200 mg/kg] as a single dose on 15th day of experiment, Fourth group [protective group] was given intraperitoneal ZnCl [4 mg/kg] every other day for 20 days and injected intraperitoneal single dose by CP [200 mg/kg] on 15th day.Results: There were significant changes in blood cells, mitotic index and increased frequency of structural and numerical changes in chromosomes compared with the control group and these outcomes attributed to effects of free radicals of CP on health cells. The protective effect of Zn Cl which decrease blood cell changes, the structural and numerical aberrations in relation to the test group. Conclusion: CP has harmful effects on the blood cells and chromosomes. Zinc Chloride has a protective effect against the harmful effects of CP.

Heterocyclic aromatic amines (HAAs) are mutagenic/carcinogenic compounds that can be formed during the cooking process of proteinaceous foods such as meat. Therefore, it is needed to inhibit or reduce their formations in cooked meats. Hereby, the effects of sumac usage (0.5%, w/w) in beef meatball preparation on the formation of HAAs and some quality parameters (water, pH, cooking loss, and lipid oxidation values) of meatballs cooked at 150 and 250 °C were investigated. The sumac usage caused a reduction in pH (p < 0.01), cooking loss (p < 0.05), lipid oxidation level (TBARS, p < 0.01), and total HAA amount (p < 0.05) of the samples. In addition, increasing the cooking temperature significantly decreased the pH value (p < 0.01) and increased the cooking loss (p < 0.05) of the samples. Only one compound, 2-amino-3,8-dimethylimidazo [4,5-ƒ]quinoxaline (MeIQx), from nine different HAAs studied in this study, could be determined, and the levels of the other HAAs studied were lower than their detection limits. On the other hand, MeIQx was not detected in the samples cooked at 150 °C, it was only determined in the control group samples cooked at 250 °C. The sumac usage completely inhibited MeIQx formation in the samples. Due to its positive effect on cooking loss value, lipid oxidation level, and MeIQx formation, it can be suggested to use sumac powder in meatball preparation. [ABSTRACT FROM AUTHOR]

Aflatoxins (AFs) are natural contaminants of agricultural products and other food, produced by the filamentous fungi Aspergillus flavus and A. parasiticus. Warm and humid environmental conditions favor its development and production. The AFs get inside the organism throughout the intake of contaminated food or indirectly throughout the consumption of products as milk, meat and eggs, among others, derived from animals exposed to diets with AFs. They are stable at temperatures above 100°C, with less or null decomposition during pasteurization, roasting and baking processes. They have an important carcinogenic, mutagenic and teratogenic potential, having an impact on human and animal health and are consider as toxic and lethal. Aflatoxins are classified as AFB1, AFB2, AFG1 and AFG2. Once ingested, their metabolism in the liver causes the highly reactive metabolite AFB1-exo-8, 9 epoxide (AFBO), responsible for acute or chronic toxicity inside the organism, and two hydroxylated metabolites AFM1 and AFM2, which are eliminated throughout human and animal milk. AFs mainly cause liver damage and tumor induction. This article addresses the matter of AFs from its chemical composition, classification, mechanism of toxicity, contaminated food and damage to human and animal health, highlighting the need to establish standardized regulations among countries that contribute to guarantee the cultivation, import and export of food products and grains free of AFs, safe for human and animal consumption. [ABSTRACT FROM AUTHOR]

Mutagenic testing of portable water is fast becoming an important protocol for assessing water quality. Two potable water samples were selected from both ground and surface water sources within the Okerenkoko community, Gbaramatu Kingdom, Delta State Nigeria. Ame's test was employed in the assessment of potential carcinogens in the potable water available to the community. The study was carried out in triplicate to broaden the reproducibility of the study. Sensitivity of the test organism was evaluated using the Salmonella TA98 and Salmonella TA100 which was reconstituted for the study. The average revertant colonies from the study was enumerated to indicate that the test conducted on S3OK (Surface water) had 428.1 and 637.84 revertant colonies using Salmonella TA 100 for both +S9 mix and -S9 mix-conditions respectively while similar replica result was for Salmonella TA 98 was 629.7 and 66.12 revertant colonies. The samples obtained from S1OK had slightly lower number of revertant colonies of 209.16 and 115.94 colonies for Salmonella T.A 100 while for Salmonella T.A 98 had 116.82 and 108.90 colonies for treatments containing S9 mix preparations. The study identified the test organism was Salmonella T.A 98 was more sensitive to the carcinogen present in the S3OK sample being used by a wide population of indigenes of the lower economic class. This study further buttresses the need to develop a more robust monitoring protocol for packaged water sources in Nigeria. Regulatory agencies such as NAFDAC must enforce strict intervention limits for potable water sources. [ABSTRACT FROM AUTHOR]

The Ag/AgCl composite can be synthesized using various chemical, physical, and biological methods. Biosynthesis of nanoparticles is a rapid technology and has advantages over physical and chemical synthesis methods. This research is based on the bacterial formation of silver nanoparticles by bacterial strain Tmas-01. The bacterial strain Tmas-01 was isolated from soil samples and screened for its potential to form Ag/AgCl composite. The formation of Ag/AgCl composite was investigated at the 300–800 nm range using UV–Vis spectrophotometer. Also, the structural and morphological synthesized nanoparticles were characterized using FTIR, SEM–EDS, and XRD. These results showed that Ag/AgCl composite have the SPR absorption peak at 410 nm and a size range of 10–30 nm with a spherical shape. The Ag/AgCl composite exhibited antibacterial and antibiofilm effects against uropathogenic organisms with a range of 5–100%. The results of the genotoxic effects of Ag/AgCl composite by Salmonella typhimurium reverse mutation bioassay (Ames test) indicated which Ag/AgCl composite had no mutation effect. Moreover, Ag/AgCl composite determined an anti-mutagenic effect with a percentage between 97 and 100%. Furthermore, the toxicity of biosynthesized nanoparticles was measured against brine shrimp to evaluate the cytotoxic effect and displayed LC50 (1 µg/ml). The Ag/AgCl composite could effectively photocatalytic degrade up to 64% of Rhodamine B dye. The phylogenetic analysis showed that strain Tmas-01 belonged to Bacillus paralicheniformis sp. with 99.29% similarity. [ABSTRACT FROM AUTHOR]

The goal of this paper is to assess the mutagenicand genotoxic potentials of avocado oil made from the fruit pulp of Persea Americana, a member of the Lauraceae family.Michigan Cancer Foundation-7 (MCF-7) cells are used in the 3-4,5 dimethylthiazol-2yl-2,5-diphenyl tetrazolium bromide (MTT) test to examine the possible antiproliferative and cytostatic qualities of different doses of avocado oil, and MCF-7 cells are used in the comet assay to examine the potential cytostatic effects of avocado oil extracted from the avocado fruit. DNA in human breast cancer cells is partially damaged by avocado oil. However, DNA damage at low, medium, and high levels was discovered in the positive control. Without positive control, the DNA damage level falls in the low, middle, and high ranges. The MTT assay shows that avocado oil exerts a dose-dependent cytostatic impact on human breast cancer MCF-7 cells with an IC50 value of 379.2 μg/mL, which is the IC50 value that causes genotoxicity in the comet assay.

In vitro and in silico tests were used to assess the possible genotoxicity and mutagenicity of five impurities that may be present in levothyroxine, a drug used for thyroid hormone replacement therapy. Neither ToxTree nor VEGA (Virtual Models for evaluating the properties of chemicals within a global architecture) identified cause for concern for any of the impurities. Ames test results (doses up to 1 mg per plate), with or without metabolic activation, were negative. The micronucleus test with TK6 (human lymphoblastoid) cells, at doses up to 500 µg/mL, with or without metabolic activation, also gave negative results. • In vitro and in silico tests were used to assess genotoxicity and mutagenicity of levothyroxine impurities. • Neither ToxTree nor VEGA software identified genotoxic concerns for the impurities. • Neither the Ames test nor the micronucleus test showed mutagenic activity for the impurities. [ABSTRACT FROM AUTHOR]

An inflammation response occurs when the body reacts to exogenous and endo enous noxious stimuli, and it helps the body respond to infection and repair tissues, adapt to stress, and remove dead or damaged cells. Anti-inflammatory drugs such as non-steroidal anti-inflammatory drugs are traditionally used to treat inflammation; however, these drugs often cause negative side effects. For this reason, developing and establishing effective alternative medicines for treating many chronic diseases with underlying inflammation is critically dependent on the identification of new organic molecules and bioactive substances. Aromatic and volatile compounds found in essential oils isolated from Pimenta dioica (allspice), Cuminum cyminum (cumin), and Citrus sinensis (sweet orange) are a source of bioactive compounds. Allspice essential oil reduces ear inflammation more than 65% and the anti-inflammatory activity of allspice essential oil is enhanced when combined with sweet orange peel and cumin essential oils, resulting in the reduction of edema inflammation by more than 85%, similar to indomethacin. As an alternative to anti-inflammatory treatment, essential oil mix is pharmacologically safe as it is neither toxic nor mutagenic. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) due to their detrimental threat to human life, widespread existence in food chains and incremental lifetime cancer risk are of great concern around the globe. Ensuing their carcinogenic, genotoxic, and mutagenic effects, this paper reviews the status of PAHs pollution in air, sediment, soil and water of different world regions and food chains. Besides this, the review will also summarize the data available on the content of PAHs in various food types and effects of PAHs intake on human health along with some preventive measures. The result showed that the overall concentration of PAHs ranged from 0- 3842 ng.m-3 in air, 0- 205398.76 ng. L-1 in water and 0-233320 ng. g-1 in sediment while agriculture soil possesses lower concentration of PAHs than urban soil. Moreover, higher content of PAHs in air, water and sediment have found in Asia, Middle East, and Africa, respectively. At the end, discussion will be extended to describe some recommendations to reduce emission rate of PAHs around the world.

Abstract Introduction Exposure to chemical compounds occurs in numerous occupational settings, among which the research and healthcare laboratories have not been adequately investigated. These settings are characterized by an extreme variability of the used compounds and by the frequent turnover of young researchers. The main objectives of the study were to explore the occupational exposure to hazardous chemical substances among research laboratory workers; to assess their awareness and perceptions regarding chemical hazards; to investigate adherence to guidelines on safe handling of chemical compounds; and to analyze the effects of several factors on these outcomes of interest. Methods The survey was conducted among research laboratories workers who were exposed to chemical substances during their activity. Subjects completed a questionnaire exploring knowledge, attitudes and behaviors related to chemical hazards involved in research activities. Results Enrolled subjects were 237, for an 81.7% response rate. More than 90 hazardous chemical substances were used in the surveyed laboratories. A correct knowledge on hazardous chemicals was significantly more likely in younger researchers, in those manipulating a higher number of hazardous chemicals, and in those with a higher number of years of training in the attended laboratory; 54.4% of the workers said they felt very exposed to chemical risk. Correct practices in the laboratories were significantly more likely in researchers who perceived to have a low exposure to chemicals, but a high exposure to biological risk, who agreed with the statement that colleagues handle chemicals following safety procedures and who perceived to have received an adequate training in the management of accidents and first aid. Conclusions Our results showed significant gaps in knowledge and scarce preparedness in the adherence to safety processes to prevent and contain risks related to use of chemical compounds in research laboratories.

We recently discovered that sphaeropsidin A (SphA), a fungal metabolite from Diplodia cupressi, overcomes apoptosis resistance in cancer cells by inducing cellular shrinkage by impairing regulatory volume increase. Previously, we prepared a pyrene-conjugated derivative of SphA by a cross-metathesis reaction involving the phytotoxin's C15,C16-alkene. This derivative's evaluation in a cancer cell panel revealed a significant increase in potency, with the IC 50 values 5-10× lower than those displayed by the original natural product. Herein, we describe the preparation and anticancer evaluation of fifteen novel C15,C16-alkene cross-metathesis analogues in which the pyrene moiety was replaced with other aromatic or non-aromatic hydrophobic groups. The idea for this replacement was to prepare a family of compounds that would not be predicted to be mutagenic compared with the original pyrene analogue. We predict several of our new compounds to be non-mutagenic, while retaining the high potency of the original pyrene-containing analogues. Examples of these potential lead compounds included those containing pentamethylphenyl and triphenylethylene pendant groups. As an additional feature of the current investigation, we prepared several deuterated pyrene-containing compounds to overcome intellectual property issues associated with non-patentability of the original pyrene derivative., (© 2024 Wiley-VCH GmbH.)

The present work done on three antipyretic drugs used in Egypt, and these drugs are Ibuprofen, Acetyl salicylate (Acetyl salicylic acid) and Alexopirine, these drugs are tested on white blood cells in human and bone marrow on bones of mice and cells chromosome Mice Mus muscles 2n=40 i.e Vicia faba and Allium cepa. Many different concentrations are used. The obtain result showed that different effect had been observed from these three different drugs from small type which represent on sister chromosome exchange and also big type represent on Bridge chromosome, Fragmentation and Replication. [ABSTRACT FROM AUTHOR]

Paraquat is the most widely used herbicide and the third most sold pesticide in the world, applied in more than 120 countries despite being banned in the European Union. It is a risk to ecosystems. The genotoxic effect of paraquat was evaluated using the Lens culinaris test. L. culinaris seeds were subjected to 6 concentrations of paraquat (0.1, 0.5, 1, 1.5, 1.5, 2, and 3 ppm) plus a control (distilled water). During 72 h, root development was measured every 24 h. After 3 days, root apices were analyzed to obtain the inhibition of the mitotic index, as well as the type and rate of chromosomal abnormalities present. A decrease in root growth of more than 50% (72 h of exposure) and an inhibition of the mitotic index of 2.9 times in the treatment with 3 ppm compared to the control were observed. The 2 ppm concentration presented all the anomalies found with a frequency of 84 ± 2.5 of micronuclei, 106 ± 3.5 of nuclear lesions, 14 ± 4.7 of nucleus absence, 8 ± 2.7 of telophase bridges, 7 ± 2.7 of binucleated cells, among others. It is also recommended to establish comparisons of L. culinaris with multiple biomarkers since it is presented as a practical and economic alternative. [ABSTRACT FROM AUTHOR]

Introduction: Exposure to chemical compounds occurs in numerous occupational settings, among which the research and healthcare laboratories have not been adequately investigated. These settings are characterized by an extreme variability of the used compounds and by the frequent turnover of young researchers. The main objectives of the study were to explore the occupational exposure to hazardous chemical substances among research laboratory workers; to assess their awareness and perceptions regarding chemical hazards; to investigate adherence to guidelines on safe handling of chemical compounds; and to analyze the effects of several factors on these outcomes of interest. Methods: The survey was conducted among research laboratories workers who were exposed to chemical substances during their activity. Subjects completed a questionnaire exploring knowledge, attitudes and behaviors related to chemical hazards involved in research activities. Results: Enrolled subjects were 237, for an 81.7% response rate. More than 90 hazardous chemical substances were used in the surveyed laboratories. A correct knowledge on hazardous chemicals was significantly more likely in younger researchers, in those manipulating a higher number of hazardous chemicals, and in those with a higher number of years of training in the attended laboratory; 54.4% of the workers said they felt very exposed to chemical risk. Correct practices in the laboratories were significantly more likely in researchers who perceived to have a low exposure to chemicals, but a high exposure to biological risk, who agreed with the statement that colleagues handle chemicals following safety procedures and who perceived to have received an adequate training in the management of accidents and first aid. Conclusions: Our results showed significant gaps in knowledge and scarce preparedness in the adherence to safety processes to prevent and contain risks related to use of chemical compounds in research laboratories. [ABSTRACT FROM AUTHOR]

Background: Iraq is an oil country in addition to an agricultural economie so the using of pesticide has raised very dramatically to cater the food demands of increasing population. Thus, a continuous examination of pesticides is required. Ames test is a standard method for determining the carcinogenic compounds by induce back mutations in auxotrophic strain of Salmonella typhimurium- histidine negative (his-) and biotinnegative (bio-), but in our country-Iraq, this bacterial strain was unavailable in most time. However, this study designed to guess the possibility of employment prototrophic Escherichia coli according to phenotype features instead of S. typhimurium. Method: A prototrophic Escherichia coli was sensitive to amikacin, erythromycin, chloramphenicol, ciprofloxacin, tobramycin and trimethoprim. The strain was exposed to different concentration of Chlorpyrifos (CPF)as a mutation inducer. The potentiality of mutagenesisof CPF was detected according to phenotype featuresusing antibiotics susceptibility test (AST). Result: Our result showed that the mutations were induced in some chromosomal genes of E. coli when exposed to CPF in high concentration 80-100%, while con. 10-70% were not. These genes encoded resistance to erythromycin, trimethoprim and tobramycin. Conclusions: The modified Ames test can consider as a predictive tool for screening a potential carcinogenicity. The potential of genotoxic of the CPF has been detected. [ABSTRACT FROM AUTHOR]

This study assesses the antigenotoxic activity, antimutagenic and inhibiting cytotoxic conferred for the extract of seeds of Salvia hispanica L. (ShE) in culture of human leukocytes. Phytochemical methods were used by HPLC for determination of compounds: chlorogenic acid, caffeic acid, gallic acid, kaempferol, quercetin and rutin. Cellular cultures were placed in contact with the extract at concentrations of 100 µg/mL and 10 µg/mL in addition to hydrogen peroxide as causative agent of damage. The results showed a reversal rate of DNA damage of 31%, 41.4% in the frequency of micronuclei, 21.7% in cytoplasmic rates of chromosomal abnormalities and a 17.7% improvement in cell viability in the sample containing 100 µg/mL of ShE. The samples that contained the ShE in low concentration of 10 µg/mL did not show such reversals against the effects of H2O2. We demonstrated that the use of ShE has beneficial and promising effects.

In this article the amount of polycyclic aromatic hydrocarbon (PAHs) on the sediment of Caspian Sea predicted by artificial neural networks multi-layer perceptron (MLP) and generalized regression (GRNN) models. PAH is a most important pollutant in a marine environment derived from an anthropogenic and natural source. This component is mutagenic and Carcinogenic extremely. In this investigation, a multi-layer perceptron and Generalized regression neural network models have been developed by experimental data (organic matter, latitude, longitude, depth and effective matter (particle size)) reported in the literature. As a result, experimental data compared to the output of models by calculation of mean squared error (MSE), root mean squared error (RMSE), mean absolute error percent (MEAE), maximum absolute error percent (MAAE) and R2. Results have shown an appropriate fitting for experimental data with predicted values.Also, MLP neural network has the best performance to predicating of PAHs. [ABSTRACT FROM AUTHOR]

In the present work, the production of mutant Bacillus thuringiensis H-14 var. israelensis (Bacillaceae) by the action of hydroxylamine chloride, was evaluated. The experimental design was completely randomized, with a control and three mutagen concentrations 10, 20 and 30 ppm with three repetitions for each. The bioprocess was carried out using agitated and aerated cylindrical tank bioreactors, with a microbial inoculum of 108 CFU / ml for 48 hours at a temperature of 30 ° C and an initial pH of 7,0, which decreased to a final value of 6,0. Obtaining the highest production of bioinsecticide at the concentration of 20 ppm. Which was quantified in grams of dry weight per liter (2,10 g / L). Evidence that there is no direct relationship between the production of bioinsecticide and the concentration of the mutagen. [ABSTRACT FROM AUTHOR]

Dust samples were collected from four indoor environments, including childcare facilities, houses, hair salons, and a research facility from the USA and were analyzed for brominated compounds using full scan liquid chromatography high-resolution mass spectrometry. A total of 240 brominated compounds were detected in these dust samples, and elemental formulas were predicted for 120 more abundant ions. In addition to commonly detected brominated flame retardants (BFRs), nitrogen-containing brominated azo dyes (BADs) were among the most frequently detected and abundant. Specifically, greater abundances of BADs were detected in indoor dusts from daycares and salons compared to houses and the research facility. Using authentic standards, a quantitative method was established for two BADs (DB373: Disperse Blue 373 and DV93: Disperse Violet 93) and 2-bromo-4,6-dinitroaniline, a commonly used precursor in azo dye production, in indoor dust. Generally, greater concentrations of DB373 (≤3850 ng/g) and DV93 (≤1190 ng/g) were observed in indoor dust from daycares highlighting children as a susceptible population to potential health risk from exposure to BADs. These data are important because, to date, targeted analysis of brominated compounds in indoor environments has focused mainly on BFRs and appears to underestimate the total amount of brominated compounds. Image 1 • Brominated azo dyes (BADs) were detected at relatively greater abundances than brominated fire retardants in indoor dusts from across USA. • BAD concentrations were determined, for the first time, in indoor dusts with maximum concentration of Disperse Blue, 3850 ng/g. • BAD concentrations in indoor dust from childcare were greater than in indoor dusts from houses, salons and a research facility. • Estimated BADs ingestion via dust was as much as 10-fold greater for infants compared to other age groups. Brominated azo dyes were detected at biologically significant concentrations in indoor dust using liquid chromatography ultrahigh-resolution mass spectrometry. [ABSTRACT FROM AUTHOR]

The present study primarily aims at informing regulators and policy makers in Europe and examines the evolution of self-classifications and study availability for the endpoints of carcinogenicity, mutagenicity, reproductive toxicity (CMR) and specific target organ toxicity after repeated exposure (STOT RE) for the first ten years of the REACH legislation. Our knowledge on chemical safety keeps increasing due to the registration obligations under REACH, in combination with proactive actions by registrants and regulatory actions by Authorities, which jointly lead to new testing and critical reassessment of existing studies. The improvements become evident by the constant increase in the number of substances that are self-classified by the registrants for human health endpoints. Moreover, there is a slow but steady increase in the number of substances for which there is at least one experimental study available for the human health endpoints in scope of this analysis. However, the increase is slow given the generally limited data availability at the beginning of REACH. Manual examination of about 350 classified substances reveals that the impact of newly generated data and regulatory action by Authorities is greater for reproductive toxicity than for carcinogenicity or mutagenicity, reflecting the strengthening of the information requirements for reproductive toxicity with the introduction of REACH. The results of the study should inform regulators and policy makers at EU and national level in the discussion on potential changes to information requirements or testing strategies under REACH. • REACH brings new information on chemicals, impacting their safe use. • Steady increase in hazardous substances classified for human health endpoints. • Authority action affects reproductive toxicity more than carcinogenicity. • Substance composition a significant reason for classification. [ABSTRACT FROM AUTHOR]

Pellucida peperomia, commonly known as jabuti herb, little heart, glass herb, is used in popular medicine as an antibiotic, wound healing, abdominal pain, cramps, acnes, boils, headaches, kidney disorders and pains in the articulations. Thus, the objective of this study was to evaluate the possible toxic and mutagenic effects of the aqueous extract (EA) of P. pellucida. The in vivo test of Allium cepa was used to determine cytotoxicity and mutagenicity, in which concentrations of 100 and 50% for AE were used. For the in vitro test with Artemia salina, the concentrations of 100, 50, 25, 12 and 6.25% were used, for analysis of the cytotoxic activity and determination of LD50. The cytotoxicity test resulted in an LD50 of 8799 µg/ mL for EA, which was considered to be non toxic or inactive. The A. strain strain demonstrated a reduction in root growth indicating cytotoxicity by EA. All treatments resulted in the presence of micronuclei, but there was a statistically insignificant difference in comparison to the positive control group. It was concluded that the extracts revealed cytotoxic and non-mutagenic effects, and there were no significant data regarding the mitotic index when compared to the controls. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are Canceriogenic and mutagenic substances. These compounds are released in the environment by anthropogenic and natural sources. In this work, an adaptive neuro-fuzzy inference system (ANFIS) was employed to model the PAHs formation in sea sediment. Development of ANFIS model is on the basis of the Gaussian membership function. The result obtained by ANFIS model was analyzed with the statistical parameters such as mean squared error (MSE), mean absolute error percent (MEAEP), maximum absolute error percent (MAAEP) and R2. The prediction capability of ANFIS model was compared with the previous developed models. According to results obtained by statistical parameters, the ANFIS model has the best performance in estimating of PAHs with the lowest error values. [ABSTRACT FROM AUTHOR]

Fishes in the aquatic food web are at the top of most aquatic food chains and form an important link in the aquatic-terrestrial food chain also. They are easily available in the wild, market, can be easily maintained in the laboratory and act as important models for indicating the outcome of exposure of human populations to toxic and genotoxic chemicals in drinking water. They respond to toxicants in a manner similar to higher vertebrates and metabolize and accumulate pollutants. Food is a major route for exposure of human populations to toxic chemicals in water so fish and shell fish have been recognized as major vectors for transfer of contaminants to humans, as these major sources of protein in many countries, are often contaminated with high concentrations of pollutants. In living systems, these are biotransformed to various toxic derivatives which react with DNA and lead to tumour development are carcinogenic and/or mutagenic to life leading to the number of cancer cases. Epidemiological studies have revealed that workers in the dye industry had a higher incidence of urinary bladder tumours than that of the general population. Therefore, in the present review an attempt has been made to document the work done in past on the use of fishes for studying toxicological changes induced by pollutants. Actually, toxicity and genotoxicity of dyes in fish has not been much explored, therefore along with the few reports available on dyes, literature on toxicity and genotoxicity of other aquatic pollutants has also been reviewed in the present study. [ABSTRACT FROM AUTHOR]

Explanation the topic: Changes in genetic material can lead to aberrant cell in the direction of disorders of cellular regulation, malignant transformation, cell death, or if the adjustment was made at the level of the reproductive cells, to genetic changes in some of the consequent off spring. The topic position in scientific/professional public: Breaking of chromosomes can occur spontaneously or can be induced. Chromatid/chromosome breakings can be induced by different environmental factors: chemicals, biological clastogenic agents, accidentally or intentionally. Conclusions: The authors suggest: - making conditions for strong respect of environmental regulations; - to use higher plants for the early detection of environmental mutagens; - create and orderly update National radionuclide database.

The title compound, glycidamide (systematic name: oxirane-2-carboxamide), C3H5NO2, is the mutagenic and genotoxic metabolite of acrylamide, a food contaminant and industrial chemical that has been classified as being probably carcinogenic to humans. Synthesized via the reaction of acrylonitrile and hydrogen peroxide, it crystallizes with both enantiomers occurring as two crystallographically independent molecules (A and B) in the asymmetric unit. They have similar conformations with an r.m.s. deviation of 0.0809 Å for molecule B inverted on molecule A. In the crystal, molecules are linked by N—H...O hydrogen bonds, which lead to the formation of β-sheet structures enclosing R22(8) and R42(8) loops. The β-sheets are linked by weaker C—H...O hydrogen bonds, forming a supramolecular three-dimensional structure.

Smoked cigarette butt (SCB) discharged in the environment became an issue of unknown consequences for plants. Thus, we aim at assessing the impact of water containing SBC leachate on the meristem cells of Allium cepa roots. We defined the following experimental groups: negative control (water), positive control (cyclophosphamide); water with SCB leachate at environmental concentration (1.9 μg/L of nicotine) (EC1× group) and water with SCB leachate concentration 1000 times higher than EC1 (EC1000× group). Mitotic index, total number of abnormal cells, index of abnormal cells per mitotic/phase, relative growth index, and inhibition index were calculated after 48 exposure hours. Root meristems were used to prepare slides in order to investigate chromosomal and nuclear abnormalities. According to our data, plants exposed to SCB leachate presented low relative growth index, high inhibition index, large number of abnormal cells, and high abnormality frequency at metaphase/anaphase. The exposed A. cepa recorded a wide variety of abnormalities such as diagonal metaphase/anaphase, metaphase/anaphase presenting chromosome fragments, binucleated cells, displaced nucleus, chromosome bridges, micronuclei, necrotic cells, stick metaphase, chromosome adherence, notched nucleus, among other cell disturbances. The chemicals in the SBC leachate had aneugenic and clastogenic effect on the genetic material of the tested plants, either when they acted individually, synergistically, or additively. Thus, our study is a pioneer in reporting that the mere disposal of cigarette butts in the environment can have cytotoxic, genotoxic, and mutagenic effects on plants. [ABSTRACT FROM AUTHOR]

In the case of serotype O foot-and-mouth disease virus (FMDV), antibodies against five neutralizing sites play a pivotal role in protection of animals, with site 1 being considered the most crucial. However, recent studies indicated that the antibodies of vaccinated farm animals are mainly against site 2 rather than site 1. In Taiwan, blanket vaccination had been implemented for more than fifteen years, in which the porcinophilic isolate O/Penghu/2012 showed significant amino acid alterations in site 2 compared to the early isolate O/TW/97. To study the antigenicity of site 2, MAbs against site 2 are required. In this study, we generated site 2 mutated virus-like particles (mVLPs) with only VP2-S72 N mutation, and successfully identified five site 2 MAbs from a previously prepared O/TW/97 MAb panel by immunofluorescence assay (IFA) and ELISA based on the different reactivity to wild-type VLP and mVLP. In conclusion, the established model was proved as an effective method to reveal the epitope that a MAb recognizes. By applying this MAb panel and sequence alignment, we demonstrated that the O/Penghu/2012 isolate not only showed significant genetic difference in site 2 but also significant antigenic difference from the ancestral O/TW/97. [ABSTRACT FROM AUTHOR]

Medicinal plants have been used in primary healthcare since the earliest days of humankind. Turnera subulata and Spondias mombin × Spondias tuberosa are widely used in the Brazilian Northeast to treat several diseases. The aim of this study was to evaluate the genotoxic effects of the leaf extracts of these species by the somatic mutation and recombination test in the somatic cells of Drosophila melanogaster wings. The experiments were performed using standard and high-bioactivation cross and three concentrations of the test substance [aqueous extract (AET and AES) at 5.0, 10.0, and 20.0 mg/mL and ethanolic extract (EET and EES) and ethyl acetate fraction (EAFT and EAFS) at 0.625, 1.25, and 2.5 mg/mL]. Results indicated that the extracts and fractions induced spontaneous frequencies of mutant spots in both D. melanogaster crosses. Nevertheless, the highest concentrations of the tested plant chemical agents were responsible for the statistically significant genotypic effect. T. subulata and S. mombin × S. tuberosa displayed genotoxic effect under the experimental conditions. The results from this study are crucial as they indicated the deleterious and side effects, considering the indiscriminate use of the extracts of these plants for disease treatment. [ABSTRACT FROM AUTHOR]

Adverse outcome pathways (AOPs) are frameworks starting with a molecular initiating event (MIE), followed by key events (KEs) linked by KE relationships (KERs), ultimately resulting in a specific adverse outcome. Relevant data for the pathway and each KE/KER are evaluated to assess biological plausibility, weight-of-evidence, and confidence. We aimed to describe an AOP relevant to chemicals directly inducing mutation in cancer critical gene(s), via the formation of chemical-specific pro-mutagenic DNA adduct(s), as an early critical step in tumor etiology. Such chemicals have mutagenic modes-of-action (MOA) for tumor induction. To assist with developing this AOP, Aflatoxin B1 (AFB1) was selected as a case study because it has a rich database and is considered to have a mutagenic MOA. AFB1 information was used to define specific KEs, KERs, and to inform development of a generic AOP for mutagen-induced hepatocellular carcinoma (HCC). In assessing the AFB1 information, it became clear that existing data are, in fact, not optimal and for some KEs/KERs, the definitive data are not available. In particular, while there is substantial information that AFB1 can induce mutations (based on a number of mutation assays), the definitive evidence - the ability to induce mutation in the cancer critical gene(s) in the tumor target tissue - is not available. Thus, it is necessary to consider the patterns of results in the weight-of-evidence for KEs and KERs. It was important to determine whether there was sufficient evidence that AFB1 can induce the necessary critical mutations early in the carcinogenic process, which was the case. [ABSTRACT FROM AUTHOR]

In recent years, goat's milk has shown a number of advantages over the milk from other ruminant species. Some milk substances can alter the milk quality and also present potential carcinogenic activity. In this work, chemical composition and mutagenic compounds were determined using Ames test on goat milk from different geographical locations of northern Argentina. In Tucumán, two extensive farms were analyzed, one of them near to soybean culture, La Perla Farm, where the goat́s milk showed 788 ± 33 colonies/plate and the Sunchales Farm, which milk contained 655 ± 51 colonies/plate. The third is a public organization with semi-extensive INTA Farm, where Ames test indicated 210 ± 28 colonies/plate. A goat probiotic mixture (GPM): Lactobacillus reuteri DDL19, Lactobacillus alimentarius DDL48, Bifidobacterium bifidum DDBA and Enterococcus faecium DDE39 was orally administered as a treatment to diminish toxic substances. Ames test after a 25-days treatment with probiotics bacteria, showed 455 ± 47; 300 ± 33, and 102 ± 36 colonies/plate from goat milk obtained from La Perla, Sunchales and INTA farms, respectively. After a 50-days treatment, the Ames test detected 289 ± 23, 126 ± 26, and 60 ± 5 colonies/plate, in goat milk from La Perla, Sunchales and INTA farms, respectively. Moreover, the probiotic administration did not modify the milk physical-chemical composition; with the exception of fatty acid. The diminution of the mutagen capacity of milk could respond to observed modification on fat content. These results reinforce previous results about adsorption of mutagens by the strains contained in the GPM and define the first scientific results on this topic. The GPM, added to goat diet, did not influence protein and nonfat solids contents, acidity and density values, but allowed the obtaining of milk characterized by improving the concentration of beneficial compounds. The study supports the use of probiotics to enhance the quality of goat products. [ABSTRACT FROM AUTHOR]