No Observed Adverse Effect Concentration Research Articles

The anti-non-small cell lung cancer effect of Diosbulbin B: Targeting YY1 induced cell cycle arrest and apoptosis

BackgroundToxic components frequently exhibit unique characteristics and activities, offering ample opportunities for the advancement of anti-cancer medications. As the main hepatotoxic component of Dioscorea bulbifera L. (DB), Diosbulbin B (DIOB) has been widely studied for its anti-tumor activity at nontoxic doses. However, the effectiveness and mechanism of DIOB against non-small cell lung cancer (NSCLC) remains unclear. PurposeTo evaluate the anti-NSCLC activity of DIOB and to elucidate the specific mechanism of action. MethodThe effect of DIOB on NSCLCL in vitro was evaluated through CCK8, colony formation, and flow cytometry. The in vivo efficacy and safety of DIOB in treating NSCLC were assessed using various techniques, including HE staining, tunel staining, immunohistochemistry, and biochemical index detection. To understand the underlying mechanism, cell transfection, western blotting, molecular docking, cellular thermal shift assay (CESTA), and surface plasmon resonance (SPR) were employed for investigation. ResultsDIOB effectively hindered the progression of NSCLC both in vitro and in vivo settings at a no-observed-adverse-effect concentration (NOAEC) and a safe dosage. Specifically, DIOB induced significant G0/G1 phase arrest and apoptosis in A549, PC-9, and H1299 cells, while also notably inhibiting the growth of subcutaneous tumors in nude mice. Mechanistically, DIOB could directly interact with oncogene Yin Yang 1 (YY1) and inhibit its expression. The reduction in YY1 resulted in the triggering of the tumor suppressor P53, which induced cell cycle arrest and apoptosis in NSCLC cells by inhibiting the expression of Cyclin A2, B2, CDK1, CDK2, CDK4, BCL-2, and inducing the expression of BAX. In NSCLC cells, the induction of G0/G1 phase arrest and apoptosis by DIOB was effectively reversed when YY1 was overexpressed or P53 was knocked down. Importantly, we observed that DIOB exerted the same effect by directly influencing the expression of YY1-regulated c-Myc and BIM, particularly in the absence of P53. ConclusionFor the inaugural investigation, this research unveiled the anti-NSCLC impact of DIOB, alongside its fundamental mechanism. DIOB has demonstrated potential as a treatment agent for NSCLC due to its impressive efficacy in countering NSCLC.

Toxicity of ciprofloxacin and ofloxacin to Moina macrocopa and investigation of p-value adjustments for (eco)toxicological studies

Ciprofloxacin (CFX) and ofloxacin (OFX) are commonly found as residual contaminants in aquatic environments, posing potential risks to various species. To ensure the safety of aquatic wildlife, it is essential to determine the toxicity of these antibiotics and establish appropriate concentration limits. Additionally, in (eco)toxicological studies, addressing the issue of multiple hypothesis testing through p-value adjustments is crucial for robust decision-making. In this study, we assessed the no observed adverse effect concentration (NOAEC) of CFX and OFX on Moina macrocopa across a concentration range of 0–400 µg L−1. Furthermore, we investigated multiple p-value adjustments to determine the NOAECs. Our analysis yielded consistent results across seven different p-value adjustments, indicating NOAECs of 100 µg CFX L−1 for age at first reproduction and 200 µg CFX L−1 for fertility. For OFX treatment, a NOAEC of 400 µg L−1 was observed for both biomarkers. However, further investigation is required to establish the NOAEC of OFX at higher concentrations with greater certainty. Our findings demonstrate that CFX exhibits higher toxicity compared to OFX, consistent with previous research. Moreover, this study highlights the differential performance of p-value adjustment methods in terms of maintaining statistical power while controlling the multiplicity problem, and their practical applicability. The study emphasizes the low NOAECs for these antibiotics in the zooplanktonic group, highlighting their significant risks to ecological and environmental safety. Additionally, our investigation of p-value adjustment approaches contributes to a deeper understanding of their performance characteristics, enabling (eco)toxicologists to select appropriate methods based on their specific needs and priorities.

Application of physiologically-based pharmacokinetic modeled toluene blood concentration in the assessment of short term exposure limits

Toluene is a volatile hydrocarbon with solvent applications in several industries. Acute neurological effects in workers exposed to toluene have been reported in various publications. To inform the basis for a toluene Short Term Exposure Limit (STEL), studies of toluene-exposed workers were modeled using customized exposure scenarios within an existing physiologically-based pharmacokinetic (PBPK) model to simulate blood concentrations during individual studies. Maximum simulated blood concentration ranged from 0.3 to 1.7 (mean = 0.74 mg/L, median = 0.73, upper 95th percentile = 1.07) at the studies identified No Observed Adverse Effect Concentration (NOAEC). Maximum simulated blood concentration ranged from 0.7 to 4.1 mg/L (mean = 1.81, median = 1.63, lower 95th percentile = 0.92) at the studies identified Lowest Observed Adverse Effect Concentration (LOAEC). The maximum blood concentration for a 100 ppm STEL-like simulation was 0.4 mg/L, at the lower end of the NOAEC range and below the 95th percentile of the LOAEC. Therefore, it appears that a STEL <100 ppm would be unnecessary to protect workers due to peak occupational exposures to toluene.

Exposure of chlorothalonil and acetamiprid reduce the survival and cause multiple internal disturbances in Apis mellifera larvae reared in vitro.

Background: Chlorothalonil and acetamiprid are chemical pesticides commonly used in agricultural production and have been shown to have negative effects on bee's fitness. Despite many studies have revealed that honey bee (Apis mellifera L.) larvae are posting a high risk on exposure to pesticides, but the toxicology information of chlorothalonil and acetamiprid on bee larvae remain limited. Results: The no observed adverse effect concentration (NOAEC) of chlorothalonil and acetamiprid for honey bee larvae were 4μg/mL and 2μg/mL, respectively. Except for CarE, the enzymic activities of GST and P450 were not influenced by chlorothalonil at NOAEC, while chronic exposure to acetamiprid slightly increased the activities of the three tested enzymes at NOAEC. Further, the exposed larvae showed significantly higher expression of genes involved in a series of different toxicologically relevant process following, including caste development (Tor (GB44905), InR-2 (GB55425), Hr4 (GB47037), Ac3 (GB11637) and ILP-2 (GB10174)), immune system response (abaecin (GB18323), defensin-1 (GB19392), toll-X4 (GB50418)), and oxidative stress response (P450, GSH, GST, CarE). Conclusion: Our results suggest that the exposure to chlorothalonil and acetamiprid, even at concentrations below the NOAEC, showed potentially effects on bee larvae's fitness, and more important synergistic and behavioral effects that can affect larvae fitness should be explored in the further.

The effects of 4-week inhalation exposure to titanium nitride on lungs of Sprague-Dawley rats.

Titanium nitride (TiN) is a ceramic material with physical properties such as extreme hardness, high decomposition temperature, defect structure, and gold-yellow color. TiN is generally considered non-toxic and safe; however, hazards have not been identified, especially in workers after inhalation exposure. Here, we conducted a four-week inhalation toxicity study of TiN using a nose-only inhalation exposure system in Sprague-Dawley rats. Rats were exposed to TiN for 4 weeks (6h a day, 5 days per week) at target concentrations of 45, 90, and 180mg/m3. Clinical signs, mean body weight changes, hematology, blood biochemistry, necropsy, organ weight, bronchoalveolar lavage fluid analysis, and histopathological findings were observed. Analytical concentrations of the low, middle, and high-concentration groups were 45.55 ± 3.18mg/m3, 90.69 ± 7.30mg/m3, and 183.87 ± 15.21mg/m3, respectively. The mass median aerodynamic diameter (MMAD) for the low, middle, and high-concentration groups were 1.44 ± 0.07μm, 1.47 ± 0.18μm, and 1.68 ± 0.16μm, and the geometric standard deviation (GSD) was 2.24 ± 0.03, 2.31 ± 0.16, and 2.43 ± 0.11, respectively. No systemic adverse effects were observed after inhalation exposure to TiN; however, histopathological findings (increased phagocytic macrophages and alveolar/bronchiolar epithelial hyperplasia) and Bronchoalveolar Lavage Fluid (BALF) analysis (elevated lactate dehydrogenase and gamma-glutamyltransferase values) showed adverse effects on the lungs in the middle and high-concentration groups. Based on these results, the no observed adverse effect concentration (NOAEC) is suggested to be 45mg/m3.

Sodium dichloroisocyanurate toxicity in rats during a 90-day inhalation toxicity study

Sodium dichloroisocyanurate-96% (NaDCC) is commonly used to treat drinking water, industrial water, and wastewater. However, exposure to NaDCC by inhalation can have toxic pulmonary effects in humans. In the present study, we evaluated the potential toxicity of NaDCC following a 90-day inhalation toxicity study in Sprague-Dawley/Crl:CD (SD) rats. The animals were exposed to 0.4, 2.0, or 10.0 mg/m3 NaDCC for 90 days. In addition, male and female rats from the 10.0 mg/m3 group were set up as the recovery group for 14 days. The bronchoalveolar lavage fluid showed a concentration-dependent increase in the total cell count, with a significant increase in neutrophils in both the sexes in the 10.0 mg/m3 group compared to the negative control group. In the 10.0 mg/m3 group, lung organ weight was significantly increased among the female rats. Histopathological examination showed eosinophilic droplets in the olfactory/respiratory epithelium, mucous cell hyperplasia, atrophy/degeneration of the tracheal branches, and wall thickening of the alveolar ducts in the nasal cavity of both sexes in the 10.0 mg/m3 group. The adverse effects of NaDCC exposure were observed to decrease during the 14-day recovery period in both sexes. Based on pathological observations, the “no observed adverse effect concentration (NOAEC)” of inhaled NaDCC was 2.0 mg/m3 for both sexes. These results are expected to provide a scientific basis for inhalation toxicity data of NaDCC.

Combined transcriptome and metabolite profiling analyses provide insights into the chronic toxicity of carbaryl and acetamiprid to Apis mellifera larvae

Despite many studies have revealed that developing honey bee (Apis mellifera) larvae are posting a high risk on exposure to insecticides, the toxicology information on bee larvae remain limited. The present study demonstrated the first assessment of the effects of no observed adverse effect concentration (NOAEC) of carbaryl (CR) and acetamiprid (ACE) on transcriptome and metabolome in honeybee larvae reared in vitro. Chronic exposure to carbaryl caused transcriptional disorders associated with oxidative stress. In addition, a series of metabolic homeostasis were disrupted by carbaryl stress, such amino acid metabolism, purine and pyrimidine metabolism and flavone and flavonol biosynthesis. The activities of enzymic biomarkers including GST, P450, CAT, AChE and SOD were not influenced by ACE stress, while the CR exposure slightly decreased the activity of CAT and SOD. Our results clearly show that ACE and CR display different potential to modulate transcriptome and metabolome associated with their different toxicity against bee larvae.

Dose–response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats

BackgroundIn Japan, six workers handling cross-linked water-soluble acrylic acid polymer (CWAAP) at a chemical plant suffered from lung diseases, including fibrosis, interstitial pneumonia, emphysema, and pneumothorax. We recently demonstrated that inhalation of CWAAP-A, one type of CWAAP, causes pulmonary disorders in rats. It is important to investigate dose–response relationships and recoverability from exposure to CWAAPs for establishing occupational health guidelines, such as setting threshold limit value for CWAAPs in the workplace.MethodsMale and female F344 rats were exposed to 0.3, 1, 3, or 10 mg/m3 CWAAP-A for 6 h/day, 5 days/week for 13 weeks using a whole-body inhalation exposure system. At 1 h, 4 weeks, and 13 weeks after the last exposure the rats were euthanized and blood, bronchoalveolar lavage fluid, and all tissues including lungs and mediastinal lymph nodes were collected and subjected to biological and histopathological analyses. In a second experiment, male rats were pre-treated with clodronate liposome or polymorphonuclear leukocyte-neutralizing antibody to deplete macrophages or neutrophils, respectively, and exposed to CWAAP-A for 6 h/day for 2 days.ResultsCWAAP-A exposure damaged only the alveoli. The lowest observed adverse effect concentration (LOAEC) was 1 mg/m3 and the no observed adverse effect concentration (NOAEC) was 0.3 mg/m3. Rats of both sexes were able to recover from the tissue damage caused by 13 weeks exposure to 1 mg/m3 CWAAP-A. In contrast, tissue damage caused by exposure to 3 and 10 mg/m3 was irreversible due to the development of interstitial lung lesions. There was a gender difference in the recovery from CWAAP-A induced pulmonary disorders, with females recovering less than males. Finally, acute lung effects caused by CWAAP-A were significantly reduced by depletion of alveolar macrophages.ConclusionsPulmonary damage caused by inhalation exposure to CWAAP-A was dose-dependent, specific to the lung and lymph nodes, and acute lung damage was ameliorated by depleting macrophages in the lungs. CWAAP-A had both a LOAEC and a NOAEC, and tissue damage caused by exposure to 1 mg/m3 CWAAP-A was reversible: recovery in female rats was less than for males. These findings indicate that concentration limits for CWAAPs in the workplace can be determined.Graphical

Toxicity evaluation in rats following 28days of inhalation exposure to xylitol aerosol.

Xylitol has reported to decrease gingival inflammation and nasopharyngeal pneumonia, which indicated that xylitol may have potential application in respiratory diseases. Although some studies have reported the inhalation toxicity of xylitol, however, the longest period tested was only for 14days. The inhalation toxicity of xylitol is insufficient. This work investigated the potential subacute toxicity of xylitol according to the OECD TG 412. Rats were randomly divided into a control group and different dosage groups (2g/m3, 3g/m3, 5g/m3), and exposed for 6hours/day, 5days/week for 28days. At the end of the exposure or recovery period, clinical signs, mortality, body weight, food consumption, hematology, blood biochemistry, gross pathology, organ weight, and histopathology were examined. Compared with the control group, rats of both sexes in the exposure groups exhibited no significant changes in body weight, organ mass, and food uptake. After the xylitol exposure, aspartate aminotransferase activity in the xylitol group (3g/m3) was significantly higher than that in the control group, while other blood indicators and pathological changes of liver and the analysis of the recovery group showed no changes, suggesting that xylitol exerted no observable toxic effect on the liver. Finally, other observations including the histopathology of target organs and hematology also showed no alterations. These results indicated that xylitol had no significant inhalation toxicity at doses up to 5g/m3. These subacute inhalation toxicity results of xylitol showed that its no-observed-adverse-effect concentration (NOAEC) in rats was determined to 5g/m3.

QSAR modelling of inhalation toxicity of diverse volatile organic molecules using no observed adverse effect concentration (NOAEC) as the endpoint

Nowadays, air pollution due to urbanization and reduction of forestry is emerging as a serious threat to humans and the environment. According to the World Health Organization, respiratory diseases are the third most mortality factor in the world. Chemical research organizations and industries are producing a large number of new chemical compounds continuously. Although toxicity testing of those chemicals on animals is costly, resource and time consuming, these data cannot be properly extrapolated to humans and other animals, and also these raise ethical issues. In this background, we have developed Quantitative Structure-Activity Relationship (QSAR) models using the No Observed Adverse Effect Concentration (NOAEC) as the endpoint to assess inhalation toxicity of diverse organic chemicals, commonly used and exposed by us in our daily life. No Observed Adverse Effect Concentration (NOAEC) can be used for long term toxicity studies towards the human inhalation risk assessment, as recommended by Organization for Economic Co-operation and Development (OECD) in guidance document 39. A particular QSAR model may not be equally effective for prediction of all query compounds from a given set of compounds; therefore, we have developed multiple models, which are robust, sound and well predictive from the statistical point of view to forecast the NOAEC values for the new untested compounds. Subsequently the validated individual models were employed to generate consensus models, in order to improve the quality of predictions and to reduce prediction errors. We have investigated some crucial structural features from these models which may regulate inhalation toxicity for newly produced molecules. Thus, our developed models may help in toxicity assessment towards reducing the health hazards for new chemicals.

N-Methylformamide. Documentation of proposed values of occupational exposure limits (OELs)

N-Methylformamide is a colorless liquid with an ammoniacal odor, used as a solvent and an intermediate for chemical reactions. There are no data on occupational exposure in Poland. N-Methylformamide is very well absorbed into the human body. The LD50 values for N-methylformamide administered to animals in various routes are similar (2600 ÷ 4000 mg/kg bw). After single or short-term administration of the compound in doses of 100 ÷ 1200 mg/kg bw. worsening symptoms of liver damage have been observed. No-observed adverse effect concentration (NOAEC) was established at 120 mg/m3 (two-week inhalation exposure in rats). Increase of hepatotoxic effect of N-methylformamide were observed at concentrations of 320 mg/m3 and 980 mg/m3. There are no data on sub-chronic, chronic and carcinogenic effects of the compound in laboratory animals. N-Methylformamide was not mutagenic and genotoxic. It caused embryotoxic and teratogenic effects. The NOAEC value (120 mg/m3) was used as the basis for determining the MAC (maximum acceptable concentration) value for N-methylformamide, and the MAC value for N-methylformamide was calculated at 3.3 mg/m3. There are no basis to determine the short-term value (STEL) and biological limit value (BLV). It has been proposed to label the compound as "Ft" (toxic for reproduction) and "skin" (skin absorption of the substance may be as important as inhalation exposure). This article discusses the problems of occupational safety and health, which are covered by health sciences and environmental engineering

Risk assessment for irritating chemicals - Derivation of extrapolation factors.

Irritation of the eyes and the upper respiratory tract are important endpoints for setting guide values for chemicals. To optimize the use of the often-limited data, we analysed controlled human exposure studies (CHS) with 1-4h inhalation of the test substance, repeated dose inhalation studies in rodents, and Alarie-Tests and derived extrapolation factors (EF) for exposure duration, inter- and intraspecies differences. For the endpoint irritating effects in the respiratory tract in rodents, geometric mean (GM) values of 1.9 were obtained for the EF for subacute→subchronic (n=16), 2.1 for subchronic→chronic (n=40), and 2.9 for subacute→chronic (n=10) extrapolation. Based on these data we suggest an EF of 2 for subchronic→chronic and of 4 for subacute→chronic extrapolation. In CHS, exposure concentration determines the effects rather than exposure duration. Slight reversible effects during 4h exposure indicate that an EF of 1 can be considered for assessing chronic exposures. To assess species extrapolation, 10 chemicals were identified with both, reliable rat inhalation studies and CHS. The GM of the ratio between the No Observed Adverse Effect Concentration (NOAEC) in rats and humans was 2.3 and increased to 3.6 when expanding the dataset to all available EF (n=25). Based on these analyses, an EF of 3 is suggested to extrapolate from a NOAEC in a chronic rat study to a NOAEC in a CHS. The analysis of EFs for the extrapolation from a 50% decrease in respiratory frequency in the Alarie test in mice (RD50) to a NOAEC in a CHS resulted in a GM of 40, for both, the reliable (n=11) and the overall dataset (n=19). We propose to use the RD50 from the Alarie test for setting guide values and to use 40 as EF. Efs for intraspecies differences in the human population must account for susceptible persons, most importantly for persons with chemical intolerance (CI), who show subjective signs of irritation at low concentrations. The limited data available do not justify to deviate from an EF of 10 - 20 as currently used in different regulatory settings.

Prediction of No Observed Adverse Effect Concentration for inhalation toxicity using Monte Carlo approach

ABSTRACT Ideal correlation is one variable model based on so-called optimal descriptors calculated with simplified molecular input-line entry systems (SMILES). The optimal descriptor is calculated according to the index of ideality of correlation, a new criterion of predictive potential of quantitative structure–property/activity relationships (QSPRs/QSARs). The aim of the present study was the building and estimation of models for inhalation toxicity as No Observed Adverse Effect Concentration (NOAEC) based on the OECD guidelines 413. Three random distributions into the training set and validation set were examined. In practice, a structured training set that contains active training set, passive training set and calibration set is used as the training set. The statistical characteristics of the best model for negative logarithm of NOAEC (pNOAEC) are for training set n = 108, average r 2 = 0.52 + 0.62 + 0.76/3 = 0.63 and for validation set n = 35, r 2 = 0.73.

Impacts of Bt rice on non-target organisms assessed by the hazard quotient (HQ)

The potential risk of Bt (Bacillus thuringiensis) crops on non-target organisms (NTOs) has drawn a lot of public concerns. Despite a series of risk assessments of Bt crops on NTOs has been conducted, a quantitative approach which could support a precise judgment of their safety is required. In the present work, hazard quotient (HQ) was applied in the safety evaluation of three Bt rice events (Cry1Ab, Cry1C and Cry2Aa rice) on NTOs. Eight NTOs in different functional guilds associated with Bt rice were selected to conduct the tests. The results showed that the HQs of three Bt rice events for eight NTOs were all below the trigger value 1, while the HQ of Cry1Ab rice for one target pest Chilo suppressalis was three times higher than 1. Our results assured the reliability of the HQ and indicated that the three Bt rice events would pose no risks to the eight NTOs. Further testing of three Bt proteins on biological parameters of one NTO Nasonia virtipennis under no observed adverse effect concentration (NOAEC) confirmed the robustness of HQ assessment. We recommend that the HQ could be applied in tier-1 risk assessments of Bt crops on NTOs as a reference data standard, which would provide more clear and credible safety information of transgenic crops for the public and policy makers.

Human health risk assessment of Tire and Road Wear Particles (TRWP) in air

This risk assessment addresses potential human health impact of exposure to tire and road wear particles (TRWP), which are formed at the interface of the pavement and road comprising rubber with embedded mineral from the pavement. To conduct the risk assessment, we reviewed literature on hazards associated with and exposures to TRWP and developed a screening value for TRWP reliant on the available hazard data and appropriate dosimetric adjustments. The species- and time- adjusted no-observed-adverse-effect-concentration (NOAEC) for respirable TRWP was 55 µg/m3. This NOAEC was compared to exposure estimates for respirable TRWP for both typical and worst case exposure scenarios based on age-specific activity patterns to determine the margin of exposure for TRWP. The estimated daily exposure to TRWP ranged from 0.079 to 0.147 µg/m3, resulting in a margin of exposure for TRWP ranging from approximately 400 to 700. Though there remain uncertainties in the risk assessment stemming from both the hazard and exposure assessments, the current weight of evidence suggests that TRWP presents a low risk to human health.

Acute and chronic toxicity of acetamiprid, carbaryl, cypermethrin and deltamethrin to Apis mellifera larvae reared in vitro.

The effects of exposing Apis mellifera larvae to common insecticides were tested in the laboratory. The acute toxicity values of the four insecticides that we tested ranged from high toxicity to low toxicity: deltamethrin > cypermethrin > carbaryl > acetamiprid. The NOAEC (no observed adverse effect concentration) values of the chronic toxicity tests for each compound are 5mg L-1 for acetamiprid, 2mg L-1 for carbaryl, 1mg L-1 for cypermethrin, and 0.2mg L-1 for deltamethrin. According to the risk quotient (RQ) values of acute and chronic toxicity that we obtained, the risk is acceptable at exposure rates that have been identified in the field. Overall, our results are valuable for evaluating the acute and chronic toxicities of these insecticides to developing honey bees. © 2019 Society of Chemical Industry.

Development of QSAR Model for Subchronic Inhalation Toxicity Using Random Forest Regression Method

Subchronic inhalation toxicity assessment is mainly used to evaluate both workers and occupational risk. Since the assessment requires repeated experiment of chemical exposure to model animals, this type of studies is laborious and expensive. Computational methods for estimating toxicity play an increasingly important role in assessing toxicity of chemicals. They not only predict toxicity of chemicals but can also analyze molecular features of a chemical causing toxic effect. Here we present a computational model to predict the subchronic inhalation toxicity. We retrieved repeated dose inhalation toxicity information and chemicals from OECD eChemPortal website and compile 143 chemical compounds with NOAEC (No Observed Adverse Effect Concentration) values. The random forest regression approach has been applied to learn inhalation toxicity data using a number of molecular descriptors, such as physicochemical properties and fingerprints. Recursive feature selection with nested cross‐validation was applied to efficiently select essential molecular features. In results, we successfully obtained a model performing with r 2ext = 0.70 and RMSEext = 0.74 for external set.

Acute and 28-Day Repeated Inhalation Toxicity Study of Glycolic Acid in Male Sprague-Dawley Rats.

The use of glycolic acid is present in a variety of consumer products, including medicines, cleaners, cosmetics, and paint strippers. It has recently led to concerns about toxicity from inhalation exposure. Herein, the pulmonary toxicity of glycolic acid was investigated in rats. We conducted acute (~458 mg/m3) and sub-acute (~49.5 mg/m3) inhalation tests to identify the potential toxicities of glycolic acid. Inhalation exposure to glycolic acid in the acute and subacute inhalation tests did not cause any specific changes in clinical examinations, including body weight, organ weight, hematology, serum biochemistry, and histopathology. The polymorphonuclear neutrophils (PMNs) and inflammatory cytokines in Bronchoalveolar lavage fluid (BALF) increased in rats exposed to single and repeated inhalations. In the sub-acute test, the changes induced by glycolic acid were minor or returned to normal during the recovery period. The No Observed Adverse Effect Concentration (NOAEC) for the nasal and pulmonary toxicity of glycolic acid was determined to be over 50 mg/m3 at the end of a 28-day inhalation test in male rats.

A pilot toxicology study of biogenic silver nanoparticles: in vivo by intraperitoneal and intravenous infusion routes in rats

Toxic effects of nanoparticles on human health are considerably increasing their worldwide recognition. Currently silver nanoparticles are being widely used in consumer medical products, due to its uniqueness in biomedical applications. Uptake of these particles via various administration routes can also lead to different toxic effects. In this study, we assessed the toxic effect of 11–75 nm ranged biogenic silver nanoparticles (Bio-AgNPs) on male wistar rats by using two different administration routes namely, intraperitoneal and intravenous routes. The three different concentrations, No Observable Adverse Effect Concentration (NOAEC), Inhibitory concentration (IC50) and Total lethal concentration (TLC) was appraised at the dose range of 97.64 to 132 µg/kg for both i/p and i/v routes. There is no considerable changes in hematological parameters in i/p and i/v routes on 14th and 28th day of observation, but the increase was trivial significant for platelet count at the dose of 97–105 µg/kg (IC50) for i/p route of injection. There is no remarkable adverse impact on liver, spleen and kidney were observed in IC50 and TLC treated group, when determined by biochemical and histopathological analysis both in i/p and i/v routes treated rats. This estimation confirms that, Bio-AgNPs are not going effect the human metabolic system.

Plant toxicity and accumulation of biosolids-borne ciprofloxacin and azithromycin

Trace organic chemicals (TOrCs) in land applied biosolids can cause phytotoxicities and contaminate human and animal food chains. Information on phytotoxicity and phytoaccumulation of environmentally relevant concentrations of two antibiotic TOrCs, ciprofloxacin (CIP) and azithromycin (AZ), from biosolids-amended soils is limited. Greenhouse studies were conducted to assess the plant toxicity and accumulation of a range of environmentally relevant concentrations of biosolids-borne CIP and AZ in biosolids-amended soils. Separate studies assessed phytotoxicity potential of soil-borne CIP and AZ (soils directly spiked with the target antibiotics without biosolids) at concentrations much greater than those of environmental relevance in biosolids-amended soils. Both the biosolids-borne and the soil-borne antibiotic studies involved three plants (radish (Raphanus sativus), lettuce (Lactuca sativa), and tall fescue grass (Festuca arundinacea)) of different morphologies, physiologies, and chemical exposure scenarios. Phytotoxicity and phytoaccumulation from the biosolids-borne antibiotics were minimal at environmentally relevant concentrations, even in sand. The separate phytotoxicity experiments involving the soil-borne antibiotics revealed no observed adverse effect concentration (NOAEC) of 3.2 mg kg−1 (AZ) and 36.1 mg kg−1 (CIP) for the three plants grown in soils mimicking typical agricultural soils. These NOAEC values are about 100-fold greater than the antibiotic concentrations expected in biosolids-amended soils. NOAEC values under an unrealistic worst-case where the antibiotics were directly spiked to sand (NOAEC = 3.2 mg kg−1 for AZ; and ≥0.36 mg kg−1 for CIP) were also greater than the environmentally relevant concentrations of the biosolids-borne antibiotics. The results suggest that land application of biosolids-borne CIP and AZ pose De minimis risks to plants. Point estimates of plant bioaccumulation factors (dry weight basis) were 0.01 (CIP) and 0.1 (AZ), suggesting minimal impacts of the target TOrCs on human and/or animal food chains.