Lowest Observed Adverse Effect Concentration Research Articles

Early-life long-term ibuprofen exposure reduces reproductive capacity involved in spermatogenesis impairment and associated with the transcription factor DAF-5 in Caenorhabditis elegans

Pharmaceuticals and personal care products (PPCPs) are emerging environmental contaminants and have raised significant concern due to their potential adverse impact on the environment. Ibuprofen is one of the most extensively used non-steroidal anti-inflammatory drugs (NSAIDs) and is also considered an environmental contaminant. The negative impact of ibuprofen on non-target organisms has been documented; however, the molecular mechanisms behind its reproductive toxicity remain unclear. We investigated the impact of early-life long-term ibuprofen exposure on reproductive capacity and its involvement of spermiogenesis in the non-target model organism Caenorhabditis elegans. Hermaphrodites were exposed to various ibuprofen concentrations (0.1, 1, 10, and 100 mg/L), resulting in a dose-dependent inhibition of reproduction. In addition, the lowest observed adverse effect concentration (LOAEC) for ibuprofen exposure on the total brood size of C. elegans was 0.1 mg/L, a concentration that falls within the environmentally relevant range for ibuprofen. Outcross progeny assays revealed a significant 47% reduction in total brood size for larval males (him-5) exposed to ibuprofen, while females (fog-2) exhibited only a minor effect. We found that early-life long-term ibuprofen exposure impairs spermatogenesis. The number of mitotic cells significantly reduced by 31%. The rate of sperm malformation in exposed males was 63%, much higher than in unexposed males (11%). Additionally, the percentage of sperm activation decreased from 89% to 39% in ibuprofen-exposed worms. Mechanistic insights indicated that ibuprofen downregulated mRNA levels of genes related to spermatogenesis and DAF-7/TGF-β signaling. RNAi assays provided evidence for the crucial role of the transcription factor DAF-5 in mediating the spermatogenesis impairment by ibuprofen. Our study provides insight into the environmental impacts of pharmaceutical contaminants, such as ibuprofen, on both male and female reproductive systems to safeguard environmental health.

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.

Genotoxicity in the absence of inflammation after tungsten inhalation in mice

Tungsten is used in several applications and human exposure may occur. To assess its pulmonary toxicity, we exposed male mice to nose-only inhalation of tungsten particles at 9, 23 or 132 mg/m3 (Low, Mid and High exposure) (45 min/day, 5 days/week for 2 weeks). Increased genotoxicity (assessed by comet assay) was seen in bronchoalveolar (BAL) fluid cells at Low and High exposure. We measured acellular ROS production, and cannot exclude that ROS contributed to the observed genotoxicity. We saw no effects on body weight gain, pulmonary inflammation, lactate dehydrogenase or protein in BAL fluid, pathology of liver or kidney, or on sperm counts. In conclusion, tungsten showed non-dose dependent genotoxicity in the absence of inflammation and therefore interpreted to be primary genotoxicity. Based on genotoxicity, a Lowest Observed Adverse Effect Concentration (LOAEC) could be set at 9 mg/m3. It was not possible to establish a No Adverse Effect Concentration (NOAEC).

Pulmonary toxicity of molybdenum disulphide after inhalation in mice

Molybdenum disulphide (MoS2) is a constituent of many products. To protect humans, it is important to know at what air concentrations it becomes toxic. For this, we tested MoS2 particles by nose-only inhalation in mice. Exposures were set to 13, 50 and 150 mg MoS2/m3 (=8, 30 and 90 mg Mo/m3), corresponding to Low, Mid and High exposure. The duration was 30 min/day, 5 days/week for 3 weeks. Molybdenum lung-deposition levels were estimated based on aerosol particle size distribution measurements, and empirically determined with inductively coupled plasma-mass spectrometry (ICP-MS). Toxicological endpoints were body weight gain, respiratory function, pulmonary inflammation, histopathology, and genotoxicity (comet assay). Acellular reactive oxygen species (ROS) production was also determined. The aerosolised MoS2 powder had a mean aerodynamic diameter of 800 nm, and a specific surface area of 8.96 m2/g. Alveolar deposition of MoS2 in lung was estimated at 7, 27 and 79 µg/mouse and measured as 35, 101 and 171 µg/mouse for Low, Mid and High exposure, respectively. Body weight gain was lower than in controls at Mid and High exposure. The tidal volume was decreased with Low and Mid exposure on day 15. Increased genotoxicity was seen in bronchoalveolar lavage (BAL) fluid cells at Mid and High exposures. ROS production was substantially lower than for carbon black nanoparticles used as bench-mark, when normalised by mass. Yet if ROS of MoS2 was normalised by surface area, it was similar to that of carbon black, suggesting that a ROS contribution to the observed genotoxicity cannot be ruled out. In conclusion, effects on body weight gain and genotoxicity indicated that Low exposure (13 mg MoS2/m3, corresponding to 0.8 mg/m3 for an 8-hour working day) was a No Observed Adverse Effect Concentration (NOAEC,) while effects on respiratory function suggested this level as a Lowest Observed Adverse Effect Concentration (LOAEC).

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

Health hazards resulting from occupational exposure to enfluran - overview of tests and analysis of admissible concentration values

The aim of this work is to analyze the health hazards of enflurane exposure and to analyze the occupational exposure limits (OEL). The method of obtaining evidence based on a review of online databases of scientific journals was used. Enflurane is an inhalation anesthetic. Malignant hyperthermia, seizures, arrhythmias, respiratory depression and hypotension have been observed in patients. Occupational exposure to enflurane may occur in healthcare professionals. The target organ for enflurane is the central nervous system with a critical consequence of deterioration in psychomotor performance. In studies on volunteers recruited from the medical staff of operating rooms exposed to enflurane, a significant deterioration in the results of the Simple Reaction Time Test was shown. World experts' groups assume that the LOAEC (lowest observed adverse effect concentration) value for the deterioration of psychomotor test results is 5-10% of the MAC value (minimal anesthetic concentration), i.e., 6342-12 684 mg/m3. Assessment of the nephrotoxic potential of enflurane has shown that it is unlikely to occur because biotransformation of enflurane in humans results in a low peak serum fluoride concentration of 15 μmol/l. Early reports about liver damage in patients were not be supported. Occupational exposure epidemiological studies have raised concerns about the effects of anesthetic gas mixtures on the abortion rate or on fetal development and birth defects in children, but none of these studies specifically determined the type and concentration of anesthetic gases used. The carcinogenicity and mutagenicity studies were negative. Occupational exposure to enflurane is not monitored in Poland, as no standard value has been established for it in the air of the working environment. It is necessary to quickly introduce this anesthetic along with the applicable limit value to the OEL list. Med Pr. 2022;73(1):51-69.

Differences in the effects of sodium selenate and sodium selenite on the mortality, reproduction, lipid peroxidation and glutathione redox status of Folsomia candida Willem 1902 (Collembola)

The average selenium content of the soils worldwide is 0.4 mg kg−1; however, the selenium concentration can be much higher in some areas. Selenium is essential to humans and animals, but it can also be a risk based on the narrow gap between the beneficial and toxic concentrations. There is scarce information in the literature on the effects of various inorganic forms of selenium on soil invertebrates, such as collembolans. Consequently, the goal of our study was to determine if selenium has a negative effect on the collembolan species Folsomia candida and to verify if there is a difference between the effects of the two oxidation forms. The effect of sodium selenite and sodium selenate on Folsomia candida was studied in the laboratory by mortality and reproduction tests also by various sub-lethal and biochemical methods. The methods used in our study included a standard OECD test according to the 232 guideline, and we measured the life history parameters such as relative growth, egg production, and egg volume. For the investigation of lipid peroxidation and glutathione redox status, malondialdehyde (MDA) content, reduced glutathione (GSH) concentration and glutathione peroxidase (GPx) activity were measured. Our results showed that up to a concentration of 0.5 mg kg−1 Se in soil, both selenium forms were beneficial for F. candida. For mortality, the LOAEC (lowest observable adverse effect concentration) was 8 mg kg−1 Se in the soil in the experiments according to the OECD 232 test for both selenium forms. In case of juveniles, sodium selenite was much more toxic than sodium selenate. The LOAEC was 0.5 mg kg−1 for sodium selenite and 8 mg kg−1 in the case of sodium selenate. Sub-lethal parameters showed to be potentially more sensitive than the parameters measured in the OECD 232 test in the case of sodium selenate contamination. For instance, both the number of eggs laid and the relative growth showed significant differences compared to the control group in lower concentrations than the juvenile number or mortality. In the groups treated with sodium selenite, the juvenile number was the most sensitive parameter. Based on our results, it can be stated that sodium selenite may be potentially more toxic to collembolans than sodium selenate. Lipid peroxidation was not initiated by selenium exposure. The glutathione redox system also did not activate either, which suggested that selenium toxicity in collembola is not a consequence of selenium-induced oxidative stress.

Key event-informed risk models for benzene-induced acute myeloid leukaemia

Occupational exposure to benzene at levels of 10 ppm or more has been associated with increased risk of acute myeloid leukaemia (AML). The mode of action (MOA) for AML development leading to mortality is anticipated to include multiple earlier key events, which can be observed in hematotoxicity and genetic toxicity in peripheral blood of exposed workers. Prevention of these early events would lead to prevention of the apical, adverse outcomes, the morbidity and mortality caused by the myelodysplastic syndromes (MDS) and AML. Incorporation of key event information should modify the risk model, but few modification approaches have been suggested. To that end, two approaches to risk model modification are described that use sub-linear and segmented linear increases in risk below key events, while maintaining a linear increase in AML mortality risk beginning at 2 ppm, the lowest observed adverse effect concentration (LOAEC) identified for hemato- and geno- toxicity in high quality studies of human occupational exposure. Below 2 ppm two different modification approaches to quantitative risk models were applied: a continuously decreasing slope model and a segmented modification in slope. These two approaches provide greater flexibility to incorporate MOA information in risk model development and selection.

Polychlorinated biphenyl tissue-concentration thresholds for survival, growth, and reproduction in fish.

Polychlorinated biphenyls (PCBs) have left a legacy of environmental contamination. Even though they were banned from production and active use in the 1970s, they persist in the environment and still have the potential to impact aquatic life. Our objective was to identify data from controlled laboratory studies of PCB-related adverse effects in fish and to conduct a meta-analysis on mortality, growth, and reproductive (MGR) threshold responses. For each endpoint type, we compiled data on the lowest-observed-adverse effect concentration (LOAEC) and the degree of effect at the LOAEC as a percentage of control. The LOAECs were expressed as tissue concentrations, so the term lowest-observed-adverse-effect residue concentration (LOAER) was used to represent PCB exposures. The lower limit of applicability was set at 0.1 μg/g total PCB tissue concentration, below which adverse MGR effects in fish were not supported by the data. Sensitivity distributions identifying the probability of adverse effects in fish populations or communities predicted that 25% of fish species would be impacted between 0.1 and 7.5 μg/g. Concentration-response threshold regressions were developed from the MGR datasets. For example, a 1 μg/g total PCB tissue concentration would predict effects of 17% mortality, 15% growth, and 39% reproductive. The analysis determined the degree of adverse response, with uncertainty estimates, expected across a broad range of PCB tissue exposure concentrations in fish. Data generated from MGR endpoints were combined to determine an approach for overall effect thresholds for PCB-related injury in fish. The MGR datasets included only laboratory data; however, responses were compared with field-observed effects. The present review provides a comprehensive assessment of PCB-induced injury in fish utilizing a data-inclusive approach. Environ Toxicol Chem 2019;38:712-736. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Concentration-dependent alterations in gene expression induced by cadmium in Solanum lycopersicum.

Cadmium (Cd) toxicity in agricultural soil has received significant attention because of its higher transformation in the food chain and toxicity to humans. The aim of the present study was to develop sensitive and specific biomarkers for Cd stress. Therefore, transcriptional analyses were performed to investigate concentration-response characteristics of Cd responsive genes identified from a Solanum lycopersicum microarray. The results showed that the lowest observable adverse effect concentrations (LOAECs) of Cd to S. lycopersicum were 1mg/kg for seed germination, 8mg/kg for root dry weight, 8mg/kg for root elongation, and 8mg/kg for root morphology. Furthermore, the genes were differentially expressed even at the lowest Cd concentrations (0.5mg/kg), indicating that the detection of Cd in soil at the molecular level is a highly sensitive method. Cd in soil was positively correlated with the expression of the F-box protein PP2-B15 (r=0.809, p<0.01) and zinc transporter 4 (r=0.643, p<0.01), indicating that these two genes could be selected as indicators of soil Cd contamination.

A comparison of electronic and traditional cigarette butt leachate on the development of Xenopus laevis embryos.

Potential developmental toxicities of three different cigarette butt leachates were evaluated using the frog embryo teratogenesis assay–Xenopus (FETAX). Xenopus laevis embryos were exposed to regular cigarette butt (RCB), menthol (MCB) and electronic (ECB) in concentrations ranging from 0 to 4 butts/l for RCB and MCB and 0–10 butts/l for ECB. The embryos were from stage 8 to 11 and were exposed for a 96-h period in static renewal test conditions. Median lethal concentration (LC50), malformation (EC50), non-observed adverse effect concentration (NOAEC), and lowest observed adverse effect concentration (LOAEC) were calculated. Results from these studies suggest that each tested leachate is teratogenic for X. laevis embryos. The lowest LC50 was determined for ECB exposure at 17.9 cigarette butts/L. The LC50 value was the highest with RCB and MCB having LC50 s of approximately 1 cigarette butt/L. There were notable EC50 differences with RCB having the highest and ECB the lowest. The NOAEC and LOAEC levels for RCB and MCB were below 1 cigarette butt/L for both mortality and malformations; over 8 butts/L for ECB mortality and over 4 butts/L for malformations. From these results, we conclude that RCB leachate is the most toxic compound, while MCB leachate has the higher teratogenicity. ECB leachate has the lowest toxic and teratogenic effects on embryos but there were still noticeable effects. The results confirmed that the FETAX assay can be useful in an integrated biological hazard assessment for the preliminary screening for ecological risks of cigarette butts, and electronic cigarettes, in aquatic environment.

Nanoceria and bulk cerium oxide effects on the germination of asplenium adiantum-nigrum spores

Aim of study: The effect of cerium oxide engineered nanoparticles on the spore germination of the fern. Asplenium adiantum-nigrum.Area of study: France, Britanny Region, Finistére Department, Plougonvelin, in rocks near the sea.Material and methods: Asplenium spores were cultured in vitro on agar medium with Nano-CeO2 (less than 25 nm particle size) and bulk-CeO2. The addition of each nano- and bulk particles ranged from 0 to 3000 mg L-1. Observations on rhizoidal and prothallial cells during first stages of gametophyte development were made. The No-Observed-Adverse-Effect concentration (NOAEC) and Lowest-Observed-Adverse-Effect-Concentration (LOEC) values for spore germination rate data were analyzed. Main results: Germination was speeded up by 100 to 2000 mg L-1 nanoceria, while bulk cerium oxide had the same effect for 500 to 200 mg L-1 concentrations. Present results showed cellular damage in the protonema while rhizoid cells seemed not to be affected, as growth and membrane integrity remained.Research highlights: Both nanosized and bulk cerium oxide are toxic for the fern Asplenium adiantum-nigrum, although diverse toxicity patterns were shown for both materials. Diverse toxic effects have been observed: chloroplast membrane damage and lysis, cell wall and membrane disruption which leads to cell lysis; and alterations in morphology and development.Keywords: Nanoparticles; rhizoid; prothallus; chloroplast; fern.

Evaluating the teratogenicity of the selective ß3-adrenoceptor agonist, CL 316.243 hydrate by employing FETAX (frog embryo teratogenesis assay)

In this study, the frog embryo teratogenesis assay (FETAX – Xenopus) technique was employed to evaluate the potential teratogenicity of the selective ß-adrenoceptor (AR) agonist, CL 316.243. In this context, CL 316.243 was applied to the South African clawed frog (Xenopus laevis) embryos. The media containing the CL 316.24-exposed embryos were monitored and changed/replaced once every 24 hours. Using FETAX, we determined the minimum concentrations to inhibit growth (MCIG) for CL 316.243. The 96-hour no observable adverse effect concentration (NOAEC), the 96-hour lowest observable adverse effect concentration (LOAEC), the 96-hour EC50 (malformation) and the 96-hour LC50 (lethal concentration) for mortality and malformation could not be determined because the used concentrations did not affect viability or the presence of abnormalities. On the other hand, the MCIG of CL 316.243 was determined as 1 mg/L. Our results demonstrated that CL 316.243 administration was associated with no of teratogenic and toxic effects. However, from first concentration we used (1 to 5 mg/L) length of embryos reduced significantly (p < 0.001) when compared to control of Xenopus embryos. Further studies should be conducted with different concentrations in order to investigate the optimal concentrations for treating preterm labor with these substances.

Reproductive effects in fathead minnows (Pimphales promelas) following a 21 d exposure to 17α-ethinylestradiol.

17α-ethinylestradiol (EE2) is a synthetic estrogen that is an active ingredient in oral contraception and hormone replacement therapy. Surveys of wastewater treatment plant effluents and surface waters throughout the world have reported EE2 concentrations in the ng/L range, and these low levels can cause significant reproductive effects in fish. This study tested the effects of three environmentally relevant EE2 concentrations: 0.47, 1.54 and 3.92 ng/L using a 21 d short-term reproductive assay to investigate the effects of EE2 on fathead minnow (Pimephales promelas) reproduction. The two highest EE2 concentrations tested in this study caused significant liver gene expression and induction of vitellogenin plasma protein in male fathead minnows. Exposure to 3.92 ng EE2/L increased the production of plasma vitellogenin in the females. Plasma estradiol concentrations were significantly reduced in females exposed to 1.54 and 3.92 ng EE2/L. All three tested concentrations significantly reduced fathead minnow egg production after a 21 d exposure to EE2. The results of this study indicate that the previously reported no observed adverse effect concentration (NOAEC) for EE2 on fathead minnow egg production (1.0 ng/L) may be too high. Because all three treatments resulted in significantly reduced egg production, the lowest observed adverse effect concentration (LOAEC) for EE2 on fathead minnow egg production is 0.47 ng EE2/L. This research estimates a NOAEC for fathead minnow reproduction at 0.24 ng EE2/L following a 21 d exposure. Additionally, induction of vitellogenin is a sensitive indicator of estrogen exposure but does not appear to be predictive of fathead minnow egg production.

Biomarker discovery and gene expression responses in Lycopersicon esculentum root exposed to lead

Gene expression analysis has shown particular promise for the identification of molecular biomarkers that can be used for further evaluation of potential toxicity of chemicals present in agricultural soil. In the study, we focused on the development of molecular markers to detect Pb toxicity in agricultural soil. Using the results obtained from microarray analysis, twelve Pb-responsive genes were selected and tested in different Pb concentrations to examine their concentration–response characteristics using real-time quantitative polymerase chain reaction (RT-qPCR). All the Pb treatments set in our study could generally induce the differential expression of the 12 genes, while the lowest observable adverse effect concentration (LOAEC) of Pb for seed germination, root elongation, biomass and structural modification derived from 1,297, 177, 177, and 1,297mgPb/kg soil, respectively, suggesting that the transcriptional approach was more sensitive than the traditional end points of death, growth, and morphology for the evaluation of Pb toxicity. The relative expression of glycoalkaloid metabolism 1 (P=−0.790), ethylene-responsive transcription factor ERF017 (P=−0.686) and CASP-like protein 4C2 (P=−0.652) demonstrates a dose-dependent response with Pb content in roots, implying that the three genes can be used as sensitive bioindicators of Pb stress in Lycopersicon esculentum.

Indoor air guide values for ethyl acetate. Communication of the German Ad Hoc Working Group on Indoor Air Guidelines of the Indoor Air Hygiene Committee and the Supreme State Health Authorities

The German Ad Hoc Working Group on Indoor Air Guidelines of the Indoor Air Hygiene Committee and the Supreme State Health Authorities issues indoor air guide values to protect public health. No suitable human studies are available for health evaluation of ethyl acetate in indoor air. In a well-documented subchronic inhalation rat study, assessed as reliable, local effects were observed in nasal epithelia. The incidence and severity of degeneration of the nasal olfactory epithelium was dose-dependent. This study leads to a lowest observed adverse effect concentration (LOAEC) of 1280mg ethyl acetate/m(3) indoor air, corresponding to a LAEC for continuous exposure of 230mg ethyl acetate/m(3), for the endpoint nasal epithelium degeneration. By applying an interspecies factor of 1, a factor of 10 for interindividual variability and a factor of 2 to account for the higher respiratory rate of children compared to adults, a health hazard guide value (RW II) of 6mg ethyl acetate/m(3) is obtained. A health precaution guide value (RW I) of 0.6mg ethyl acetate/m(3) indoor air is recommended.

Evaluating the Teratogenicity of Ritodrine and Nifedipine using a Frog Embryo Teratogenesis assay (FETAX)

The Frog Embryo Teratogenesis Assay—Xenopus (FETAX) was used to assess the teratogenic potential of two tocolytics. Embryos of the South African clawed frog, Xenopus laevis, were exposed to ritodrine or nifedipine. Exposure media were changed and monitored at 24-hour intervals. The 96-hour LC50 (Lethal concentration), the 96-hour EC50 (Malformation), and the No Observable Adverse Effect Concentrations (NOAEC) and the Lowest Observable Adverse Effect Concentration (LOAEC) for mortality, malformation and length were determined for each drug. Nifedipine was determined to be the more toxic and teratogenic than ritodrine, with a LC50 of 0.606 µg/L, an EC50 of 0.006 µg/L, and a teratogenicity Index (TI) value (LC50/EC50) of 101. On the other hand, the LC50 of ritodrine was 28.571 mg/L. In addition; the LC50, EC50 and TI values for nifedipine in the 5 mg/L ritodrine + nifedipine combination group were determined as 1.050 µg/L, 0.868 µg/L and 1.5 respectively. For ritodrine, the NOAEC and LOAEC values were determined as 2 mg/L and 4 mg/L, respectively. For the nifedipine and the ritodrine + nifedipine groups; while the LOAEC values of these groups were 0.0001 µg/L and 0.1 µg/L, respectively. NOAEC value couldn’t be determined. Our results demonstrated that nifedipine administration was associated with higher levels of teratogenic and toxic effects. However, the ritodrine + nifedipine combination form reduced the toxic and teratogenic effects of nifedipine on Xenopus embryos. Further studies should be conducted in order to investigate the optimal combination concentrations of these substances for the treatment of preterm labor.

Algal growth stimulation and toxicity in response to exposure to the new insensitive military high‐nitrogen energetic triaminoguanidinium‐1‐methyl‐5‐nitriminotetrazolate

Triaminoguanidinium-1-methyl-5-nitriminotetrazolate (TAG-MNT) is a nitrogen-rich energetic compound being developed as a potential component of insensitive munition formulations. The purpose of the present study was to assess the toxicity of TAG-MNT to the green alga Pseudokirchneriella subcapitata as well as to determine whether the high N content of TAG-MNT could result in increased algal growth in aquatic systems and potentially contribute to eutrophication using a 96-h algal growth bioassay in N-limited test media. Results were compared with algal exposures to current-use energetics 2,4,6-trinitrotoluene (TNT) and royal demolition explosive (RDX). The TNT exposure resulted in a lowest-observed-adverse-effect concentration (LOAEC) for algal growth of 1.72 mg/L and a 50% inhibition concentration (IC50) and 95% confidence limits of 0.972 mg/L (0.955, 0.973). The RDX algal growth LOAEC was 0.10 mg/L, and the RDX IC50 was 0.635 (0.416, 0.875). Neither TNT nor RDX exposure resulted in stimulation of algal growth. In repeated testing, TAG-MNT exposure resulted in LOAECs of 0.55 and 5.20 mg/L. Stimulation of algal growth was observed at 0.06 mg/L at a mean increase of 163.2% (± 71.7) relative to the control in TAG-MNT test A and at the 0.005 mg/L treatment at a mean increase of 174.3% (± 59.9) in TAG-MNT test B. The authors' results indicate the potential for high-N energetics to significantly stimulate algal growth at low concentrations in N-limited systems.

Determining the Ecological Impacts of Organic Contaminants in Biosolids Using a High-Throughput Colorimetric Denitrification Assay: A Case Study with Antimicrobial Agents

Land application accounts for ∼ 50% of wastewater solid disposal in the United States. Still, little is known regarding the ecological impacts of nonregulated contaminants found in biosolids. Because of the myriad of contaminants, there is a need for a rapid, high-throughput method to evaluate their ecotoxicity. Herein, we developed a novel assay that measures denitrification inhibition in a model denitrifier, Paracoccus denitrificans Pd1222. Two common (triclosan and triclocarban) and four emerging (2,4,5 trichlorophenol, 2-benzyl-4-chlorophenol, 2-chloro-4-phenylphenol, and bis(5-chloro-2-hydroxyphenyl)methane) antimicrobial agents found in biosolids were analyzed. Overall, the assay was reproducible and measured impacts on denitrification over 3 orders of magnitude exposure. The lowest observable adverse effect concentrations (LOAECs) were 1.04 μM for triclosan, 3.17 μM for triclocarban, 0.372 μM for bis-(5-chloro-2-hydroxyphenyl)methane, 4.89 μM for 2-chloro-4-phenyl phenol, 45.7 μM for 2-benzyl-4-chorophenol, and 50.6 μM for 2,4,5-trichlorophenol. Compared with gene expression and cell viability based methods, the denitrification assay was more sensitive and resulted in lower LOAECs. The increased sensitivity, low cost, and high-throughput adaptability make this method an attractive alternative for meeting the initial testing regulatory framework for the Federal Insecticide, Fungicide, and Rodenticide Act, and recommended for the Toxic Substances Control Act, in determining the ecotoxicity of biosolids-derived emerging contaminants.

The critical importance of defined media conditions in Daphnia magna nanotoxicity studies

Due to the widespread use of silver nanoparticles (AgNPs), the likelihood of them entering the environment has increased and they are known to be potentially toxic. Currently, there is little information on the dynamic changes of AgNPs in ecotoxicity exposure media and how this may affect toxicity. Here, the colloidal stability of three different sizes of citrate-stabilized AgNPs was assessed in standard strength OECD ISO exposure media, and in 2-fold (media2) and 10-fold (media10) dilutions by transmission electron microscopy (TEM) and atomic force microscopy (AFM) and these characteristics were related to their toxicity towards Daphnia magna. Aggregation in undiluted media (media1) was rapid, and after diluting the medium by a factor of 2 or 10, aggregation was reduced, with minimal aggregation over 24h occurring in media10. Acute toxicity measurements were performed using 7nm diameter particles in media1 and media10. In media10 the EC50 of the 7nm particles for D. magna neonates was calculated to be 7.46μgL−1 with upper and lower 95% confidence intervals of 6.84μgL−1 and 8.13μgL−1 respectively. For media1, an EC50 could not be calculated, the lowest observed adverse effect concentration (LOAEC) of 11.25μgL−1 indicating a significant reduction in toxicity compared to that in media10. The data suggest the increased dispersion of nanoparticles leads to enhanced toxicity, emphasising the importance of appropriate media composition to fully assess nanoparticle toxicity in aquatic ecotoxicity tests.