scholarly journals Imbalance in the Blood Concentrations of Selected Steroids in Pre-pubertal Gilts Depending on the Time of Exposure to Low Doses of Zearalenone

Toxins ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 561 ◽  
Author(s):  
Anna Rykaczewska ◽  
Magdalena Gajęcka ◽  
Ewa Onyszek ◽  
Katarzyna Cieplińska ◽  
Michał Dąbrowski ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Biological Effect ◽  
Control Group ◽  
Low Doses ◽  
Blood Concentrations ◽  
Qualitative And Quantitative ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Quantitative Changes ◽  
Control Group Group

Zearalenone (ZEN) is a mycotoxin that not only binds to estrogen receptors, but also interacts with steroidogenic enzymes and acts as an endocrine disruptor. The aim of this study was to verify the hypothesis that low doses, minimal anticipated biological effect level (MABEL), no-observed-adverse-effect level (NOAEL) and lowest-adverse-effect level (LOAEL), of ZEN administered orally for 42 days can induce changes in the peripheral blood concentrations of selected steroid hormones (estradiol, progesterone and testosterone) in pre-pubertal gilts. The experiment was performed on 60 clinically healthy gilts with average BW of 14.5 ± 2 kg, divided into three experimental groups and a control group. Group ZEN5 animals were orally administered ZEN at 5 μg ZEN/kg BW, group ZEN10 — at 10 μg ZEN/kg BW, group ZEN15 — at 15 μg ZEN/kg BW, whereas group C received a placebo. Five gilts from every group were euthanized on analytical dates 1, 2 and 3 (days 7, 14 and 42 of the experiment). Qualitative and quantitative changes in the biotransformation of low ZEN doses were observed. These processes were least pronounced in group ZEN5 (MABEL dose) where ZEN metabolites were not detected on the first analytical date, and where β-ZEL was the predominant metabolite on successive dates. The above was accompanied by an increase in the concentration of estradiol (E2) which, together with “free ZEN”, probably suppressed progesterone (P4) and testosterone (T) levels.

scholarly journals Safety Assessment of TGT Primaage using Wistar Rats through Oral Gavage Administration

2021 ◽  
Vol 10 (5) ◽  
pp. 298-315
Author(s):  
Kunjan Shah ◽  
◽  
Sudhakar Jadhav ◽  
Manish Patel ◽  
Jaydip Mistry ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Wistar Rats ◽  
Clinical Pathology ◽  
Centella Asiatica ◽  
Control Group ◽  
High Dose ◽  
Delayed Effect ◽  
Adverse Effect Level ◽  
Effect Level

TGT Primaage is one of the astonishing extracts, obtained from a combination of Moringa oleifera and Centella asiatica. At present, there is no finding reported regardin g the repeated exposure of this extract. This study investigates the No Observed Adverse Effect Level (NOAEL) and effects of repeated-dose administration of Astragalin and Isoquercetin (components of interest) present in TGT Primaage on Wistar rats. Rats were divided into 3 treatment and a control group (10 rats/sex/group). To assess reversibility, persistence, or delayed effect, additional control and high dose groups were treated similarly and observed further without any treatment. TGT Primaage was administered orally, through gavage for 90 days, at 0, 250, 500, and 1000 mg/kg body weight/day. No mortality, morbidity, and clinical sign of toxicity was observed. Abnormality related to neurological and functional parameters was not seen. No change in body weight and food consumption was observed. Treatment did not lead to any adverse effect in clinical pathology parameters and organ weights. TGT Primaage did not alter morphological and histopathological characteristics of organs. From these results, it is evident that TGT Primaage appears to be safe and devoid of any toxicity. The No Observed Adverse Effect Level (NOAEL) of TGT Primaage for both sexes were found to be 1000 mg/kg body weight/day

scholarly journals Determination of No-Observed-Adverse-Effect Level Ammonia in White Mice Through CD4 Expression

Dose-Response ◽  
2018 ◽  
Vol 16 (4) ◽  
pp. 155932581880779 ◽  
Author(s):  
Abdul Rohim Tualeka ◽  
Jihan Faradisha ◽  
Rizky Maharja
Keyword(s):  
Adverse Effect ◽  
Chemical Compounds ◽  
Control Group ◽  
Control Group Design ◽  
Post Test ◽  
Adverse Effect Level ◽  
Safe Limit ◽  
Effect Level ◽  
Acute And Chronic Effects

Background: Ammonia is one of the chemical compounds that can cause acute and chronic effects to the workers. The purpose of this study is to determine the no-observed-adverse-effect level (NOAEL) ammonia in white mice. Methods: This study applied a laboratory experimental with design post test-only control group design using white mice as an object. The process of finding the safe limit began by determining the highest dose and the lowest dose of ammonia without effect in white mice. Results: The latest research showed that the highest dose without effect is 0.0456 mg/kg and the lowest dose without effect is 0.0046 mg/kg. After determining the highest and the lowest dose of ammonia, the researcher started to determine the middle dose. The middle dose is the dose between the highest and the lowest doses with the multiplication of 1.5 starting from the lowest dose (there are 5 middle-dose variations from 5 middle concentration variations), consisting of 0.0872, 0.1309, 0.1963, 0.2944, and 0.4416 mg/m3. Conclusion: From the result of the middle dose and the lowest dose without effect, it is found the value of the highest NH3 dose without effect, which showed the highest Index Remmele Scale (IRS) CD4 before the reduction of IRS. The study concludes that the NOAEL of ammonia contained in white mice is 0.0103 mg/kg body weight of the mice.

Safety of a novel galacto-oligosaccharide: Genotoxicity and repeated oral dose studies

2009 ◽  
Vol 28 (10) ◽  
pp. 619-630 ◽  
Author(s):  
T. Kobayashi ◽  
N. Yasutake ◽  
K. Uchida ◽  
W. Ohyama ◽  
K. Kaneko ◽  
...  
Keyword(s):  
Oral Dose ◽  
Kluyveromyces Lactis ◽  
Clinical Signs ◽  
Chinese Hamster ◽  
Metabolic Activation ◽  
Blood Chemistry ◽  
Control Group ◽  
Sprague Dawley ◽  
Adverse Effect Level ◽  
Effect Level

A series of safety tests were undertaken on a novel galacto-oligosaccharide (GOS) produced from lactose by a two-step enzymatic process involving Sporobolomyces singularis and Kluyveromyces lactis. Bacterial reverse mutation and chromosomal aberration tests, with or without metabolic activation, were performed. These tests showed no mutagenesis in the Ames assay or in Escherichia coli WP2uvrA, and no chromosomal aberrations in cultured fibroblast cells from Chinese hamster lungs (CHL/IU). Micronuclei were not induced in the reticulocytes of mouse peripheral blood following oral administration of GOS. In a 90-day repeated oral dose toxicity study in rats, GOS was administered at 0, 500, 1000 and 2000 mg/kg to male and female Sprague-Dawley rats. There were no GOS-related changes in clinical signs, body weight, water intake, feed intake, urinalysis, ophthalmology, haematology, blood chemistry, organ weights, gross pathology or histopathology in any of the treatment groups compared to the control group. The no observed adverse effect level (NOAEL) of GOS was at least 2000 mg/kg/day in both males and females.

Selective Vulnerability of Dopaminergic Systems To Industrial Chemicals: Risk Assessment of Related Neuroendocrine Changes

1998 ◽  
Vol 14 (1-2) ◽  
pp. 311-323 ◽  
Author(s):  
Antonio Mutti ◽  
Audrey Smargiassi
Keyword(s):  
Adverse Effect ◽  
Selective Vulnerability ◽  
Common Finding ◽  
Serum Prolactin ◽  
Industrial Chemicals ◽  
Limit Values ◽  
Reference Limit ◽  
Individual Level ◽  
Adverse Effect Level ◽  
Effect Level

Increased serum prolactin (PRL) is a common finding among subjects exposed to styrene, perchloroethylene, lead (Pb), and manganese (Mn) at levels below the current threshold limit values. On a group basis, abnormally high basal PRL shows a dose-related distribution among workers exposed to styrene, Pb, and Mn. On the basis of dose-response relationships, the benchmark doses (BMD) for styrene metabolites in urine, lead in blood (Pb-B), and Mn in urine (Mn-U), are 4 mg/g creatinine, 112 μg/L, and 0.3 μg/L, respectively. Noteworthy, the BMD for Mn-U and Pb-B is well below the upper reference limit. A shift in the distribution but not in the prevalence of abnormally high values of serum PRL was observed among perchloroethylene-exposed dry cleaners, which makes interpretation in terms of risk difficult. The measurement of PRL thus provides opportunities for early identification of excess exposure to neurotoxic chemicals affecting dopaminergic control of pituitary secretion. For styrene, Pb, and Mn the BMD provides an objective and statistically determined threshold, which seems to be in good agreement with the estimated no-observed-adverse-effect-level (NOAEL). The NOAEL, however, is based on traditional approaches that require the application of uncertainty factors, e.g., a default factor of 10 when extrapolating the NOAEL from the lowest-observed- adverse-effect-level (LOAEL). Due to its sensitivity to a number of potential confounders, caution must be exercised when using PRL as a screening test at the individual level. Also, age and sex dependent variations in susceptibility may hamper extrapolations from the occupational settings to the general population.

scholarly journals Lowest observed adverse effect level of pulmonary pathological alterations due to nitrous acid exposure in guinea pigs

2020 ◽  
Vol 25 (1) ◽  
Author(s):  
Masayuki Ohyama ◽  
Hiroshi Nishimura ◽  
Kenichi Azuma ◽  
Chika Minejima ◽  
Norimichi Takenaka ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Smooth Muscle ◽  
Electron Microscope ◽  
Epithelial Cells ◽  
Guinea Pigs ◽  
Pulmonary Emphysema ◽  
Nitrous Acid ◽  
Bronchial Epithelial ◽  
Adverse Effect Level ◽  
Effect Level

Abstract Background We previously demonstrated that continuous exposure to nitrous acid gas (HONO) for 4 weeks, at a concentration of 3.6 parts per million (ppm), induced pulmonary emphysema-like alterations in guinea pigs. In addition, we found that HONO affected asthma symptoms, based on the measurement of respiratory function in rats exposed to 5.8 ppm HONO. This study aimed to investigate the dose-response effects of HONO exposure on the histopathological alterations in the respiratory tract of guinea pigs to determine the lowest observed adverse effect level (LOAEL) of HONO. Methods We continuously exposed male Hartley guinea pigs (n = 5) to four different concentrations of HONO (0.0, 0.1, 0.4, and 1.7 ppm) for 4 weeks (24 h/day). We performed histopathological analysis by observing lung tissue samples. We examined samples from three guinea pigs in each group under a light microscope and measured the alveolar mean linear intercept (Lm) and the thickness of the bronchial smooth muscle layer. We further examined samples from two guinea pigs in each group under a scanning electron microscope (SEM) and a transmission electron microscope (TEM). Results We observed the following dose-dependent changes: pulmonary emphysema-like alterations in the centriacinar regions of alveolar ducts, significant increase in Lm in the 1.7 ppm HONO-exposure group, tendency for hyperplasia and pseudostratification of bronchial epithelial cells, and extension of the bronchial epithelial cells and smooth muscle cells in the alveolar duct regions. Conclusions These histopathological findings suggest that the LOAEL of HONO is < 0.1 ppm.

1,1,2,2-Tetrafluoroethane (HFC-134) (2018)

2019 ◽  
Vol 35 (3) ◽  
pp. 196-203
Keyword(s):  
Adverse Effect ◽  
Adverse Effects ◽  
Toxicity Study ◽  
Whole Body ◽  
Exposure Level ◽  
Inhalation Toxicity ◽  
Hfc 134A ◽  
Adverse Effect Level ◽  
Effect Level ◽  
Whole Body Inhalation

1,1,2,2-Tetrafluoroethane (HFC-134) is a colorless gas used as a foam expansion agent and heat transfer fluid. HFC-134 has a low acute inhalation toxicity with an LC50 of >244,000 ppm. The no-observed adverse effect level (NOAEL) and lowest-observed adverse effect level for cardiac sensitization (in epinephrine-challenged beagle dogs) were 75,000 and 100,000 ppm, respectively. A subacute 4-week GLP inhalation toxicity study exposed male and female Crl: CD®BR rats (10/sex) to 0, 2000, 10,000, or 50,000 ppm via whole-body inhalation. Transient and non-dose-response–related body weight changes were observed throughout the exposure period, but no statistically significant, test substance-related adverse effects were observed in any clinical observations, chemistry, hematology, or pathology. This study identified a NOAEL for HFC-134 of 50,000 ppm, the highest exposure level tested. HFC-134 is not genotoxic in in vitro studies; however, no in vivo studies are available. No developmental or maternal toxicity was found in female rats exposed to HFC-134 up to 50,000 ppm via whole-body inhalation in two different studies. Based on data for a similar material (HFC-134a), HFC-134 is not expected to be extensively metabolized or to cause genetic toxicity or carcinogenicity. The HFC-134 workplace environmental exposure level (WEEL) is based primarily on the subacute 4-week inhalation toxicity study in rats with the NOAEL of 50,000 ppm selected as the point of departure for the derivation of the 8-h TWA, health-based WEEL value. The developmental toxicity study also had a NOAEL of 50,000 ppm and was the highest exposure level tested. The subacute inhalation NOAEL was adjusted to account for interindividual variability, subacute to chronic duration, animal to human extrapolation, daily duration of exposure, and residual uncertainty. In addition, the lack of adverse effects noted in the toxicology studies for HFC-134a was considered. The resulting 8-h TWA WEEL value of 1000 ppm is expected to provide a significant margin of safety against the production of any potential adverse health effects in workers following long-term inhalation exposure to HFC-134.

Toxicity Assessment of 4-Amino-2-Nitrotoluene

2013 ◽  
Vol 32 (2) ◽  
pp. 113-122 ◽  
Author(s):  
John T. Houpt ◽  
Glenn J. Leach ◽  
Larry R. Williams ◽  
Mark S. Johnson ◽  
Gunda Reddy
Keyword(s):  
Adverse Effect ◽  
Body Weight ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Toxicity Study ◽  
Female Rats ◽  
Male Rats ◽  
Toxicity Data ◽  
Adverse Effect Level ◽  
Effect Level

4-Amino-2-nitrotoluene (4A2NT; CAS 119-32-4) is a degradation product of 2,4-dinitrotoluene. The toxicity data on 4A2NT are limited. Therefore, we collected toxicity data from rats to assess environmental and human health effects from exposures. The approximate lethal dose for both sexes was 5000 mg/kg. A 14-day toxicity study in rats was conducted with 4A2NT in the feed at concentrations of 0, 125, 250, 500, 1000, and 2000 ppm. Based on a 14-day oral dose range toxicity study with 4A2NT in the feed, 2000 ppm was selected as highest concentration for a subsequent 90-day study. An oral 90-day subchronic toxicity study in rats was conducted with concentrations of 0, 500, 1000, or 2000 ppm of 4A2NT in the feed. The calculated consumed doses of 4A2NT in the feed were 0, 27, 52, or 115 mg/kg/d for males and 0, 32, 65, or 138 mg/kg/d for females. A no-observed adverse effect level could not be determined. The lowest observed adverse effect level was 27 mg/kg/d for males and 32 mg/kg/d for female rats based upon decreased body weight gain. The decreased body weight gain in male rats was the most sensitive adverse event observed in this study and was used to derive a benchmark dose (BMD). A BMD of 23.1 mg/kg/d and BMD with 10% effect level of 15.5 mg/kg/d were calculated for male rats, which were used to derive an oral reference dose (RfD). The human RfD of 1.26 μg/kg/d was derived using current United States Environmental Protection Agency guidelines.

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