Clinical Chemistry Values Research Articles

Evaluate the safety of a novel photohydrolysis technology used to clean and disinfect indoor air: A murine study.

There is a pressing need to develop new technologies that continuously eliminates harmful pollutants and pathogens in occupied indoor spaces without compromising safety. This study was undertaken to test the safety of a novel air cleaning and disinfection technology called Advanced Photohydrolysis. Advanced Photohydrolysis generates a complex mixture of ions and molecules that are released into the air and has been shown to reduce airborne and surface pathogens. Mice (6-8-week-old) were exposed to therapeutic levels of Advanced Photohydrolysis for 90-days. During the study, the Advanced-Photohydrolysis-exposed and control mice were monitored for food consumption, body weight gain, and any overt adverse effects. In addition, at the conclusion of the study, the blood chemistry and hematology values of both groups were determined. Finally, the tissues of the conduction and respiratory portions of the airways of mice from both groups were examined for any pathological changes. The mice of both groups were found to be normal and healthy throughout the 90-day study; there were no differences in the behavior, food consumption and weight gain. Analysis of clinical chemistry values found no differences in hepatocellular function or other markers of cellular and organ function, and clinical hematology values were also unremarkable. Finally, and importantly, histopathology of the upper and lower airway tissues showed no deleterious effects. These results are the first to demonstrate directly the safety of Advanced Photohydrolysis on live mammals and encourage additional studies.

Feeding dogs a high-fat diet induces metabolic changes similar to natural aging, including dyslipidemia, hyperinsulinemia, and peripheral insulin resistance.

The goal of this study was to characterize changes induced by a high-fat diet in body composition, insulin levels and sensitivity, blood lipids, and other key biomarkers also associated with the metabolic dysfunction that occurs with natural aging. 24 male Beagle dogs, 3 to 7 years of age, of mixed castration status. Dogs were randomly assigned to continue twice daily feeding of the commercial adult maintenance diet (n = 12, including 2 intact) that they were previously fed or to a high-fat diet (12, including 2 intact) for 17 weeks between December 1, 2021, and April 28, 2022. Assessments included body composition (weight, body condition score, and adipose mass determined by deuterium enrichment), clinical chemistries, plasma fatty acid quantification, oral glucose tolerance test, and histology of subcutaneous and visceral adipose biopsy samples. The high-fat diet led to increased body weight, body condition score, fat mass and adipocyte size, hyperinsulinemia and peripheral insulin resistance, and elevations in serum lipids, including cholesterol, triglycerides, and several species of free fatty acids. Leptin levels increased in dogs fed a high-fat diet but not in control dogs. There were no significant changes in routine clinical chemistry values in either group. Feeding a high-fat diet for 17 weeks led to potentially deleterious changes in metabolism similar to those seen in natural aging in dogs, including hyperinsulinemia, insulin resistance, and dyslipidemia. A high-fat diet model may provide insights into the similar metabolic dysfunction that occurs during natural aging.

Safety assessment and gastrointestinal retention of orally administered cerium oxide nanoparticles in rats

Cerium oxide nanoparticles (CeO2 NPs, NM-212) are well-known for their catalytic properties and antioxidant potential, and have many applications in various industries, drug delivery, and cosmetic formulations. CeO2 NPs exhibit strong antimicrobial activity and can be used to efficiently remove pathogens from different environments. However, knowledge of the toxicological evaluation of CeO2 NPs is too limited to support their safe use. In this study, CeO2 NPs were orally administered to Sprague Dawley rats for 13 weeks at the doses of 0, 10, 100, and 1000 mg/kg bw/day, followed by a four week recovery period. The hematology values for the absolute and relative reticulocyte counts in male rats treated with 1000 mg/kg bw/day CeO2 NPs were lower than those in control rats. The clinical chemistry values for sodium and chloride in the treated male rat groups (100 and 1000 mg/kg/day) and total protein and calcium in the treated female rat groups (100 mg/kg/day) were higher than those in the control groups. However, these changes were not consistent in both sexes, and no abnormalities were found in the corresponding pathological findings. The results showed no adverse effects on any of the parameters assessed. CeO2 NPs accumulated in the jejunum, colon, and stomach wall of rats administered 1000 mg/kg CeO2 NPs for 90 days. However, these changes were not abnormal in the corresponding histopathological and immunohistochemical examinations. Therefore, 1000 mg/kg bw/day may be considered the “no observed adverse effect level” of CeO2 NPs (NM-212) in male and female SD rats under the present experimental conditions.

Establishment of Reference Intervals for Renal Function Clinical Chemistry Parameters in an Indonesian Tertiary Hospital.

Reference intervals aid clinical decision-making for clinical chemistry values. Laboratory test results are compared to reference intervals to aid in the diagnosis, therapy, and monitoring decisions. Due to the differences in ethnicity, gender, age, and analytical methods, reference intervals (RIs) vary between populations. This study aimed to establish the reference values for renal function tests in targeted populations in Indonesia. This research was conducted with a cross-sectional observational analytic design. The research sample consisted of medical check-up data from health professionals at Dr. Mohammad Hoesin Hospital in Palembang, Indonesia. The Kolmogorov-Smirnov test was used to determine the normality of data distribution. The RIs were computed using reference limits at the 2.5th and 97.5th percentiles(abnormal distribution) or ±two standard deviations (±2 SD) (normal distribution). The independent t-test (parametric) or Mann-Whitney test was used to compare the RIs of males and females (non-parametric). Males and females had a significant difference (P<0.001) regarding the values of uric acid, urea, and creatinine parameters, requiring the reference intervals to be separated. The following reference intervals were established: uric acid: 230,78-526,99 mol/L for males and 179,03-415.17 mol/L for females, urea: 2,22-4,99 mmol/L for males and 1,78-4,28 mmol/L for females, and creatinine: 61,01-106,99 mol/L for males and 40,67-77,81 mol/L for females. This study defined gender-specific RIs for three renal function test parameters for the adult population of Palembang, Indonesia. The deployment of population-specific RIs may facilitate better laboratory testing.

Effects of Dietary Milk Thistle (Silybum marianum) Supplementation in Ducks Fed Mycotoxin-Contaminated Diets

The medicinal plant milk thistle (Silybum marianum) has been widely used due to its hepatoprotective properties. The main objective of our study was to investigate the health protective effects of dietary milk thistle seed (MS), oil (MO), and seed cake (MSC) in ducks fed diets naturally contaminated with deoxynivalenol (DON; 3.43-3.72 mg/kg feed) and zearalenone (ZEN; 0.46-0.50 mg/kg feed). Female White Hungarian ducks were randomly allocated to four dietary treatments consisting of the control diet (C), the control diet supplemented with 0.5% MS, 0.5% MSC, or 0.1% MO. The feeding of experimental diets did not result in mortality cases, clinical signs of mycotoxicosis, or in differences of clinical chemistry values of blood serum. The positive effect of MO on vacuolar hepatocyte degeneration exceeded that of the MSC on d14 and both MS and MSC on d42. Each treatment was equally effective in the decrease of the severity of solitary cell death and infiltration of lympho- and histiocytes in the liver on d28 as well as in the prevention of lymphocyte depletion in the spleen and bursa of Fabricius on d14. In conclusion, the applied treatments have been proven effective in the prevention of histopathological changes caused by DON and ZEN.

Proof-of-Concept Study of an Alpha-Fetoprotein-Derived Peptide for the Management of Canine Mammary Cancer.

Novel, well-tolerated drugs are needed for the management of canine mammary cancer. Many of these cancers are promoted in their growth by estrogen. Alpha-fetoprotein (AFP) is a ubiquitous mammalian protein that has anti-estrogenic properties. AFPep (the anti-estrogenic site of AFP) has been developed into a readily synthesizable drug. AFPep has been shown to have anti-mammary cancer activity in several models of this disease, both in cell culture and in rodents. The purpose of the study reported herein was to determine the tolerability of AFPep in normal and tumor-bearing dogs. AFPep was given to dogs via both parenteral and oral routes in a single application and in repeated daily doses. Full clinical chemistry and hematology values were determined before and after drug administration. Blood levels of the drug were achieved in dogs that had been previously found to be oncostatic in rodents. No changes in clinical chemistry, hematology, and clinical behaviors were found in dogs following drug administration. The data support the further development of AFPep for clinical use against canine mammary cancer.

Safety and toxicologic evaluation of Edible Pongamia Oil: A novel food ingredient

Edible Pongamia Oil (EPO) was evaluated in an acute oral toxicity study, GLP 14-Day and 90-Day repeated dose isocaloric dietary toxicity studies in rats, and in vitro Bacterial Reverse Mutation, and in vivo Mammalian Bone Marrow Chromosome Aberration genotoxicity studies for potential use as a food ingredient. In a non-GLP acute study, an LD50 > 5000 mg/kg was determined. Subacute 14-day repeated dose dietary administration of 0, 5, 10 and 15% oil revealed no adverse changes in clinical pathology, liver histology, body weight or weight gain, food consumption or food efficiency. In a 90-day dietary study fed 0, 2.5, 5.0, 7.5 and 10.0%, no mortalities, clinical or ophthalmologic signs, body weight, body weight gain, food consumption, food efficiency or Functional Observational Battery/Motor Activity changes occurred with EPO consumption, nor were there any adverse changes in hematology, clinical chemistry, coagulation, urinalysis, or thyroid hormone values. There were no adverse macroscopic, estrus cycle, histopathologic or spermatogenesis findings, or absolute or relative organ weight changes related to administration of EPO. The No-Adverse-Effect-Level (NOAEL) was 10% in the diet, the highest dose tested, equivalent to 5163 (male) and 6469 (female) mg/kg/day in rats. No mutagenic or clastogenic genotoxic potential was reported.

Inoculation route-dependent Lassa virus dissemination and shedding dynamics in the natural reservoir – Mastomys natalensis

ABSTRACT Lassa virus (LASV), a Risk Group-4 zoonotic haemorrhagic fever virus, affects sub-Saharan African countries. Lassa fever, caused by LASV, results in thousands of annual deaths. Although decades have elapsed since the identification of the Natal multimammate mouse (Mastomys natalensis) as a natural reservoir of LASV, little effort has been made to characterize LASV infection in its reservoir. The natural route of infection and transmission of LASV within M. natalensis remains unknown, and the clinical impact of LASV in M. natalensis is mostly undescribed. Herein, using an outbred colony of M. natalensis, we investigate the replication and dissemination dynamics of LASV in this reservoir following various inoculation routes. Inoculation with LASV, regardless of route, resulted in a systemic infection and accumulation of abundant LASV-RNA in many tissues. LASV infection in the Natal multimammate mice was subclinical, however, clinical chemistry values were transiently altered and immune infiltrates were observed histologically in lungs, spleens and livers, indicating a minor disease with coordinated immune responses are elicited, controlling infection. Intranasal infection resulted in unique virus tissue dissemination dynamics and heightened LASV shedding, compared to subcutaneous inoculation. Our study provides important insights into LASV infection in its natural reservoir using a contemporary infection system, demonstrating that specific inoculation routes result in disparate dissemination outcomes, suggesting intranasal inoculation is important in the maintenance of LASV in the natural reservoir, and emphasizes that selection of the appropriate inoculation route is necessary to examine aspects of viral replication, transmission and responses to zoonotic viruses in their natural reservoirs.

Polymyxin B hemoperfusion in septic patients with acute myeloblastic and premyelocytic leukemia cytomegalovirus reactivation

Introduction: Infections are frequent complications in patients with malignant hematological disease and are associated with high morbidity and mortality. The use of polymyxin B hemoperfusion (PMX-HP) as an additional therapy in hematological patients who develop sepsis or septic shock following chemo- or immunosuppressive therapy is not often described in literature. Case Series: This study included patients with hematological neoplasms (acute myeloblastic or promyelocytic leukemia) who were undergoing chemotherapy (pre- or post-transplant) and developed sepsis or septic shock requiring organ support. The patients received one session of polymyxin B hemoperfusion generally followed by at least 72 hours of continuous renal replacement therapy (CRRT) as renal support. The clinical condition, hemodynamic parameters, and blood chemistry values of the patients were monitored until discharge from the intensive care unit (ICU). Nine patients were included in this study. Of the 9 patients, 6 survived and were discharged from the ICU. In the 6 surviving patients a drastic reduction in procalcitonin (PCT) and C-reactive protein (CRP) were observed after treatment with PMX-HP. No adverse events related to the PMX-HP treatment occurred. Conclusion: Patients with hematological neoplasms complicated with septic shock have a very high mortality. In our experience, polymyxin B hemoperfusion therapy and CRRT in addition to conventional therapy may be a valid strategy to improve outcome in this type of patients.

Subchronic Toxicity Assessment of Phytolacca americana L. (Phytolaccaceae) in F344 Rats

Phytolacca americana L. is traditionally used in Korea, Japan, and China as a diuretic, antibacterial, antiviral, anticancer, and anti-inflammatory agent, and also in the treatment of hepatitis B, psoriasis, edema, and rheumatism. In this study, we evaluated the subchronic toxicity of an aqueous extract of P. americana (PAAE) in male and female F344 rats. The rats were orally administered PAAE (0, 500, 1000, and 2000 mg/kg body weight) once daily for 13 weeks. Mortality rate, body weight, food consumption, and organ weights were measured and assessed. Additionally, ophthalmological, hematological, and histopathological parameters were evaluated. Urinalysis and necropsy were also performed. The clinical chemistry values for potassium in the treated female groups (500, 1000, and 2000 mg/kg/ body weight/day) were higher than those in the control. Further, the relative weights of the kidneys in the treated female groups (1000 and 2000 mg/kg/ body weight/day) were higher than those in the control. However, these changes were not consistent in either sex, and no abnormalities were found in the corresponding pathological findings. Thus the results showed no adverse effects in all the parameters assessed. The findings show that after 13 weeks of treatment, the “no-observed-adverse-effect level” of PAAE is 2000 mg/kg body weight in both male and female F344 rats under the experimental conditions applied. Although treatment-related adverse effects were not seen, potassium-level changes in the blood should be examined to establish the safety profile of PAAE after long-term treatment.

Persistent Crimean-Congo hemorrhagic fever virus infection in the testes and within granulomas of non-human primates with latent tuberculosis.

Crimean-Congo hemorrhagic fever (CCHF) is the most medically important tick-borne viral disease of humans and tuberculosis is the leading cause of death worldwide by a bacterial pathogen. These two diseases overlap geographically, however, concurrent infection of CCHF virus (CCHFV) with mycobacterial infection has not been assessed nor has the ability of virus to persist and cause long-term sequela in a primate model. In this study, we compared the disease progression of two diverse strains of CCHFV in the recently described cynomolgus macaque model. All animals demonstrated signs of clinical illness, viremia, significant changes in clinical chemistry and hematology values, and serum cytokine profiles consistent with CCHF in humans. The European and Asian CCHFV strains caused very similar disease profiles in monkeys, which demonstrates that medical countermeasures can be evaluated in this animal model against multiple CCHFV strains. We identified evidence of CCHFV persistence in the testes of three male monkeys that survived infection. Furthermore, the histopathology unexpectedly revealed that six additional animals had evidence of a latent mycobacterial infection with granulomatous lesions. Interestingly, CCHFV persisted within the granulomas of two animals. This study is the first to demonstrate the persistence of CCHFV in the testes and within the granulomas of non-human primates with concurrent latent tuberculosis. Our results have important public health implications in overlapping endemic regions for these emerging pathogens.

Metabolic Surgery Comparing Sleeve Gastrectomy with Jejunal Bypass and Roux-en-Y Gastric Bypass in Type 2 Diabetic Patients After 3Years.

Sleeve gastrectomy with jejunal bypass (SGJB) and Roux-en-Y gastric bypass (RYGB) has shown good results with respect to type 2 diabetes mellitus (T2D) remission in our institution. In this study, we compared the efficacy and safety of SGJB versus RYGB in terms of T2D remission up to 3years postoperatively. A retrospective cohort study of two groups of patients with T2D who underwent SGJB or RYGB. All patients were matched by age, presurgical body mass index (BMI), glycated hemoglobin (HbA1c), and diabetes duration. Complete remission was defined as HbA1c of < 6%, fasting plasma glucose (FPG) of < 100mg/dL, and no antidiabetic drugs. In total, 57 and 55 patients in the SGJB and RYGB groups, respectively, met the inclusion criteria. The diabetes remission rate was similar between the SGJB and RYGB groups at 1year postoperatively (69.2 vs. 64.7%) and 3years postoperatively (56.1 vs. 58.8%). There were no significant differences in HbA1c or FPG at 1 or 3years between the two groups. Additionally, weight loss and other metabolic parameters were similar between the groups. Clinical chemistry values were similar at 12months except for hematocrit and calcium, which were significantly lower in the RYGB group. There were no differences in surgical complications. Both procedures showed similar results in terms of T2D remission and other metabolic markers at 3years. Hematocrit and calcium were significantly higher in the SGJB than RYGB group. SGJB is as effective and safe as RYGB in obese patients with T2D.

Evaluation of Three Doses of Dietary Sialyllactose on Growth and Intestinal Development in the Neonatal Piglet

Oligosaccharides are the third most abundant component in human milk and modulate neonate microbiota, gut and immune development. This study investigated potential dose‐dependent effects of sialyllactose (Lacprodan SAL‐10®, SL) on growth and gut development of neonatal piglets. Beginning at 2 d of age, 38 vaginally‐derived male piglets (mean body weight (BW) 1.64 ± 0.04 kg) were randomized to diets formulated to contain: control (CONT) [0 mg SL/L milk replacer], low (LOW) [130 mg SL/L], moderate (MOD) [380 mg SL/L], and high (HIGH) [760 mg SL/L]. Diets contained 4 g/L of a 1:1 mixture of polydextrose and galactooligosaccharides. Diets were prepared at 20% (wt/vol) and piglets received 285 mL and 325 mL per kg BW on d2–5 and 5–33, respectively. On d32 or 33, piglets were euthanized and samples were collected. Outcomes were analyzed using a one‐way ANOVA; significance was set at p ≤ 0.05 and trends at 0.05 &lt; p &lt; 0.10. Dietary SL was well tolerated regardless of dose and growth patterns were similar among the groups. Weight gain between d2 and 33 did not differ among the groups and the average gain was 4.23 ± 0.29 kg (CONT: 4.19 kg ± 0.42; LOW: 4.08 kg ± 0.64; MOD: 4.43 kg ± 0.69; HIGH: 4.22 kg ± 0.68). Similarly, intestinal length and weight, villus and crypt morphology in the small and large intestine and the number of acidic sulfated mucin‐secreting goblet cells did not differ among the groups. Short‐chain and branched‐chain fatty acid profiles in colonic contents were similar between all four groups. No differences in complete blood counts were observed and serum clinical chemistry values were similar (minerals, electrolytes, protein, enzymes, kidney function, liver function and acid:base balance and prothrombin time), except for activated partial thromboplastin time (aPTT) and glutathione dehydrogenase (GLDH). APTT (seconds) in HIGH (12.6 ± 0.5) was lower (p&lt;0.02) than CONT (14.1 ± 0.2), LOW (13.8 ± 0.4) and MOD (13.6 ± 0.2). GLDH (U/L) in CONT (0.9 ± 0.1) was lower (p&lt;0.02) than LOW (1.3 ± 0.1) and MOD (1.5 ± 0.2) and tended (p&lt;0.09) to be lower than HIGH (1.2 ± 0.08). Due to the low magnitude of differences and lack of a clear dose response, the differences in aPTT were not clinically significant. In addition to a lack of dose‐response in our study, normal values for other liver enzymes suggest that slightly higher GLDH values are also unlikely of clinical significance. In conclusion, dietary SL at up to 760 mg/L was well tolerated and supported similar growth and intestinal development as the CONT formula in neonatal piglets.Support or Funding InformationMead Johnson Nutrition

Usefulness of clinical observations and blood chemistry values for predicting clinical outcomes in dairy goats with pregnancy toxaemia.

BackgroundPregnancy toxaemia (PT) is a disease that affects pregnant goats during their last month of gestation and is characterized by a high case fatality rate. This study involved 32 does maintained on a commercial dairy goat farm that were diagnosed with PT. A physical examination was performed on and haematology parameters obtained from each doe, at the time of diagnosis. The data from the 24 PT goats that died was compared with the corresponding data from the 8 PT goats that survived.ResultsPolypnea, swollen limbs, anorexia with absence of ruminal motility, recumbency, nervous signs and drooping ears were the most frequently observed clinical manifestations. Nineteen out of 21 recumbent goats died. Sixteen out of 17 goats with anorexia and absence of ruminal motility died. Mean beta-hydroxybutyric acid (BHBA) values in the goats that died were not significantly different from those in goats that survived. The blood values for pH and pCO2 (p < 0.005) as well as for HCO3 −, BE and K+ (p < 0.001) were significantly lower in the goats that died than in those that survived.ConclusionsThe clinical signs most indicative of a poor prognosis are anorexia with absence of ruminal motility and recumbency. Among the blood parameters to be considered, hypokalaemia and metabolic acidosis are the most relevant. Goats with PT have a high mortality and their condition can deteriorate very fast. Based on the authors’s experience, a good strategy to minimize the economic losses caused by PT is to focus on the offspring survival rate since an early decision (induction of kidding or caesarian surgery) can increase the number of alive kids.

4-Week repeated dose oral toxicity study of N-ethyl-2-pyrrolidone in Sprague Dawley rats

The solvent N-ethyl-2-pyrrolidone (NEP) was evaluated in a 4-week repeated dose study in rats. NEP diluted in distilled water was orally administered by gavage to male and female Sprague-Dawley rats at doses of 0 (vehicle control), 5, 50, and 250 mg/kg/day for 28 consecutive days. Transient decreases in the body weight and in the body weight gain of the males was observed during the first days of treatment at the 50 and 250 mg/kg/day doses. There was a marked increase in urine volume at the beginning of treatment in males and female rats at doses of 50 and 250 mg/kg/day. No biologically significant differences were observed in hematological and clinical chemistry values in males and females at necropsy. Histological examination revealed an increase in hyaline droplets in the renal tubules of the kidneys and hepatocellular centrilobular hypertrophy in the liver of males at 250 mg/kg/day. Cytochrome P450 concentration in liver microsomes was slightly increased at 250 mg/kg/day in males. The results of this study demonstrate that NEP has mild to no effects at doses up to 250 mg/kg/day when administered orally to rats for 28 days with males being more susceptible than females.

Toxicology and immunology of Ganoderma lucidum polysaccharides in Kunming mice and Wistar rats

In the present work, the toxicology and immunology of polysaccharides from fruiting body of Ganoderma lucidum (GPs) were investigated. No abnormal clinical-symptoms or deaths and no significant difference in body weight and food in-taking rate were found in Wistar rats during the 30-day feeding administration. No significant differences were found in each hematology value, clinical chemistry value and organ/body weight ratio, either. It had no mutagenicity due to the negative experimental results of Ames test, micronucleus test of polychromatic erythrocyte, sperm abnormality test, and chromosome aberration test in Kunming mice, respectively. The immune experiments indicated that high-dose GPs had immune effects in increasing the degree of toe swelling and enhancing the primary immune response to SRBC (P<0.01). But no-significant influence of GPs on the phagocytic function of mononuclear macrophages (MΦ) could be obtained.

Deoxynivalenol induces cytotoxicity and genotoxicity in animal primary cell culture

Deoxynivalenol (DON), a mycotoxin produced by Fusarium graminearum, is widely found as a contaminant of food. DON is responsible for a wide range of toxic activities, including gastro-intestinal, lymphoid, bone-marrow and cardiotoxicity. But, the complete explorations of toxicity in terms of hepatotoxicity, nephrotoxicity, cytotoxicity and genotoxicity as well have not been documented well. Again, the mechanisms through which DON damages the DNA and promotes cellular toxicity are not well established. Considering the above fact, this research article is focused on the effects of DON-induced toxicities on experimental animal model as well as its effects on cellular level via various toxicological investigations. DON treatment showed cytotoxicity and DNA damage. Further, flow cytometric analysis of hepatocytes showed cellular apoptosis, suggesting that DON-induced hepatotoxicity is, may be partly, mediated by apoptosis. Moreover, significant differences were found in each haematology and clinical chemistry value, either (p > 0.05). No abnormality of any organ was found during histopathological examination. Hence, it can be concluded that DON induces oxidative DNA damage and increases the formation of centromere positive micronuclei due to aneugenic activity.

Preclinical Safety Assessment of Standardized Extract of Centella asiatica (L.) Urban Leaves.

Context:Centella asiatica (CA) leaves extract has been shown therapeutic potential. However, safety information is lacking.Aims:To evaluate acute oral toxicity (AOT), sub-chronic toxicity, and mutagenic potential of standardized extract of CA (L.) Urban leaves (INDCA).Materials and Methods:For the acute toxicity study, INDCA was orally administered to Sprague-Dawley rats at a dose range of 0–2000 mg/kg. For the repeated dose toxicity study, the rats of either sex were orally administered with INDCA at the doses of 250, 500, and 1000 mg/kg/day for a period of 90 days. The effects on body weight, food and water consumption, organ weight, hematology, clinical chemistry as well as histology were studied. The mutagenic potential of INDCA was tested using reverse mutation assay (Ames test).Statistical Analysis Used:Data of each parameter were analyzed by one-way ANOVA followed by Dunnett's test to compare the difference between treated groups.Results:The administration of INDCA did not produce mortality or significant changes in the clinical signs included but not limited to changes in the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, somatomotor activity, and behavior pattern. The appearance, progress, and disappearance of these signs were recorded. The lethal dose and no observable adverse effect level of INDCA were 2000 mg/kg and 1000 mg/kg, respectively. There were no significant differences in the organ weights, hematological parameters, clinical chemistry values, or gross and microscopic appearance of the organs from the treatment groups as compared to the control group. It was found to be nonmutagenic in reverse mutation assay.Conclusions:INDCA was found safe in AOT, sub-chronic toxicity, and mutagenicity studies when tested in rats.

Safety assessment of Superba™ krill powder: Subchronic toxicity study in rats

The safety of krill powder was assessed in a subchronic 13-week toxicity study where rats were fed krill powder or control diets. The krill powder inclusion in the test diet was 9.67% (w/w). There were no differences noted in body weight or food consumption in either gender. Differences in clinical chemistry values were noted in the krill powder-treated animals, but these findings were of no toxicological significance. A significant decrease in absolute heart weight, but not relative heart weight, was observed in both sexes given krill powder, although no corresponding histological changes were observed. Hepatocyte vacuolation was noted histologically in males fed krill powder. This finding was not associated with other indications of hepatic dysfunction. The no observed adverse effect level (NOAEL) for the conditions of this study was considered to be 9.67% krill powder.

Disposition of phenolic and sulfated metabolites after inhalation exposure to 4-chlorobiphenyl (PCB3) in female rats.

PCBs, such as PCB3, are air contaminants in buildings and outdoors. Metabolites of PCB3 are potential endocrine disrupting chemicals and genotoxic agents. We studied the disposition of phenolic and sulfated metabolites after acute nose-only inhalation exposure to airborne PCB3 for 2 h in female rats. Inhalation exposure was carried out in three groups. In the first group, rats exposed to an estimated dose of 26 μg/rat were euthanized at 0, 1, 2, and 4 h after exposure. Highest concentrations of phenols and sulfates were observed at 0 h, and the values were 7 ± 1 and 560 ± 60 ng/mL in serum, 213 ± 120 and 842 ± 80 ng/g in liver, 31 ± 27 and 22 ± 7 ng/g in lung, and 27 ± 6 and 3 ± 0 ng/g in brain, respectively. First-order serum clearance half-lives of 0.5 h for phenols and 1 h for sulfates were estimated. In the second group, rats exposed to an estimated dose of 35 μg/rat were transferred to metabolism cages immediately after exposure for the collection of urine and feces over 24 h. Approximately 45 ± 5% of the dose was recovered from urine and consisted mostly of sulfates; the 18 ± 5% of the dose recovered from feces was exclusively phenols. Unchanged PCB3 was detected in both urine and feces but accounted for only 5 ± 3% of the dose. Peak excretion of metabolites in both urine and feces occurred within 18 h postexposure. In the third group, three bile-cannulated rats exposed to an estimated dose of 277 μg/rat were used for bile collection. Bile was collected for 4 h immediately after 2 h exposure. Biliary metabolites consisted mostly of sulfates, some glucuronides, and lower amounts of the free phenols. Control rats in each group were exposed to clean air. Clinical serum chemistry values, serum T4 level, and urinary 8-hydroxy-2′-deoxyguanosine were similar in treated and control rats. These data show that PCB3 is rapidly metabolized to phenols and conjugated to sulfates after inhalation and that both of these metabolites are distributed to liver, lungs, and brain. The sulfates elaborated into bile are either reabsorbed or hydrolyzed in the intestine and excreted in the feces as phenols.