Cobalt Uptake by Food Plants and Accumulation in Municipal Solid Waste Materials Compost-amended Soil: Public Health Implications.

One of the most pressing environmental issues is how to properly dispose of municipal solid waste (MSW), which represents both a substantial source of concern and a challenge. The current study evaluated cobalt (Co) accumulation in MSW, their uptake by different vegetables grown for two years, and related human health risks. Vegetables were grown in four different groups, such as one control (ground soil), and the remaining treatment groups (T1, T2, and T3) received varying concentrations of MSW. The analysis of Co was done through an atomic absorption spectrophotometer (AAS). Results revealed that the concentration of Co was higher in all the vegetables (n = 15) grown in soil supplemented with 75% MSW during 2nd growing year. Among all vegetables, the highest concentration of Co was observed in Solanum tuberosum at T3 during 2nd growing year. The pollution load index (PLI) value for vegetables during both growing years was more than 1 except in control soil. The findings indicated that the highest enrichment factor (EF) and hazard resilience index (HRI) value of 0.09 was present in S. tuberosum. Health index values for cobalt in the study were below 1. The HRI < 1 indicated that consumers do not face any immediate health risks. The investigation of Co concentrations in blood samples obtained from individuals residing in different areas contributes a human health perspective to the research. The findings indicate that the concentration of Co rises with an increasing proportion of MSW. While the metal levels in MSW-treated soil were not high enough to classify the soil as polluted, the results recommend that recycling MSW can substitute mineral fertilizers. Nevertheless, the presence of cobalt in MSW may directly affect soil fertility and could impact crop production and human health.

Chromium accumulation in soil, water and forage samples in automobile emission area.

Environmental contamination caused by various pollutants due to automobile emissions is an alarming issue. One important type of the pollutants are heavy metals, including chromium (Cr) added by the exhaust of toxic smoke of vehicles. These pollutants are added to forage crops cultivated near roadsides, soil and irrigation water. However, rare studies have been conducted to infer Cr accumulation near heavy automobile emission areas. This study was conducted to determine Cr concentration in irrigation water, soil and forage. Water, forage and soil samples were collected from area impacted by heavy traffic. Atomic absorption spectrophotometer was used to appraise Cr values in the collected samples. Chromium values ranged from 0.50 to 1.14 mg/kg in water samples and from 0.04 to 2.23 mg/kg in soil samples. It was highest in Zea mays grown soil, whereas minimum in Brassica campestris soil. The Cr values in forages ranged from 0.09 to 1.06 mg/kg. Z. mays observed the highest Cr accumulation, whereas the lowest Cr accrual was noted for B. campestris. The pollution load index (PLI) was the highest for Trifolium alexandrinum, while the lowest for Z. mays. Bio-concentration factor (BCF) ranged from 0.14 to 8.63. The highest BCF was noted for T. alexandrinum, while the lowest for Z. mays. The highest and the lowest daily intake of metal (DIM) was noted for Z. mays at different sites. Health risk index (HRI) was highest for Z. mays and lowest for B. campestris. The results add valuable information on heavy metal accumulation in water, soil and forage samples near to automobile emission area.

Evaluation of transfer of lead in soil plant animal system: assessment of consequences of its toxicity.

The instant endeavor was undertaken for determination of lead (Pb) in water, soil, forage, and cow's blood domesticated in contaminated area of heavy automobiles' exhaust in Sahiwal town of District Sargodha, Pakistan. Water samples showed that the concentration of Pb ranged from 1.14 to 0.44 mg kg-1 at all sites. It was maximum at site 5 and minimum at site 2. Soil samples showed the concentration of Pb at all sites ranged from 1.58 to 0.279 mg kg-1. It was maximum in soil where Avena sativa was grown at site 5 and was found minimum in soil where Zea mays was grown at site 2. While among samples of forage, the concentration of Pb ranges from 0.048 to 2.002 mg kg-1. The highest Pb amount was found in Brassica campestris at site 1 and the minimum was recorded in Trifolium alexandrinum at site 2. Finally, the blood samples of cow depicted that concentration of Pb ranged from 4.468 to 0.217 mg kg-1. It was the maximum at site 1 and the minimum at site 3. It is recommended that such study should be conducted in other districts for public awareness.

Monitoring of copper accumulation in water, soil, forage, and cows impacted by heavy automobiles in Sargodha, Pakistan.

The instant endeavor was undertaken to monitor copper (Cu) contents in water, soil, forage, and cow's blood impacted by heavy automobiles in Sahiwal town of district Sargodha, Pakistan. The samples were collected in triplicates with a total of 120 soil and water samples with corresponding forage samples. For the analysis of metal concentration in cows, 60 blood samples were collected from the cows feeding on these forages on selected sites. Metal contents were analyzed by atomic absorption spectrophotometry. The results showed that water samples contained mean values of Cu concentration ranged from 1.01 to 0.444 mg/kg at all sites. It was maximum at site 3 and minimum at site 6. The soil samples of all the forage fields showed Cu mean values concentration ranged from 1.94 to 0.286 mg/kg at all sites. It was maximum in Trifolium alexandrinum grown field at site 2, and minimum in Avena sativa at site 2. All the forage samples showed the mean value of Cu concentration ranged from 0.151 to 1.86 mg/kg at all sites. The concentration of Cu was maximum in Zea mays grown at site 5 and minimum in Trifolium alexandrinum at site 4. The cow blood samples showed the mean concentration of Cu ranged from 1.368 to 0.53 mg/kg at all sites. It was maximum at site 2 and minimum at site 6. Owing to the results of pollution index and transfer factors, metal content was found to be in permissible range in forages as well as animal samples.

Bioaccumulation of cadmium in different genotypes of wheat crops irrigated with different sources of water in agricultural regions.

The study was carried out to evaluate the health risks associated with accumulation of cadmium in the different genotypes of wheat, grown in agricultural regions of Punjab, Pakistan. Five genotypes irrigated with three varied water sources were selected randomly from each region. Among all sources of water, types of soil, and grain samples, the cadmium (Cd) quantities were found (2.24-2.82 mg/L, 1.75-4.16 mg/kg, 0.86-1.90, respectively), exceeding the maximum permissible limits (0.01 mg/L, 1.1 mg/kg, 0.2 mg/kg, respectively) described by FAO/WHO. The pollution load index (PLI) exhibited by all of the samples was higher than 1.00, the permissible limit; however, other factors including bioaccumulation, translocation, bio-concentration, daily intake, and enrichment values of Cd were less than 1.00. Moreover, the health risk index for cadmium in all types of wheat grain samples was less than 1.00. The study concluded that the continuous use of wastewater resources may lead to the accumulation of cadmium in the vital body organs that may cause severe health hazards.

Appraisal of chromium in chicken reared on maize irrigated with sewage water.

In the present study, the outcome of sewage, canal, and ground water on the chromium (Cr) concentration in corn and ultimately in chicken body parts was reported. To evaluate Cr level, atomic absorption spectrophotometer (Flame Atomic Absorption Spectrophotometer AA 6300, Shimadzu Japan) was used. The highest level of Cr in grains (0.50 ± 0.05 mg/kg), shoots (0.90 ± 0.01 mg/kg), and roots (1.01 ± 0.02 mg/kg) were noticed in the Sadaf variety watered with canal water. The least concentration of Cr was recorded in grains (0.07 ± 0.01 mg/kg), shoots (0.59 ± 0.01 mg/kg), and roots (0.71 ± 0.01 mg/kg) of Pearl variety irrigated with ground water. The maximum concentration of chromium in the blood (1.68 ± 0.02 mg/kg) and bones (1.26 ± 0.24 mg/kg) was observed in chicks fed on Millet Research Institute (MMRI) grains reared with the sewage water. The lowest concentration was observed in the blood (1.60 ± 0.04 mg/kg) and in bone (0.80 ± 0.01 mg/kg) of the chicks fed Pearl variety grains reared with canal water. In the second experiment, the maximum content of Cr was determined in the blood (0.74 ± 0.04 mg/kg) and bones (1.76 ± 0.02 ppm) of chicks consuming Sadaf variety grains reared with canal water and the least concentration in the blood (0.26 ± 0.03 mg/kg) and bones (1.64 ± 0.01 mg/kg) was determined on the consumption of the Pearl variety grains reared with ground water. A similar trend was observed in other body organs. It was concluded that polluted water causes higher accumulation levels of Cr in plant parts and even in animals' body parts after the utilization of such plants.

The impact of seed burial depths and post-emergence herbicides on seedling emergence and biomass production of wild oat (Avena fatua L.): Implications for management.

Wheat (Triticum aestivum L) is among the most important cereal crops widely cultivated in the world. Wild oat (Avena fatua L.) competes with wheat for moisture, sunlight, space and nutrition. The successful management of weeds requires sound knowledge of their biology and response to different herbicides. This study inferred the impact of different constant temperature regimes and seed burial depths on seedling emergence and biomass production of wild oat. Moreover, the impact of different post-emergence herbicides applied at different growth stages on biomass production of wild oat was tested. The influence of different wild oat-wheat density (WWD) combinations on biomass production of wheat and wild oat was also inferred. Different constant temperature regimes significantly altered seed germination and biomass production of wild oat. The highest seed germination percentage and biomass production were noted under 15°C and 20°C, whereas the lowest values were recorded under 30°C. Similarly, days to start emergence, seedling emergence percentage and biomass production of wild oat was significantly affected by different seed burial depths. The lowest and the highest values of these parameters were observed under 4 and 10 cm depth, respectively. Different post-emergence herbicides and wild oat growth stages significantly altered biomass production. The highest reduction in fresh and dry biomass was recorded with herbicides' application at 2-4 leaf stage compared with anthesis stage. Clodinofop resulted in higher reduction of fresh biomass, whereas higher reduction in dry biomass was noted with Sulfosulfuron. Seed germination of both species was not affected by different WWD combinations, except for the treatment where no seed was sown of both species. These results indicate that deep burial of seeds could prevent seedling emergence, whereas post-emergence herbicides must be applied at 2-4 leaf stage of wild oat for its effective management.

Correction to: A study on the transfer of chromium from meadows to grazing livestock: an assessment of health risk.

The affiliation of Shahzadi Mahpara is shown in this paper.

A study on the transfer of chromium from meadows to grazing livestock: an assessment of health risk.

The present investigation was performed in different district of Punjab to determine the chromium level in soil, forages, and blood plasma of the small ruminants (goat and sheep). The results showed that the mean concentrations of chromium in the soil of Sargodha, Mianwali, and Bhakkar districts were ranged from 1.8 to 2.3, 3.01 to 4.99, and 2.04 to 2.87 mg/kg, respectively. The chromium level was higher in Mianwali compared with Sargodha and Bhakkar. The mean concentrations of chromium in forages which were used for feeding purposes were found between 0.672 and 1.631, 1.493 and 2.612, and 0.7804 and 1.047 mg/kg for Sargodha, Mianwali, and Bhakkar, respectively. The mean concentrations of chromium in blood plasma of goat which consumed the contaminated forages were between 0.666 and 1.269 mg/L in Sargodha, 0.657 and 0.752 mg/L in Mianwali, and 1.39 and 2.37 mg/L in Bhakkar. In blood plasma of sheep, the residual levels of chromium in the districts Sargodha, Mianwali, and Bhakkar were ranged from 0.673 to 1.384, 0.83 to 1.086, and 1.496 to 3.611 mg/L, respectively. In the present research, there was a higher concentration of chromium in blood plasma of sheep from Bhakkar and the lowest was in Sargodha. The chromium level in blood samples was found to be higher than the tolerable level of 1.0 mg/L in all districts. In light of these results, it was concluded that chromium levels in the soil and forages of all sites were present within the safe limit while in blood samples of sheep and goats were found to be above the acceptable limit. Sheep and goats also consume water from river, streams, and ponds and other contaminated water sources. So it might be the reason of higher level of chromium in their blood plasma. Hence, the proper monitoring of study sites will be necessary to prevent the excessive accumulation of chromium in ruminants in the near future.

WB-PBPK approach in predicting zidovudine pharmacokinetics in preterm neonates.

Antiretroviral therapy has been the mainstay of treatment for neonates born to HIV infected mothers. Neonates born prematurely to HIV positive mothers are underdeveloped not only in anatomical terms but also in their physiological systems. Zidovudine, the first antiretroviral drug in clinical therapy for the treatment of HIV has been approved for use in preterm neonates both prophylactically and therapeutically. The present work describes the whole body physiologically based pharmacokinetic (WB-PBPK) model development for zidovudine in preterm neonates of varying gestational ages, to observe the pharmacokinetic behavior of the drug in this vulnerable group of the population. Along with the height, weight, post-natal, and gestational ages of the preterm neonates, metabolic enzymes CYP2A6, CYP2C8, etc. were incorporated for each neonate. The composition of the different organs in terms of water and lipid components, blood flow rates, etc. were specified during simulations according to the gestational ages of these neonates. The following PK parameters were estimated for preterm neonates using simulated plasma profiles: AUC 2686.41 ± 123.49 µmol min/L, Cmax 6.46 ± 0.74 µmol/L, half-life 8.98 ± 2.36 hr, mean residence time 12.23 ± 3.43 hr, and total plasma clearance 1.48 ± 0.19 ml/min/kg in comparison with the observed PK parameters of a clinical study by Mirochknic et al. in preterm neonates with AUC 2020.04 µmol/min/L, Cmax 6.10 µmol/L, and total plasma clearance 1.62 ml/min/kg. PBPK simulations provide an opportunity to visualize the possible impact of physiological maturity levels at varying gestational ages on the pharmacokinetic behavior of zidovudine in preterm neonates.

Enzyme and Transporter Kinetics for CPT-11 (Irinotecan) and SN-38: An Insight on Tumor Tissue Compartment Pharmacokinetics Using PBPK.

BACKGROUND: Computational tools are becoming more and more powerful and comprehensive as compared to past decades in facilitating pharmaceutical, pharmacological and clinical practice. Anticancer agents are used either as monotherapy or in combination therapy to treat malignant conditions of the body. A single antineoplastic agent may be used in different types of malignancies at different doses according to the stage of the disease. OBJECTIVE: To study the behavior of CPT-11 (Irinotecan) and its metabolite SN-38 in tumor tissue compartment through the Whole Body-Physiologically Pharmacokinetics (WB-PBPK) and to determine the activity of metabolic enzymes and transporters participating in the disposition of CPT-11 and SN-38 working in their physiological environment inside the human body. METHODS: Whole body PBPK approach is used to determine the activity of different metabolic enzymes and transporters involved in the disposition of CPT-11 and its active metabolite, SN-38. The concentrations and pharmacokinetic parameters of the parent compound and its metabolite administered at clinically applicable dose via the intravenous route in the tumor tissue are predicted using this approach. RESULTS: The activity rate constants of metabolic enzymes and transporters of CPT-11 are derived at their natural anatomic locations. Concentration-time curves of CPT-11 and SN-38 with their 5th to 95th percentage range are achieved at the tumor tissue level. Mean tumor tissue pharmacokinetics of both compounds are determined in a population of 100 individuals. CONCLUSION: Tumor tissue concentration-time curves of CPT-11 and SN-38 can be determined via PBPK modeling. Rate constants of enzymes and transporters can be shown for healthy and tumor bearing individuals. The results will throw light on the effective concentration of active compound at its target tissue at the clinically applied IV dose.

Prediction of Clearance and Dose of Midazolam in Preterm and Term Neonates: A Comparative Study Between Allometric Scaling and Physiologically Based Pharmacokinetic Modeling.

Children are not small adults because besides size there are subtle physiological and biochemical differences between children and adults. Like adults, children also require medicine for the management or cure for the underlying diseases. To select a right dose in children, pharmacokinetic (PK) information is warranted. However, in many instances, a PK study in neonates and infants may not be possible. Therefore, various methods are used to predict PK parameters in this group of population, and these predicted parameters may help to calculate a safe dose for the very young children. Allometry is widely used for the prediction of PK parameters in children and subsequently one can predict dose from these predicted PK parameters. Physiologically based pharmacokinetic modeling (PBPK) has also become a useful tool to achieve these goals. Therefore, the objective of this study was to compare the predictive performance of allometry and PBPK for a test compound, midazolam in preterm, and term neonates. In this study, there were 5 preterm neonates (gestational age ranging from 34 to 37 weeks) and 5 term neonates (gestational age ranging from 38 to 41 weeks). PBPK modeling was performed using PK-Sim 6.0 and clearance, as well as midazolam dose in neonates was predicted. Clearance and midazolam dose in neonates was also predicted by allometric scaling. In this study, the allometric exponents for the prediction of midazolam clearance in preterm neonates and term neonates were 1.2 and 1.1, respectively. Similarly, for the prediction of midazolam neonatal dose, the exponent of allometry was either 0.9 or 1.0. The predicted midazolam clearance and dose by both methods were then compared with observed midazolam clearance and dose in neonates. The results of the study showed a slightly better prediction of midazolam clearance in neonates by PBPK than allometric scaling. However, the projected dose of midazolam in neonates was comparable between the 2 methods. Overall, it was noted that both PBPK and allometric model can be used to predict clearance and dose of midazolam in neonates.

Physiologically based pharmacokinetic modeling for predicting irinotecan exposure in human body.

Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Treatment of colorectal cancer remains a challenge to clinicians as well as drug developers. Irinotecan, a Camptothecin derivative, is successfully used for the treatment of this rapidly progressing malignancy and finds its place in the first line of therapeutic agents. Irinotecan is also effective in treating SCLC, malignant glioma and pancreatic adenocarcinoma. However, its adverse effects limit its clinical application. Mainly metabolized by hepatic route, and excreted through biliary tract, this dug has been found to possess high variation in patients in its pharmacokinetic (PK) profile. Physiologically based pharmacokinetic (PBPK) models using compartmental approach have attained their position to foresee the possible PK behavior of different drugs before their administration to patients and such models have been proposed for several anticancer agents. In this work, we used WB-PBPK technology to develop a model in a population of tumor patients who used IV irinotecan therapy. This model depicted the concentration of drug and its pharmacologically active metabolite in human body over a specific period of time. Knowledge about pharmacokinetic parameters is extracted from this profile and the model is evaluated by the observed results of clinical study presented in literature. The predicted behavior of the drug by this approach is in good agreement with the observed results and can aid in further exploration of PK of irinotecan in cancer patients, especially in those concomitantly suffer from other morbidity.

Prediction of Clearance in Neonates and Infants (≤ 3 Months of Age) for Drugs That Are Glucuronidated: A Comparative Study Between Allometric Scaling and Physiologically Based Pharmacokinetic Modeling.

The objective of this study was to evaluate the predictive performances of allometric models and a physiologically based pharmacokinetic model (PBPK) to predict clearance of glucuronidated drugs in neonates (≤ 3 months of age). From the literature, clearance values for 9 drugs (glucuronidated) for neonates and adults were obtained. Three allometric models were used to predict clearances of these glucuronidated drugs. A PBPK model was developed using the physicochemical, biopharmaceutical, and metabolic properties together with known pediatric physiology and enzymatic ontogeny. The model was first developed for adult subjects and then verified using external data and then applied to simulations in neonates. The predictive performances of allometric and PBPK models were evaluated by comparing the predicted values of clearance with the observed clearance values in the neonates. For 9 drugs, there were 13 age groups (preterm and term neonates) for which prediction error in mean clearance values within 0.5- to 1.5-fold was observed in 10 and 11 age groups by 2 allometric models and a PBPK model, respectively. The proposed allometric methods can predict mean clearances of glucuronidated drugs in preterm and term neonates (≤ 3 months of age) with reasonable accuracy (within 0.5- to 1.5-fold or 50% error) and are of practical value during neonatal drug development. The predicted mean clearance values of glucuronidated drugs in neonates ≤ 3 months of age by 2 allometric methods were comparable with the PBPK model.