Bayesian analysis of physiologically based toxicokinetic (PBTK) modeling for pentachlorophenol exposure in pregnant women.

Pentachlorophenol (PCP) is a persistent organic compound that is widely present in the environment. The estimation of internal exposure levels for a given external exposure using toxicokinetic models is key to the human health risk assessment of PCP. The present study developed a physiologically based multicompartmental pharmacokinetic (PBTK) model to describe and predict the behavior of pentachlorophenol (PCP) in an organism. The model consists of stomach, intestines, adipose tissue, kidneys and fast- and poorly perfused tissues that are interconnected via blood circulation. We constructed a PBTK model of PCP in rats and extrapolated it to human dietary PCP exposure. The toxicokinetic data of PCP in human tissues and excreta were obtained from the published literature. Based on the collected PCP dietary survey and internal exposure data of pregnant women in Shanghai, Bayesian statistical analysis was performed for the model using Markov chain Monte Carlo (MCMC) simulation. The posterior distributions of the sensitive parameters were estimated, and the model was parameter optimized and validated using the pregnant women's test dataset. The results showed that the root mean square error (RMSE) improved 37.3% compared to the original model, and a systematic literature search revealed that the optimized model achieved acceptable prediction results for other datasets in China. A PCP metabolism model based on the exposure characteristics of pregnant women in China was constructed in the present study. The model provides a theoretical basis for the study of PCP toxicity and risk assessment.

Cyanobacterium Microcystis aeruginosa response to pentachlorophenol and comparison with that of the microalga Chlorella vulgaris.

Pentachlorophenol (PCP) effects on a strain of the cyanobacterium Microcystis aeruginosa were investigated at laboratory scale. This is the first systematic ecotoxicity study of the effects of PCP on an aquatic cyanobacterium. The microalga Chlorella vulgaris was studied in the same conditions as the cyanobacterium, in order to compare the PCP toxicity and its removal by the species. The cells were exposed to environmental levels of PCP during 10 days, in Fraquil culture medium, at nominal concentrations from 0.01 to 1000 µg L(-1), to the cyanobacterium, and 0.01 to 5000 µg L(-1), to the microalga. Growth was assessed by area under growth curve (AUC, optical density vs time) and chlorophyll a content (chla). The toxicity profiles of the two species were very different. The calculated effective concentrations EC20 and EC50 were much lower to M. aeruginosa, and its growth inhibition expressed by chla was concentration-dependent while by AUC was not concentration-dependent. The cells might continue to divide even with lower levels of chla. The number of C. vulgaris cells decreased with the PCP concentration without major impact on the chla. The effect of PCP on M. aeruginosa is hormetic: every concentration studied was toxic except 1 µg L(-1), which promoted its growth. The legal limit of PCP set by the European Union for surface waters (1 µg L(-1)) should be reconsidered since a toxic cyanobacteria bloom might occur. The study of the removal of PCP from the culture medium by the two species is an additional novelty of this work. M. aeruginosa could remove part of the PCP from the medium, at concentrations where toxic effects were observed, while C. vulgaris stabilized it.

Enhanced bioaccumulation of pentachlorophenol in carp in the presence of multi-walled carbon nanotubes.

The impact of suspended particles on the bioavailability of pollutants has long been a controversial topic. In this study, adsorption of pentachlorophenol (PCP) onto a natural suspended particulate matter (SPM) and multi-walled carbon nanotubes (MWCNTs) was studied. Facilitated transports of PCP into carp by SPM and MWCNTs were evaluated by bioaccumulation tests exposing carp (Carassius auratus red var.) to PCP-contaminated water in the presence of SPM and MWCNTs, respectively. Desorption of PCP on SPM and MWCNTs in simulated digested fluids was also investigated. The results demonstrate that MWCNTs (K F = 7.99 × 10(4)) had a significantly stronger adsorption capacity for PCP than the SPM (K F = 19.0). The presence of SPM and MWCNTs both improved PCP accumulation in the carp during the 21 days of exposure, and the 21 days PCP concentration in the carp was enhanced by 25.9 and 12.8 % than that without particles, respectively. The enhancement in bioaccumulation by MWCNTs was less than that by the SPM. Considerably more PCP was accumulated in the viscera of the fish (BCF = 519495 for SPM and 148955 for MWCNTs), and the difference in PCP concentrations between different tissues became greater with particles. PCP desorption in the simulated digestive fluids was faster than that in the background solution. Compared to MWCNTs-bound PCP, more SPM-bound PCP was desorbed, and K F of desorption for SPM was at least 4 orders of magnitude higher than that for MWCNTs, which can explain the greater enhancement in bioaccumulation in the presence of SPM. Particle-bound pollutants might pose more risk than pollutants alone.

Toxicity of pentachlorophenol to native aquatic species in the Yangtze River.

INTRODUCTION: While the literature is replete with studies of the toxic potency of pentachlorophenol (PCP), site-specific criteria for native aquatic species that can be used in ecological risk assessments has been lacking and application of toxicity information for non-native species is controversial. MATERIALS AND METHODS: In the present study, acute and chronic toxicities of PCP to six aquatic species native to the Yangtze River were determined. The HC5 and HC50 (hazardous concentration for 5% and 50% of species) were derived from dose-response curves for these native aquatic species and were then compared with those derived for non-native species. RESULTS: The acute toxicity values for the native species ranged from 8.8 × 10⁻² mg l⁻¹ (Plagiognathops microlepis) to 1.1 mg l⁻¹ (Soirodela polyrhiza), while chronic toxicity values based on no observed effect concentrations (NOECs) ranged from 0.01 mg l⁻¹ (Macrobrachium superbum) to 0.25 mg l⁻¹ (Soirodela polyrhiza). Native aquatic benthos was more sensitive to acute PCP exposure than non-native species. There was no significant difference in NOECs derived from native fish species and those based on non-native fish species. The median acute HC5 and HC50 derived from the toxicity data of native taxa were both less than those derived from non-native taxa. There was no significant difference between chronic HC5s derived from the two sets of taxa. However, the median chronic HC50 derived from native taxa was less than that derived from non-native taxa. CONCLUSION: The study upon which we report here provides site-specific toxicity information developed for native species which can be used for the protection of local aquatic life from a common contaminant, PCP.

Effect of bamboo biochar on pentachlorophenol leachability and bioavailability in agricultural soil.

In this study, bamboo biochar (BBC) was proposed as a practical carbonaceous material for the in situ remediation of organic pollutants. Column leaching experiments were used to evaluate the leachability of pentachlorophenol (PCP) in soil amended with BBC (0, 1, 2, and 5%; w/w). After leaching, the residual bioavailability of PCP in the soil column was determined by chemical extraction methods (methanol and distilled water). The results showed that compared to the control, the addition of 5% BBC decreased the cumulative leach-loss content of PCP by 42%, and also reduced PCP concentrations by 56 and 65% in methanol and distilled water extracts, respectively. Moreover, the linear leaching curves for the 10-h leaching time indicated that the rapid release process may be dependent on the continuous diffusion and partition mechanism. Regression analyses showed a significant (p<0.001) relationship between the BBC percentage and cumulative content of leached PCP, in addition, a significant relationship between BBC percentage and the chemical extraction of PCP with correlation coefficients (R(2)) greater than 0.9. Therefore, adding BBC to soil could prevent PCP further contamination such as bioavailability, surface or groundwater contamination through leaching.

Degradation pathway of pentachlorophenol by Mucor plumbeus involves phase II conjugation and oxidation-reduction reactions.

Environmental pollution by pentachlorophenol (PCP) is a critical concern worldwide and fungal bioremediation constitutes an elegant and environment-friendly solution. Mucorales from the Zygomycota phylum are often observed to be competitive in field conditions and Mucor plumbeus, in particular, can efficiently deplete PCP from media. The pathway for PCP degradation used by this fungus has not been investigated. In this study, PCP-derived metabolites were identified by liquid chromatography coupled with quadrupole time-of-flight mass spectrometry, including tetra- and tri-chlorohydroquinones and phase II-conjugated metabolites. Amongst the latter are the previously reported glucose, sulfate and ribose conjugates, and identified for the first time in fungi sulfate-glucose conjugates. A PCP transformation pathway for M. plumbeus is proposed, which excludes the involvement of cytochrome P-450 and extracellular ligninolytic enzymes.

Lymphatic and portal vein absorption of organochlorine compounds in rats.

The route of absorption of ingested compounds is a determinant of their distribution and metabolism. Portal vein absorption results in direct transport to the liver, where metabolism may take place before extrahepatic delivery. Lymphatic absorption can result in delivery of parent compound to nonhepatic tissues. Understanding the fate of an ingested compound requires determination of the importance of each of these routes. Portal vein absorption can be estimated from the difference in concentrations of an ingested compound between the portal vein and peripheral vessel blood. To make these estimations, one must make assumptions on the basis of estimates of flow rate and dilution. We report here methodology that allows a direct measurement of portal vein absorption that is independent of these assumptions. Mesenteric lymph was diverted from rats by cannulation. Portal blood was sampled after duodenal infusion of a bolus of compound of interest along with a portal absorption marker, 3-O-methylglucose. Since lymph was diverted, the appearance in portal blood was solely the result of portal absorption. Absorption was quantified by the areas under the curve for the compound and marker. Portal absorption was a function of the octanol/water partition coefficients for four organochlorine compounds: hexachlorobenzene, pentachlorophenol, DDT, and its metabolite 1,1,1-trichloro-2,2-bischlorophenylethylene.

Toxicity and bioaccumulation of xenobiotic organic compounds in the presence of aqueous suspensions of aggregates of nano-C(60).

The potential of C(60)-nanoparticles (Buckminster fullerenes) as contaminant carriers in aqueous systems was studied in a series of toxicity tests with algae (Pseudokirchneriella subcapitata) and crustaceans (Daphnia magna). Four common environmental contaminants (atrazine, methyl parathion, pentachlorophenol (PCP), and phenanthrene) were used as model compounds, representing different physico-chemical properties and toxic modes of action. The aggregates of nano-C(60) formed over 2 months of stirring in water were mixed with model compounds 5 days prior to testing. Uptake and excretion of phenanthrene in 4-days-old D. magna was studied with and without addition of C(60) in aqueous suspensions. It was found that 85% of the added phenanthrene sorbed to C(60)-aggregates >200 nm whereas about 10% sorption was found for atrazine, methyl parathion, and pentachlorophenol. In algal tests, the presence of C(60)-aggregates increased the toxicity of phenanthrene with 60% and decreased toxicity of PCP about 1.9 times. Addition of C(60)-aggregates reduced the toxicity of PCP with 25% in tests with D. magna, whereas a more than 10 times increase in toxicity was observed for phenanthrene when results were expressed as water phase concentrations. Thus, results from both toxicity tests show that phenanthrene sorbed to C(60)-aggregates is available for the organisms. For atrazine and methyl parathion no statistically significant differences in toxicities could be observed in algal and daphnid tests as a result of the presence of C(60)-aggregates. In bioaccumulation studies with phenanthrene in D. magna it was found that the uptake of phenanthrene was faster when C(60) was present in suspension and that a 1.7 times higher steady-state concentration was reached in the animals. However, a very fast clearance took place when animals were transferred to clean water resulting in no accumulation of phenanthrene. This study is the first to demonstrate the influence of C(60)-aggregates on aquatic toxicity and bioaccumulation of other environmentally relevant contaminants. The data provided underline that not only the inherent toxicity of manufactured nanoparticles, but also interactions with other compounds and characterisation of nanoparticles in aqueous suspension are of importance for risk assessment of nanomaterials.

Effects of pentachlorophenol on Galba pervia, Tubifex sinicus and Chironomus plumousus larvae.

The 24-h median lethal concentrations of pentachlorophenol to Chironomus plumousus, Tubifex sinicus and Galba pervia were 0.302, 0.977 and 0.293 mg/L, respectively. Bioconcentration factors of C. plumousus, T. sinicus and G. pervia to pentachlorophenol were 108, 367 and 85 at 0.02 mg/L pentachlorophenol, respectively. As pentachlorophenol concentration increased, the G. pervia egg hatching rates became lower, and the total hatched time became longer. Pentachlorophenol teratogenesis was demonstrated by observing the deformation of C. plumousus larvae mentum.

Bioavailability and toxicity of pentachlorophenol in contaminated soil evaluated on coelomocytes of Eisenia andrei (Annelida: Lumbricidae).

Pentachlorophenol (PCP) is widely distributed and highly persistent in soil, and represents a threat to the health of ecosystems. The present study aimed to assess the toxicity and bioavailability of PCP in soils as a function of different aging periods with the attempt to select a good toxicological assay for Eisenia andrei Bouché (Annelida: Lumbricidae). The experiments were performed on soil contaminated with PCP at 15 and 150ppm. After different aging periods (20, 60 and 120 days from spiking), bioavailability and toxicity were evaluated on E. andrei kept for 7 and 14 days in treated soils. The actual bioavailability decreased in relation to the aging for both PCP concentrations. No membrane damage was observed on coelomocytes collected by ethanol extrusion. Modifications in distribution of coelomocyte subpopulations were detected by flow cytometry on samples aged for 60 and 120 days at 150ppm PCP contamination. The reduction of lysosomal membrane stability, measured by neutral red retention time, was observed in all treatments. Worm mortality increased with aging in soils spiked with 150ppm of PCP. In conclusion, aging did not seem to reduce PCP cytotoxicity. This is the first report on in vivo toxicity of PCP evaluated on coelomocytes of E. andrei using different assays.

Uptake and elimination of chlorpyrifos and pentachlorophenol into the freshwater amphipod Gammarus pulex.

Uptake and elimination rates were determined for chlorpyrifos (CPF) and pentachlorophenol (PCP) in the freshwater amphipod Gammarus pulex. Internal concentrations of the two pesticides were measured over a three-day exposure phase and a subsequent three-day elimination phase. Rate constants were obtained by fitting measured internal concentrations to a one-compartment single first-order model. The uptake rate constants were 747+/-61 [L kg-1 day-1] for CPF and 89+/-7 [L kg-1 day-1] for PCP. The elimination rate constants were 0.45+/-0.05 [day-1] for CPF and 1.76+/-0.14 [day-1] for PCP. The resulting bioconcentration factors at steady state were 1660 and 51 for CPF and PCP, respectively. The parameter estimation method and possible variability due to varying lipid content are briefly discussed.

Pentachlorophenol removal from aqueous matrices by sorption with almond shell residues.

Sorption with activated carbon has been the technique preferred for pentachlorophenol (PCP) removal from contaminated waters, but regeneration needs and high operation costs are supporting a renewed interest in the search for alternative sorbents. Among them, almond shell, an agricultural by-product, provides interesting economical advantages, once shells account for 50% (in mass) of the whole almond. In this work, the capacity of almond shells to remove PCP from waters without previous activation was studied in batch conditions. While PCP analysis was performed solid-phase microextraction (SPME) followed by gas chromatography with electron capture detection (GC-ECD), mercury porosimetry and Fourier transform infrared spectroscopy (FTIR) provided a preliminary physical and chemical characterization of the sorbent. Almond shells were essentially a macroporous material, with an average surface area of 12.9+/-2.8 m2/g. The efficiency of PCP removal was 93+/-14%, in 24 h, with an initial concentration of 100 microg/l PCP and 5 microg PCP/g shell. Isotherm data adjusted better to Freundlich equation, where K(F) and 1/n were 0.075+/-0.081 mg(1-1/n) l(1/n) and 1.882+/-0.289, respectively. Average desorption efficiency was 7%, indicating strong adsorption capacity. Results proved that almond shells may be an excellent low-cost alternative for PCP removal from contaminated waters.

Body residues as dose for sublethal responses in alevins of landlocked salmon (Salmo salar m. sebago): a direct calorimetry study.

Questions of organism-specific factors, toxicity endpoints, and their relation to mode-of-action all are related to consistency and applicability of body residue-based approaches. To address this issue, direct calorimetry was used to evaluate metabolic responses of alevins of landlocked salmon (Salmo salar m. sebago) to pentachlorophenol (PCP) exposure ranging from 0 to 1.04 microM for 24 h or 24, 48, and 72 h (0, 0.26, and 0.55 microM, respectively). The body residues were used as a dose metric for sublethal responses. The body size, rapid ontogenetic development, and exposure to a specific pollutant all were heat output-modifying factors. The acute exposure (24-72 h) to PCP led to a heat output-enhancing effect, which directly was related to an internal concentration of PCP in the range of 0.01 to 0.15 micromol/g. Within the treatments, body size per level of metabolic rate and magnitude of physiological response were not correlated, thus the alevins with higher mass-specific metabolic rate were not more sensitive to PCP. Primarily, increasing metabolic rate during posthatch development controls PCP toxicity only by affecting bioaccumulation kinetics, not the toxic potency of the chemical. New information of a relationship between observed natural variation in measured physiological trait of fish and PCP-induced response and its body residue-based level is of ecotoxicological importance.

Bioavailability of pentachlorophenol to earthworms (Eisenia fetida) in artificially contaminated soils.

The bioaccumulation of pentachlorophenol in earthworms (Eisenia fetida) was studied for two artificially contaminated soils (S1 and S2). The uptake kinetics of pentachlorophenol (PCP) in earthworms increased quickly within the initial 10 days. This was followed by a nearly steady state for the next 20 days that fit with the equilibrium partitioning model. The correlation coefficients were 0.812 and 0.715 for S1 and S2, respectively. The average biota-to-soil accumulation factor of PCP in S1 was 0.51 +/- 0.09, whereas that of S2 was 0.79 +/- 0.12. There was a significant correlation between log Csoil and log Cworm, demonstrating the validity of the equilibrium partitioning model. The bioavailability of PCP was assessed by chemical extraction methods. The results demonstrated a close correlation between extractable amounts of PCP freshly added in soils and those in earthworms. With increasing residence time of PCP in soil, there was a progressively smaller amount of PCP assimilated by the earthworms. In contrast, the amount extracted by Soxhlet extraction did not show a similar decline. However, the extractable amount of PCP by methanol and methanol-water (1:1) significantly decreased over 440 days. Compared with the methanol-water (1:1) extraction method, the methanol extraction method was preferred to the prediction of the bioavailability of PCP in aged soils.

Bioconcentration factor of relatively low concentrations of chlorophenols in Japanese medaka.

Bioconcentration factors (BCF) for pentachlorophenol (PCP) and 2,4-dichlorophenol (2,4-DCP) in Japanese medaka (Oryzias latipes) were determined at five different concentrations of the chemicals, between 0.1 and 10 microg/l (PCP), 0.3 and 30 microg/l (2,4-DCP), in the ambient water. Medaka were exposed to each chemicals in a continuous-flow system during the embryonic development period and 60 days after hatching from eggs collected in the laboratory. Both the exposure time and the aqueous concentrations are much more realistic and closer to natural aquatic environments than those used in conventional BCF studies. The BCF values of PCP were from (4.9+/-2.8)x10(3) at the aqueous concentration of 0.074+/-0.028 microg/l to (2.1+/-1.4)x10(3) at 9.70+/-0.56 microg/l. The BCF value of 2,4-DCP were from (3.4+/-3.0)x10(2) at 0.235+/-0.060 microg/l to 92+/-27 at 27.3+/-1.6 microg/l. Generally, BCF values increased as the aqueous concentrations of PCP or 2,4-DCP decreased. This finding suggests that a relatively low and realistic aqueous concentration of these compounds is necessary to more accurately determine their BCF values in natural aquatic environments. Conventional BCF experiments at higher aqueous concentrations may underestimate the BCF values.

Residue of pentachlorophenol in freshwater sediments and human breast milk collected from the Pearl River Delta, China.

Pentachlorophenol (PCP) was investigated in freshwater sediments and human breast milk collected from the Pearl River Delta, China. The average level of PCP in river sediments was 7.93 ng/g based on dry weight, ranging from 1.44 to 34.4 ng/g. As to the sediments from fishponds, samples from Zhongshan had the highest PCP levels (37.5 ng/g on average), followed by Dongguan (21.1 ng/g on average) and the least in Shenzhen (3.69 ng/g on average) and Shunde (2.20 ng/g on average). Negative relationship was obtained between the PCP level and pH value in sediment (r=0.553, n=13, p<0.05), while positive relationship was found between the PCP levels and the total organic matter (TOM) levels in sediment (r=0.700, n=17, p<0.01). These results indicated that pH and TOM played important roles during the process of PCP settling down to the sediment. PCP was also detected in human breast milk with an average of 2.15 ng/g. The PCP concentration increased with the age increasing of donors. The estimated PCP body burden for mother, daily and yearly PCP intake of infants ranged from 0.16 to 4.17 mg/person, from 0.26 to 10.23 mug/infant.day and from 0.09 to 3.73 mg/infant.year, respectively.

Insight into pollutant bioavailability and toxicity using Raman confocal microscopy.

Raman confocal microscopy was used to discriminate between cultures of Burkholderia xenovorans LB400 exposed to four different common environmental pollutants: phenanthrene, dodecane, 3-chlorobiphenyl and pentachlorophenol. Evidence is presented for the application of Raman spectroscopy as a bioassay for pollutant bioavailability and toxicity.

Pentachlorophenol (PCP) bioaccumulation and effect on heat production on salmon eggs at different stages of development.

In this study, pentachlorophenol (PCP) bioaccumulation and its effect on heat dissipation was studied in eggs of the lake salmon (Salmo salar m. sebago). In bioaccumulation studies, the eggs were exposed to low concentrations (0.051-0.056 micromol/l, 13.583-14.915) of waterborne [14C]-labeled PCP at two developmental stages: (1) 3 weeks after fertilization, and (2) just before hatching. The effect of PCP on egg heat dissipation was measured by a microcalorimeter after exposing the eggs to gradual concentrations (0-0.992 micromol/l) of PCP for 48 h. After both the bioaccumulation and heat dissipation experiments, the eggs were dissected and the concentrations of PCP in tissue were determined separately for eggshell, yolk and embryo. The bioaccumulation studies showed that PCP accumulates more in the eggs at the late developmental stage. Bioconcentration factors (BCF) for different tissues were 3-42 times higher for the eggs at the late developmental stage compared with the eggs that were incubated only for 3 weeks. In early developmental stage, the eggshell adsorbs a large portion of the chemical. In late developmental stage, the actual embryo accumulated both proportionately and totally more than other dissected tissues in the beginning of the exposure, but eventually the yolk accumulated highest total amount of the chemical. A probable reason for the higher PCP body burden in the late developmental stage is that the respiration rate and metabolic activity of the embryo increases as it grows. The salmon eggs responded to an exposure to PCP with an elevated rate of heat dissipation. The threshold concentration above which the embryo heat dissipation was amplified was 29.64 micromol/kg embryo wet weight (ww) or 0.28 micromol/l. The highest embryo heat production was measured at the exposure concentration of 0.992 micromol/l. At higher exposure concentrations the heat dissipation decreased. The basic findings of the study are that PCP accumulates in growing embryonic tissue and is able to change the physiology of developing embryo.

Pentachlorophenol poisoning.

Despite being banned in many countries and having its use severely restricted in others, pentachlorophenol (PCP) remains an important pesticide from a toxicological perspective. It is a stable and persistent compound. In humans it is readily absorbed by ingestion and inhalation but is less well absorbed dermally. Its distribution is limited, its metabolism extensive and it is eliminated only slowly. Assessment of the toxicity of PCP is confounded by the presence of contaminants known to cause effects identical to those attributed to PCP. However, severe exposure by any route may result in an acute and occasionally fatal illness that bears all the hallmarks of being mediated by uncoupling of oxidative phosphorylation. Tachycardia, tachypnoea, sweating, altered consciousness, hyperthermia, convulsions and early onset of marked rigor (if death occurs) are the most notable features. Pulmonary oedema, intravascular haemolysis, pancreatitis, jaundice and acute renal failure have been reported. There is no antidote and no adequate data to support the use of repeat-dose oral cholestyramine, forced diuresis or urine alkalinisation as effective methods of enhancing PCP elimination in poisoned humans. Supportive care and vigorous management of hyperthermia should produce a satisfactory outcome. Chronic occupational exposure to PCP may produce a syndrome similar to acute systemic poisoning, together with conjunctivitis and irritation of the upper respiratory and oral mucosae. Long-term exposure has also been reported to result in chronic fatigue or neuropsychiatric features in combination with skin infections (including chloracne), chronic respiratory symptoms, neuralgic pains in the legs, and impaired fertility and hypothyroidism secondary to endocrine disruption. PCP is a weak mutagen but the available data for humans are insufficient to classify it more strongly than as a probable carcinogen.