PubMed Health⌕ Search

PubMed · 16903294

Bioavailability models for predicting copper toxicity to freshwater green microalgae as a function of water chemistry.

Abstract

We investigated whether an earlier-developed bioavailability model for predicting copper toxicity to growth rate of the freshwater alga Pseudokirchneriella subcapitata could be extrapolated to other species and toxicological effects (endpoints). Hardness and dissolved organic carbon did not significantly affect the toxicity of the free Cu2+ ion to P. subcapitata (earlier study) and Chlorella vulgaris(this study), but a higher pH resulted in an increased toxicity for both species. Regression analysis showed significant linear relationships between ECxpCu (= "effect concentration" that produces x% adverse effect, expressed as pCu = -log of the Cu2+ activity) and pH. By linking these regression models with a geochemical metal speciation model, dissolved copper concentrations that elicit a given adverse effect (EC(X)dissolved) can be predicted. Within the pH range investigated (5.5-8.7), slopes of the linear EC(X)pCu vs pH regression models varied between 1.301 and 1.472 depending on the species and the effect level (10% or 50%) considered. In a statistical sense these slopes were all significantly different from one another (p < 0.05), suggesting that this empirical regression model does not yet capture the full complexity of toxicological copper bioavailability to algae. However, we demonstrated that regression models with an "average" slope of 1.354 had predictive power very similar to those of regression models with species and effect-specific slopes. Additionally, the "average" regression model was further successfully validated for other species (Chlamydomonas reinhardtii and Scenedesmus quadricauda) and for different toxicological effects/endpoints (growth rate, biomass yield, and phosphorus uptake rate). For all these toxicity datasets effect concentrations of copper could be predicted with this "average" model by errors of less than a factor of 2 in 94-100% of the cases. The success of this "average" model suggests the possibility that the pH-based linear regression model may form a sound conceptual basis for modeling the toxicological bioavailability of copper to green algae in regulatory assessments, although a full mechanistic understanding is lacking and should be the focus of future studies.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Karel A C De Schamphelaere, Colin R Janssen. 2006-07-15. Bioavailability models for predicting copper toxicity to freshwater green microalgae as a function of water chemistry.. https://doi.org/10.1021/es0525051

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Curvature-adjusted optimal design of sampling times for the inference of pharmacokinetic compartment models.

In pharmacokinetics, compartment models are often used to describe the time course of blood concentration after the administration of a drug. In this article, we propose an optimal design criterion for precise estimation of parameters included in the compartment model and illustrate the non-sequential design of sampling times of blood drug concentration data in individual pharmacokinetics. The proposed optimal design criterion minimizes the determinant of the mean-squared error matrix of the parameter estimator that is quadratically approximated by the curvature array. Therefore, the proposed criterion considers the intrinsic and parameter-effects nonlinearity underlying the compartment model, and so is applicable in a pharmacokinetic experiment where the sample size of the blood drug concentration data is quite small.

Biological Availability↗

Biowaiver monographs for immediate release solid oral dosage forms: isoniazid.

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing isoniazid as the only active pharmaceutical ingredient (API) are reviewed. Isoniazid's solubility and permeability characteristics according to the Biopharmaceutics Classification System (BCS), as well as its therapeutic use and therapeutic index, its pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA) problems were taken into consideration. Isoniazid is "highly soluble" but data on its oral absorption and permeability are inconclusive, suggesting this API to be on the borderline of BCS Class I and III. For a number of excipients, an interaction with the permeability is extreme unlikely, but lactose and other deoxidizing saccharides can form condensation products with isoniazid, which may be less permeable than the free API. A biowaiver is recommended for IR solid oral drug products containing isoniazid as the sole API, provided that the test product meets the WHO requirements for "very rapidly dissolving" and contains only the excipients commonly used in isoniazid products, as listed in this article. Lactose and/or other deoxidizing saccharides containing formulations should be subjected to an in vivo BE study.

Biological Availability↗

Experimental approaches for studying uptake and action of herbal medicines.

In order to gain wider credibility, herbal medicines must go through the rigorous scientific scrutiny to which synthetic drugs are subjected, and this includes investigating their absorption, bioavailability and metabolism. This review describes approaches for determining how active compounds in herbal formulations enter the systemic circulation. To assess how bioactive molecules enter the target organs and cells, specific cell lines and organ culture models can be used, followed by in vitro models to show how they may regulate digestion, energy balance and metabolism. This could lead to a better understanding of how herbal medicines affect digestion and absorption; fundamental questions which should be answered in addition to their mechanism of action.

Biological Availability↗