Octanol-water partition toxicity

Usually aquatic toxicity of chemicals with general narcosis mechanism of action is described by the octanol/water partition coefficient [73]. However, log is a composite descriptor which has components of molecular volume and H-bond acceptor terms. Raevsky and Dearden [74] therefore used molecular polarizabihty (as a volume-related term) and the H-bond acceptor factor instead of log to model aquatic toxicity (log LC50) to the guppy for 90 chemicals with general narcosis mechanisms. This excellent correlation has statistical criteria better than that obtained for the same data using log Pofy, ... 

Kamlet, M. J., Doherty, R. M., Carr, P. W., Mackay, D., Abraham, M. H., Taft, R. W. (1988) Linear solvation energy relationships. 44. Parameter estimation rules that allow accurate prediction of octanol/water partition coefficients and other solubility and toxicity properties of polychlorinated biphenyls and polycyclic aromatic hydrocarbons. Environ. Sci. Technol. 22, 503-509. 

Wasik, S.P., Tewari, Y.B., Miller, M.M., Martire, D.E. (1981) Octanol/Water Partition Coefficients and Aqueous Solubilities of Organic Compounds. NBSIR 81-2406, report prepared for Office of Toxic Substances, Environmental Protection Agency, Washington, DC. 

The SPs have been shown to be highly toxic to fish and aquatic invertebrates, particularly arthropods, with toxicities as low as the nanogram per liter range in laboratory studies (see Sect. 3). However, due to their high lipophilicity and octanol water partition coefficient (Koc) values, they are rapidly adsorbed to suspended and bottom sediments [1], effectively limiting the exposure of water column organisms. 

The octanol-water partition coefficient, Kow, is the most widely used descriptor of hydrophobicity in quantitative structure activity relationships (QSAR), which are used to describe sorption to organic matter, soil, and sediments [15], bioaccumulation [104], and toxicity [105 107J. Octanol is an amphiphilic bulk solvent with a molar volume of 0.12 dm3 mol when saturated with water. In the octanol-water system, octanol contains 2.3 mol dm 3 of water (one molecule of water per four molecules of octanol) and water is saturated with 4.5 x 10-3 mol dm 3 octanol. Octanol is more suitable than any other solvent system (for) mimicking biological membranes and organic matter properties, because it contains an aliphatic alkyl chain for pure van der Waals interactions plus the alcohol group, which can act as a hydrogen donor and acceptor. 

Dithiocarbamates and xanthates form particularly stable, neutral complexes with Cu(II), Cd(II) (and also Ni, Hg, Pb), which are membrane permeable and increase the apparent bioaccumulation of these metals [13]. In the series of sulfoxine, oxine, and chloroxine, the hydrophobicity of the neutral and the charged form, as well as of the Cu complex, increases. While the sulfoxine is not hydrophobic and does not modulate copper toxicity [220], the Cu-oxine complex is hydrophobic with an octanol-water partition constant, log Kok, of 1.7 [221] or 2.6 [222]. Chloroxine can be assumed to be even more hydrophobic, but so far its influence on uptake and toxicity has not been investigated. Uptake of Cu2+ into unilamellar liposomes was increased in the presence of 8-hydroxy-chinoline, and decreased again after adding HA [223],... 

Park. Y.-S. and Park, S.-J. Determination and prediction of octanol/water partition coefficients and air-water partition coefficients for environmental toxic chemicals. Kongop Hwahak, ll(7) 773-779, 2000. 

Figure 1. Relationship between the mosquito larvicidal toxicity (log LC50) of the thiocarbamate derivatives of carbofuran, propoxur and m-isopropylphenyl methylcarbamate (MIP) and logarithm of the octanol/water partition coefficient (log P).

The first phase of ToxCast profiled a 309-chemical library consisting mostly of pesticidal actives as well as several other compounds of high interest. The acceptance criteria for chemical selection for inclusion in Phase I were as follows (a) availability of in vivo data from bioassays on chronic/cancer, multigenerational reproductive, and/or prenatal developmental toxicity (95% Phase I chemicals met this criteria) (b) solubility in DMSO (the vehicle for HTS assays) with a log of the octanol/water partition coefficient (logP) between -1 and +6 (97.5% met this criteria) (c) molecular weight in the range of 250-1,000 (90% met this criteria) and (d) commercially available at a purity >90% (98% met this criteria) (16). Current information about the Phase I (and Phase II) chemical library can be found at the NCCT website address http //www. epa.gov/ncct/toxcast/chemicals.html. 

The partition coefficient Kq of an organic compound in the 1-octanol/water system is used to assess the bioaccumulation potential and the distribution pattern of drugs and pollutants. The partition coefficient of imidazole and ILs strongly depends on the hydrogen bond formed by these molecules and is less than one due to the high solubility in water. The low value of the 1-octanol/water partition coefficient is required for new substances, solvents, insecticides to avoid bioaccumulation. Kqw is an extremely important quantity because it is the basis of correlations to calculate bioaccumulation, toxicity, and sorption to soils and sediments. Computing the activity of a chemical in human, fish, or animal lipid, which is where pollutants that are hydrophobic will appear, is a difficult task. Thus, it is simpler to measure the 1-octanol/water partition coefficient. This parameter is used as the primary parameter characterizing hydrophobisity. 

Table 13.1 Example of two chemicals with similar predicted properties [octanol-water partition coefficient (logPQ/w) and lowest unoccupied molecular orbital (LUMO) energy] and similar acute aquatic toxicity (LC50) values to the fathead minnow [6].

According to McFarland [26], aquatic toxicity can be considered the result of penetration of toxicant into biophases and its interaction with one or more biochemical sites of action. Thus, he and others have postulated that toxicity is a function of the ability of the chemical to enter biophases and its ability to react with cellular compounds. Bioavailability of chemicals in fish has been shown to be related to chemical flux across fish gills [27], an identified exposure pathway. Flux across fish gills is in turn related to the ability of the chemical to partition between organic and aqueous phases, which is usually correlated with the its octanol-water partition coefficient (logPo/w) [28]. It is therefore not surprising that the acute toxicity of narcotic chemicals has been shown to be related to their propensity to accumulate in the membranes, and hence their logPe/w [29]. 

Octanol-water partition coefficient (logP0/w) lipophilicity (logPo/w) usually correlates well with acute aquatic toxicity. For nonionic organic chemicals that are toxic through narcosis, acute and chronic toxicity increases exponentially with increases in logPo/w up to a value of about 5-7. For those with logPo/w >5, bioavailability decreases along with toxicity, but bioaccumulation also increases. Minimal toxicity is likely for chemicals with log/ ( w <2 [32]... 

When is the n-octanol-water partition constant an acceptable parameter for the quantification of nonspecific membrane toxicity In what situations does it fail ... 

The parameter is measured using low-solute concentrations less than 0.01 mol/L, where /< , is not affected by solute concentration. Values of Kow are usually measured at room temperature (20 or 25°C). Numerous studies have shown that it is useful to correlate K,r with biological, biochemical, or toxic properties. In recent years, the octanol/water partition coefficient has become a key parameter in studies of the environmental fate of organics,... 

PAHs have been found all over the globe in all compartments of the environment. They are ubiquitous because the are persistent. Recalcitrance in PAHs may stem, in part, from the delocalized electrons in the planar pi orbitals of the aromatic structure. Their relatively high octanol-water partition coefficients, Kows, make them rather lipophilic. The lipophilicity of PAHs forces them from the dissolved phase to particles and also into lipid rich organisms, but they can be metabolized in higher organisms. However, these metabolites are often more toxic than their parent PAHs. When combined with other stressors, particularly ultraviolet radiation, PAHs can exert enhanced toxicity. 

Kamlet, M.J., R.M. Doherty, P.W. Carr, D. Mackay, M.H. Abraham, and R.W. Taft. 1988. Linear Solvation Energy Relationships. 44. Parameter Estimation Rules which Allow Accurate Prediction of Octanol/Water Partition Coefficients and other Solubility and Toxicity Properties of Polychlorinated Biphenyls and Polycyclic Aromatic Hydrocarbons. Environ. Sci. Technol. 22 503-509. 

Morall, S.W., R.R. Herzog, P. Kloepper-Sams, and M.J. Rosen. 1996. Octanol-water partitioning of surfactants and its relevance to toxicity and environmental behavior. In Proceedings of the 4th World Surfactant Congress, Barcelona, Spain, 3-6 June 1996, Vol. C, pp. 220. 

Chiou, C.T., Schmedding, D.W. (1981) Measurement and interrelation of octanol-water partition coefficient and water solubility of organic chemicals. In Test Protocols for Environmental Fate and Movement of Toxicants. J. Assoc. Anal. Chem. 28 12, Arlington, Virginia. 

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