Theo L. Sinnige

The joint acute toxicity to Daphnia magna of industrial organic chemicals at low concentrations

The joint acute toxicity of a mixture of 50 nonreactive organic chemicals towards Daphnia magna was investigated. It was found that the observed toxicity is accurately predicted by the model of concentration addition, even at very low concentrations of the individual compounds. The implications these findings may have on the prediction of the toxicity of mixtures of chemicals occurring in nature are briefly discussed.

Quantitative structure-activity relationships for the toxicity and bioconcentration factor of nitrobenzene derivatives towards the guppy (Poecilia reticulata)

The acute toxicity and bioconcentration factor of a series of nitrobenzene derivatives was determined for the guppy. Toxicity is found to be determined by both hydrophobicity (expressed by the octanol/water partition coefficient) and rate of reduction of the nitro group (expressed by either electrochemical halfwave reduction potential or Hammett σ values). The acute toxicity of mononitro compounds can be adequately described by hydrophobicity, and their bioconcentration factor is found to be approximately equal to the octanol/water partition coefficient. The dinitro compounds that are likely to be most easily reduced are found to have substantially lower bioconcentration factors than expected, accompanied by a marked increase in toxicity. Electrochemical reduction potentials are found to be a better descriptor of toxicity than Hammett σ− values. Nitroanilines do not fit the QSARs established for nitrobenzene derivatives. These compounds are probably to be considered aniline derivatives.

Adsorption of polar, nonpolar, and substituted aromatics to colloidal graphene oxide nanoparticles

We conducted batch adsorption experiments to understand the adsorptive properties of colloidal graphene oxide nanoparticles (GONPs) for a range of environmentally relevant aromatics and substituted aromatics, including model nonpolar compounds (pyrene, phenanthrene, naphthalene, and 1,3-dichlorobenzene) and model polar compounds (1-naphthol, 1-naphthylamine, 2,4-dichlorophenol, and 2,4-dinitrotoluene). GONPs exhibited strong adsorption affinities for all the test compounds, with distribution coefficients on the order of 10(3)-10(6) L/kg. Adsorption to GONPs is much more linear than to carbon nanotubes (CNTs) and C60, likely because GO nanoflakes are essentially individually dispersed (rendering adsorption sites of similar adsorption energy) whereas CNT/C60 are prone to bundling/aggregation. For a given compound GONPs and CNTs often exhibit different adsorption affinities, which is attributable to the differences in both the morphology and surface chemistry between the two nanomaterials. Particularly, the high surface O-content of GONPs enables strong H-bonding and Lewis acid-base interactions with hydroxyl- and amino-substituted aromatics.

Predicting Fish Acute Toxicity Using a Fish Gill Cell Line-Based Toxicity Assay

The OECD test guideline 203 for determination of fish acute toxicity requires substantial numbers of fish and uses death as an apical end point. One potential alternative are fish cell lines; however, several studies indicated that these appear up to several orders of magnitude less sensitive than fish. We developed a fish gill cell line-based (RTgill-W1) assay, using several measures to improve sensitivity. The optimized assay was applied to determine the toxicity of 35 organic chemicals, having a wide range of toxicity to fish, mode of action and physicochemical properties. We found a very good agreement between in vivo and in vitro effective concentrations. For up to 73% of the tested compounds, the difference between the two approaches was less than 5-fold, covering baseline toxicants but as well compounds with presumed specific modes of action, including reactivity, inhibition of acetylcholine esterase or uncoupling of oxidative phosphorylation. Accounting for measured chemical concentrations eliminated two outliers, the hydrophobic 4-decylaniline and the volatile 2,3-dimethyl-1,3-butadiene, with an outlier being operationally defined as a substance showing a more than 10-fold difference between in vivo/in vitro effect concentrations. Few outliers remained. The most striking were allyl alcohol (2700-fold), which likely needs to be metabolically activated, and permethrin (190-fold) and lindane (63-fold), compounds acting, respectively, on sodium and chloride channels in the brain of fish. We discuss further developments of this assay and suggest its use beyond predicting acute toxicity to fish, for example, as part of adverse outcome pathways to replace, reduce, or refine chronic fish tests.

Experimental octanol/water partition coefficients of chlorinated paraffins

Abstract Octanol/water partition coefficients (K OW ) of chlorinated paraffins (CPs) from a commercial mixture (‘Cereclor 60L’) were determined using a “slow-stirring” method. Log K OW values for the different congener groups ranged from 5.85 to 7.14. Equilibrium was reached within a few days, and K OW values were the same at two CP-concentrations. A clear relationship is found between the total number of chlorine and carbon atoms and log K OW for the CP-congener groups and a series of smaller chlorinated alkanes from the literature.

A quantitative structure-activity relationship for the acute toxicity of some epoxy compounds to the guppy

The 14 day LC50 values of various epoxy compounds to the guppy (Poecilia reticulata) were determined, and investigated through the construction of a quantitative structure-activity relationship (QSAR). Both hydrophobicity and alkylating potency of the compounds are found to be necessary parameters for the satisfactory description of the LC50 data. The findings of the present study are compared to results published for halogenated alkylating agents (Hermens, 1985), some of which are considerably more toxic than predicted on the basis of the QSAR established for the epoxy compounds.

The use of biochemical parameters in comparative toxicological studies with the cormorant (Phalacrocoraxcarbo) in the Netherlands

Abstract 38 Cormorant eggs were collected in two dutch colonies from which 18 were hatched after laboratory incubation. Levels in yolksac of total mono ortho PCBs and PCDD(F)s ranged between 10 to 250 mg/kg and 1 to 8 μg/kg lipid weight. At these levels concentration dependent alterations in EROD activity, free T4 plasma content, head length, size of the yolksac and relative liver weight were observed.

Cytochrome P450 1A induction in the common carp (Cyprinus carpio) following exposure to contaminated sediments with halogenated polyaromatics

Abstract Exposure of common carp to PCDD/F and PCB-containing sediments from Ketelmeer caused obvious inductions of 7-ethoxyresorufin O-deethylation (EROD) activity and cytochrome P450 1A protein content, which was significantly correlated with the amount of TCDD-toxic equivalents (TEQs) in the liver. In addition, in the carp exposed to Ketelmeer sediment, histopathological evaluation revealed inflammations in the liver, and the presence of fibrosis and melano-macrophage centers in the spleen. Exposure to a reference sediment from Oostvaardersplassen caused only a slight induction in EROD activity and P450 1A content, in spite of a comparable contamination of polycyclic aromatic hydrocarbons (PAHs) of all three sediments. Therefore the role of non-halogenated polyaromatics appears to be less significant as far as P450 1A induction is concerned.

Inhibition of ethoxyresorufin-O-deethylase (EROD) activity in mixtures of 2,3,7,8-tetrachlorodibenzo-p-dioxin and polychlorinated biphenyls

Induction of ethoxyresorufin-O-deethylase (EROD) activity and porphyrin accumulation shows different structure-activity relationships for different polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Interactions between the two responses can strongly influence the induction and activity of EROD. The results support the conclusion that there are nonadditive interactions between nondioxin-like PCBs and dioxin-like compounds. The interaction between EROD activity and the porphyrin biosynthesis makes the prerequisite of additivity in the toxic equivalency factor concept for environmental mixtures highly spurious. Inhibition of EROD activity caused by non-dioxin like compounds could have a significant impact on the value of EROD activity as a biomarker in the present methods of risk assessment for these compounds.

Inhibition of ethoxyresorufin-O-deethylase (EROD) activity in mixtures of 2,3,7,8-tetrachlorodibenzo-p-dioxin and polychlorinated biphenyls: EROD activity as biomarker in TCDD and PCB risk assessment

Induction of ethoxyresorufin-O-deethylase (EROD) activity and porphyrin accumulation shows different structure-activity relationships for different polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD). Interactions between the two responses can strongly influence the induction and activity of EROD. The results support the conclusion that there are non-additive interactions between nondioxin-like PCBs and dioxin-like compounds. The interaction between EROD activity and the porphyrin biosynthesis makes the prerequisite of additivity in the toxic equivalency factor concept for environmental mixtures highly spurious. Inhibition of EROD activity caused by nondioxin-like compounds could have a significant impact on the value of EROD activity as a biomarker in the present methods of risk assessment for these compounds.