Production of male neonates in Daphnia magna (Cladocera, Crustacea) exposed to juvenile hormones and their analogs

We exposed the water flea Daphnia magna (Cladocera, Crustacea) to either juvenile hormone I (JH I), juvenile hormone II (JH II), or the juvenile hormone-mimicking insecticides kinoprene, hydroprene, epofenonane, or fenoxycarb. By 21-day reproduction tests, we investigated the effects on the number of neonates born per female and the offspring sex ratio. All six chemicals induced D. magna to produce male neonates; the male sex ratio of the offspring increased as the chemical concentration increased. EC50 values for production of male neonates were estimated as 400 (JH I), 410 (JH II), 190 (kinoprene), 2.9 (hydroprene), 64 (epofenonane), and 0.92 (fenoxycarb) microg/l. The number of neonates produced was reduced with all chemicals at the concentrations investigated. At the EC50 for male production, five of the six chemicals reduced the reproductive rate to less than 50%; the exception was epofenonane, which caused only a slight reduction in reproductive rate. These results were similar to those obtained for five juvenoids studied previously, one of which was studied here again. There are now 10 chemical substances--all juvenile hormones or their analogs-that are known to induce D. magna to produce male neonates. This suggests that juvenile hormone is involved in initiating male production followed by sexual reproduction in D. magna, and probably in most cladocerans that exhibit cyclic parthenogenesis.     

Ecotoxicological Characterisation and Classification of Existing Chemicals

GOAL, SCOPE AND BACKGROUND: In 1998, the International Council of Chemical Associations (ICCA) launched a global initiative to investigate more than 1,000 HPV chemicals (High Production Volume, > or = 1,000 t/a) within the refocused OECD HPV Chemicals Programme. Up to the OECD SIDS Initial Assessment Meeting in April 2004 (SIAM 18) 147 ICCA dossiers (ca. 230 CAS-No) have been assessed based on a harmonised data set. The environmental profile and an ecotoxicological characterisation of these chemicals are presented here. Data for acute aquatic toxicity were correlated among each other, as well as data for fish (LC50, LD50) and rodents (LD50). The data for acute aquatic toxicity are compared with other existing chemicals. METHODS: Data of the ICCA HPV chemicals from the OECD SIAM 11-18 are presented for: log Kow (as an indicator for bioaccumulation potential), biodegradation, acute aquatic toxicity and availability of long-term toxicity data. Correlation analysis was performed with log transformed data and a linear regression model was fitted to the data, if a significant correlation was found. Acute toxicity for fish and acute oral toxicity for rodents were correlated on a molar basis. Acute aquatic toxicity of the chemicals is compared with data from BUA reports 1-234 and a random EINECS sample (Knacker et al. 1995). RESULTS AND DISCUSSION: According to the dossier information, 71 of the 147 ICCA chemicals are not 'readily biodegradable', 21 have a log Kow > or = 3, and 44 are 'toxic' (LC/EC50 < or = 10 mg/L) or 'very toxic' (LC/EC50 < or = 1 mg/L) to aquatic organisms. For 77, only the base set (acute fish, Daphnia and algae) is available, for the rest at least one long-term test (fish or Daphnia) is available and three tests for a mere 14 others. Based on the data presented, the SIAM gives recommendations for Environment and Human Health. 22 chemicals have been identified as a 'candidate for further work' for Environment and 16 for Human Health. The highest correlation coefficient was obtained correlating fish and Daphnia (r2 = 0.79). LC50 (fish) is significantly correlated with LD50 (rodent), but data are widely scattered. The correlation is not improved after transforming LC50 (fish) to LD50 (fish), using BCF QSAR. Based on acute aquatic toxicity, 25.1% of the chemicals from the BUA reports 1-234 are classified as 'very toxic' (LC/EC50 < or = 1 mg/L). This proportion is 2.5-fold higher than the ICCA HPV chemicals and 1.4-fold higher than the random EINECS sample. CONCLUSIONS: Correlation coefficients for aquatic toxicity data are rather uniform (0.57-0.79) compared with literature data, but also the best correlation was observed between fish and Daphnia. Because the scatter around the regression lines is still considerable, simple predictions of ecotoxicity between species are not possible. Correlation of LC50 (fish) and LD50 (rodent) indicates that toxicity is different. Surprisingly, the correlation of fish and rodent toxicity is not improved by transforming LC50 values to internal LD50s. The selection of ICCA chemicals by market significance (production volume) leads to a classification of toxicity, which is more comparable to a random sample of EINECS chemicals than to German BUA chemicals. The latter were chosen for concern (for Environment or Human Health). RECOMMENDATIONS AND OUTLOOK: Of 147 dossiers assessed between SIAM 11-18, ca. 75% were sponsored by the three following countries: Germany (42), USA (37) and Japan (33). The current output is about 50 dossiers per year (70-100 CAS-No), but a trend for an increase of output is noticeable. Industry, national authorities, and OECD work on a further development to speed up the output. The number of chemicals with 'low priority for further work' and the work recommended for the 'candidates' (mainly exposure assessment) indicate that the data presented were adequate for an initial hazard assessment according to OECD requirements. From the ICCA HPV list (n = 880, state of 1999) 44% of the chemicals have data available to cover all SIDS endpoints for Environment and only 33% for Human Health (Allanou et al. 1999). This indicates the importance of the Initiative to provide information on existing chemicals. The authors agree with the expectation "...that the scientific information provided by this global initiative will be considered as an internationally accepted and harmonised basis for further steps of chemicals management." (ICCA 2002 b).     

Derivation of soil values for the path ‘Soil-Soil Organisms’ for metals and selected organic compounds using species sensitivity distributions

BACKGROUND, AIMS AND SCOPE: According to the German Federal Soil Protection Act, the natural function of soil as a habitat for human beings, animals, plants and soil organisms is, among other things, to be protected by deriving soil values for important chemicals regarding their amounts in the environment, their persistence and/or their toxicity. This contribution presents the results of the mathematical derivation of such values for nine metals and ten organic substances from soil ecotoxicological effect values available in the literature for microbial processes, plants and soil invertebrates. MATERIAL AND METHODS: Ecotoxicological data were mostly extracted from published papers and reports and had to originate from valid studies that were performed according to internationally standardised guidelines (e.g. ISO) or were otherwise well documented, plausible and performed according to accepted laboratory practice. As test results, both structural (i.e., effects on mortality, growth or reproduction) and functional (i.e., effects on microbial activity or organic matter breakdown) parameters were included. The derivation of soil values was performed using the distribution based extrapolation model (DIBAEX) and EC(50)s (Effective Concentration) as input data. RESULTS: For 19 compounds, soil values could be calculated. In 18 of these 19 cases clear laboratory ecotoxicological effects (i.e., EC50 values) below the calculated soil value have been found in the literature. DISCUSSION: In those few cases where a comparison with field studies is possible, effects have been observed in the same order of magnitude as the calculated soil values. A comparison with other similar approaches confirmed the plausibility of the calculated values. CONCLUSIONS: The DIBAEX-method is a feasible and widely accepted method for deriving soil values from ecotoxicological input data. Data availability was already satisfactory for some substances, but other substances, especially organics, were only poorly covered. The soil values presented here were based on EC50 input data. However, depending on the protection level aimed at by using soil values in legislation, it might be appropriate to use other input data such as NOECs in the derivation process. RECOMMENDATIONS AND PERSPECTIVES: It is recommended to generate an appropriate number of data for further relevant substances by means of a test battery or multi-species approaches such as terrestrial model ecosystems. These tests should also consider the influence of the bioavailability of substances. A final recommendation for legally binding soil values demands a plausibility check of the mathematically derived values. This should include a comparison with natural background concentrations, soil values for other pathways and soil values used in legislation of other countries. Finally, expert judgement always has to be considered.     

Estrogenicity and acute toxicity of selected anilines using a recombinant yeast assay

Suspected estrogen modulators include industrial organic chemicals (i.e., xenoestrogens), and have been shown to consist of alkylphenols, bisphenols, biphenylols, and some hydroxy-substituted polycyclic aromatic hydrocarbons. The most prominent structural feature identified to be important for estrogenic activity is a polar group capable of donating hydrogen bonds (i.e., hydroxyl) on an aromatic system. The present study was undertaken to explore the estrogenic activity and acute toxicity of chemicals containing a weaker hydrogen bond donor group on aromatic systems, i.e., the amino substituent. There is a great deal of chemical similarity between aromatic amines (anilines) and aromatic alcohols (phenols). The chemicals chosen for the current study contained an amino-substituted benzene ring with hydrophobic constituents varying in size and shape. Thus, 37 substituted aromatic amines were assayed for estrogenic activity EC50 and acute toxicity LC50 using the Saccharomyces cerevisiae recombinant yeast assay. While the EC50 of 17-beta-estradiol occurs at the 10(-10) range, the aniline with the greatest activity had an EC50 of 10(-6) M. Thus, anilines, in general, are capable only of very weak estrogenic activity in this assay. A comparison of estrogenic potency between the present group of anilines and a set of previously tested analogous phenols indicated that anilines are consistently less estrogenic than phenols. A comparison of hazard indices (EC50/LC50) of these chemicals revealed that, for the vast majority of anilines, the EC50 and LC50 were in the same order of magnitude. More specifically, estrogenic activity of para-substituted alkylanilines increases with alkyl group size up to 5 carbons in length, after which the acute toxicity of the larger alkyl-substituents precluded the ability of the compound to induce the estrogenic response.     

Phytotoxicity of low-weight carboxylic acids

Presence of low-weight carboxylic acids (LWCAs) can be the reason for phytotoxicity of green manures, treated bio-waste or digestates from biogas production applied to soils. As the phytotoxic concentrations of LWCA are poorly known, this work presents data on six acids (C(1)C(6): formic, acetic, propionic, butyric, valeric, and caproic). Phytotoxicity was measured in acute (72 or 120 h) and subchronic (21 d) assays for seed germination, seedling elongation, and plant growth for garden cress Lepidium sativum and ryegrass Lolium multiflorum. The dose-response relationship was modeled using Weibull model. Results showed a trend that toxicity of LWCA increases with the length of the carbon chain, formic acid (C(1)) being the least and caproic acid (C(6)) the most toxic. EC50 values in the acute seed germination of cress ranged between 1.9 and 4.2mM and for ryegrass between 1.8 and 6.4mM. In subchronic assays EC50 values for germination were in a range from 11 to 46mMkg(-1)dm for cress, and from 18 to 127 mM kg(-1) dm for ryegrass. EC50 values for early seedling growth of cress based on acute assays ranged from 0.7 to 2.3mM and that of ryegrass from 1.2 to 1.8mM. Range of EC50 values for shoot biomass of cress was between 8 and 40 mM kg(-1) dm and of ryegrass between 12 and 93 mM kg(-1) dm.     

Multi-generational effects of four selected environmental oestrogens on Daphnia magna

The objective of this study was to determine whether vertebrate-type oestrogens have ecotoxicological effects on a crustacean species. The effects of 17beta-oestradiol (E2), diethylstilbestrol (DES), bisphenol A (BPA) and 4-nonylphenol (4-NP) on the freshwater invertebrate Daphnia magna were assessed over first and second generations. The acute EC(50) 48 h, based on immobilisation, for E2, DES, BPA and 4-NP were 2.87 mg/l, 1.55 mg/l, 7.75 mg/l and 0.13 mg/l, respectively. The impact of the test chemicals on moulting frequency was also assessed. The EC(50) 48 h, based on the inhibition of moult number for E2, DES and 4-NP were 2.04 mg/l, 1.87 mg/l and 0.14 mg/l, respectively. BPA was not observed to impact the moulting frequency of D. magna at concentrations tested. In a series of separate studies, the effects of the four selected test compounds on the survival, moulting frequency and reproduction of first and second generational D. magna were assessed over a period of 21 d. Exposure of D. magna to 4-NP decreased the number of offspring produced in both first and second generation testing. DES proved to have no significant (p0.05) inhibition of fecundity in first generation but when second generation daphnids were exposed to DES, a significant (p0.05) reduction in the number of offspring was recorded. When D. magna were exposed to E2 or BPA, no statistically significant (p0.05) inhibition in the number of moults or offspring produced was observed.     

The acute toxicity of agricultural surfactants to the tadpoles of four Australian and two exotic frogs

Nonionic surfactants are frequently incorporated into pesticide formulations, and are therefore a group of chemicals to which amphibians may be exposed in agricultural or urban landscapes. However, little is known about the effects of surfactant exposure in amphibians. Feeding stage tadpoles of Bufo marinus, Xenopus laevis and four species of Australian frogs (Crinia insignifera, Heleioporus eyrei, Limnodynastes dorsalis and Litoria moorei) were exposed to nonylphenol ethoxylate (NPE) and alcohol alkoxylate in static-renewal acute toxicity tests. All species exhibited nonspecific narcosis following exposure to both these surfactants. The 48-h EC50 values for NPE ranged between 1.1 mg/l (mild narcosis) and 12.1 mg/l (full narcosis). The 48-h EC50 values for alcohol alkoxylate ranged between 5.3 mg/l (mild narcosis) and 25.4 mg/l (full narcosis). Replicate acute toxicity tests with B. narinus exposed to NPE at 30 degrees C over 96 h indicated that the narcotic effects were not particularly time dependant. The mean 24, 48, 72, and 96-h EC50 (mild narcosis) values were 3.6, 3.7, 3.5 and 3.5 mg/l, respectively. The mean 24, 48, 72 and 96-h EC50 (full narcosis) were 4.0, 4.1, 4.2 and 4.0, respectively. Acute toxicity tests with B. marinus exposed to NPE at 30 degrees C under conditions of low dissolved oxygen (0.8-2.3 mg/l) produced a two to threefold increase in toxicity.     

Environmental impact assessment (EIA): Equilibrium fugacity calculations and worst case approach

A mathematical model UNITRISK which can be used for screening purposes and risk ranking was set up to calculate relative risk values of single chemicals and mixtures of chemicals towards single or mixtures of organisms via contamination of air, water, soil and food dose. The concentration values are calculated by applying the fugacity concept or a dose must be defined. The dose-response is assumed to be linear versus concentration and degradative processes are not considered which is the worst case. The assumption that equilibria between the environmental phases exist is simplifying the model and is also representing the worst case. A mean risk factor is calculated which is 1 if the endpoint values (LC₅₀, LD₅₀, ADI, etc.) are exceeded for the investigated organisms and man.     

Embryonic development assay with Daphnia magna: application to toxicity of aniline derivatives.

An assay system using Daphnia magna embryos was applied to investigate the adverse effects of aniline derivatives. The data were compared with our previous data for chlorophenols. This new assay provides useful information to evaluate the toxicity of chemicals and the differences in sensitivity between the life stages. The effects of 15 aniline derivatives on embryonic development of D. magna embryos were determined. At the start of exposure, 2-6-h old eggs (between stages 1 and 2, round in shape, diameter approx. 400 microm), were used. In control and solvent control groups, embryonic development from an egg to a free-swimming animal proceeded completely within 3 days with more than 90% hatchability. Median effective concentrations (EC50s) to reduce the numbers hatched were determined and gross morphological abnormalities of hatched animals recorded. Anilines induced no obvious morphological abnormalities and no developmental delay although premature deaths occurred. However, they affected the number of embryos hatching in a dose-dependent manner. In addition, this embryo assay was more sensitive to aniline derivatives (except for aniline) than acute juveniles immobilization assay. Ratios of 48-h EC50 (juvenile)/3-day EC50 (embryo) for eight anilines were greater than 5.0. Particularly, the ratios of 4-methyl-, 4-ethyl- and 3-methylaniline were 77, 23 and 11, respectively. EC50s for embryos and juveniles were poorly correlated (r = 0.41). This indicated that the sensitivities of the two life stages were different to the effects of anilines. EC50s were poorly correlated (r = -0.097) with the log Kow (1-octanol/water partition coefficient). These results were compared with previous results for phenols.     

Evaluation of a novel high throughput screening tool for relative emissions of industrial chemicals used in chemical products

Tens of thousands of chemicals are currently marketed worldwide, but only a small number of these compounds has been measured in effluents or the environment to date. The need for screening methodologies to select candidates for environmental monitoring is therefore significant. To meet this need, the Swedish Chemicals Agency developed the Exposure Index (EI), a model for ranking emissions to a number of environmental matrices based on chemical quantity used and use pattern. Here we evaluate the EI. Data on measured concentrations of organic chemicals in sewage treatment plants, one of the recipients considered in the EI model, were compiled from the literature, and the correlation between predicted emission levels and observed concentrations was assessed by linear regression analysis. The adequacy of the parameters employed in the EI was further explored by calibration of the model to measured concentrations. The EI was found to be of limited use for ranking contaminant levels in STPs; the r² values for the regressions between predicted and observed values ranged from 0.02 (p = 0.243) to 0.14 (p = 0.007) depending on the dataset. The calibrated version of the model produced only slightly better predictions although it was fitted to the experimental data. However, the model is a valuable first step in developing a high throughput screening tool for organic contaminants, and there is potential for improving the EI algorithm.     

Determination of detoxification to Daphnia magna of four pharmaceuticals and seven surfactants by activated sludge

Pharmaceuticals are bioactive compounds generally resistant to biodegradation, which can make them problematic when they are released into nature. The use pattern for pharmaceuticals means that they are discharged into water via sewage treatment plants. Also surfactants are discharged through sewage treatment plants, primarily due to their use in detergents and shampoos and other cleaners. In this study the acute toxicity to Daphnia magna of four pharmaceuticals (ciprofloxacin, ibuprofen, paracetamol and zinc pyrithione) and seven surfactants (C8 alkyl glucoside, C6 alkyl glucoside, sodium caprylimidiopropionate, tallow-trimethyl-ammonium chloride, potassium decylphosphate, propylheptanol ethoxylate and alkylmonoethanolamide ethoxylate) was determined. Abiotic (without activated sludge bacteria) and biotic (with activated sludge bacteria) detoxification was also determined. The 24-h EC50s ranged from 2 μg L(-1) for the most toxic substance (zinc pyrithione) to 2 g L(-1) for the least toxic compound (C6 alkyl glucoside). Detoxification rates determined as the ratio between initial EC50 and EC50 after 1 week in water with activated sludge bacteria ranged from 0.4 (paracetamol) to 13 (zinc pyrithione). For most of these chemicals detoxification rate decreased after 1 week, but for one (alkylmonoethanolamide ethoxylate) it increased from about 2 to 30 times after 2 weeks. Many of these chemicals were "detoxified" also abiotically at about the same rate as biotically. Further studies are needed to determine the degradation products that were precipitated (aggregated) for some of the tested chemicals. Altogether, this study has shown that there are large differences in toxicity among chemicals entering sewage treatment plants, but also that the detoxification of them can differ. Therefore, the detoxification should receive more attention in the hazard and risk assessment of chemicals entering sewage treatment plants.     

Evaluation of an ecosystem model in ecological risk assessment of chemicals

We used a Lake Suwa version of Comprehensive Aquatic Systems Model (CASM_SUWA) to demonstrate the risk estimation of 10 different chemicals and examined the applicability and reliability of the model in ecological risk assessment by qualitatively and quantitatively comparing with the results of studies on multiple species using mesocosm tests. The qualitative comparison of the model results with those of the reported mesocosm tests indicated that some evidence observed in mesocosm studies supported the indirect effects predicted from simulation using the model. The comparison of the concentration levels at which 20% biomass reduction (BR20) in the most sensitive population estimated from the model with the no-observed effect concentration values derived from multiple species mesocosm tests (MS-NOEC) suggested that both data were related to each other and the model can be used to help in the determination of an ecological acceptable level of chemicals in aquatic environments. The analysis of the potential of indirect effects of a chemical for fish population indicated that the magnitude of the potential of indirect effects was quantified based on the ratio of BR50 to LC50 for fish population.     

A comparative study on characterization of textile wastewaters (untreated and treated) toxicity by chemical and biological tests

Toxicity of textile wastewaters (untreated and treated) and their ingredient chemicals was quantified in terms of their chemical characteristics, fish (Gambusia affinis) mortality and end point growth responses of duckweed (Lemna aequinoctialis) in short-term bioassays. Other parameters of fish bioassay were erythrocyte morphology and its counts. Despite of a definite correlation between data of biological tests (LC/EC(50) values) with that of chemical tests, biological tests were found to be relatively more sensitive to both wastewaters and ingredient chemicals. Amongst all the examined parameters of test organisms, fish RBCs (morphology and counts) sensitivity to pollutants in the wastewaters was usually maximum and therefore, their study should be included in the routine fish bioassay. Other advantage of biological test such as on Lemna is even detection of eutrophic potential of wastewaters, as noted at their higher dilutions. The ingredient chemicals (major) contributing maximum toxicity to textile dye wastewater were, acids (HCl and H(2)SO(4)), alkali (Na(2)O SiO(2)), salt (NaNO(2)) and heavy metal (Cu), whereas dyes (4) were relatively less toxic.     

Statistical uncertainty in hazardous terrestrial concentrations estimated with aquatic ecotoxicity data

Since chemicals’ ecotoxic effects depend for most soil species on the dissolved concentration in pore water, the equilibrium partitioning (EP) method is generally used to estimate hazardous concentrations (HC50) in the soil from aquatic toxicity tests. The present study analyzes the statistical uncertainty in terrestrial HC50s derived by the EP-method. For 47 organic chemicals, we compared freshwater HC50s derived from standard aquatic ecotoxicity tests with porewater HC50s derived from terrestrial ecotoxicity tests. Statistical uncertainty in the HC50s due to limited species sample size and in organic carbon–water partitioning coefficients due to predictive error was treated with probability distributions propagated by Monte Carlo simulations. Particularly for specifically acting chemicals, it is very important to base the HC50 on a representative sample of species, composed of both target and non-target species. For most chemical groups, porewater HC50 values were approximately a factor of 3 higher than freshwater HC50 values. The ratio of the porewater HC50/freshwater HC50 was typically 3.0 for narcotic chemicals (2.8 for nonpolar and 3.4 for polar narcotics), 0.8 for reactive chemicals, 2.9 for neurotoxic chemicals (4.3 for AChE agents and 0.1 for the cyclodiene type), and 2.5 for herbicides–fungicides. However, the statistical uncertainty associated with this ratio was large (typically 2.3 orders of magnitude). For 81% of the organic chemicals studied, there was no statistical difference between the hazardous concentration of aquatic and terrestrial species. We conclude that possible systematic deviations between the HC50s of aquatic and terrestrial species appear to be less prominent than the overall statistical uncertainty.     

Preliminary investigation on the environmental occurrence and effects of antibiotics used in aquaculture in Italy

A preliminary investigation has been carried out on the occurrence and effects of antibiotics used in Italian aquaculture with the objective of identifying priorities for monitoring programmes. According to the information available on the most pertinent and diffuse fish diseases and their related therapies, the presence of flumequine and oxytetracycline in sediments sampled from two trout farms and three sea-bass farms and in their surrounding environments was selected for an analytical investigation. The concentrations of oxytetracycline and flumequine varied up to a maximum of 246.3 and 578.8 microg/kg d.w., respectively. Flumequine was seen to have the highest toxicity in a bioluminescence assay with EC50 values varying within the range of 12-15 mg/l, while the EC50 values for oxytetracycline were within the range of 121-139 mg/l. The results of the present study indicate flumequine and oxytetracycline as priority chemicals to be monitored for possible environmental side effects of aquaculture in Italy. Apart from peak concentrations the chronic presence of flumequine and oxytetracycline in sediments both inside and outside farms should also be considered. In spite of the potential risks related to the use of antibiotics, the concentrations found in the sediments of the studied fish farms are significantly lower than those found in other areas.     

Toxicological response of a bioluminescent microbial assay to Zn, Pb and Cu in an artificial soil solution: relationship with total metal concentrations and free ion activities.

The relationship between toxicological response and both total concentrations and free ion activities of Pb, Cu and Zn in an artificial soil solution has been investigated using lux-marked Escherichia coli HB101 (pUCD607) as a bioassay. SO4(2-) (as K2SO4) was added as an inorganic complexing agent up to 0.01 M representing the range of ionic strengths found in soil solutions and giving a wide range of free metal ion activities. EC50 values expressed in terms of concentration, varied significantly with K2SO4 molarity for all metals. However, when EC50 values were expressed in terms of free ion activity they were not significantly different for Pb and Zn, supporting the free ion activity model. Conversely, EC50 values expressed as free Cu activity did vary significantly with K2SO4 molarity, possibly due to a greater degree of adsorption of Cu onto inactive sites on the cell surfaces than for Zn and Pb. Linear regression analysis of bioluminescence on free ion activity revealed significant correlations for each metal above the toxicity threshold. In conclusion, lux-marked E. coli is suitable for investigating the toxicity of metal ions and complexes in non saline systems although cell surface adsorption effects could be important for some metals, e.g. Cu.     

Evaluation of EU risk assessments existing chemicals (EC Regulation 793/93)

An evaluation was performed on the first group (41) of completed risk assessments for chemicals of the EU priority lists (Existing Chemicals; EC Regulation 793/93). The evaluation focussed on the conclusions of the risk assessments. The EU risk assessment process detected a high number of substances of concern. Furthermore priority chemicals may pose potential risks to the whole range of protection goals of the risk assessment. The predictability of the risk assessments for priority chemicals was investigated. Our a priori knowledge on possible risks of priority chemicals is found to be poor, especially for consumers. Both for environment and human health the potential risks were linked with a broad spectrum of use patterns. It is concluded that no industry category can in advance be excluded from performing risk assessments. For a great number of chemicals, additional testing was found to be needed to finalize the risk assessment. This evokes questions about the completeness of the current base-set, but also about the suitability of some of the submitted human health tests that should initially fulfil the base-set needs. The results of this evaluation are useful for ongoing discussions on risk assessment processes for chemicals.     

First report on development of quantitative interspecies structure-carcinogenicity relationship models and exploring discriminatory features for rodent carcinogenicity of diverse organic chemicals using OECD guidelines

Different regulatory agencies in food and drug administration and environmental protection worldwide are employing quantitative structure-activity relationship (QSAR) models to fill the data gaps related with properties of chemicals affecting the environment and human health. Carcinogenicity is a toxicity endpoint of major concern in recent times. Interspecies toxicity correlations may provide a tool for estimating sensitivity towards toxic chemical exposure with known levels of uncertainty for a diversity of wildlife species. In this background, we have developed quantitative interspecies structure-carcinogenicity correlation models for rat and mouse [rodent species according to the Organization for Economic Cooperation and Development (OECD) guidelines] based on the carcinogenic potential of 166 organic chemicals with wide diversity of molecular structures, spanning a large number of chemical classes and biological mechanisms. All the developed models have been assessed according to the OECD principles for the validation of QSAR models. Consensus predictions for carcinogenicity of the individual compounds are presented here for any one species when the data for the other species are available. Informative illustrations of the contributing structural fragments of chemicals which are responsible for specific carcinogenicity endpoints are identified by the developed models. The models have also been used to predict mouse carcinogenicities of 247 organic chemicals (for which rat carcinogenicities are present) and rat carcinogenicities of 150 chemicals (for which mouse carcinogenicities are present). Discriminatory features for rat and mouse carcinogenicity values have also been explored.     

QSAR modeling of bioconcentration factors in fish based on fragment constants and structural correction factors

The quantitative structure-activity relationship between the BCF and fragment constant of organic chemicals was studied using a database containing 337 experimental BCF values. The database covered a large variety of chemicals ranging from the very hydrophobic to the very hydrophilic with logKow values between 0.39 and 8.60. The structural features affecting the BCFs were identified and evaluated during a preliminary modeling. A final linear multivariate regression model was derived that was able to account for as much as 98.0% of the variation in the experimental BCF values. The mean absolute error for the final model was 0.315 log-units. In addition, the predictability and robustness of the model was also evaluated.     

Toxicity of chlorophenols to Pseudokirchneriella subcapitata under air-tight test environment

A closed-system algal toxicity test with no headspace was applied to evaluate the toxicity of chlorophenols to Pseudokirchneriella subcapitata. The dissolved oxygen production and the growth rate based on cell density were the response endpoints. Phenol and seven chlorophenols were tested using the above test technique. Median effective concentrations (EC50) range from 0.004 to 25.93 mg/l (based on DO production) and 0.0134 to 20.90 mg/l (based on growth rate). No-observed-effect concentration (NOEC) is within the range of 0.001-8.19 mg/l. In general, growth rate is a more sensitive response endpoint than the oxygen production, except for the case of pentachlorophenol. However, the differences in sensitivity between the two parameters were marginal. Furthermore, quantitative structure-activity relationships (QSAR's) based on the n-octanol/water partition coefficient (log P) and the acid dissociation constant (pK(a)) values were established with R(2) ranged from 0.90 to 0.96. From literature data also based on P. subcapitata, the new test method is 1.65-108 times more sensitive than the conventional algal batch tests. A completely different relative-sensitivity relationship among various aquatic organisms was thus observed. The results of this study indicate that the toxicity data of volatile organic chemicals derived by conventional algal toxicity tests may severely underestimate the impact of these toxicants. Our results show that alga is very sensitive to chlorophenols compared to other aquatic organisms such as the luminescent bacteria (the Microtox test), Daphnia magna, and rainbow trout.