Experimental assessment of the environmental fate and effects of triazoles and benzotriazole.

The environmental fate and effects of triazoles and benzotriazoles are of concern within the context of chemical regulation. As part of an intelligent testing strategy, experimental tests were performed on endpoints that are relevant for risk assessment. The experimental tests included the assessment of ecotoxicity to an alga, a daphnid and zebrafish embryos, and the assessment of ready biodegradability. Triazole and benzotriazole compounds were selected for testing, based on existing toxicity data for vertebrate and invertebrate species, as well as on the principal component analysis of molecular descriptors aimed at selecting the minimum number of test compounds in order to maximise the chemical domain spanned for both compound classes. The experimental results show that variation in the toxicities of triazoles and benzotriazole across species was relatively minor; in general, the largest factor was approximately 20. The study conducted indicated that triazoles are not readily biodegradable.

Evaluation of CADASTER QSAR models for the aquatic toxicity of (benzo)triazoles and prioritisation by consensus prediction.

QSAR regression models of the toxicity of triazoles and benzotriazoles ([B]TAZs) to an alga (Pseudokirchneriella subcapitata), Daphnia magna and a fish (Onchorhynchus mykiss), were developed by five partners in the FP7-EU Project, CADASTER. The models were developed by different methods - Ordinary Least Squares (OLS), Partial Least Squares (PLS), Bayesian regularised regression and Associative Neural Network (ASNN) - by using various molecular descriptors (DRAGON, PaDEL-Descriptor and QSPR-THESAURUS web). In addition, different procedures were used for variable selection, validation and applicability domain inspection. The predictions of the models developed, as well as those obtained in a consensus approach by averaging the data predicted from each model, were compared with the results of experimental tests that were performed by two CADASTER partners. The individual and consensus models were able to correctly predict the toxicity classes of the chemicals tested in the CADASTER project, confirming the utility of the QSAR approach. The models were also used for the prediction of aquatic toxicity of over 300 (B)TAZs, many of which are included in the REACH pre-registration list, and were without experimental data. This highlights the importance of QSAR models for the screening and prioritisation of untested chemicals, in order to reduce and focus experimental testing.

Safety and efficacy of Panavital feed (d-glyceric acid) for chickens for fattening.

Panavital feed is a preparation of d-glyceric acid intended to be used as a zootechnical additive in chickens for fattening. The active substance (d-glyceric acid) of the additive ■■■■■ by fermentation with Gluconobacter frateurii. The additive is intended to be used in chickens for fattening at a concentration from ■■■■■. The FEEDAP Panel notes that the data provided for the characterisation of the active substance are incomplete and that data on the characterisation of the formulated additive are not provided. Based on the information available, the FEEDAP Panel cannot assess the qualitative and quantitative composition of Panavital feed. Due to lack of data, the safety of the production strain claimed to be used to produce the active substance cannot be evaluated. Based on the data provided by the applicant, the FEEDAP Panel cannot conclude on the safety of Panavital feed for the target species, the consumer, the user and the environment and on the efficacy of Panavital feed when used as feed additive.

Efficacy of methyl ester of conjugated linoleic acid (t10,c12 isomer) for sows and cows for reproduction.

A mixture of methylated conjugated linoleic acid (CLA) isomers (t10,c12 and c9,t11) in equal proportions is the subject of this assessment. The active substance is considered to be CLA (t10,c12) methyl ester (ME). The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) of EFSA previously issued an opinion on the safety and efficacy of the product, in which it could not conclude on the efficacy of this additive for sows for reproduction and for cows for reproduction. The European Commission asked EFSA to deliver an opinion on the efficacy of this additive for sows and cows for reproduction, based on additional data submitted by the applicant. The FEEDAP Panel has performed the assessment of the new data following an approach in line with the principles laid down in Regulation (EC) No 429/2008 and the relevant guidance documents. In relation to the data on efficacy in sows for reproduction, owing to methodological shortcomings of the study submitted, including the duration of the study and the limited biological relevance of the effect observed, the FEEDAP Panel cannot conclude on the efficacy of CLA (t10,c12)-ME for sows for reproduction. The data related to dairy cows indicate that dietary CLA (t10,c12)-ME supplementation in the late dry period and/or lactation period showed an increase of the probability of pregnancy and a reduction of time to conception in the same reproductive cycle. However, considering that the minimum duration of efficacy studies for reproductive parameters is of at least two reproductive cycles, the FEEDAP Panel is not in a position to conclude on the efficacy of the additive for cows for reproduction.

Safety and efficacy of aluminosilicate of sodium, potassium, calcium and magnesium as a feed additive for pigs.

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on aluminosilicate of sodium, potassium, calcium and magnesium as a feed additive for pigs. The additive, that contains at least 66% of aluminosilicate of sodium, potassium, calcium and magnesium as main component, is intended for use as a technological additive (functional groups: (i) anticaking agents) in premixtures and feedingstuffs for pigs at a maximum inclusion level of 30,000 mg/kg. In the absence of data, the FEEDAP Panel could not conclude on the safety of the additive for the target species and the users. The additive is considered safe for the consumer and the environment at the proposed conditions of use. The additive has the potential to act as an anticaking agent in complete feed of pigs at a concentration of 30,000 mg/kg feed.

Safety and efficacy of Monteban® G100 (narasin) for chickens for fattening.

The feed additive Monteban® G100, containing the active substance narasin, an ionophore anticoccidial, is intended to control coccidiosis in chickens for fattening at a dose of 60-70 mg/kg complete feed. Narasin is produced by fermentation. Limited data on the taxonomic identification of the production strain did not allow the proper identification of strain NRRL 8092 as Streptomyces aureofaciens. The FEEDAP Panel cannot conclude on the absence of genetic determinants for antimicrobial resistance in Streptomyces spp. under assessment. Based on the available data set, the FEEDAP Panel cannot conclude on the safety of Monteban® G100 for chickens for fattening. The simultaneous use of Monteban® G100 and certain antibiotic drugs (e.g. tiamulin) is contraindicated. Narasin is not genotoxic. No indication of carcinogenicity or developmental toxicity was found at the doses tested in the mouse, rat and rabbit. The lowest no observed effect level (NOEL) identified in the oral toxicity studies was 0.5 mg/kg body weight (bw) per day for the neuropathy seen in a one-year dog study. The acceptable daily intake (ADI) derived from this NOEL is 0.005 mg narasin/kg bw applying a uncertainty factor of 100. Monteban® G100 is safe for the consumer. Maximum residue limits (MRLs) of 50 µg narasin/kg for all wet tissues ensure consumer safety. Monteban® G100 is irritatant to the eyes but not to the skin. It has the potential to induce skin sensitisation. Inhalation exposure would pose a risk to persons handling the additive. Narasin, when used as a feed additive for chickens for fattening at 70 mg/kg feed, is not expected to pose a risk to the environment. The risk for sediment compartment cannot be assessed. The FEEDAP Panel cannot conclude on the efficacy of Monteban® at the minimum applied dose of 60 mg narasin/kg complete feed for chickens for fattening.

Distribution of PAHs and PCBs to dissolved organic matter: high distribution coefficients with consequences for environmental fate modeling.

Dissolved organic carbon/water distribution coefficients (K(DOC)) were measured for a selection of PCBs with octanol/water partition coefficients (K(OW)) ranging from 10(5.6) to 10(7.5). A solid phase dosing and sampling technique was applied to determine K(DOC) to Aldrich humic acid. This technique is in particular suitable for determining the distribution of very hydrophobic chemicals to complex matrices like humic acids. The K(DOC) values were calculated from the experimental data using a linear model. Determined K(DOC)'s were evaluated in relation to octanol/water partition coefficients of the test compounds, and compared to literature data. Measured K(DOC) values were somewhat higher than literature data, which can probably be attributed to the overestimation of freely dissolved aqueous concentration as a result of incomplete phase separation in other studies, and to the unique character of Aldrich humic acid as a "sorbent" or co-solute or to the fact that Aldrich humic acid is not a typical DOC, and other (adsorption) processes can occur. This study reports DOC distribution coefficients that belong to the highest ones ever measured. In addition, the DOC distribution was discussed in relation to current risk assessment modeling.

The toxic effect of oxytetracycline and trimethoprim in the aquatic environment.

The objective of our study was the investigation of the toxic properties of two antimicrobial drugs: oxytetracycline (OTC) and trimethoprim (TMP) in the aquatic environment. The toxic effects were tested according to the OECD guidelines for the testing of chemicals, on the cyanobacteria Anabaena flos-aque, on the alga Pseudokirchneriella subcapitata, on the daphnid Daphnia magna as well as on the activated sludge. We discussed the short term and long term results of tests on cyanobacteria and microalgae. Both experiments were concluded in 72h allowing direct comparison of sensitivity of the two tested species. The results of our study showed toxic effect in the same range for both groups. In the test on the toxicity of OTC to P. subcapitata we obtained the 72hErC50 of 1.04mgL(-1) (72hErC10 0.47mgL(-1)) which are lower in comparison to the results on the toxicity to A. flos-aque of ErC50 of 2.7mgL(-1) (72hErC101.5mgL(-1)). TMP is less toxic to both photosynthetic plankton species. Similar to the test results on OTC, the P. subcapitata is more sensitive to TMP (ErC50129mgL(-1); ErC1065mgL(-1)) than A. flos-aque (72hErC50253mgL(-1); 72hErC1026mgL(-1)). OTC is toxic to the activated sludge (3hEC50 17.9mgL(-1)), while the calculated 3hEC50 value for TMP exceeded solubility for the compound. In comparison to other species, both tested antimicrobials showed low toxicity to daphnids.

Assessing bioaccumulation of polybrominated diphenyl ethers for aquatic species by QSAR modeling.

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in textiles, foams and plastics. Highly bioaccumulative with toxic effects including developmental neurotoxicity estrogen and thyroid hormones disruption, they are considered as persistent organic pollutants (POPs) and have been found in human tissues, wildlife and biota worldwide. But only some of them are banned from EU market. For the environmental fate studies of these compounds the bioconcentration factor (BCF) is one of the most important endpoints to start with. We applied quantitative structure-activity relationships techniques to overcome the limited experimental data and avoid more animal testing. The aim of this work was to assess the bioaccumulation of PBDEs by means of QSAR. First, a BCF dataset of specifically conducted experiments was modeled. Then the study was extended by predicting the bioaccumulation and biomagnification factors using some experimental values from the literature. Molecular descriptors were calculated using DRAGON 6. The most relevant ones were selected and resulting models were compared paying attention to the applicability domain.