Use of LC50 in aquatic regulatory toxicology-Disharmony in global harmonization of hazard classification of chemicals

In regulatory aquatic toxicology, acute toxicity studies with chemicals are conducted with a species of fish, crustacea, and or alga. The LC50/EC50 obtained from these studies is used for the hazard classification and labeling of the chemicals. The methods like probit or logit analysis and Litchfield and Wilcoxon method are prescribed in the OECD guidelines to determine the LC50. In the present study, LC50s were calculated using probit analysis, Litchfield & Wilcoxon method, and also using the method by Trevan (the inventor of median lethal dose) using three sets of concentration-mortality data of fish acute toxicity tests. The slopes of the concentration-mortality curves, fiducial limits (95% confidence interval) of LC50s, and ‘mode’ of the concentration-mortality curves were compared. Though the methods used in the study resulted in more or less similar LC50s, the LC10 and LC90, slopes and ‘mode’ differed considerably, indicating that LC50 does not reveal the exact toxicity profile of a chemical. The LC50 calculated using Finney’s probit analysis provides better information on the toxicity profile of a chemical than the LC50calculated by Litchfield & Wilcoxon method. While interpreting LC50, the mortality occurred below 16 % (eg.,LC10) and above 84 % (eg.,LC90), slope and ‘mode’ of the concentration-mortality curve may also be considered. It is worth having a relook at the current practice of hazard classification and labeling of the chemicals based only on LC50 in regulatory aquatic toxicology.

Study of acute oral toxicity of organotin compounds containing a 2,6-di-tert-butylphenol fragment

The aim of the study was to evaluate the safety of the use of organotin compounds containing a fragment of 2,6-di-tert-butylphenol as pharmaceutical substances when administered intragastrically to Wistar outbred rats (females). Material and methods. The objects of the study were three organotin compounds: ((3,5-di-tertbutyl-4-hydroxyphenylthiolate) triphenyltin (Me-5), (3,5-di-tert-butyl-4-hydroxyphenylthiolate)trimethyltin (Me-4), bis(3,5-di-tert-butyl-4-hydroxyphenylthiolate) dimethyltin (Me-3). Acute toxicity study were performed on 106 Wistar rats (female) weighing 190-210 g by "fixed dose" and "up and down" methods according to the OECD protocols. Results. According to the harmonized system of hazard classification and labeling of chemical products (GHS) the studied organotin compounds should be assigned to the following toxicity classes: Me-5 — IV, Me-3 — V, Me-4 — II. Average lethal dose in intragastric administration for Me-5 is LD50 = 955.0 ± 58.3 mg/kg, the value of LD50 for Me-3 is conventionally assumed to be much more than 2000 mg/kg, for Me-4 is in the range of 5 to 50 mg/kg. Discussion. The modification of tin-organic molecules in the course of directed synthesis opens broad prospects for the creation of a new class of anticancer drugs. In the course of the experimental study, the regularities of the "structure-toxicity" relationship of organic tin derivatives were revealed: the introduction of the 2,6-di-tert-butylphenol group significantly reduces toxicity compared to the corresponding initial substances; methyl derivatives are more toxic than their phenyl analogues. Compounds of GHS toxicity classes IV and V can be considered as leading candidates for promising preclinical studies in the field of experimental oncology. Conclusion. Substances of Me-3 and Me-5, which have the highest safety for intragastric use, were recommended for further study as antitumor drug agents.

Low Toxicity Solvent Compositions for Varnishes Formulations for Use in Art Conservation

Varnishes consist basically of a resin and solvent. Aromatic solvents are widely used for varnish formulations, but they present considerable toxicity which requires their replacement. Two binary solvent systems with an oxygenated solvent (ethyl acetate or isoamyl acetate) and cyclohexane were studied as possible substitutes for xylene in varnish formulations. The toxicity of solvents was analyzed using data from the Globally Harmonized System of Classification and Labeling of Chemicals and the National Institute for Occupational Safety and Health. The solubility of Damar, Paraloid B72, Regalrez 1094, and Laropal K80 resins in these solvents was evaluated by Hansen and Teas Solubility Parameters, sigma profiles, and experimental method. Vapor pressure measurements were obtained from solvents and viscosity and gloss measurements from varnish formulations. The results indicated the potential of binary solvent systems as substitutes for xylene, but require further studies on their effects on pictorial materials on which they are applied.

Assessing Agricultural Toxicity in Brazil: Advances and Opportunities in the 21st Century

Agriculture in the 21st century faces multiple challenges to produce food for the growing population using ethical/sustainable and efficient methods safely for humans and the environment. Brazil today is a world leader in terms of production of food of plant origin, both for human consumption and animal feed. Agriculture and livestock raising are critical economic activities in maintaining a positive balance in its economy. As a consequence, the registration and use of pesticides in Brazil have grown at an accelerated rate. This work shows the current situation in Brazil in terms of the prevailing laws about the registration of pesticides, with a focus on the toxicological aspects related to human health. The regulatory aspects of registration of pesticides in Brazil, the mandatory testing for evaluating pesticide toxicity, adoption of the Globally Harmonized System of Classification and Labeling of Chemicals, and recent progress toward nonanimal methods to toxicity evaluation were explored in this work. In this field, Brazil has advanced and there are opportunities and challenges. There is still much to be done and investments to be made so that Brazil can definitively consolidate its conduct within the context of a Modern Regulatory Toxicology, which has entered the 21st century.

An Alternative Approach to Mapping Pigments in Paintings With Hyperspectral Reflectance Image Cubes Using Artificial Intelligence

Spectral imaging modalities, including reflectance and X-ray fluorescence, play an important role in conservation science. In reflectance hyperspectral imaging, the data are classified into areas having similar spectra and turned into labeled pigment maps using spectral features and fusing with other information. Direct classification and labeling remain challenging because many paints are intimate pigment mixtures that require a non-linear unmixing model for a robust solution. Neural networks have been successful in modeling non-linear mixtures in remote sensing with large training datasets. For paintings, however, existing spectral databases are small and do not encompass the diversity encountered. Given that painting practices are relatively consistent within schools of artistic practices, we tested the suitability of using reflectance spectra from a subgroup of well-characterized paintings to build a large database to train a one-dimensional (spectral) convolutional neural network. The labeled pigment maps produced were found to be robust within similar styles of paintings.

Priority Setting for Management of Hazardous Biocides in Korea Using Chemical Ranking and Scoring Method

Biocides are non-agricultural chemical agents for the prevention of unhygienic pests. The worldwide demand for biocidal products has been rapidly increasing. Meanwhile, biocides have been causing negative health effects for decades, resulting in public health scares. Therefore, governments around the world have tried to strictly control biocides, and it is necessary to prioritize the health risks of biocides for efficient management. Chemical ranking and scoring (CRS) methods have been developed for the effective management of chemicals. However, existing methods do not use suitable variables to evaluate biocides, thus possibly underestimating or overestimating the actual health risks. We developed a new CRS method that reflects the exposure and toxicity characteristics of biocides. Eleven indicators were chosen as appropriate for prioritizing biocides, and scoring based on the globally harmonized system of classification and labeling of chemicals (GHS) improved the efficiency of the method. Correlations between individual indicators in this study were low (−0.151–0.325), indicating that each indicator was independent and well-chosen for prioritizing biocides. The effect of each indicator on the total score showed that carcinogenicity, mutagenicity, and reproductive toxicity (CMR) chemicals ranked high with r = 0.558. This result demonstrated that the most dangerous toxicants should play a more decisive role in the top ranking than the others. We expect that our method can be efficiently used to screen regulated biocides by prioritizing their health hazards, thus leading to better policy decision making about biocide use.

POTENTIAL ECOLOGICAL HAZARD OF PURE METALS

The potential environmental hazard of a number of pure metals was assessed. A comparative analysis of hazard indicators established by various international organizations (WHO, ACGIH, etc.) and hazard factors regulated by the Globally Harmonized System of Classification and Labeling of Chemicals was conducted. The assessment was carried out for the following metals: aluminum, beryllium, vanadium, cadmium, manganese, arsenic, nickel, lead, titanium, zinc, zirconium.