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The primary objective of the present study was to examine the influence of early systemic toxicity resulting from copper (Cu) exposure on metamorphic processes in Xenopus laevis. A 28-day exposure study with copper, initiated at developmental stage 10, was performed using test concentrations of 3.0, 9.0, 27.2, 82.5, and 250 μg Cu/L. The primary endpoints included mortality, developmental stage, embryo-larval malformation, behavioral effects, hindlimb length (HLL), growth (snout-vent length [SVL] and wet body weight), and histopathology. The 28-day LC50 value with 95% confidence intervals was 61.2 (51.4-72.9) μg Cu/L with 250 μg Cu/L resulting in complete lethality. Developmental arrest in the 82.5 and delay in the 27.2 μg Cu/L treatments was observed as early as study day 10 continuing throughout the remainder of exposure. SVL-normalized HLL, body weight, and SVL in the 27.2 and 82.5 μg Cu/L treatments were significantly decreased relative to control. At 82.5 μg Cu/L, and thyroid gland size was markedly reduced when compared with controls consistent with the stage of developmental and growth arrest. Concentration-dependent findings in the intestine, liver, gills, eyes, and pharyngeal mucosa were consistent with non-endocrine systemic toxicity. These were prevalent in the 9.0 and 27.2 μg Cu/L treatment groups but were minimally evident or absent in the 82.5 μg/L group, which was attributed to developmental arrest. In conclusion, developmental delay in larvae exposed to 27.2 and 82.5 μg Cu/L was the result of systemic toxicity occurring in early development prior hypothalomo-pituitary-thyroid axis (HPT)-driven metamorphosis and was not indicative of endocrine disruption.

Inhalation exposure to copper may occur during a range of occupational activities and the purpose of this study was to characterise the toxicological response to repeated inhalation of two copper compounds, representative of copper substances in large-scale production/use. Crl:CD(SD) rats were repeatedly exposed to aerosols of dicopper oxide (Cu

Bioelution, the measuring of in vitro metal ion release from metals or metal compounds in simulated body fluids, can be used as a tool to measure bioaccessibility of metals and metal compounds, and as such provide an estimate of their bioavailability. Comparable bioelution results can allow grouping of substances within a “metal” family. By referring to toxicity data on a metal substance (reference substance) within the group, predictions on the hazard of the other substances in the group can be established. This paper discusses how bioelution testing of metals and metal compounds can be used as an alternative to animal testing for obtaining basic information on their potential toxicity, while allowing compliance with strict information requirements. Two human health hazard endpoints are used to illustrate how bioelution can become part of a testing programme and in particular, target the requirement for new studies and minimise the need for animal testing. In these cases, it is shown how bioelution can be used to predict the hazard of several indium compounds as a first screening.

The appropriate assessment of the human health hazards of complex inorganic materials is required to ensure their adequate risk management. This requires that the collection of data fulfils information requirements outlined in different chemicals management systems and identifies gaps in the knowledge of the material. Toxicity data on complex inorganic materials allowing to fulfil these human health information requirements and derive dose–responses/effect levels are usually scarce. Although testing could be theoretically envisaged to complete data gaps, the number of complex inorganic materials to be assessed would have significant implications for animal welfare and represent a disproportionate burden. For some materials like the Unknown or Variable composition, Complex reaction products or Biological materials (UVCBs), the variability will also prevent selecting a representative sample. The assessment will therefore often be based on the constituents of the complex materials. This chapter will discuss some alternatives to collect hazard information, like grouping and read-across of complex materials, the use of data on the constituents, and present recent refinements, illustrated with examples that can be of help.