This glossary, a revision of the IUPAC "Glossary for Chemists of Terms Used in Toxicology" [Pure Appl. Chem. 65, 2003 (1993)] incorporating new and redefined terms from the "Glossary of Terms Used in Toxicokinetics" [Pure Appl. Chem. 76, 1033 (2004)], contains definitions and explanatory notes, if needed, for terms frequently used in the multidisciplinary field of toxicology. The glossary is compiled primarily for those scientists and others who now find themselves working in toxicology or requiring a knowledge of the subject, especially for hazard and risk assessment. Many medical terms are included because of their frequent occurrence in the toxicological literature. There are three annexes, one containing a list of abbreviations and acronyms used in toxicology, one containing a list of abbreviations and acronyms used by international bodies and by legislation relevant to toxicology and chemical safety, and one describing the classification of carcinogenicity according to the weight of evidence available.

The objective of the "Glossary of Terms Used in Ecotoxicology" is to give clear definitions for those who contribute to studies relevant to ecotoxicology but are not themselves ecotoxicologists. This applies especially to chemists who need to understand the ecotoxicological literature without recourse to a multiplicity of dictionaries. The Glossary includes terms related to chemical speciation in the environment, sampling, monitoring and environmental analysis, as well as to adverse ecological effects of chemicals, ecological biomarkers, and the environmental distribution of chemicals. The dictionary consists of about 1139 terms. The authors hope that among the groups who will find this glossary helpful, in addition to chemists, are pharmacologists, toxicologists, ecotoxicologists, risk assessors, regulators, medical practitioners, and regulatory authorities. In particular, the glossary should facilitate the use of chemistry in relation to environmental risk assessment.

Background: Exposure to cadmium (Cd) has long been recognized as a health hazard, both in industry and in general populations with high exposure. Under the currently prevailing health risk assessment, the relationship between urinary Cd (U-Cd) concentrations and tubular proteinuria is used. However, doubts have recently been raised regarding the justification of basing the risk assessment on this relationship at very low exposure. Objectives: Our objective was to review available information on health effects of Cd exposure with respect to human health risk assessment. Discussion: The associations between U-Cd and urinary proteins at very low exposure may not be due to Cd toxicity, and the clinical significance of slight proteinuria may also be limited. More importantly, other effects have been reported at very low Cd exposure. There is reason to challenge the basis of the existing health risk assessment for Cd. Our review of the literature found that exposure to low concentrations of Cd is associated with effects on bone, including increased risk of osteoporosis and fractures, and that this observation has implications for the health risk assessment of Cd. Other effects associated with Cd should also be considered, in particular cancer, although the information is still too limited for appropriate use in quantitative risk assessment. Conclusion: Non-renal effects should be considered critical effects in the health risk assessment of Cd. Citation: Åkesson A, Barregard L, Bergdahl IA, Nordberg GF, Nordberg M, Skerfving S. 2014. Non-renal effects and the risk assessment of environmental cadmium exposure. Environ Health Perspect 122:431–438; http://dx.doi.org/10.1289/ehp.1307110

More than one and a half centuries ago, adverse human health effects were reported after use of a cadmium-containing silver polishing agent. Long-term cadmium exposure gives rise to kidney or bone disease, reproductive toxicity and cancer in animals and humans. At present, high human exposures to cadmium occur in small-scale mining, underlining the need for preventive measures. This is particularly urgent in view of the growing demand for minerals and metals in global climate change mitigation. This review deals with a specific part of cadmium toxicology that is important for understanding when toxic effects appear and, thus, is crucial for risk assessment. The discovery of the low-molecular-weight protein metallothionein (MT) in 1957 was an important milestone because, when this protein binds cadmium, it modifies cellular cadmium toxicity. The present authors contributed evidence in the 1970s concerning cadmium binding to MT and synthesis of the protein in tissues. We showed that binding of cadmium to metallothionein in tissues prevented some toxic effects, but that metallothionein can increase the transport of cadmium to the kidneys. Special studies showed the importance of the Cd/Zn ratio in MT for expression of toxicity in the kidneys. We also developed models of cadmium toxicokinetics based on our MT-related findings. This model combined with estimates of tissue levels giving rise to toxicity, made it possible to calculate expected risks in relation to exposure. Other scientists developed these models further and international organizations have successfully used these amended models in recent publications. Our contributions in recent decades included studies in humans of MT-related biomarkers showing the importance of MT gene expression in lymphocytes and MT autoantibodies for risks of Cd-related adverse effects in cadmium-exposed population groups. In a study of the impact of zinc status on the risk of kidney dysfunction in a cadmium-exposed group, the risks were low when zinc status was good and high when zinc status was poor. The present review summarizes this evidence in a risk assessment context and calls for its application in order to improve preventive measures against adverse effects of cadmium exposures in humans and animals.