Humans neurotoxicity risk assessment

WHO/IPCS. 2001a. Neurotoxicity risk assessment for human health Principles and approaches. Environmental Health Criteria 223. Geneva WHO. http //www.inchem.org/documents/ehc/ehc/ehc223.htm... 

Mycotoxins, selected ochratoxins, trichothecenes, ergot (No. 105,1990) Nephrotoxicity associated with exposure to chemicals, principles and methods for the assessment of (No. 119,1991) Neurotoxicity associated with exposure to chemicals, principles and methods for the assessment of (No. 60,1986) Neurotoxicity risk assessment for human health, principles and approaches (No. 223,2001)... 

Harry, J., B. Kulig, M. Lotti, H. Tilson, and G. Winneke, eds. Neurotoxicity Risk Assessment for Human Health. Environmental Health Criteria 223. Geneva World Health Organization, 2001. 

Cory-Slechta DA, Crofton KM, Foran JA, et al. Methods to identify and characterize developmental neurotoxicity for human health risk assessment. I Behavioral effects. Environ Health Perspect. 109(Suppl. 1) 79—91. 

Dorman, D., Allen. S Byezkowski, J., Claudio, L., Fisher, J. I., Fisher, L, Harry, G., Li, A, Makris, S., Padilla, S., Sultatos, L., and Milcson, B. (2001). Methods to identify and characterize developmental neurotoxicity for human health risk assessment. Ill Pharmacokinetic and pharmacodynamic considerations. Environ. Health Perspect. 109,101-111. 

Full understanding of this broad exposure—toxic outcome relationship did not occur overnight. Evolving comprehension is readily apparent in the historical record of lead and its various human health hazard relationships across decades and centuries (see previous chapter). This chapter, in common with the other chapters on toxicological harm from Pb exposures in humans, is not intended to be an encyclopedic recapitulation of the neurotoxicity record of Pb exposures in children, adults, and experimental test animals and wildlife. Rather, these chapters are distillations of the most reliable health science literature, i.e., literature that is most useful for addressing the principal end uses of the monograph the science of lead as it elucidates and propels both human health risk assessment and regulatory initiatives. 

This chapter s characterization of lead as a neurotoxic hazard does not include detailed dose—response relationships with various levels of biomarkers such as PbB linked to various neurotoxic outcomes. The topics of dose/ exposure metrics and defining full-spectrum dose—response relationships are presented in the next part, the section dealing with the elements of human health risk assessment for environmental lead. Here, for ease of discussion, only a broad yardstick is provided for toxic lead exposures. Specifically, general PbB ranges associated with the various categories of lead neurotoxicity, especially in children, are noted. 

Following receipt of data the Commission drew up priority lists of substances that, on the basis of that data, were thought to have the potential to pose a risk of harm to human health or the environment. By the publication of the EU White Paper in 2001, four lists, containing a total of 141 substances, had been adopted by the relevant technical committee (CEC, 2001). The progress of these risk assessments was very slow. Risk assessment of hexabromocyclododecane (HBCD), for example, commenced in 1997 but was still not completed nine years later (ENDS, 2006). In 2006 around 16,700 tonnes of HBCD were produced every year for use as a flame retardant. It may have neurotoxic effects and interfere with the metabolism of thyroid hormone, but because risk assessment of it had not reached a conclusion there were no restrictions on its use. By 2006 final risk assessment reports were available for only about 70 substances (European Commission, 2006b) — less than 0.5 per cent of the 30,000 or so existing substances on the European market at quantities of above 1 tonne per annum. 

With respect to the hazard identification part of the risk assessments, the main uncertainties discussed in these documents relate to the human health relevance of the observed developmental neurotoxicity in rodents. These are uncertainties that have been highlighted in all three documents. Likewise, the predicted no effect concentration for contaminated sediments is considered uncertain in all three risk assessments. The predicted no-effect concentration (NOEC) for water is considered uncertain for Octa and Deca, and the predicted no-effect concentration for the terrestrial compartment is identified as uncertain for Octa. 

Buelke-Sara. J., and Maetiuus, C. K (1990). Workshop on the qualitative and quantitative comparability of human and animal developmental neurotoxiciiy. Work Group II repon Testing methods in developmental neurotoxicity for use in human risk assessment. Neurotoxicoi TeraU>i 12(3), 269-274. 

MDMA studies in monkeys are of value because they will help to define the risk that MDMA poses to humans. Additionally, these studies could help identify functional consequences of MDMA neurotoxicity in primates, and thus guide the clinical assessment of MDMA-exposed individuals. 

Zhou et al. 2001, 2002). The available data indicate that the thyroid is a particularly sensitive target of acute oral exposure and justify using thyroid effects as the basis for an acute oral MRL, but acute effects of PBDEs on the liver are not as well characterized as thyroid effects. Other studies indicate that immunosuppression and neurobehavior are important and potentially critical health end points for acute exposure to PBDEs that need to be further investigated (see discussions of data needs for Immunotoxicity and Neurotoxicity). Studies in other species would help to clearly establish the most sensitive target and species for acute exposure, as well as which animal toxicity data are the most relevant to humans and useful for assessing acute health risks. 

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