Neurotoxicity guidelines

The developmental neurotoxicity guideline, accepted by OECD in 2007, has added the important aspect of behavioral effects of pre- and postnatal exposure to chemicals. This development arose from the notion that behavioral disorders in man such as anxiety, depression, phobias, autism, and attention deficit hyperactivity disorder, which appear to show increasing prevalences in western societies, may have a perinatal origin (4, 5). In the absence of causal inferences with respect to chemicals it seems nevertheless prudent to assess in a risk assessment whether such causal relations may exist. 

EPA, U.S. Environmental Protection Agency, Developmental Neurotoxicity Study, Health Effects Test Guidelines, OPPTS 870.6300, EPA 712-C-98-239, 1998c. http //www.epa. gov/opptsfrs/OPPTS Harmonized/870 Health Effects Test Guidelines/Series/870-6300. pdf... 

U.S. Environmental Protection Agency. OPPTS 870-6300, Developmental Neurotoxicity, Health Effects Test Guidelines. EPA 712-C98-239, 1998. 

US Environmental Protection Agency (1998) Guidelines for neurotoxicity risk assessment. Federal Register 63 26926-26954 http //www.epa.gov/raf/publications/pdfs/NEUROTOX. PDF Accessed 15 Feb 2011... 

Environmental Protection Agency (1991). Pesticide Assessment Guidelines Subdivision F, Hazard Evaluation Human and Domestic Animals. Addendum 10, Neurotoxicity Series... 

Delayed Neurotoxicity of Organophosphoms Substances Following Acute Exposure (Updated Guideline, adopted 27 July 1995)... 

Neurotoxicity Study in Rodents (Original Guideline, adopted 21 July 1997)... 

Developmental Neurotoxicity Study, Draft New Guideline (September 2003)... 

In addition to these standard acute toxicity studies, the OECD, US-EPA, and EU have developed a specific test guideline for delayed neurotoxicity of organophosphorus substances in the domestic laying hen following acute exposure, see Table 4.6. 

The standard repeated dose toxicity guideline studies include a number of parameters relevant for the evaluation of a substance s neurotoxic potential. In addition to these standard... 

The US-EPA has adopted four different test guidelines for neurotoxicity ... 

The Neurotoxicity Screening Battery test guideline (OPPTS 870.6200) consists of a functional observational battery, motor activity, and neuropathology. The test battery is not intended to provide a complete evaluation of neurotoxicity, and additional functional and morphological evaluation may be necessary to assess completely the neurotoxic potential of a chemical. 

The series of Risk Assessment Guidelines includes a guideline for neurotoxicity risk assessment (US-EPA 1998), see Section 4.7.7.3. 

The neurotoxicity studies will provide information on major neurobehavioral and neuropatho-logical effects in adult rodents. The protocol for the OECD/EU test guideline studies has been developed so that it can be tailored to meet particular needs to confirm the specific histopathological and behavioral neurotoxicity of a substance as well as to provide a characterization and quantification of the neurotoxic responses, and can thus form the basis for an estimate of a NOAEL for neurotoxicity. See also Section 4.7.7. 

The 1998 OECD test guidelines for the oral 28-/90-day studies (see Table 4.12) examine a number of simple nervous system endpoints, e.g., clinical observations of motor and autonomous nervous system activity, and histopathology of nerve tissue. It should be recognized that the standard 28-/90-day tests measure only some aspects of nervous system stmcture and function, while other aspects, e.g., learning and memory and sensory function is not or only superficially tested. Primarily the standard 28-/90-day tests are intended as a screening for neurotoxicity and depending on the results, further testing may be needed. 

In addition to the test guidelines mentioned above, the following test guideline methods are also directed toward neurotoxicity testing ... 

The series of Risk Assessment Guidelines includes a guideline for neurotoxicity risk assessment (US-EPA 1998). This Guideline sets forth principles and procedures to guide US-EPA scientists in evaluating environmental contaminants that may pose neurotoxic risks, and inform US-EPA decision-makers and the public about these procedures. The Guideline includes a discussion of general dehnitions and issues, an overview of test methods, and the interpretation of data within the U.S. framework for risk assessment. 

This OECD site contains general information on chemical safety as well as specific testing guidelines for neurotoxic effects of chemicals. 

OECD (2007) Test Guideline 426. OECD Guideline for Testing of Chemicals. Developmental Neurotoxicity Study, http // www.oecd-ilibrary.org/environment/test-no-426-developmental-neurotoxicity-study 9789264067394-en. Accessed 12 Feb 2012... 

Developmental neurotoxicity study (OECD Test Guideline... 

Geriatric Considerations - Summary Age is not a contraindication to INH prophylaxis or treatment of tuberculosis. Follow adult guidelines for treatment. INH maybe used in patient wit h stable hepatic disease. The risk of clinical hepatitis increases with age and has been reported in 2% of adults aged greater than 50. INH interferes with the metabolism of pyridoxine therefore concomitant pyridoxine therapy at 25mg/day is recommended to prevent neurotoxicity. INH is metabolized via acetylation in the liver. Older adults who are slow acetylators of the drug may require lower doses to achieve effective serum concentrations and prevent adverse effects. Food, especially high-fat meals, delays and reduces absorption therefore administer INH on an empty stomach. 

In a few cases, studies to evaluate developmental neurotoxicity or other postnatal functions may have been conducted, and these can provide amore complete evaluation of potential developmental effects. In addition to the standard guideline studies, data from experimental studies on mechanisms of action, etc., can provide useful data for consideration in the risk assessment process. 

OECD (1999c) Test Guideline 426 Prenatal developmental neurotoxicity study (draft). Paris, Organisation for Economic Co-operation and Development. 

US EPA (1998c) Health effects test guidelines OPPTS 870.6300 Developmental neurotoxicity. Washington, DC, US Environmental Protection Agency (EPA 712-0-98-239). 

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