Toxicant requirements

A toxic reaction may take place during or soon after exposure, or it may only appear after a latency period. Chronic toxicity requires exposure of several years for a toxic effect to occur in humans. With respect to experimental animals, the animals are usually exposed for most or all of their life time to ascertain the occurrence of chronic toxicity. Acute toxic reactions that occur immediately are easy to associate with the exposure and the exposure-effect relationship can readily be demonstrated. The longer the time interval between exposure and effect, the more difficult it is to delineate the relationship between exposure and effect. 

A tested product is allocated into one of four product classes based on its intended use. The more intensively a product comes into contact with the skin, the stricter the human toxicity requirement must be fulfilled by the product. A certificate is issued and will be valid for 1 year and can be renewed. 

Treatment is continued until toxicity requires discontinuation or disease progression... 

The directions for thorough mixing of the reagents in disposable plastic beakers are included with commercially available resin kits. Most embedding media are toxic, requiring the use of chemical hoods. In addition, certain reagents can cause dermatitis and thus require the use of gloves. 

NDS slurry-type adsorption HCI and NaOH High SO brine 0 0 0 Low SO4 level. Low running cost. Non-toxic. Requires repeated maintenance. 

The glycolate pipeline continued to supply new candidate agents, each one a related compound with differing properties, and they all seemed deserving of clinical evaluation. It seemed necessary to study any compound that an enemy might conceivably use against us. We felt it important to know whether any of them possessed some unique type of toxicity, requiring novel medical countermeasures. 

There are several known polymorphisms in TPMT (4). Alleles TPMT 2, TPMT 3A, and TPMT 3C account for up to 95% of reduced TPMT activity. Patients heterozygous for these alleles have intermediate TPMT levels (5), and patients homozygous for the variant TPMT alleles are at high risk for severe, sometimes life-threatening, toxicity requiring significant reductions in mercaptopurine doses (5). 

The toxicity requirements are established per type of industry, in terms of the maximum number of times the effluents needs to be diluted to produce a no observed effect concentration (NOEC), defined as Gf for fish, Gd for daphnia, Ga for algae, and G1 for luminescent bacteria. Testing is limited to the exposure to only the appropriate Gx level, which should not produce any observed effect [the G-value corresponds with the dilution of the effluent, expressed as the lowest dilution factor (1,2,4,...) causing less than 10% mortality]. The level of maximum allowable toxicity per industrial branch is based on the level that is considered to be attainable with state-of-the-art process and/or treatment technology. Violating the toxicity requirements results in a levy, which makes state-of-the-art compliance a more economic option [12]. 

The use of filtration to polish biological treatment system effluent has become more popular in recent years because of more stringent discharge requirements. The 1977 EPA survey of petroleum refineries indicated that 27 of 259 plants used filtration as part of the existing treatment scheme and 16 others planned to install filtration systems in the near future [5]. Filtration can improve effluent quality by removing oil, suspended solids, and associated BOD and COD, and carryover metals that have already been precipitated and flocculated. Improved effluent filtration in one recent instance helped a Colorado refinery to meet the newly adopted discharge toxicity requirements [49]. 

The report provides the following descriptions of these two terms Identifying a mechanism of toxicity requires rigorous investigation to obtain a comprehensive understanding of the entire sequence of events that result in the toxic effect of interest In practice, mechanisms of toxicity are rarely established. For the mode of action concept it is sufficient to develop an understanding of key events within the complete sequence of events leading to toxicity. This does not require the amount or depth of data needed to provide a detailed explanation of the complete sequence of events. ... 

Pemoline has effect of rare serious hepato-toxicity requires monitoring of liver function tests... 

Lithium levels >2 mEq/L can be life threatening Sedation, nausea, liver toxicity (requires baseline and close monitoring) Thrombocytopenia, pancreatitis... 

The in vitro bioassay for dioxins with cleaned sediment extracts (DR-CALUX) proved to comply with the QA/QC criteria needed to guarantee the reliability of data in an inter- and intralaboratory study (Besselink et al., 2004). The chemical stability of dioxins makes it possible to apply destructive clean-up procedures which remove all matrix factors. Sample extraction and cleanup for other in vitro bioassays for specific mechanisms of toxicity require further development to make sure that the chemicals of interest are not lost or unwanted chemicals included in the sediment extract to be tested. Table 4 summarizes possible bioassays that could be performed in addition to chemical analyses with the dredged sediment in a licensing system. 

A human single-dose exposition trial must be preceded by 2 4 week rodent and 2-week non-rodent toxicity studies. The animal toxicity requirements are incremental by exposition for up to 1 month the Phase I and II trials require 1-month rodent and 1-month non-rodent toxicity studies (see Table 5.2). 

III. Animal toxicity requirements for clinical trials and marketing of a new drug. 

Even though many of the catalysts mentioned above have shown good homogeneous phase catalytic activity, they also exhibit high toxicity, requiring highly efficient catalyst removal processes. In order for this type of catalysts to... 

The management of toxicity requires monitoring of electrolytes, regular CNS observations, use of anticonvulsants should seizures occur, increased fluid intake to promote excretion (unless renal function is impaired) and cardiac monitoring. Haemodialysis should be considered if conservative measures are ineffective or serum lithium is above 3.0 mmol L-l. However, it may be of limited additional value as the volume of distribution of lithium is high. 

A weight of evidence approach to assessing reproductive toxicity requires rigorous evaluation of all available data. However, often only limited information is available, and default assumptions must be made because of uncertainties in understanding mechanisms, dose-response relationships at low dose levels and human exposure patterns. Several of these assumptions are basic to the extrapolation of toxicity data from animals to humans, while others are specific to reproductive toxicity. The general default assumptions for reproductive toxicity stated in the IPCS (1995) report are summarized as follows ... 

In general these factors determine cost, mechanical and visco-elastic properties, resistance to degrading environments and influences, processing characteristics of the compound, and special requirements such as flame resistance, oil resistance, low temperature flexibility, chemical resistance wear and abrasion resistance and non-toxicity requirements for application in contact with foodstuff, etc. 

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