Negligible risks

Exempted investigations may be conducted where the studies pose negligible risk to... 

While there is no FDA involvement in such investigations, ethical considerations and institutional regulations would generally dictate that informed consent and the approval of the local institutional review board be obtained. However, due to the negligible risks involved these are likely to be a formality and will not involve extensive review or scrutiny. 

If one pound of trifluralin containing 1 ppm NDPA were applied to, and left on, the surface of a one-acre field, 400 pg NDPA could conceivably enter the atmosphere over a several hour period. To calculate how much of that could be inhaled by a single person would require, among other things, a knowledge of dispersion rates, but without them it is apparent that some very small numbers would be encountered. We must resist the temptation, however, to casually equate small numbers with negligible risk without solid justification. 

A protocol that described the work to be done and protected the rights of the volunteers in the dosimeter studies was developed for consideration by the Human Subjects Review Committee, University of California, Riverside. Paid volunteers were considered to be at "negligible risk." The approved protocol was designated HS-95-048. The document, including informed consent, was reviewed with participants at an orientation meeting prior to the study. 

Radiocesium concentrations in muscle of fishes from the southern Baltic Sea increased 3 to 4 times after Chernobyl (Grzybowska 1989), and 134+137Cs and 106Ru in fishes from the Danube River increased by a factor of 5. However, these levels posed negligible risk to human consumers... 

Substances of very high concern will have to be authorised for use for specific purposes that have been demonstrated either to present a negligible risk or are essential for socio-economic reasons. It is estimated that ca 1,400 substances will be subject to authorisation. 

Possible Risk Addftioriat Consideration al DiscrenofTean> 3- Negligible RISK Additicmel Considereiion NoiReqiired... 

In one double-blind, randomized, placebo-controlled study, patients were given a daily dose of 40 or 120 mg ziprasidone or placebo for 28 days in 132 patients ( 136). There was a statistically significant improvement in psychotic symptoms versus placebo in the 120 mg/day ziprasidone group as measured by the total BPRS and the CGI scores. Evaluations for parkinsonian symptoms, akathisia, abnormal movements, and sedation did not reveal any notable treatment effects. No significant differences existed between drug and placebo in the total number of adverse events, laboratory test abnormalities, or more serious adverse events. Thus, this study documented that 60 mg ziprasidone twice daily was an effective strategy with negligible risks. 

The negligible risk concept considered here is based strictly on individual risk rates and exposure. It does not include other economic or technical considerations that are part of setting the enforceable standards (i.e, the MCLs). The levels for the MCLs (not RMCLs) would thus be considered to be the upper limits of risk that are considered to be acceptable on the basis of current evaluations of the feasibility and costs of controls. 

Despite its ban in the UK, residues of vinclozolin have been detected in UK-grown winter lettuce for at least six years (Table 10.6). These residues present a negligible risk to the consumer because their concentration is far too low to result in an anti-androgen effect. Nevertheless residues indicate that the pesticide has been used illegally by UK growers and therefore action must be taken. 

Waste would be classified as exempt if the concentrations of hazardous substances are sufficiently low that it poses no more than a negligible risk to a hypothetical inadvertent intruder at a municipal/industrial landfill for nonhazardous waste. A negligible risk, or the associated dose, is a value so low that further efforts at risk reduction generally are unwarranted (e.g., an excess lifetime cancer risk less than about 10 4 or doses of noncarcinogenic hazardous substances substantially less than nominal thresholds for induction of health effects in the general population). 

Waste that exceeds concentration limits for exempt waste would be classified as low-hazard if it poses no more than an acceptable (i.e., barely tolerable) risk to a hypothetical inadvertent intruder at a dedicated near-surface disposal facility for hazardous wastes, with the important condition that an acceptable risk or dose used to determine low-hazard waste should be substantially higher than a negligible risk or dose used to determine exempt waste. 

Exempt Waste. Waste classified as exempt would be regulated as if it were nonhazardous, and would be generally acceptable for disposition as nonhazardous material (e.g., disposal in a municipal/ industrial landfill). As noted in Section 1.4.1, disposal is the only disposition of exempt materials considered in this Report. Limits on concentrations of hazardous substances in exempt waste would be derived based on an assumption that the risk or dose to a hypothetical inadvertent intruder at a disposal site should not exceed negligible levels. The use of a negligible risk or dose to determine exempt waste is based on an assumption that a disposal facility for nonhazardous waste could be released for unrestricted use by the public soon after the facility is closed. 

Negligible risks or doses used to classify exempt waste could be established based on a variety of considerations, consistent with the different approaches to risk management for radionuclides and hazardous chemicals described in Section 1.5.3. For noncarcinogenic hazardous chemicals, NCRP recommends that a negligible dose should be set at a small fraction (e.g., 10 percent) of a nominal threshold for deterministic responses in humans the recommended approach to estimating this threshold is described in Section I.5.5.3. For radionuclides, NCRP has recommended that an annual effective... 

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