Threshold dose level

Increase of shelf life under refrigeration and control of pathogenic nonsporeforming bacteria in fresh meat and poultry can be achieved by a 1-3 kGy dose. Doses for irradiation are selected under the consideration of threshold dose levels for sensory changes (off-odor), which depends on the type of animal meat (Table 7) [45]. Off-odor is due to the generation of volatile compounds from lipids and nitrogenous compounds formed by the reaction of these constituents with the reactive species produced by the radiolysis of water. 

The point at which toxicity first appears is known as the threshold dose level. From that point on, the curve rises with higher dose levels. In the hypothetical curve above, no toxicity occurs at x mg, whereas at 5jc mg, 100% of the individuals experience toxic effects and even death. 

Threshold A level or dose of a pollutant below which it is assumed to have no effect on life. 

Threshold dose A dosage or exposure level below which the adverse effects of a substance are not realized or expressed by the exposed population. 

Toxicity and Hazards. The odor cf ozone can be detected in concn as low as several parts per hundred million by vol (pphm). The threshold limit value (TLV) is O.lppmor 0.2mg/m3 its toxic dose level (TDL), 50% kill concn is 2ppm (Ref 6) Pure 100% liq ozone may be kept safely at 90°K (cooled by liq oxygen) for indefinite periods of time, but the smallest provocation, such as a spark or fast warming, even only up to bp (161°K), causes detonation. The evapn of liq ozone, for example, in the process of the prepn of pure gaseous ozone is, therefore, a dangerous procedure (Ref 3, p 224)... 

Acute-Duration Exposure. Information is available regarding the effects of acute-duration inhalation exposure of humans to acrylonitrile and the effects are characteristic of cyanide-type toxicity. Quantitative data are limited but are sufficient to derive an acute inhalation MRL. Further studies of humans exposed to low levels of acrylonitrile in the workplace would increase the confidence of the acute MRL. Studies in animals support and confirm these findings. No studies are available on the effects of acute-duration oral exposure in humans however, exposure to acrylonitrile reveals neurological disturbances characteristic of cyanide-type toxicity and lethal effects in rats and mice. Rats also develop birth defects. Animal data are sufficient to derive an acute oral MRL. Additional studies employing other species and various dose levels would be useful in confirming target tissues and determining thresholds for these effects. In humans, acrylonitrile causes irritation of the skin and eyes. No data are available on acute dermal exposures in animals. 

OSHA has defined its own threshold dose, called a permissible exposure level (PEL). 

Such low-dose extrapolation is typically only conducted for tumors believed to be caused by a genotoxic effect, which some, but by no means all, scientists believe have no threshold. For other types of tumors and for many nonneoplastic endpoints a threshold cannot be estimated directly from data at a limited number of dose levels a no observed effect level (NOEL) can be estimated by finding the highest dose level at which there is no significant increase in effects. 

A mutated cell may reproduce and begin the formation of a carcinogenic mass (tumor), and mutations may occur after acute or chronic exposure. The specific relationship between acute or chronic exposure rate and cancer risk is hotly debated, although current U.S. regulations conservatively adopted the linear no threshold (LNT) model. This model states that risk is linearly proportional to the total dose even at the smallest possible dose levels (risk is associated with all levels of dose no matter how small). An alternate model theorizes that no measurable adverse health effects appear below doses of about 10 to 25 rem (0.1 to 0.25 Sv). Data supporting both models are limited and, to be conservative, levels of exposure should be kept as low as reasonably achievable (ALARA). Victim and emergency responder doses and dose rate may not be easily controlled in the event of a terrorist attack. However, methods to achieve ALARA exposures are described in Chapters 4 and 5. 

Human and animal evidence suggests there is a health risk for neurological effects only when exposures are high. There remains uncertainty in predicting dose levels for neurobehavioral effects, but 0.2 mg/kg body weight has been proposed as a threshold for convulsions in humans (Hayes 1963). 

As has been emphasized so many times in the preceding chapters, these various manifestations of toxicity all display dose-response characteristics, where by response we refer to the incidence or severity of specific adverse health effects. As we demonstrated in earlier chapters, toxic responses increase in incidence, in severity, and sometimes in both, as dose increases. Moreover, just below the range of doses over which adverse effects can be observed, there is usually evidence for a threshold dose, what we have called the no-observed adverse effect level (NOAEL). The threshold dose must be exceeded before adverse effects become observable (Chapter 3). Deriving from the literature on toxic hazards, descriptions of the dose-response relationships for those hazards comprise the dose-response assessment step of the four-step process. 

Well, it was nothing more than a crude expression of the nothreshold hypothesis, as described in earlier chapters. Under this hypothesis, any exposure to a carcinogen increases the probability that cancer will occur. As we have emphasized several times, it does not mean that any exposure to a carcinogen will cause cancer. If the exponents of the no safe level view meant that an absolutely safe level of exposure could not be identified, then they were correct, assuming the no-threshold hypothesis is correct. (Even assuming the threshold hypothesis is correct, as we have noted earlier, does not establish that we can ever be certain we have identified the completely safe threshold dose for any agent.)... 

Whether or not the threshold is reached, is related to the dose level of the substance to which the individual organism (human or experimental animal) is exposed, i.e., for a given route of exposure, there will be a threshold, which must be attained before the effect is induced. Ideally, in the hazard... 

Acute toxic effects are considered as being threshold effects, i.e., effects for which there are expected to be a threshold of substance concentration below which the effects will not be manifested. For the hazard and risk assessment, it is important to identify those dose levels at which signs of acute toxicity are observed, and the dose level at which acute toxicity is not observed, i.e., to derive a NOAEL for acute toxicity. However, it should be noted that a NOAEL is usually not derived in the classic acute toxicity smdies, partly because of the limitations in smdy design. 

---