Adverse health effects thresholds

The main objective of air quality guidelines and standards is the protection of human health. Since fme particulates (PM,) are more likely to cause adverse health effects than coarse particulates, guidelines and standards referring to fine particulate concentrations are preferred to those referring to TSP, which includes coarse particulate concentrations. Scientific studies provide ample evidence of the relationship between exposure to short-term and long-term ambient particulate concentrations and human mortality and morbidity effects. However, the dose-response mechanism is not yet fully understood. Furthermore, according to the WHO, there is no safe threshold level below which health damage does not occur. 

Hazard characterization is a quantitative or semi-quantitative evaluation of the nature, severity, and duration of adverse health effects associated with biological, physical, or chemical agents that may be present in food. The characterization depends on the nature of the toxic effect or hazard. Eor some hazards such as genotoxic chemicals, there may be no threshold for the effect and therefore estimates are made of the possible magnitude of the risk at human exposure level (dose-response extrapolation). 

AEGLs represent threshold exposure limits (exposure levels below which adverse health effects are not likely to occur) for the general public and are applicable to emergency exposures ranging from 10 min to 8 h. Three levels—... 

Critical research needs include definition of thresholds for adverse health effects and how these thresholds vary with exposure concentration and duration. Such data would be valuable for affirming AEGL values. Additionally, the mode of dimethylhydrazine toxicity is not fully understood and, therefore, research providing insight into the underlying mechanism(s) of dimethylhydrazine toxicity would reduce current uncertainties in quantitative health risk issues. 

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. 

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. 

The MOE does not quantify risk (the increased probability of an adverse health effect). Instead, the MOE indicates how far the dose from exposure is below the benchmark dose. If the MOE is sufficiently large, then the increased probability of an adverse health effect is either zero (because the dose is below a threshold for the adverse health effect) or de minimis (without appreciable risk or practical certainty of no harm) and, hence, acceptable or safe. 

Exposure Limits PELs and TLVs. Threshold limit values (TLVs) were developed in the 1940s, long before the existence of OSHA. The TLV is defined as the airborne concentration of a contaminant to which it is believed that most workers may be repeatedly exposed, day after day, without developing adverse health effects. Developed and maintained by the American Conference of Governmental Industrial Hygienists (ACGIH), these values have been determined based on industrial experience and animal and human studies. 

For occupational exposures, Permissible Exposure Levels (PELs), Threshold Limit, Values (TLVs), and NIOSH Recommended Exposure Levels (RELs) are developed. They represent dose levels that will not produce adverse health effects from repeated daily exposures in the workplace. The method used to derive them is conceptually the same. Safety factors are used to derive the PELs, TLVs, and RELs. 

The acceptable daily intake (ADI) is the level of daily intake of a toxic substance that does not produce an adverse health effect. ADIs are based on NOAELs, but are not considered an absolute physiological threshold they are based on safety factors that reflect variations in the population. Therefore, values for ADIs are significantly lower than values of corresponding NOAELs (US EPA, 1986, pp. 33992-34003). 

Ambient mercury vapor concentrations of 100 pg/ m or higher have been measured during chloralkah production and mercury mining [18]. Adverse health effects were common sequelae from such exposures. During recent years, most countries have reduced mercury s occupational threshold limit value to 50... 

In general, criteria developed to protect against noncancer effects are based on the assumption that there is a threshold below which no adverse health effects will occur. A critical evaluation of available human health and animal toxicity studies is performed to identify the most sensitive adverse effect relevant to humans. Noncancer exposure criteria are often based on an experimentally defined dose at which no adverse effects were observed (i.e., the no-observed-adverse-effect level - NOAEL). If no adequate NOAEL is available, the lowest dose at which adverse effects were observed (lowest-observed-adverse-effect level - LOAEL) is used. Another commonly used approach is to fit study data to dose-response models to identify appropriate values (e.g., dose corresponding to the upper bound of the 10% response level or BMDLio) as the basis for deriving the exposure criteria. 

Additional animal studies to investigate the acute effects of hydrazines after inhalation, oral, and dermal exposures would better define the threshold dose for adverse health effects. Such studies would be useful in predicting adverse health effects in humans following acute exposures. 

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