Hazard assessment critical effects identification

The last step in the hazard assessment is the identification of the critical effect(s). 

Safety forecasting is the activity a manager carries out to estimate the probability, frequency, and severity of accidents that may occur in a future time span. Safety forecasting is risk assessment. This is usually done by means of physical risk assessment, critical task identification, and task risk assessment. It also entails estimating the effects of risk reduction brought about by a stable safety management system. Hazard and operability studies are part of this function. 

For chemicals in general the identification of a potential hazard normally arises from the application of in vitro tests or from short-term toxicity studies undertaken in laboratory animals (up to a period of 90 days in the case of the rat where the test material normally should not exceed 1% of the total diet). This usually enables a critical effect to be assessed. 

The distinction between non-adverse effects and adverse effects can seem academic, but is essential in the hazard assessment in relation to, e.g., evaluation of no-effect levels and lowest-effect levels (Section 4.2.4), identification of the critical effect(s) (Section 4.2.7), and to the magnitude of the assessment factor to be used for taking into account the uncertainty due to the nature and severity of effects (Section 5.8). 

For noncancer toxicity, the process includes an evaluation of the target organ or critical effects (i.e., the first adverse effect or its known precursor that occurs as the dose rate increases). In some cases, one needs to determine whether an effect is adverse or not. The choice of critical effect in the hazard identification process for noncancer toxicity is used as a basis for the dose-response assessment. 

Dose-response concepts. Dose-response assessment for hazardous chemicals that can cause deterministic effects begins with the toxicology data developed during the hazard identification step described in Section 3.1.4.1.2. In many cases, hazard identification and dose-response assessment occur simultaneously. For each chemical, the critical response (a specific response in a specific organ) is identified in the hazard identification process. Using the available data for the critical response, one of the following is established ... 

Although dose-response assessments for deterministic and stochastic effects are discussed separately in this Report, it should be appreciated that many of the concepts discussed in Section 3.2.1.2 for substances that cause deterministic effects apply to substances that cause stochastic effects as well. The processes of hazard identification, including identification of the critical response, and development of data on dose-response based on studies in humans or animals are common to both types of substances. Based on the dose-response data, a NOAEL or a LOAEL can be established based on the limited ability of any study to detect statistically significant increases in responses in exposed populations compared with controls, even though the dose-response relationship is assumed not to have a threshold. Because of the assumed form of the dose-response relationship, however, NOAEL or LOAEL is not normally used as a point of departure to establish safe levels of exposure to substances causing stochastic effects. This is in contrast to the common practice for substances causing deterministic effects of establishing safe levels of exposure, such as RfDs, based on NOAEL or LOAEL (or the benchmark dose) and the use of safety and uncertainty factors. 

---