Hazardous Waste and Risk Management - H&R characterisation - W3&4 - Fall Semester 2024 PDF

Hazardous Waste and Risk Management – PCE5333 Dr Ahmad B. Albadarin PCE Program Fall Semester 2024 1  Summary In the context of chemicals management, hazard means the ability of a chemical substance or...

Hazardous Waste and Risk Management – PCE5333 Dr Ahmad B. Albadarin PCE Program Fall Semester 2024 1  Summary In the context of chemicals management, hazard means the ability of a chemical substance or mixture to cause harm and risk relates to the probability to cause harm under certain conditions. While hazard is an intrinsic property of the chemical, risk varies depending on exposure to the chemical. The hazard of chemical substances is frequently assessed by using test systems and comparing the test results with preset criteria for specific effects. The risk depends on the hazard in combination with exposure. Exposure can be measured or, more frequently, estimated by using exposure models. Such models cover e.g. how chemicals are used, emitted, and their fate in the environment as well as within the human body. Hazard identification is the process of determining whether exposure to a substance can cause a specific adverse effect on human health or organisms in the environment. 2 2 Objectives: Hazard characterization Environmental hazard characterization The PBT/vPvB concern Human exposure assessment Risk characterization 3  Hazard characterization a quantitative description of the intrinsic property of a chemical having the potential to cause adverse effects. It is also referred to as dose-response assessment. One purpose of the hazard characterization step is to identify a numeric value that can be used as a reference value when exposure is considered in the risk characterization step. 4 Threshold effects For most adverse effects, it is assumed that chemicals show a threshold value below which the adverse effect does not occur. Regulatory efforts are generally made to keep exposures below the population threshold, which is the threshold of the most sensitive members in the population. The adverse effect that occurs at the lowest dose, or in the most sensitive test species in the case of environmental assessment, is selected as the critical effect and applied in the risk assessment. The underlying assumption is that if the critical effect is prevented from occurring, then no other more serious effects will occur. 5 With the addition of extrinsic factors, such as exposure to hazardous chemicals and/or non-chemical stressors, values of the physiological parameter in the population increase, resulting in an increased proportion of the population above the clinically-defined threshold and thus experiencing the adverse outcome. 6  Health hazard characterization The No-Observed-Adverse-Effect-Level (NOAEL) is the highest exposure level at which no statistically or biologically significant increases are seen in the frequency or severity of adverse effects, comparing the exposed population and its appropriate control population. In an experiment with NOAELs for several different endpoints, the regulatory focus is normally on the lowest one. In cases where a NOAEL has not been demonstrated experimentally, the Lowest- Observed-Adverse-Effect-Level (LOAEL) is used, which is the lowest tested dose where adverse effects are observed. 7 Alternatively, mathematical modelling can be used to determine the so-called Benchmark Dose (BMD) using several data sets. A predetermined change in the response rate of an adverse effect is selected, such as 10% increase in body weight or a 10% increase in the incidence of cancer in test animals in a long-term study. The Benchmark Dose Lowerconfidence Limit (BMDL) is the statistical lower confidence limit of the dose that produces the selected response. 8 Side note: Therapeutic Index 9 The dose descriptors (such as NOAEL, LOAEL, BMD) can be used to derive a reference value for use in the health risk assessment. The dose is generally derived by dividing the value of the dose descriptor by assessment factors (AF). The reference value is called Derived No-Effect Level - DNEL in EU legislation. 10 Non-threshold effects This is based on the ability of some chemicals to cause mutations, where even a single molecule of a mutagenic or genotoxic chemical may damage the DNA in a cell. Through cell division, this damaged cell may give rise to a group (clone) or permanently abnormal cells which may ultimately develop into e.g. a tumour or a birth defect. A genotoxic event that ultimately may lead to cancer can theoretically be induced by any exposure. 11 Non-threshold effects Any exposure will increase the likelihood of an adverse outcome. 12 A straight line is drawn from the point of departure for the observed data to the origin (where there is zero dose and zero response), or to the background level of an unexposed control population. The slope of this straight line is called the slope factor (SF). The US EPA uses the slope factor to estimate the increased lifetime cancer risk from daily oral exposure to a chemical at a dose of 1 mg/kg bw. The oral SF can be multiplied by an estimate of lifetime exposure (in mg/kg per day) to estimate the lifetime cancer risk. Cancer Risk = Exposure (dose) x Slope Factor The oral SF factor is also applied to estimate lifetime excess cancer risk upon dermal exposure to carcinogenic chemicals. In this case, the fraction of the exposure dose that is absorbed through the skin is important to consider. 13 For exposure through inhalation, the inhalation unit risk (UR) is an estimate of the increased cancer risk at an exposure level to a chemical at a concentration of 1 μg/m3 for a lifetime. The UR can be multiplied by an estimate of lifetime exposure (in μg/m3) to estimate the lifetime cancer risk. Chemicals that act through a non-threshold mechanism are usually among those chemicals that are prioritized by authorities for regulatory action, such as bans or restrictions. 14 The number of species that can be tested are limited, and since the intention is to protect the whole ecosystem, assessment factors need to be applied. For risk assessment within the EU, a toxicity reference value for the environment, the predicted no effect concentration (PNEC), below which adverse effects will most likely not occur is calculated by applying an assessment factor (AF) to the EC10 or NOEC for the most sensitive among the tested organisms. The endpoints most frequently used for derivation of PNEC are mortality (LC50), growth (EC10 or NOEC) and reproduction (EC10 or NOEC). PNEC = LC50 or EC10 or NOEC / AF 15 Example Use of slope factors. What are the maximum number of excess lifetime cancer cases expected for a population of 1,100,000 adults with a daily intake of 0.24 mg of benzene? 16 17 Acceptable daily intake (ADI) represents the amount of daily intake of a given substance which does not produce any adverse health effects. Toxicologists use ADI instead of establishing a threshold value. An ADI value is much lower than the theoretical threshold. For regulatory purpose, the safe concentration of most chemicals in food and drinking water is established by dividing the NOAEL by safety factors to obtain a value for ADI. The reference dose (RfD) is a contemporary alternative used by the EPA instead of ADI. The derivation of RfD follows a somewhat stricter scheme than what is used for an ADI, resulting in lower values for acceptable intake in some cases. 18 Derivation of a RfD. In a subchronic oral toxicity study in mice, a lowest observed-adverse-effect level (LOAEL) of 15 mg/kg–day was determined for a specific agent. The quality of the data is given a high rating by the expert evaluating the data. What is the RfD? 19 Environmental hazard characterization The objective of the environmental hazard assessment is to classify the substance regarding intrinsic hazardous properties for the environment and to determine a no-effect concentration below which adverse effects in the environmental spheres are not expected to occur. Characterization of environmental hazards for most chemicals primarily use data from testing on aquatic organisms from different trophic levels, such as algae, invertebrates, and fish. Test data on species from different trophic levels, algae, invertebrates and fish, is used to assess hazards from chemicals on aquatic systems. Such test data is also extrapolated to assess the hazard for other environmental spheres such as sediments and soils. 20 The methodology used for hazard assessment of chemicals in water and soil cannot be applied yet in the same manner to the atmosphere. The data used for environmental hazard assessment usually results from single species laboratory toxicity tests. The data is typically reported as the concentrations at which x % (e.g. 50%) mortality or inhibition of a function (e.g. growth) was observed and are expressed as the lethal concentration, LCx, or the effect concentration, ECx (e.g. LC50 or EC50). The LCx or ECx are obtained from dose-response curves. 21 LC50-values are usually obtained from short term tests, while the result of long-term tests (e.g. reproductive success) are most frequently reported as ECx (x being very often equal to 10) or as the NOEC (No Observed Effect Concentration). 22 The PBT/vPvB concern Substances that persist for long periods of time in the environment and have a high potential to accumulate are of specific concern because their long-term effects are rarely predictable. Once they have entered the environment, exposure to these substances is very difficult to reverse, even if emissions are stopped. Therefore, the EU legislation also consider whether a substance fulfils the decision-making criteria as being persistent, bioaccumulative or toxic (PBT), very persistent/very bioaccumulative (vPvB) or a persistent organic pollutant (POP). 23 The PBT/vPvB concern The PBT and vPvB criteria are agreed by the EU member states. The criteria are based on the time it takes for the substance to degrade to half of the initial concentration (T1/2) in water or sediment, the bioconcentration factor (BCF), normally between water and fish, and the toxicity (EC10 or NOEC). 24 25 Human exposure assessment Exposure (dose) assessment considers both the exposure pathways (the course a chemical takes from its source to the person(s) being exposed) as well as the exposure routes (means of entry of the chemical into the body). Exposure is usually expressed as amount per unit body weight per unit time, e.g. mg/kg bw per day. The uptake of the chemical following exposure through ingestion, inhalation or dermal contact is followed by distribution and metabolism and finally elimination. Absorption is critical for the internal dose and ensuing systemic effects 26 Risk Characterization In this step, the risk is calculated (for both carcinogens and noncarcinogens) for all receptors that may be exposed to the hazardous wastes. Noncarcinogenic risk is calculated as the hazard index (HI) which is computed as HI = I / RfD HI = the hazard index (dimensionless) I = intake (mg/kg–day) RfD = reference dose (mg/kg–day) Example: A population is exposed to lindane with an intake of Estimate the hazard index. 27 28