Appendix 2 – How to Estimate Human Exposure

 1 Introduction

Appendix 2 presents the various steps in human health risk assessment associated with the discharge water from EGCS.

 2 The steps in the human health risk assessment

2.1 Hazard characterization

2.1.1 Establishing guidance levels (DNELs and DMELs) for the general public

2.1.1.1 Derivation of guidance levels

The derivation of guidance levels involves the following steps:

• Hazard identification;

• Hazard characterization;

  • ‣Definition of dose descriptor; and

  • ‣Definition of assessment factor.

As part of the hazard identification the type and nature of adverse health effects to humans are identified. The data may consist of information from epidemiological studies and animal-based toxicology studies.

The hazard characterization includes establishing guidance levels (DNELs and DMELs).

The guidance levels are levels, for chemicals with a threshold effect, below which no adverse health effects to humans are expected to occur.

However, for chemicals with a non-threshold effect, such as genotoxic carcinogens, where no lower safe limit exists, the guidance levels are associated with a low, possibly hypothetical, acceptable risk.

2.1.1.2 Dose descriptor

For all chemicals, an effect level, or reference dose, linked to potential adverse effects has to be defined. The Benchmark Dose (BMD) approach is regarded to represent a scientifically more advanced method compared to the NOAEL approach for deriving a reference dose (sometimes referred to as point-of-departure (EFSA, 2017)). The BMD₁₀ is defined as the dose for a predetermined level of response, 10% increase or decrease, compared with the background response. It is recommended to use the lower bound of a BMD₁₀, i.e. the BMDL₁₀ (US EPA, 2012).

2.1.1.3 Assessment factor or adjustment factor

When results from animal-based studies are extrapolated to the general public, one or more assessment factors are used to reduce the likelihood that the actual risks to humans are underestimated. When results from human are used, adjustment factors may be used to account for human variability.

2.1.2 Guidance values for the general public (threshold effects)

Guidance values based on epidemiological studies, when available, are always preferred (WHO, 2000), and may be retrieved from internationally recognized bodies. These include guidance values established by, for example, JECFA or EFSA for food contaminants, such as TDI, and by WHO for chemicals in drinking water.

Guideline values for chemicals in drinking-water have been established for chemicals that cause adverse health effects after prolonged periods of time. A guideline value normally represents the concentration of a chemical that does not result in any significant risk to health over a lifetime of consumption. The guideline values assume a water consumption of 2 litres per day, and a body weight of 60 kg.

A number of provisional guideline values have, however, been established based on the practical level of treatment performance or analytical achievability. In these cases, the guideline value is higher than the calculated health-based value.

Table 1: Summary of examples of guidance values used for the general public

2.1.3 Guidance values for the general public (non-threshold effects)

2.1.3.1 Approaches to risk assessment

Carcinogens can have a threshold or non-threshold mode of action. As a general rule, a risk for the general public from secondary exposure to a non-threshold carcinogenic substance is unacceptable. When it comes to the threshold carcinogens, these can be assessed by using a DNEL approach. In the case of the non-threshold carcinogens (i.e. with mutagenic potential), a different approach to risk assessment is recommended. In this guideline, the lifetime excess cancer risk level of 10^-5 is used where possible (in accordance with the WHO Drinking Water Methodology, (WHO, 2001)).

2.1.3.2 Derived Minimal Effect Level

Calculation of an exposure level corresponding to a defined low risk, a Derived Minimal Effect Level (DMEL) is possible based on a semi quantitative approach. In contrast to a DNEL, a DMEL does not represent a "safe" level of exposure. It is a risk related reference value that could be used to better target risk management measures.

2.1.3.3 The large assessment factor approach

The "large assessment factor" approach results in DMEL values represents a low concern from a public health point of view. The basis for this assessment factor is that for substances that are both genotoxic and carcinogenic, an MOE of 10,000 or higher, based on a BMDL₁₀ from an animal study, is regarded to be of low concern (EFSA, 2017).

When a BMDL₁₀ from an animal study (oral rat carcinogenicity study) is used the assessment factors shown in table 2 should be used.

Table 2: Default assessment factors in the "large assessment factor approach" (modified from ECHA, 2012)

(Equation 1)

A DMEL derived according to this approach represents an excess cancer risk of 10-5.

2.1.3.4 The slope factor approach

A slope factor is an estimate of the life-time cancer risk associated with a unit dose of a chemical through ingestion (or inhalation). The slope factor is defined as increased cancer risk from lifetime exposure to a substance by ingestion (or inhalation). It is expressed as an estimate of cancer risk associated with a unit concentration (mg/kg bw/d) or risk per mg/kg bw/d (US EPA, 2005). The slope factor may be used to derive the dose (mg/kg bw/d) associated with cancer at a specified risk level, for instance 10^-5 (or 1 in 100 000). This dose may then be used as a DMEL.

2.1.3.5 Drinking-water guideline values

Drinking-water guideline values are normally determined using a mathematical model (the linearised multistage model) for chemicals considered to be genotoxic carcinogens. These guideline values are presented as concentrations in drinking-water associated with an estimated upper-bound excess lifetime cancer risk of 10^-5.

2.2 Exposure assessment

2.2.1 How and where humans may be exposed to EGCS discharge water

Humans may be exposed to EGCS discharge water when swimming in the water where the EGCS discharge water has been discharged, or when consuming seafood that has been caught in the vicinity of the area where the EGCS discharge water has been discharged. In some areas of the world, desalinated seawater is used as drinking water which will add another way of probable exposure. In this guideline, the aggregate exposure approach, as defined by WHO/IPCS (WHO/IPCS, 2009), is applied, that is the combined exposure applicable to each scenario. The term "aggregated exposure" (or "combined exposure"), as defined by the WHO/IPCS, takes into account all relevant pathways (e.g. food, water and residential uses) as well as all relevant routes (oral, dermal and inhalation).

2.2.2 Human exposure scenario

The exposure assessment is carried out through an evaluation of different exposure scenarios. An exposure scenario is a set of information and/or assumptions that describes the situations associated with the potential exposure.

2.2.3 Situations in which the general public might be exposed to EGCS discharge water

2.2.3.1 Exposure scenarios for the general public

Indirect exposure of humans via the environment associated with EGCS discharge water may occur by consumption of seafood and swimming in the receiving water. As a general principle, consumer exposure is normally assessed as being chronic and thus taking place throughout the whole lifetime in order to protect the most vulnerable population groups.

The following situations, as shown in table 3, have been identified as likely exposure scenarios for the general public, and have been regarded as a worst-case exposure.

As the human activities listed in table 3 are not performed near the discharge points for MAMPEC calculations, the maximum PECs in the surroundings should be used as representative concentration in a worst-case exposure.

Table 3: Summary of exposure scenarios for the general public

A number of assumptions are being used in the human exposure scenarios for the general public. These assumptions are listed in table 4. In all scenarios, default parameters leading to worst-case assessment are applied. Accordingly, the body surface area of men is assumed, but the body weight of women (60 kg) is applied. The whole-body surface area for men is 1.94 m². One parameter, ingestion rate of water while swimming, is taken from the Swimodel (US EPA, 2003).

Table 4: Summary of physiological parameters in human exposure scenarios for the general public

2.2.3.2 Recreational activities (swimming) in the sea

• .1 Inhalation of chemicals partitioning into the air above the sea

  Exposure in this scenario is through inhalation of air above the sea while swimming. The concentration of chemicals in the air may be calculated while using the Henry's law constant as described below.

  The worst concentration of chemicals in the air may theoretically be calculated using the Henry's law constant. This physical law states that, the mass of gas dissolved by a given volume of solvent, is proportional to the pressure of the gas with which it is in equilibrium. The relative constant quantifies the partitioning of chemicals between the aqueous phase and the gas phase such as rivers, lakes and seas with respect to the atmosphere (gas phase). While making use of the concentration in the water phase, the concentration in the air phase is calculated accordingly:

  (Equation 2)

  • where:

• Cair	= concentration in air (mg/m3);
  H	= Henry's law constant (Pa m3/mole);
  R	= gas constant (8.314 Pa m3/mole K);
  T	= absolute temperature (K) (default = 293 K); and
  Cwater	= concentration in the water, i.e. maximum PECMAMPEC in surroundings (μg/L).

  The concentration in water is the maximum predicted environmental concentration (PEC) value in surroundings as calculated by MAMPEC, and taking into account a dilution factor of 100 (due to wind, turbulence and insufficient time for the chemical to reach equilibrium) (EUSES, 2016). The inhaled dose may be estimated using the equation below, while taking into account various assumptions (number of swims, etc.).

  (Equation 3)

  where:

  DoseInh	= inhalation intake of chemical during swimming (μg/kg bw/d);
  Cair	= concentration in air (mg/m3);
  VR	= ventilation rate – light activity assumed (1.25 m3/h);
  n	= number of swims per day (2/d);
  Durswim	= duration of each swim (0.5 h);
  Bioinh	= fraction of chemical absorbed through the lungs (default = 1); and
  BW	= body weight (default = 60 kg).

• .2 Dermal exposure to chemicals while swimming in the sea

  Option 1.

  • Exposure in this scenario is via dermal uptake of chemicals when swimming and where the permeability coefficient (Kp) is known, using the following equation,

  (Equation 4.1)

  where:

  Doseder	= dermal uptake per day during swimming (μg/kg bw/d);
  Cwater	= concentration in the water, i.e. maximum PECMAMPEC in surroundings (μg/L);
  Kp	= dermal permeability coefficient (cm/h);
  Durswim	= duration of each swim (0.5 h);
  n	= number of swims per day (2/d);
  Askin	= surface area of whole body being exposed to water (1.94 m2);
  Bioder	= bioavailability for dermal intake (default = 1); and
  BW	= body weight (60 kg).

  Option 2

  • If the Kp value is unknown, the following equation may be used as a conservative approach (ECHA, 2016),

  (Equation 4.2)

  where:

  Doseder	= dermal uptake per day during swimming (μg/kg bw/d);
  Cwater	= concentration in the water, i.e. maximum PECMAMPEC in surroundings (μg/L);
  THder	= thickness of the product layer on the skin (0.0001 m);
  N	= number of swims per day (2/d);
  Askin	= surface area of whole body being exposed to water (1.94 m2);
  Bioder	= bioavailability for dermal intake (default = 1); and
  BW	= body weight (default = 60 kg).

• .3 Swallowing of water contaminated with EGCS discharge water

  The oral uptake via swimming is calculated according to the following:

  (Equation 5)

  where:

  DoseOral	= amount of chemical swallowed (μg/kg bw/d);
  Cwater	= concentration in the water, i.e. maximum PECMAMPEC in surroundings (μg/L);
  IRswim	= ingestion rate of water while swimming (0.025 L/h);
  N	= number of swims per day (2/d);
  Durswim	= duration of each swim (0.5 h);
  Biooral	= bioavailability for oral intake (default = 1); and
  BW	= body weight (default = 60 kg).

2.2.3.3 Eating seafood exposed to EGCS discharge water

The concentration of chemicals in the seafood that is being consumed is calculated in this way:

C_fish = BCF · C_water (Equation 6)

where:

The calculation of concentrations in seafood has to be carried out for all chemicals. The cut-off value for the bioconcentration factor as described for the environmental risk assessment (paragraph 6.6.3) is not applicable in the risk assessment for human health. Making the assumption that people in the area only consume fish that is being caught locally (worst-case scenario), the daily intake may be calculated in the following way:

(Equation 7)

where:

2.2.3.4 Drinking water made from receiving water that may have been contaminated by EGCS discharge water:

• .1 Inhalation of chemicals volatilisation from drinking water while showering

  Exposure in this scenario is through inhalation of chemicals volatilising from drinking water while showering. The concentration of chemicals in the air may be calculated while using the Henry's law constant as already described in equation 1. The concentration in the drinking water is the same as in the scenario 2.2.3.2 and 2.2.3.3, while also taking into consideration a removal ratio of 10 in Reverse Osmosis (RO) desalination process (Smol, M. and Włodarczyk-Makuła, M., 2017), based on the concentration in the receiving water (i.e. the maximum PECs in the surroundings of MAMPEC calculation).

  (Equation 8)

  where:

  Cair	= concentration in air (mg/m3);
  H	= Henry's law constant (Pa m3/mole);
  R	= gas constant (8.314 Pa m3/mole K);
  T	= absolute temperature (K) (default = 293 K); and
  CDW	= concentration in the drinking water, i.e. maximum PECMAMPEC in surroundings (μg/L)·0.9 (μg/L).

  The inhaled dose, while showering, may be estimated using the equation below, while taking into account various assumptions,

  (Equation 9)

  where:

  DoseInh	= inhalation intake of chemical during swimming (μg/kg bw/d);
  Cair	= concentration in air (mg/m3);
  VR	= ventilation rate – light activity assumed (1.25 m3/h);
  N	= number of showers per day (1/d);
  Durshow	= duration of each shower (0.75 h);
  Bioinh	= fraction of chemical absorbed through the lungs (default = 1); and
  BW	= body weight (default = 60 kg).

• .2 Dermal exposure to chemicals while showering

  Option 1

  Exposure in this scenario is via dermal uptake of chemicals when taking a shower, and where the dermal permeability coefficient (Kp) is known, is calculated using the following equation,

  (Equation 10.1)

  where:

  Doseder	= dermal uptake per day during swimming (μg/kg bw/d);
  CDW	= concentration in the drinking water, i.e. maximum PECMAMPEC in surroundings (μg/L)·0.9 (μg/L);
  Kp	= dermal permeability coefficient (cm/h);
  Durshow	= duration of each shower (0.75 h);
  N	= number of showers per day (1/d);
  Askin	= surface area of whole body being exposed to water (1.94 m2);
  Bioder	= bioavailability for dermal intake (default = 1); and
  BW	= body weight (60 kg).

  Option 2

  If the K_p value is unknown, the following equation may be used as a conservative approach,

  (Equation 10.2)

  where:

  Doseder	= dermal uptake per day during swimming (μg/kg bw/d);
  CDW	= concentration in the drinking water, i.e. maximum PECMAMPEC in surroundings (μg/L)·0.9 (μg/L);
  THder	= thickness of the product layer on the skin (0.0001 m);
  N	= number of showers per day (1/d);
  Askin	= surface area of whole body being exposed to water (1.94 m2);
  Bioder	= bioavailability for dermal intake (default = 1); and
  BW	= body weight (default = 60 kg).

• .3 Ingestion exposure to chemicals in drinking water

  The oral uptake via drinking water is calculated according to the following,

  (Equation 11)

  where:

  DoseOral	= amount of chemical swallowed (μg/kg bw/d);
  CDW	= concentration in the drinking water. i.e. maximum PECMAMPEC in surroundings (μg/L)·0.9 (μg/L);
  IRdrink	= ingestion rate of drinking water (2 L/d);
  Biooral	= bioavailability for oral intake (default = 1); and
  BW	= body weight (default = 60 kg).

2.2.4 Concluding remarks

It should be noted that while the above situations have been identified as typical worst-case exposure scenarios, it is recognized that there will be other situations when exposure of the general public may be greater or less, and consideration should be given to such situations. In addition, the consumer exposure (general public) is normally assessed as chronic/lifetime risk in order to protect the most vulnerable population groups.

2.3 Risk characterization and acceptance criteria

2.3.1 General approach

The Risk Characterization Ratios (RCR) compares the exposure estimates to various DNELs or DMELs. The RCR is calculated according to the following formulae:

• (Equation 12)

Or

• (Equation 13)

In both cases, RCR should be used as acceptance criteria. If the RCR < 1, the exposure will lead to no unacceptable risk. However, risks are regarded to be controlled when the estimated exposure levels exceed the DNEL and/or the DMEL, that is, if the RCR ≥ 1.

2.3.2 Health risks for the general public

In the three scenarios applicable for the general public, swimming in seawater contaminated with EGCS discharge water, ingestion of seafood which has been exposed to EGCS discharge water and ingestion of drinking water prepared from receiving water that may have been contaminated by the EGCS discharge water, are taken into consideration.

Aggregated exposure (through swimming, consumption of seafood and drinking water prepared from receiving water that may have been contaminated by the EGCS discharge water), that is the combined exposure applicable to each scenario, is estimated.

The total amount of chemicals that is absorbed as a result of the exposure to the general public, whilst swimming in the sea, eating fish and being exposed to drinking water through showering and drinking water consumption, may be summarised as in table 5.

Table 5: General public scenario – DNEL approach

The risk-related reference value (DMEL) may be used to calculate an indicative RCR regarding potential cancer risk. DMELs can be used to estimate a risk dose based on the probability of increased cancer incidence over a lifetime (10^-5) for the general public (table 6).

Table 6: General public scenario – DMEL approach

2.3.3 Mixture toxicity (including dose addition approach)

EGCS discharge water frequently contains mixtures of several chemicals which lead similar mechanism in human systems. One possible way to deal with this situation is to adopt an established international risk assessment approach (known as "grouping" or "dose addition"; Kortenkamp, et al., 2009), which entails a summation of the Risk Characterization Ratios (RCRs) of all substances with recognized carcinogenic potential. This approach had, for example, been used previously for carcinogens by the US EPA (US EPA, 1989), where it is based on the assumption that for carcinogens no dose threshold exists, and that the dose-response function is therefore essentially linear. Thus, if the EGCS discharge water contains two or more chemicals with the same toxicological effect, these could be evaluated as an "assessment group". The RCR for an assessment group is calculated by the addition of all RCRs of the individual components,

• (Equation 14)

where:

RCRn = the Risk Characterization Ratios shown in table 5 or table 6.

For the group RCR, the same conclusions apply as described above, that is, if the RCR < 1 using the RCRs in table 6, the exposure is deemed to represent no unacceptable risk. If still an unacceptable risk is identified, further refinement of the exposure assessment and/or the assessment factors might be performed giving special attention to route-specific contributions and additional RMM.

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