Evaluating Concurrent Exposures to Multiple Chemicals: Minnesota Department of Health

Evaluating Concurrent Exposures to Multiple Chemicals

In many situations a sample of groundwater contains multiple chemicals. Chemicals in combination may cause adverse effects that would not be predicted based on separate exposures to the individual concentrations of each chemical present. Therefore, evaluating the safety of a mixture of chemicals based on individual HRLs may not provide an adequate margin of safety. The procedures stated in the Health Risk Limits (HRLs) Rules for Groundwater for evaluating exposure to multiple chemicals are based on an additive model. The U.S. Environmental Protection Agency (EPA) uses this model as a reasonable approach given what is unknown about how chemicals interact in the body.  Chemicals that share a common health endpoint are evaluated together. Chemicals for which no health endpoint is specified (e.g., None) are not included in any group. Similar health endpoints with or without the endocrine (E) designation are deemed equivalent (e.g., thyroid (E) = thyroid) and should be summed together in the Health Risk Index (HRI) calculation.

For each chemical sharing a health endpoint, a ratio is calculated by comparing the groundwater concentration of the chemical to the exposure duration-specific health-based guidance for that chemical. The ratios are grouped by duration and summed within each health endpoint group.   

To determine whether the sum exceeds the multiple-chemical health index of one for noncancer, the chemicals are grouped according to their noncancer health endpoints, e.g., liver, kidney, nervous system. A ratio of the measured concentration of each chemical in groundwater to the corresponding health-based guidance value for the individual chemical is calculated for each exposure duration. For example:

This equation is used to calculate the non-cancer health risk index for mixtures of chemicals for specific time duration, such as short-term. For each chemical, the concentration of the chemical detected in the water is divided by the health risk limit for that chemical for the time duration of interest. If C1 is the concentration of the first chemical in the water in micrograms per liter, and nHRL1 is the non-cancer health risk limit for the first chemical in micrograms per liter, C1 is divided by nHRL1.  This step is repeated for each chemical in the mixture.  All of the results are added to determine the non-cancer health risk index for the mixture of chemicals for that specific time duration.

Where:
C1, C2, … CN = the concentration of the first, second, …, Nth chemical that has been detected in groundwater and that causes a specific noncancer effect (μg/L).

HRI = Health Risk Index. The noncancer HRI is determined by calculating, for each chemical with a similar health endpoint (such as liver effects), the concentration of the chemical in the water divided by the health risk limit for that chemical, and summing the resulting ratios (see below for an example). An HRI over one indicates possible exceedances.

nHRL1, nHRL2, … nHRLN = the duration-specific noncancer health risk limit of the first, second, …, Nth chemical with the same health endpoint that has been detected in groundwater (μg/L).

All carcinogens are treated as members of the same group. A ratio of the measured concentration of each individual carcinogen in groundwater to the health based guidance value for that carcinogen is calculated. Ratios are added and compared to the multiple-chemical health risk limit of one. For example:

This equation is used to calculate the cancer health risk index for mixtures of chemicals for specific time duration, such as short-term. For each chemical, the concentration of the chemical detected in the water is divided by the cancer health risk limit for that chemical. If C1 is the concentration of the first chemical in the water in micrograms per liter, and nHRL1 is the cancer health risk limit for the first chemical in micrograms per liter, C1 is divided by nHRL1.  This step is repeated for each chemical in the mixture.  All of the results (quotients) are added to determine the cancer health risk index for the mixture of chemicals for that specific time duration.

Where:
C1, C2, … CN = the concentration of the first, second, …, Nth

HRI = Health Risk Index. The cancer HRI is determined by calculating, for each chemical in the water, the concentration of the chemical divided by the cancer health risk limit for that chemical and summing the resulting ratios (see below for an example). An HRI over one indicates possible exceedances.

cHRL1, cHRL2, … cHRLN = the cancer health risk limit of the first, second, …, Nth chemical that has been detected in groundwater (μg/L).

Example Health Risk Index Calculations:

To determine the health risks when benzene, chloroform and vinyl chloride are present, the duration-specific ratio for each health endpoint is added together to derive a duration-specific health risk index for each endpoint.

Chemical

Amount detected
in water (µg/L)

Duration

HRL (µg/L)

Health Endpoint

Benzene

2.8

Acute

10

Developmental

Short-term

10

Blood system; Immune system

Subchronic

3

Blood system; Immune system

Chronic

3

Blood system; Immune system

Cancer

2

Cancer

Chloroform

1.5

Acute

ND

 --

Short-term

30

Developmental; Liver; Immune system

Subchronic

30

Developmental; Liver; Immune system; Male reproductive system

Chronic

30

Developmental; Liver; Immune system; Male reproductive system

Cancer

NA

 --

Vinyl chloride

0.4

Acute

ND

 --

Short-term

20

Liver

Subchronic

20

Liver

Chronic

10

Liver

Cancer

0.2

Cancer

NA = Not Available
ND = Not Derived (due to insufficient toxicity information)

There are no common health endpoints for the acute duration. For the short-term duration, the immune system is a common health endpoint for benzene and chloroform. The short-term hazard index for immune effects is:

The equation for the non-cancer immune health risk index (HRI) for the short-term duration is equal to two terms added together. These two terms are for benzene and chloroform in this example. The first term is 2.8 micrograms per liter of water (for benzene) divided by the short-term health risk limit for benzene, which is 10 micrograms per liter. Therefore, 2.8 divided by 10 equals 0.28. After rounding, the first term is equal to 0.3.  The second term is 1.5 micrograms per liter of water for chloroform divided by the short-term health risk limit for chloroform, which is 30 micrograms per liter of water.  Therefore, the second term is equal to 0.05. Adding these two terms results in a health risk index of 0.35.

For the subchronic duration, the immune system is a common health endpoint for benzene and chloroform and the liver system is a common health endpoint for chloroform and vinyl chloride. The subchronic hazard index for immune effects is:

The equation for the non-cancer immune health risk index (HRI) for the subchronic duration is equal to two terms added together. These two terms are for benzene and chloroform in this example. The first term is 2.8 micrograms per liter of water (for benzene) divided by the subchronic health risk limit for benzene, which is 3 micrograms per liter. Therefore, 2.8 divided by 3 equals 0.93. After rounding, the first term is equal to 0.9.  The second term is 1.5 micrograms per liter of water for chloroform divided by the subchronic health risk limit for chloroform, which is 30 micrograms per liter of water.  Therefore, the second term is equal to 0.05. Adding these two terms results in a health risk index of 0.95.

The subchronic hazard index for liver effects is:

The equation for the non-cancer liver health risk index for the subchronic duration is equal to two terms added together. These two terms are for chloroform and vinyl chloride in this example. The first term is 1.5 micrograms per liter of water (for chloroform) divided by the subchronic health risk limit for chloroform, which is 30 micrograms per liter. Therefore, 1.5 divided by 30 equals 0.05.  The second term is 0.4 micrograms per liter of water for vinyl chloride divided by the subchronic health risk limit for vinyl chloride, which is 20 micrograms per liter of water. Therefore, the second term is equal to 0.02. Adding these two terms results in a health risk index of 0.07.

For the chronic duration, the immune and liver systems are common health endpoints for the same pairings of chemicals as in the subchronic case. The chronic hazard index for immune effects is:

The equation for the non-cancer immune health risk index (HRI) for the chronic duration is equal to two terms added together. These two terms are for benzene and chloroform in this example. The first term is 2.8 micrograms per liter of water (for benzene) divided by the chronic health risk limit for benzene, which is 3 micrograms per liter. Therefore, 2.8 divided by 3 equals 0.93. After rounding, the first term is equal to 0.9.  The second term is 1.5 micrograms per liter of water for chloroform divided by the chronic health risk limit for chloroform, which is 30 micrograms per liter of water. Therefore, the second term is equal to 0.05. Adding these two terms results in a health risk index of 0.95.

The chronic hazard index for liver effects is:

he equation for the non-cancer liver health risk index for the chronic duration is equal to two terms added together. These two terms are for chloroform and vinyl chloride in this example. The first term is 1.5 micrograms per liter of water (for chloroform) divided by the chronic health risk limit for chloroform, which is 30 micrograms per liter. Therefore, 1.5 divided by 30 equals 0.05. The second term is 0.4 micrograms per liter of water for vinyl chloride divided by the chronic health risk limit for vinyl chloride, which is 10 micrograms per liter of water. Therefore, the second term is equal to 0.04. Adding these two terms results in a health risk index of 0.09.

Cancer is a common health endpoint for benzene and vinyl chloride. The cancer hazard index is:

The equation for the cancer health risk index is equal to two terms added together. These two terms are for benzene and vinyl chloride, the two chemicals with cancer health risk limit values in this example. The first term is 2.8 micrograms per liter of water (for benzene) divided by the cancer health risk limit for benzene, which is 2 micrograms per liter. Therefore, 2.8 divided by 2 equals 1.4. The second term is 0.4 micrograms per liter of water for vinyl chloride divided by the cancer health risk limit for vinyl chloride, which is 0.2 micrograms per liter of water. Therefore, the second term is equal to 2. Adding these two terms results in a health risk index of 3.4.

None of the noncancer health risk indices exceeded 1. However, the health risk index for cancer does exceed one, indicating a cancer health concern for the combined exposure to benzene and vinyl chloride.

 

Updated Thursday, August 28, 2014 at 10:21AM