A Novel Approach to Chemical Mixture Risk Assessment—Linking Data from Population-Based Epidemiology and Experimental Animal Tests
Bornehag, Carl Gustaf LU ; Kitraki, Efthymia ; Stamatakis, Antonios ; Panagiotidou, Emily ; Rudén, Christina ; Shu, Huan ; Lindh, Christian LU
; Ruegg, Joelle
and Gennings, Chris
(2019)
In Risk Analysis
39(10).
p.2259-2271
- Abstract
Humans are continuously exposed to chemicals with suspected or proven endocrine disrupting chemicals (EDCs). Risk management of EDCs presents a major unmet challenge because the available data for adverse health effects are generated by examining one compound at a time, whereas real-life exposures are to mixtures of chemicals. In this work, we integrate epidemiological and experimental evidence toward a whole mixture strategy for risk assessment. To illustrate, we conduct the following four steps in a case study: (1) identification of single EDCs (“bad actors”)—measured in prenatal blood/urine in the SELMA study—that are associated with a shorter anogenital distance (AGD) in baby boys; (2) definition and construction of a “typical”... (More)
Humans are continuously exposed to chemicals with suspected or proven endocrine disrupting chemicals (EDCs). Risk management of EDCs presents a major unmet challenge because the available data for adverse health effects are generated by examining one compound at a time, whereas real-life exposures are to mixtures of chemicals. In this work, we integrate epidemiological and experimental evidence toward a whole mixture strategy for risk assessment. To illustrate, we conduct the following four steps in a case study: (1) identification of single EDCs (“bad actors”)—measured in prenatal blood/urine in the SELMA study—that are associated with a shorter anogenital distance (AGD) in baby boys; (2) definition and construction of a “typical” mixture consisting of the “bad actors” identified in Step 1; (3) experimentally testing this mixture in an in vivo animal model to estimate a dose–response relationship and determine a point of departure (i.e., reference dose [RfD]) associated with an adverse health outcome; and (4) use a statistical measure of “sufficient similarity” to compare the experimental RfD (from Step 3) to the exposure measured in the human population and generate a “similar mixture risk indicator” (SMRI). The objective of this exercise is to generate a proof of concept for the systematic integration of epidemiological and experimental evidence with mixture risk assessment strategies. Using a whole mixture approach, we could find a higher rate of pregnant women under risk (13%) when comparing with the data from more traditional models of additivity (3%), or a compound-by-compound strategy (1.6%).
(Less)
- author
- Bornehag, Carl Gustaf
LU
; Kitraki, Efthymia
; Stamatakis, Antonios
; Panagiotidou, Emily
; Rudén, Christina
; Shu, Huan
; Lindh, Christian
LU
; Ruegg, Joelle
and Gennings, Chris
- organization
- publishing date
- 2019-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Chemical exposure, mixtures, risk assessment, sexual development
- in
- Risk Analysis
- volume
- 39
- issue
- 10
- pages
- 13 pages
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:31173660
- scopus:85067401773
- ISSN
- 0272-4332
- DOI
- 10.1111/risa.13323
- language
- English
- LU publication?
- yes
- id
- 276b86e6-6070-4a52-b41f-a3cd1f35ee97
- date added to LUP
- 2019-07-03 10:28:27
- date last changed
- 2025-01-23 21:09:25
@article{276b86e6-6070-4a52-b41f-a3cd1f35ee97,
abstract = {{<p>Humans are continuously exposed to chemicals with suspected or proven endocrine disrupting chemicals (EDCs). Risk management of EDCs presents a major unmet challenge because the available data for adverse health effects are generated by examining one compound at a time, whereas real-life exposures are to mixtures of chemicals. In this work, we integrate epidemiological and experimental evidence toward a whole mixture strategy for risk assessment. To illustrate, we conduct the following four steps in a case study: (1) identification of single EDCs (“bad actors”)—measured in prenatal blood/urine in the SELMA study—that are associated with a shorter anogenital distance (AGD) in baby boys; (2) definition and construction of a “typical” mixture consisting of the “bad actors” identified in Step 1; (3) experimentally testing this mixture in an in vivo animal model to estimate a dose–response relationship and determine a point of departure (i.e., reference dose [RfD]) associated with an adverse health outcome; and (4) use a statistical measure of “sufficient similarity” to compare the experimental RfD (from Step 3) to the exposure measured in the human population and generate a “similar mixture risk indicator” (SMRI). The objective of this exercise is to generate a proof of concept for the systematic integration of epidemiological and experimental evidence with mixture risk assessment strategies. Using a whole mixture approach, we could find a higher rate of pregnant women under risk (13%) when comparing with the data from more traditional models of additivity (3%), or a compound-by-compound strategy (1.6%).</p>}},
author = {{Bornehag, Carl Gustaf and Kitraki, Efthymia and Stamatakis, Antonios and Panagiotidou, Emily and Rudén, Christina and Shu, Huan and Lindh, Christian and Ruegg, Joelle and Gennings, Chris}},
issn = {{0272-4332}},
keywords = {{Chemical exposure; mixtures; risk assessment; sexual development}},
language = {{eng}},
number = {{10}},
pages = {{2259--2271}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Risk Analysis}},
title = {{A Novel Approach to Chemical Mixture Risk Assessment—Linking Data from Population-Based Epidemiology and Experimental Animal Tests}},
url = {{http://dx.doi.org/10.1111/risa.13323}},
doi = {{10.1111/risa.13323}},
volume = {{39}},
year = {{2019}},
}