TY - JOUR
T1 - Establishing a health-based recommended occupational exposure limit for isoflurane using experimental animal data
T2 - a systematic review protocol
AU - Struijs, Fréderique
AU - Hooijmans, Carlijn R
AU - Buijs, Marije
AU - Dahan, Albert
AU - Hoffmann, Sebastian
AU - Kiffen, Romy
AU - Mandrioli, Daniele
AU - Menon, Julia
AU - Ritskes-Hoitinga, Merel
AU - Roeleveld, Nel
AU - de Ruijter, Anne
AU - Scheffer, Gert Jan
AU - Schlünssen, Vivi
AU - Scheepers, Paul T J
PY - 2023/12
Y1 - 2023/12
N2 - BACKGROUND: Isoflurane is used as an inhalation anesthetic in medical, paramedical, and veterinary practice. Epidemiological studies suggest an increased risk of miscarriages and malformations at birth related to maternal exposure to isoflurane and other inhalation anesthetics. However, these studies cannot be used to derive an occupational exposure level (OEL), because exposure was not determined quantitatively and other risk factors such as co-exposures to other inhalation anesthetics and other work-related factors may also have contributed to the observed adverse outcomes. The aim of this systematic review project is to assess all available evidence on the effects of isoflurane in studies of controlled exposures in laboratory animals to derive a health-based recommended OEL.METHODS: A comprehensive search strategy was developed to retrieve all animal studies addressing isoflurane exposure from PubMed, EMBASE, and Web of Science. Title-abstract screening will be performed by machine learning, and full-text screening by one reviewer. Discrepancies will be resolved by discussion. We will include primary research in healthy, sexually mature (non human) vertebrates of single exposure to isoflurane. Studies describing combined exposure and treatments with > = 1 vol% isoflurane will be excluded. Subsequently, details regarding study identification, study design, animal model, and intervention will be summarized. All relevant exposure characteristics and outcomes will be extracted. The risk of bias will be assessed by two independent reviewers using an adapted version of the SYRCLE's risk of bias tool and an addition of the OHAT tool. For all outcomes for which dose-response curves can be derived, the benchmark dose (BMD) approach will be used to establish a point of departure for deriving a recommended health-based recommended OEL for 8 h (workshift exposure) and for 15 min (short-term exposure).DISCUSSION: Included studies should be sufficiently sensitive to detect the adverse health outcomes of interest. Uncertainties in the extrapolation from animals to humans will be addressed using assessment factor. These factors are justified in accordance with current practice in chemical risk assessment. A panel of experts will be involved to reach consensus decisions regarding significant steps in this project, such as determination of the critical effects and how to extrapolate from animals to humans.SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022308978.
AB - BACKGROUND: Isoflurane is used as an inhalation anesthetic in medical, paramedical, and veterinary practice. Epidemiological studies suggest an increased risk of miscarriages and malformations at birth related to maternal exposure to isoflurane and other inhalation anesthetics. However, these studies cannot be used to derive an occupational exposure level (OEL), because exposure was not determined quantitatively and other risk factors such as co-exposures to other inhalation anesthetics and other work-related factors may also have contributed to the observed adverse outcomes. The aim of this systematic review project is to assess all available evidence on the effects of isoflurane in studies of controlled exposures in laboratory animals to derive a health-based recommended OEL.METHODS: A comprehensive search strategy was developed to retrieve all animal studies addressing isoflurane exposure from PubMed, EMBASE, and Web of Science. Title-abstract screening will be performed by machine learning, and full-text screening by one reviewer. Discrepancies will be resolved by discussion. We will include primary research in healthy, sexually mature (non human) vertebrates of single exposure to isoflurane. Studies describing combined exposure and treatments with > = 1 vol% isoflurane will be excluded. Subsequently, details regarding study identification, study design, animal model, and intervention will be summarized. All relevant exposure characteristics and outcomes will be extracted. The risk of bias will be assessed by two independent reviewers using an adapted version of the SYRCLE's risk of bias tool and an addition of the OHAT tool. For all outcomes for which dose-response curves can be derived, the benchmark dose (BMD) approach will be used to establish a point of departure for deriving a recommended health-based recommended OEL for 8 h (workshift exposure) and for 15 min (short-term exposure).DISCUSSION: Included studies should be sufficiently sensitive to detect the adverse health outcomes of interest. Uncertainties in the extrapolation from animals to humans will be addressed using assessment factor. These factors are justified in accordance with current practice in chemical risk assessment. A panel of experts will be involved to reach consensus decisions regarding significant steps in this project, such as determination of the critical effects and how to extrapolate from animals to humans.SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022308978.
KW - Animals
KW - Infant, Newborn
KW - Female
KW - Humans
KW - Isoflurane/adverse effects
KW - Anesthetics, Inhalation/toxicity
KW - Systematic Reviews as Topic
KW - Animals, Laboratory
KW - Occupational Exposure/adverse effects
KW - Animal studies
KW - Inhalation anesthetic
KW - Reproductive and developmental toxicity
KW - Work place standard
KW - Occupational exposure
UR - http://www.scopus.com/inward/record.url?scp=85171387578&partnerID=8YFLogxK
U2 - 10.1186/s13643-023-02331-0
DO - 10.1186/s13643-023-02331-0
M3 - Review
C2 - 37710304
SN - 2046-4053
VL - 12
JO - Systematic Reviews
JF - Systematic Reviews
IS - 1
M1 - 166
ER -