TY - BOOK
T1 - Identification and Reclassification of Mutagenic Chemicals for Improved Human Health Screening Levels
AU - Stewart, Debra J.
AU - Dolislager, Fredrick G.
AU - Begley, Sierra D.
AU - Bhat, Tara A.
AU - Manning, Karessa L.
AU - Noto, Katie A.
AU - Armstrong, Anthony Q.
PY - 2024/10
Y1 - 2024/10
N2 - The United States Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) produces the Regional Screening Levels (RSLs) for environmentally contaminated Superfund sites across all EPA regions. The RSLs are health-based screening levels for residential and commercial/industrial exposures to soil, air, and tap water that are deemed protective of human health for noncarcinogenic and carcinogenic chemicals by the EPA. The RSL website (as of May 2024) provides a calculator, default equations, and tables of screening levels for 858 chemicals, including noncarcinogenic and carcinogenic chemicals. Some chemical carcinogens cause damage by a mutagenic mode of action (MOA), which may result in irreversible changes to DNA and exhibit a greater adverse effect in early-life versus later-life exposure. For these chemicals, the RSLs include separate equations to provide an extra level of protection for the child age segments of 0-2, 2-6, and 6-16 years. In fact, this report shows that a chemical identified to act via a mutagenic mode of action will have a smaller and more protective RSL value (up to 78% decrease) than if it was not identified as a mutagen. Previous work by the EPA identified some chemicals as mutagens and provided them on a former EPA website, “Chemicals with a Mutagenic Mode of Action (MOA) for Carcinogenesis” (Web Archive 2015). That site contained 19 known mutagens, and the associated technical guidance recommended updating the list of mutagens based on future EPA IRIS and PPRTV toxicity assessments. Chemicals not included in the list were generally not treated as mutagens in the RSL calculations. Since the website was deactivated in 2015, only 8 additional chemicals were identified by EPA as mutagens and included in the RSL calculations, bringing the total to 27 chemicals identified as mutagens in the May 2024 RSLs. This report investigates mutagenicity in the toxicity profiles for the 251 non-mutagenic chemicals with an oral or inhalation cancer toxicity value in the May 2024 RSLs. Definitive evidence for a mutagenic mode of action was found in 5 chemicals that the RSL workgroup is including as mutagens in the November 2024 RSLs. Strong evidence for a mutagenic mode of action was found in 10 chemicals currently not identified in the May 2024 RSLs as mutagenic (classified as “yes” in this paper). Another 16 chemicals are classified as “likely” mutagenic, and 74 chemicals are classified as “cannot be determined (CBD)”. This research strongly recommends the 10 chemicals identified as “yes” be reclassified as mutagens by the EPA for use in the RSLs. It is recommended that the 16 chemicals classified as “Likely” mutagenic by this research be verified by EPA toxicologists for potential mutagen classification. The chemicals classified herein as “CBD” need a more extensive review and evaluation for potential classification as a mutagen.
AB - The United States Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) produces the Regional Screening Levels (RSLs) for environmentally contaminated Superfund sites across all EPA regions. The RSLs are health-based screening levels for residential and commercial/industrial exposures to soil, air, and tap water that are deemed protective of human health for noncarcinogenic and carcinogenic chemicals by the EPA. The RSL website (as of May 2024) provides a calculator, default equations, and tables of screening levels for 858 chemicals, including noncarcinogenic and carcinogenic chemicals. Some chemical carcinogens cause damage by a mutagenic mode of action (MOA), which may result in irreversible changes to DNA and exhibit a greater adverse effect in early-life versus later-life exposure. For these chemicals, the RSLs include separate equations to provide an extra level of protection for the child age segments of 0-2, 2-6, and 6-16 years. In fact, this report shows that a chemical identified to act via a mutagenic mode of action will have a smaller and more protective RSL value (up to 78% decrease) than if it was not identified as a mutagen. Previous work by the EPA identified some chemicals as mutagens and provided them on a former EPA website, “Chemicals with a Mutagenic Mode of Action (MOA) for Carcinogenesis” (Web Archive 2015). That site contained 19 known mutagens, and the associated technical guidance recommended updating the list of mutagens based on future EPA IRIS and PPRTV toxicity assessments. Chemicals not included in the list were generally not treated as mutagens in the RSL calculations. Since the website was deactivated in 2015, only 8 additional chemicals were identified by EPA as mutagens and included in the RSL calculations, bringing the total to 27 chemicals identified as mutagens in the May 2024 RSLs. This report investigates mutagenicity in the toxicity profiles for the 251 non-mutagenic chemicals with an oral or inhalation cancer toxicity value in the May 2024 RSLs. Definitive evidence for a mutagenic mode of action was found in 5 chemicals that the RSL workgroup is including as mutagens in the November 2024 RSLs. Strong evidence for a mutagenic mode of action was found in 10 chemicals currently not identified in the May 2024 RSLs as mutagenic (classified as “yes” in this paper). Another 16 chemicals are classified as “likely” mutagenic, and 74 chemicals are classified as “cannot be determined (CBD)”. This research strongly recommends the 10 chemicals identified as “yes” be reclassified as mutagens by the EPA for use in the RSLs. It is recommended that the 16 chemicals classified as “Likely” mutagenic by this research be verified by EPA toxicologists for potential mutagen classification. The chemicals classified herein as “CBD” need a more extensive review and evaluation for potential classification as a mutagen.
KW - 54 ENVIRONMENTAL SCIENCES
KW - 63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
U2 - 10.2172/2475718
DO - 10.2172/2475718
M3 - Commissioned report
BT - Identification and Reclassification of Mutagenic Chemicals for Improved Human Health Screening Levels
CY - United States
ER -