Genotoxicity and endocrine disruption potential of haloacetic acids in human placental and lung cells

Elisabet Pérez-Albaladejo; Raquel Pinteño; María Del Carmen Aznar-Luque; Marta Casado; Cristina Postigo; Cinta Porte

doi:10.1016/j.scitotenv.2023.162981

Genotoxicity and endocrine disruption potential of haloacetic acids in human placental and lung cells

Sci Total Environ. 2023 Jun 25:879:162981. doi: 10.1016/j.scitotenv.2023.162981. Epub 2023 Mar 22.

Authors

Elisabet Pérez-Albaladejo¹, Raquel Pinteño¹, María Del Carmen Aznar-Luque¹, Marta Casado¹, Cristina Postigo², Cinta Porte¹

Affiliations

¹ Environmental Chemistry Department, IDAEA -CSIC-, C/ Jordi Girona 18-26, 08034 Barcelona, Spain.
² Technologies for Water Management and Treatment Research Group, Department of Civil Engineering, University of Granada, Campus de Fuentenueva s/n, Granada 18071, Spain; Environmental Chemistry Department, IDAEA -CSIC-, C/ Jordi Girona 18-26, 08034 Barcelona, Spain; Institute for Water Research, University of Granada, C/ Ramón y Cajal 4, Granada, 18071, Spain. Electronic address: cristina.postigo@ugr.es.

PMID: 36963690
DOI: 10.1016/j.scitotenv.2023.162981

Abstract

Chlorination of water results in the formation of haloacetic acids (HAAs) as major disinfection byproducts (DBPs). Previous studies have reported some HAAs species to act as cytotoxic, genotoxic, and carcinogenic. This work aimed at further exploring the toxicity potential of the most investigated HAAs (chloroacetic (CAA), bromoacetic (BAA), iodoacetic (IAA) acid) and HAAs species with high content of bromine (tribromoacetic acid (TBAA)), and iodine in their structures (chloroiodoacetic (CIAA) and diiodoacetic acid (DIAA)) to human cells. Novel knowledge was generated regarding cytotoxicity, oxidative stress, endocrine disrupting potential, and genotoxicity of these HAAs by using human placental and lung cells as in vitro models, not previously used for DBP assessment. IAA showed the highest cytotoxicity (EC₅₀: 7.5 μM) and ability to generate ROS (up to 3-fold) in placental cells, followed by BAA (EC₅₀: 20-25 μM and 2.1-fold). TBAA, CAA, DIAA, and CIAA showed no significant cytotoxicity (EC₅₀ > 250 μM). All tested HAAs decreased the expression of the steroidogenic gene hsd17b1 up to 40 % in placental cells, and IAA and BAA (0.01-1 μM) slightly inhibited the aromatase activity. HAAs also induced the formation of micronuclei in A549 lung cells after 48 h of exposure. IAA and BAA showed a non-significant increase in micronuclei formation at low concentrations (1 μM), while BAA, CAA, CIAA and TBAA were genotoxic at exposure concentrations above 10 μM (100 μM in the case of DIAA). These results point to genotoxic and endocrine disruption effects associated with HAA exposure at low concentrations (0.01-1 μM), and the usefulness of the selected bioassays to provide fast and sensitive responses to HAA exposure, particularly in terms of genotoxicity and endocrine disruption effects. Further studies are needed to define thresholds that better protect public health.

Keywords: Endocrine disruptors; Haloacids; Iodinated disinfection byproducts; JEG-3 cells; P450 aromatase; Reprotoxicity.

MeSH terms

Acetates
DNA Damage
Disinfectants* / toxicity
Disinfection / methods
Female
Halogenation
Humans
Placenta
Pregnancy
Trihalomethanes
Water Pollutants, Chemical* / toxicity
Water Purification* / methods

Substances

tribromoacetic acid
Acetates
Disinfectants
Water Pollutants, Chemical
Trihalomethanes