# Chlorinated lipid modification of proteins: Biomarkers of chlorine gas exposure

> **NIH NIH R21** · SAINT LOUIS UNIVERSITY · 2020 · $227,250

## Abstract

Exposure to chlorine gas (Cl2) presents a significant threat to public health. Chlorine is a leading chemical
produced by volume in the US. Exposure to Cl2 has occurred as a result of train derailments, accidental
misuse by swimming pool maintenance workers, accidents at water treatment facilities, and chemical warfare.
Intentional exposure is a major concern since Cl2 is both a chemical warfare agent and potential chemical
terror agent. Diagnostic biomarkers are needed to determine the extent of Cl2 exposure to humans and to
predict outcomes, which ultimately could lead to improved therapeutic support and countermeasures. The Ford
lab discovered that both Cl2 and HOCl target host plasmalogen lipids, resulting in 2-chlorofatty aldehyde (2-CLFALD) and 2-chlorofatty acid (2-CLFA) production. These chlorinated lipids accumulate to robust levels in
lung and plasma of mice exposed to sub-lethal amounts of chlorine gas. In recent unpublished studies we have
shown plasma 2-CLFA levels are elevated 40-fold in a five-subject cohort of humans exposed to chlorine at a
water treatment facility near Birmingham, Alabama. Taken together, we have shown chlorinated lipids derived
from plasmalogen oxidation are currently the best biomarkers of Cl2 exposure to humans and have the
potential to be used to predict future outcomes that could lead to improved care following exposure.!Plasma
chlorinated lipids are quantified using LC/MS detection employing a triple quadrupole instrument. The
dependence on LC/MS detection is a limitation in implementing field analyses of Cl2 exposure using these
biomarkers. The proposed studies will address this problem by identifying chlorolipid-modified proteins
produced following Cl2 exposure. Future studies producing antibodies to chlorolipid-modified proteins could
then be used to develop diagnostic kits. It is proposed that chlorinated lipids covalently modify proteins.
The identification of specific proteins and amino acid residues modified by chlorinated lipids will be used in
future studies to develop antibodies that can be used for rapid detection assays. Additionally, it is envisioned
that identifying chlorinated lipid-modified proteins as a result of Cl2 exposure may provide new targets for future
investigations to develop countermeasures to Cl2 exposure. There are three specific aims.
Specific Aim 1 will identify amino acid motifs and proteins modified by 2-CLFALD.
Specific Aim 2 will identify amino acid motifs and proteins modified by 2-CLFA.
Specific Aim 3 will identify chlorinated lipid-modified proteins in lung and plasma from mice exposed to Cl2.
These studies will identify chlorinated lipid-modified proteins, and show that they are present in plasma of Cl2
exposed mice. Furthermore, these proposed R21 studies have the potential to lead to new investigations in the
future to develop improved countermeasures for, and improve outcomes of, Cl2 exposure.

## Key facts

- **NIH application ID:** 9936738
- **Project number:** 1R21ES031562-01
- **Recipient organization:** SAINT LOUIS UNIVERSITY
- **Principal Investigator:** DAVID A. FORD
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $227,250
- **Award type:** 1
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936738

## Citation

> US National Institutes of Health, RePORTER application 9936738, Chlorinated lipid modification of proteins: Biomarkers of chlorine gas exposure (1R21ES031562-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9936738. Licensed CC0.

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