Toxicological and environmental evaluation of the two-phase immersion cooling fluid HFO-153-10mczz-E

Overview

HFO-153-10mczz-E is a volatile, non-flammable hydrofluoroolefin (HFO) developed as a dielectric fluid in heat-transfer applications such as two-phase immersion cooling (2-PIC). Its high vapour pressure and low water solubility indicate inhalation is the primary route of exposure. The review compiles physical-chemical properties, atmospheric fate, inhalation toxicology, genotoxicity and reproductive studies, and a 2025 WEEL occupational exposure limit. The fluid falls in the short-chain PFAS category under the OECD structural definition.

Properties: boiling point of 48.8 °C, melting point below -54 °C, no flash point across 0-40 °C, autoignition temperature of 580 °C and water solubility of 794.1 µg/L. Estimated atmospheric lifetimes are 71 days for the (E)-isomer and 37 days for the (Z)-isomer; GWP of the (E)-isomer is 36, 10 and 3 for 20-, 100- and 500-year horizons. The 13-week rat inhalation study found no adverse effects up to 3,037 ppm (NOAEC), and the WEEL committee used a 3,000 ppm point of departure to set a recommended occupational exposure limit of 200 ppm. Acute data classify the compound as 'Practically Non-toxic' on the Hodge and Sterner scale (LC50 between 5,000 and 15,000 ppm).

2-PIC fluids need low boiling points (40-60 °C), high dielectric strength, non-flammability and material compatibility, so feasible substitutes are a narrow class of high-volatility dielectrics; single-phase oils and esters are not viable replacements. The authors conclude it is low-hazard with limited exposure potential, mainly by inhalation.

Limits: all underlying studies were sponsored by the manufacturer (Chemours), and the authors flag gaps in chronic, endocrine and real-world release data: limited human toxicokinetic and endocrine data, aquatic-test limitations from volatility, and scarce occupational exposure and release data. Developments in PFAS regulation may affect selection.

Key points

1. HFO-153-10mczz-E meets the OECD structural definition of a PFAS and falls in the short-chain PFAS category.
2. Boiling point 48.8 °C, melting point below -54 °C, no flash point across 0-40 °C, autoignition temperature 580 °C and water solubility 794.1 µg/L.
3. Estimated atmospheric lifetimes are 71 days for the (E)-isomer and 37 days for the (Z)-isomer; GWP of the (E)-isomer is 36, 10 and 3 for 20-, 100- and 500-year horizons.
4. The 13-week rat inhalation study found no adverse effects up to 3,037 ppm (NOAEC); the WEEL committee used a 3,000 ppm point of departure to set a recommended occupational exposure limit of 200 ppm.
5. Acute data classify the compound as 'Practically Non-toxic' on the Hodge and Sterner scale (LC50 between 5,000 and 15,000 ppm).
6. 2-PIC fluids need low boiling points (40-60 °C), high dielectric strength, non-flammability and material compatibility; single-phase oils and esters are not viable replacements.
7. Stated uncertainties include limited human toxicokinetic and endocrine data, aquatic-test limitations from volatility, scarce occupational exposure and release data, and that all toxicity studies were performed on behalf of Chemours.

Using it in design

• When selecting a two-phase immersion fluid, add toxicology and occupational exposure limit (here WEEL 200 ppm) to the specification alongside boiling point (40-60 °C), dielectric strength, non-flammability and material compatibility.
• Assess the fluid's short-chain PFAS status and regulatory risk in procurement and operating decisions.
• Document in the alternatives assessment that single-phase oils and esters are not viable 2-PIC replacements, and consider ventilation and detection for fluid release and inhalation exposure.

Who should read it

Engineers and specialists selecting two-phase immersion cooling fluids and doing procurement and EHS assessment.

Document contents

1. 1 Introduction
2. 2 Materials and methods
3. 3 Physical, chemical, and environmental fate (3.1 Physicochemical properties, 3.2 Partitioning, 3.3 Biodegradability, 3.4 Environmental fate)
4. 4 Toxicology (4.1 Acute and subacute toxicity, 4.2 Reproductive and developmental, 4.3 Genotoxicity and mutagenicity, 4.4 Cardiac sensitization, 4.5 Eye irritation, 4.6 Skin irritation and sensitization, 4.7 Environmental/aquatic toxicity)
5. 5 Discussion (5.1 Human health hazard profile, 5.2 Environmental hazard, 5.3 Alternatives assessment considerations, 5.4 Uncertainties and implications for use)
6. 6 Conclusion

Related standards

• OECD PFAS definition (2021)
• OECD Test Guidelines (GLP)

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Publication details

Authors

Grayson Abele; Sarah Smallets; My Hua; Aryatara Shakya; David Brew; Patricia Underwood; Dennis Paustenbach

Publisher

Frontiers in Toxicology (Frontiers Media SA)

Year

2026

Volume

8

Pages

1840120

Document language

English

Source type

Scientific

Access

Open licence — downloadable

DOI

10.3389/ftox.2026.1840120

Licence

CC BY 4.0 — share with attribution

Licence evidence

doi.org

Citation