The potential risk of 1,2-hexanediol

Introduction

1,2-Hexanediol is one of the most widely used preservatives in the cosmetic industry with powerful antibacterial activity. The molecular formula is C₆H₁₄O₂ and molecular weight of 1,2-Hexanediol is 118.17. It is liquid form with light yellow color (Figure 1) with boiling point of 223℃and 0.951 g/mL of density at 25℃. It is also commonly used as an emollient and moisturizing agent [1]. 1,2-Hexanediol is a relatively new compound, and is categorized as a solvent or a moisturizing agent in many countries. Therefore, personal care products containing this chemical are sometimes labeled as ‘preservative free’ or ‘antiseptic free’. This, at least in part, explains why the usage of 1,2-hexanediol has increased in recent years. However, toxicity studies of 1,2-hexanediol reported atscientific journals are not enough. Previous studies includes dermal sensitivity [2] and toxicity to Daphnia species [1], but was not able to locate more papers about toxicity or safety.Therefore, further investigation of the toxicity of 1,2-hexanediol is needed.

In this study, Uhram Song etal. tested the potential toxicity of 1,2-hexanediol using phytotoxicity testing methods and RAW 264.7/HK2 cell lines.[3]

Phytotoxicity

In L. sativa, 1,2-hexanediol blocked seed germination at the lowest concentration (0.1%), indicating that 1,2-hexanediol is highly phytotoxic, showing similar results of germination inhibition as herbicides. For B. campestris, the seeds germinated in 0.1% treatment, which did not germinate at all in 1% and 5% treatment. The possible reason is that the thickness of the seed coat reduces the penetration of 1,2-hexanediol into the embryo. Nevertheless, B.campestris seeds showed no germination at higher concentrations (1% and 5%) , indicating that 1,2-hexanediol is phytotoxic. Therefore, at low and environmentally realistic concentrations, 1,2-hexanediol would likely damage plants when released into the environment.

The effect of 1,2-hexanediol on plant root elongation had also been examined. L. sativa plants treated with 1,2-hexanediol showed no root growth. After treatment with 1,2-hexanediol, the seedlings of both plants died. This phenomenon further confirms that even at the lowest concentration (0.1%), 1,2-hexanediol may affect the environment.

These results indicate that when 1,2-hexanediol-containing products used by humans are released into the environment, the impact on plants could be considerable. Therefore, further research is required to assess the safety of 1,2-hexanediol. Furthermore, since 1,2-hexanediolwas more phytotoxic than cetrimonium bromide, which is toxic to humans, it is possible that 1,2-hexanediol is also toxic to humans.Phytotoxicity is not a direct indicator of human toxicity, but phytotoxicity testing is often used to determine the potential risk of a chemical to humans. Because the results of a dermal test do not represent those of a chemical taken orally or one that gains entryinto a blood vessel through a wound, further toxicity testing of 1,2-hexanediol is required.[3]

Cytotoxicity

LPS-induced Raw 264.7 cells significantly increased NO production and showed significantly decreased NO levels from 0.5% 1,2-hexanediol treatment. It confirmed that the viability of RAW264.7 cells was significantly reduced to < 40% upon treatment with≥0.5% 1,2-hexanediol.  The reduction in NO production was caused by the death of RAW 264.7 cells and not by the inhibition of NO production. It is proved that 1,2-Hexanediol at a concentration of 0.5% has considerable toxicity.

Cosmetic products usually contain>2% 1,2-hexanediol. Therefore, the stability of such products should be investigated further. Because 1,2-hexanediol was highly toxic to RAW 264.7 cells, we tested its effect on HK-2 cells. The viability of HK-2 cells treated with≥1.0% 1,2-hexanediol decreased to<10%. Thus, 1,2-hexanediol showed >50% cytotoxicity at 1.0% concentration.Since most personal care products contain>2% 1,2-hexanediol, it is highly likely that 1,2-hexanediol is toxic to humans.[3]

Conclusions

1,2-Hexanediol showed strong phytotoxicity, as it inhibited the germination of seeds and decreased the survival of mature plants. The toxicity of 1,2-hexanediol on plants was greater than that of cetrimonium bromide on humans, which suggests that we should not exclude the possibility that 1,2-hexanediol could be toxic to humans as notorious human toxic chemical, cetrimonium bromide. In addition, both RAW 264.7 and HK-2 cells showed high toxicity at a concentration of 1.0% 1,2-hexanediol. Since the concentration of 1,2-hexanediol in cosmetic products is usually > 2%, it is possible that the use of these products is harmful to humans. Just as silver nanoparticles, once believed to be a next-generation preservative but are not widely used by these cytotoxic problems [4], we must take more caution for using 1,2-hexanediol with cytotoxicity. Because skin application of a chemical does not produce the same results as oral intake or entry into a blood vessel through an open wound, further toxicity testing of 1,2-hexanediol is needed to ensure human safety. The results suggest that when1,2-hexanediol is released into the environment, it could have a considerable impact on plants and other organisms, which further emphasizes the need for further investigation of the toxicity of 1,2-hexanediol.

References

[1] Lee J, Park N, Kho Y, Lee K, Ji K. Phototoxicity and chronic toxicity of methyl paraben and 1,2-hexanediol in Daphnia magna. Ecotoxicology. 2017;26(1):81-89. doi:10.1007/s10646-016-1743-6

[2] Levy SB, Dulichan AM, Helman M. Safety of a preservative system containing 1,2-hexanediol and caprylyl glycol. Cutan Ocul Toxicol. 2009;28(1):23-24. doi:10.1080/15569520802636082

[3] Song U, Kim J. Assessment of the potential risk of 1,2-hexanediol using phytotoxicity and cytotoxicity testing. Ecotoxicol Environ Saf. 2020;201:110796. doi:10.1016/j.ecoenv.2020.110796

[4] Margriet, V. D Z ,Park,et al.The effect of particle size on the cytotoxicity, inflammation, developmental toxicity and genotoxicity of silver nanoparticles - ScienceDirect[J].Biomaterials, 2011, 32(36):9810-9817.DOI:10.1016/j.biomaterials.2011.08.085.

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