2,4,7,9-Tetramethyldec-5-decyne-4,7-diol: physicochemical properties and (eco)toxicological effects

Introduction

2,4,7,9-Tetramethyldec-5-decyne-4,7-diol (TMDD, CAS No:126-86-3, Figure 1) is a non-ionic surfactant with two hydrophilic moieties connected to a hydrophobic alkyne hydrocarbon chain. The physicochemical properties of TMDD allow for a broad range of applications such as adjuvant in the manufacture of paints, printing inks, adhesives, paper, pesticides, coatings, defoamers, dispersants and polymerization reactions. Due to its widespread use, 2,4,7,9-tetramethyldec-5-decyne-4,7-diol is a high-production volume chemical with a low biodegradation rate and, therefore, has a potentially high prevalence in the environment.[1] Table 1 summarizes the basic physicochemical properties of TMDD.[2]

Chemical structural characteristics of TMDD

2,4,7,9-Tetramethyldec-5-decyne-4,7-diol is a di-substituted acetylene with two hydroxyl groups arranged symmetrically to the triple bond. It is obvious that TMDD (1) can be excreted either unchanged, with one conjugated (e.g. as glucuronide) OH group (2) or with two conjugated OH groups (3) in the urine after exposure. Furthermore, hydroxylation can occur at the two alkyl residues of acetylene in different positions, which would lead to a variety of possible 2,4,7,9-tetramethyldec-5-decyne-4,7-diol metabolites including one (5), two (6) or more OH groups (7), in addition to the two hydroxyl groups of unmetabolized 2,4,7,9-tetramethyldec-5-decyne-4,7-diol. The general metabolic pathway of disubstituted alkynes [3] would suggest the formation of 4-methyl-2-pentanone (4) followed by the reduction to 4- methyl-2-pentanol (8) and the hydroxylation to 4-hydroxy-4- methyl-2-pentanone (diacetone alcohol (DAA), 9). Since the hypothetic metabolites 4, 8 and 9 are assumed to be of low specificity to TMDD exposure, this pathway was not further elaborated in the identification of suitable biomarkers for 2,4,7,9-tetramethyldec-5-decyne-4,7-diol.[1] 

(Eco)toxicological effects of TMDD

2,4,7,9-Tetramethyl-5-decyne-4,7-diol can easily reach the aquatic environment and consequently, concentrations of up to 2.5 μg/L could be detected in European rivers. TMDD is considered to have only a minor impact on the aquatic environment, whereby the risk assessment has been primarily focused around acute toxicity. The 96-h LC₅₀ values of acute fish tests with fathead minnow (Pimephales promelas) and common carp (Cyprinus carpio) are at 36 and 42 mg/L, respectively; acute tests with Daphnia magna gave 48-h EC₅₀ values of 15 mg/L. 2,4,7,9-Tetramethyl-5-decyne-4,7-diol is non-toxic after acute oral and dermal exposure. It is skin sensitizing in animal studies, slightly irritating to the skin, and causes severe eye damage. In vitro genetox tests were negative. Subchronic and reproductive toxicity studies showed NOAELs from 200 to 500 mg/kg bw . Although a study on the ecotoxicological effects of TMDD in fish revealed only minor acute toxicity, no data on the chronic and long-term toxicity of 2,4,7,9-Tetramethyl-5-decyne-4,7-diol in the aquatic environment are available, and therefore levels should be constantly monitored in surface and wastewaters.[4]

Recent studies almost exclusively focused on acute effects by 2,4,7,9-tetramethyl-5-decyne-4,7-diol , little is known about cytotoxic and genotoxic effects, reproduction and developmental toxicity, endocrine disruption, and any kind of long-term toxicity and carcinogenicity so far. The present study aims to provide more specific baseline information on the ecotoxicological effects of 2,4,7,9-tetramethyl-5-decyne-4,7-diol in fish. For this end, cyto- and genotoxicity assays were carried out in vitrowith the permanent fish cell line RTLW1; in addition, in vivo studies were conducted with the early life stages of zebrafish (Danio rerio) in order to fill the data gaps in developmental toxicity and endocrine disruption. 2,4,7,9-Tetramethyl-5-decyne-4,7-diol showed a cytotoxic and slight genotoxic potential in fish cell lines; moreover, various sublethal and lethal effects could be detected in developing zebrafish embryos. There was no evidence of endocrine-disrupting effects by TMDD; however, mortality following prolonged exposure to 2,4,7,9-tetramethyl-5-decyne-4,7-diol during fish sexual development test was clearly higher than mortality in the fish embryo test after 96-h exposure. The results thus confirmed previous findings of laboratory screening tests, suggesting short-term toxic effects of TMDD in the intermediate, and long-term effects in the lower milligram per liter range.[2]

Conclusions

Given the lack of detailed knowledge about long-term effects, mode(s) of toxic action, bioaccumulation, biotransformation,bioavailability, and mixture toxicity, it is still unclear whether 2,4,7,9-tetramethyl-5-decyne-4,7-diol can cause serious ecological damage in the aquatic environment. In any case, in response to potentially further increasing production volumes, 2,4,7,9-tetramethyl-5-decyne-4,7-diol levels should constantly be monitored in surface and wastewaters. Although the present study only revealed minor acute toxicity of TMDD, chronic and long-term effects of TMDD might have to be taken into consideration. In case of a further increase of 2,4,7,9-tetramethyl-5-decyne-4,7-diolconcentrations in waste waters, the development of appropriate elimination techniques for wastewater purification is highly recommended.[2]

References

[1] Roegner N, Pluym N, Peschel O, et al. Determination of a specific metabolite for the non-ionic surfactant 2,4,7,9-Tetramethyl-5-decyne-4,7-diol (TMDD) by UPLC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2023;1216:123584. doi:10.1016/j.jchromb.2022.123584

[2] Vincze K, Gehring M, Braunbeck T. (Eco)toxicological effects of 2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD) in zebrafish (Danio rerio) and permanent fish cell cultures. Environ Sci Pollut Res Int. 2014;21(13):8233-8241. doi:10.1007/s11356-014-2806-y

[3] Kolossa-Gehring M, Fiddicke U, Leng G, Angerer J, Wolz B. New human biomonitoring methods for chemicals of concern-the German approach to enhance relevance. Int J Hyg Environ Health. 2017;220(2 Pt A):103-112. doi:10.1016/j.ijheh.2016.10.012

[4] Pluym N, Roegner N, Peschel O, Leibold E, Scherer G, Scherer M. Human metabolism and excretion kinetics of the surfactant 2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD) after oral and dermal administration. Arch Toxicol. 2023;97(9):2419-2428. doi:10.1007/s00204-023-03547-8

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