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Description of key information

It is an inherent property of the registered substance to hydrolyse rapidly to boric acid, triethylenglycol and diethylenglycol (hydrolysis half-life < 10 minutes at pH values of 1.4, 4, 7 and 9). Therefore, absorption, distribution and metabolism of B-TEGME itself is not expected, but systemic availability of hydrolysis products of B-TEGME cannot be excluded. The hydrolysis products of B-TEGME are known to be very soluble in water and to have low partition coefficient values, i.e. logP<1. Therefore, no bioaccumulation of B-TEGME itself or its hydrolysis products is expected.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
Absorption rate - dermal (%):
Absorption rate - inhalation (%):

Additional information

There are no specific studies available in which the toxicokinetic properties (absorption, metabolism, distribution, elimination) of the tris[2-[2-(2-methoxyethoxy)ethoxy]ethyl] orthoborate (referred to as “B-TEGME”) have been investigated.


The expected toxicokinetic behaviour is derived from physico-chemical properties and results from the available acute and repeated dose toxicity studies.


Physico-chemical properties:

B-TEGME is a borated glycol ether with the molecular formula C21H45BO12 and has a molecular weight of ~500.39 g/mol. It is not possible to determine a solubility for the test substance as it hydrolyses spontaneously at pH 1.4, 4, 7 and 9 (IR spectrum of the substance is altered immediately and dramatically after addition of water). The hydrolysis products (Triethylenglycol, Diethylenglycol and Boric acid) are known to be very soluble in water as discussed in the section ‘Physical and chemical properties’ of the dossier. An experimental determination of the partition coefficient is not applicable due to spontaneous hydrolysis. The partition coefficients of the hydrolysis products are logP<1 (obtained from the ECHA dissemination view, 10/26/2018). The vapour pressure of B-TEGME is 120 Pa at 20°C and 410 Pa at 50°C. A boiling point was not measured because B-TEGME begins to decompose at 330°C and thus might have no boiling point.


Oral absorption:

Due to the nature of B-TEGME (large molecular weight) and the knowledge of the spontaneous hydrolysis an oral absorption of B-TEGME itself is assumed to be low. However, oral absorption of the hydrolysis products triethylenglycol, diethylenglycol and boric acid is possible.

In the acute oral toxicity studies [1,2] no adverse effects were observed and LD50 values of >2,000 mg/kg bw/day and >3,000 mg/kg bw/day were reported.

In the 28d repeated dose study with a brake fluid containing 17% B-TEGME [3] neither adverse effects nor unscheduled deaths were reported and the NOAEL was 1,000 mg/kg bw/day, i.e. 170 mg/kg bw/day B-TEGME. The 90d repeated dose study on B-TEGME [4] resulted in a NOAEL of 1,000 mg/kg bw/day. All observed effects were within normal ranges for rats of the strain and age used and in the absence of any associated correlates the intergroup differences were considered not to be of toxicological importance.

In the oral developmental toxicity study in pregnant New Zealand White rabbits [5] B-TEGME caused evidence of maternal toxicity at the high-dose level of 500 mg/kg bw/d, such as abortions/mortality and reduced food consumption, indicating systemic availability of the hydrolysis products of the test material. The NOAEL for maternal toxicity was 250 mg/kg bw/d. Since there was evidence for treatment-related adverse effects of the test substance on foetal morphology at the high-dose of 500 mg/kg bw/d, the NOAEL for prenatal developmental toxicity is 250 mg/kg bw/d. In a second developmental toxicity study in rats [6] no toxicological significant effects were observed for maternal females up to the maximum dose of 1,000 mg/kg bw/day B-TEGME. The foetal weights versus vehicle controls were reduced, but total live litter size was increased at 1,000 mg/kg bw/day. External and skeletal effects were seen at 300 and 1,000 mg/kg bw/day, however, no visceral effects were observed. As “TEGME” (Methyltriglycol or 2-(2-(2-methoxyethoxy)ethoxy)ethanol) was used as vehicle in all groups, maternal toxicity might have been masked by TEGME. Furthermore, the used vehicle TEGME is known for its developmental effects at high doses.

Based on the results obtained in an oral extended one-generation reproductive toxicity study in rats [7] it was concluded that the NOAEL for reproductive performance of the F0 and F1 Cohort 1B animals was 300 mg/kg bw/day due to the high incidences of reduced fertility in females of F1 Cohort 1B receiving the limit dose of 1000 mg/kg bw/day and the increased incidences of minimal epididymal cellular debris coupled with sperm motility and morphology changes in both F0 and F1 Cohort 1B males given 1000 mg/kg/day, accompanied with degeneration in the testes for F1 Cohort 1B males at the limit dose of 1000 mg/kg bw/day only. The effects of reduced fertility and male reproductive system changes at 1000 mg/kg bw/day were observed in the presence of other toxic effects, i.e. increased incidences of basophilic tubules in the kidneys of F0 females and increased incidence of decreased lymphocytes in the cortex of the thymus in the F0 generation males were observed at 1000 mg/kg bw/day, therefore the NOAEL for systemic toxicity in the F0 and F1 adult animals was concluded to be 300 mg/kg/day. The NOAEL for the F1 and F2 offspring up to weaning was concluded to be at the same dose level of 300 mg/kg/day due to reduced early post-partum survival at 1000 mg/kg/day in both generations and low litter size in F2 litters. No evidence of developmental neurotoxicity or developmental immunotoxicity was observed in this study.


Respiratory absorption:

There are no reliable data available on inhalation toxicity. Based on the physico-chemical profile, inhalation of B-TEGME appears to be unlikely. A vapour pressure of 120 Pa (20°C) suggests a low volatility. Besides, B-TEGME decomposes before boiling. No spray applications have been identified for B-TEGME.


Dermal absorption

Due to the physico-chemical characteristic of B-TEGME (high molecular weight, spontaneous hydrolysis in water) the potential to be absorbed by the skin is suggested to be low, although the substance is a liquid.

In the acute dermal toxicity study [8] there were no deaths, no signs of systemic toxicity, and no signs of dermal irritation. The reported LD50 was >2,000 mg/kg bw/day. Skin and eye irritation/corrosion tests according to OECD 404 and 405 in New Zealand White rabbits [9,10] showed no positive parameter for an irritant or corrosive potential. A sensitisation potential could not be observed with a brake fluid containing 37% B-TEGME in a GPMT sensitisation study according to OECD 406 [11].

Following this information systemic uptake of B-TEGME via the skin is expected to be limited.



The physico-chemical properties of B-TEGME do not indicate a wide distribution due to the molecular weight and the spontaneous hydrolysis of the substance in water. Because B-TEGME is hydrolytically unstable an experimental determination of a logP is not applicable. Observed effects of B-TEGME on development and foetal morphology in prenatal developmental toxicity studies as well as the reduced fertility and chnages of the male reproductive system observed in the extended one-generation reproductive toxicity study indicate systemic distribution of hydrolysis products of B-TEGME.


Accumulative potential:

Based on the high molecular weight, spontaneous hydrolysis in water, and the good water solubility of the hydrolysis products systemically absorbed B-TEGME or its hydrolysis products are expected to eliminate from the body quite rapidly. Besides, the low logP values of the hydrolysis products indicate a low potential of bioaccumulation. In the sub-chronic toxicity study, no dose-related specific target organ toxicity or indication for bioaccumulation were observed.

A low to no bioaccumulation potential is expected.



Due to spontaneous hydrolysis of B-TEGME it can be assumed that B-TEGME itself does not reach metabolising enzymes. Instead, the hydrolysis products will be metabolised.

The increase in liver weight of rats orally exposed to a brake fluid containing 17% B-TEGME observed in a 28d repeated dose study [3] indicates metabolic activity: Increase in liver weight and hypertrophy is suggested to be related to enzyme induction and metabolism of the test material (or its hydrolysis products) in the liver.

Triethylenglycol and diethylenglycol as hydrolysis products of B-TEGME are expected to undergo oxidative O-dealkylation to afford smaller molecular weight glycol and carboxylic acid metabolites, as has been shown for other polyglycols and glycol ethers such as diethylene glycol and dipropylene glycol methyl ether [12,13].



Systemically absorbed B-TEGME is expected to be rapidly excreted through urine upon spontaneous hydrolysis and metabolism of hydrolysis products. There are no experimental hints that a special excretion path is preferred. Based on the molecular weight and hydrolysis excretion via bile cannot be excluded and is taken into consideration.



There is experimental evidence that B-TEGME or its hydrolysis products can be absorbed after oral exposure. However, based on spontaneous hydrolysis of B-TEGME, it has to be assumed that observed effects in toxicological studies are mainly caused by the hydrolysis products. Accordingly, absorption, distribution and metabolism of B-TEGME itself is not expected. The physcio-chemical properties in combination with structural elements resulting in metabolic transformations allow the conclusion that there is no potential for bioaccumulation from B-TEGME or its hydrolysis products.


[1] Clariant (1995). Test for acute oral toxicity in the male and female Wistar rat. Hoechst Aktiengesellschaft, Pharma Research Toxicology, 65926 Frankfurt am Main.

[2] BASF AG (1974). Ergebnis der gewerbetoxickologischen Vorprüfung: Methyltriglykol-o-borat. BASF Medizinisch-Biologische Forschungslaboratorien.

[3] Shell (1993). Brake Fluid DOT 4: A 28 day oral (gavage) toxicity study in the rat. Sittingbourne Research Centre, Sittingbourne, Kent, ME9 8AG, England.

[4] Shell Health Services (2013). B-TEGME: Ninety Day Repeated Dose Oral (Gavage) Toxicity Study in the Rat. Harlan Laboratories Ltd., Shardlow Business Park, Shardlow, Derbyshire DE72 2GD, UK.

[5] BASF SE (2018). Methyltriglycol-o-borat: Prenatal Developmental Toxicity Study in New Zealand White Rabbits Oral Administration (Gavage). BASF SE, Experimental Toxicology and Ecology, 67056 Ludwigshafen, Germany.

[6] Shell Health Services (2015). B-TEGME: Oral (gavage) pre-natal development toxicity study in the rat. Harlan Laboratories Ltd., Shardlow Business Park, Shardlow, Derbyshire, DE72 2GD, UK.

[7] BGE Consortium (2021). Tris[2-[2-(2-methoxyethoxy)ethoxy]ethyl] orthoborate: Extended One Generation Reproductive Toxicity Study in the Sprague Dawley Rat by Oral Gavage Administration. Labcorp Early Development Laboratories Ltd., Eye, Suffolk, UK.

[8] Shell Health Services (2010). Triethylene Glycol Monomethyl Ether Borate, Acute Dermal Toxicity Study in Rats. Harlan Laboratories Ltd., Shardlow Business Park, Shardlow, Derbyshire, DE72 2GD, UK.

[9] Clariant (1995). Triethylenglykolmonomethyletherborat: Test for primary dermal irritation in the rabbit. Hoechst.

[10] Clariant (1995). Triethylenglykolmonomethyletherborat: Test for primary eye irritation in the rabbit. Hoechst.

[11] Shell (1990). Shell Brake fluid DOT 4 Super: Acute oral and dermal toxicity, skin and eye irritancy and skin sensitisation potential. Shell Research Limited. Sittingbourne Research Centre, Kent, ME9 8AG England.

[12] Miller, R. R., Hermann, E. A., Calhoun, L. L., Kastl, P. E., and Zakett, D. (1985). Metabolism and disposition of dipropylene glycol monomethyl ether (DPGME) in male rats. Fundam Appl Toxicol 5, 721-726.

[13] Mathews, J. M., Parker, M. K., and Matthews, H. B. (1991). Metabolism and disposition of diethylene glycol in rat and dog. Drug Metab. Dispos 19, 1066-1070.

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