Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

REACH_data waiving based on momoner data | Ames test

REACH_negative | S. typhimurium TA98, TA100, TA1535, TA1537, TA1538 | reverse mutation assay | with and without | #WoE##Analogy#

REACH_negative | S. typhimurium, E. coli  | Ames Test | with and without | #WoE##Analogy#

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

Monomer data:

Reference 2

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

not specified

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

abstract

Qualifier:

no guideline available

Version / remarks:

guideline not specified in the publication

Principles of method if other than guideline:

Salmonella typhimurium reverse mutation assay with and without metabolic activation

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537, TA 1538

Metabolic activation:

with and without

Test concentrations with justification for top dose:

1-113 mg/plate

Vehicle / solvent:

not specified

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Remarks:

no details given in the publication

Details on test system and experimental conditions:

no further details

Key result

Species / strain:

S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537, TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

There was no evidence for an increased mutation frequency either in the presence or absence of metabolic activation.

Conclusions:

Several in vitro genotoxicity studies have been conducted which showed that TEG is devoid of a mutagenic potential. A Salmonella typhimurium reverse mutation assay was executed with strains TA98, TA100, TA1535, TA1537 and TA1538 at a concentration range for TEG of 1–113 mg per plate in the presence and absence of a metabolic activation system. There was no evidence for an increased mutation frequency (Ballantyne and Snelligs, Appl. Toxicol. 27: 291–299, 2007).

Reference 3

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

not specified

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

abstract

Qualifier:

no guideline available

Version / remarks:

guideline not specified in the publication

Principles of method if other than guideline:

Ames Test

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium, other: TA 97, TA 98, TA 100, TA 102, TA 1535, TA 1537, TA 1538

Remarks:

Ames Test

Species / strain / cell type:

S. typhimurium, other: TA 97, TA 98, TA 100, TA 104, TA 1535

Remarks:

Preincubation Assay

Metabolic activation:

not specified

Metabolic activation system:

Aroclor induced S9 mix (rat and syrian hamster)

Test concentrations with justification for top dose:

- Ames Test: up to 240 mg/plate
- Preincubation Assay: up to 10 mg/plate

Vehicle / solvent:

not specified

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Remarks:

no details given in the publication

Details on test system and experimental conditions:

no further details

Key result

Species / strain:

S. typhimurium, other: TA 97, TA 98, TA 100, TA 102, TA 1535, TA 1537, TA 1538

Remarks:

Ames Test

Metabolic activation:

not specified

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Key result

Species / strain:

S. typhimurium, other: TA 97, TA 98, TA 100, TA 104, TA 1535

Remarks:

Preincubation Assay

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

- Ames Test: There was a weak but reproducible positive effect in TA 102 (less than 2-fold increase in revertants) but only at ethanol concentrations of 160 and 240 mg/plate. These concentrations are far excess of the generally accepted maximum concentration for routine testing (5 mg/plate; OECD, 1997, Guideline no. 471).

Conclusions:

The balance of evidence is that ethanol is not genotoxic in vitro. The results of bacterial mutagenicity assays have generally been negative for ethanol. Positive results are only found at ethanol concentrations higher than recommended for guideline testing. Ethanol is not therefore considered to be mutagenic in the Ames test (Phillips and Jenkinson, Mutagensis 16: 91-101, 2001).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine is the reaction mixture of 3-aminopropyltriethoxysilane (CAS 919-30-2) and triethylene glycol (CAS 112-27-6). 3-Aminopropyltriethoxysilane is known to hydrolyse to form silanols and ethanol (CAS 64-17-5). Silanols rapidly self-condense or condensate with triethylene glycol and/or water to form bridged and cyclic oligomers under formation of Si-O-Si bonds. Therefore, Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine comprises of various oligomeric structures based on 3-aminopropyltriethoxysilane, triethylene glycol and/or water. Triethylene glycol is the main component of Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine besides small amounts of ethanol. No free 3-aminopropyltriethoxysilane is detectable.

Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine is unstable upon contact with moisture. lt undergoes further condensation reactions that form highly polymerized poly silicic acids while liberating the triethylene glycol, that was initially bound to the oligomeric structures. The underlying chemistry is commonly known as sol-gel reaction (see Holleman, Arnold F., Lehrbuch der anorganischen Chemie/Holleman-Wiberg, 101. Auflage, de Gruyter, Berlin, New York 1995, page 924). The poly silicic acid moieties are not stable and prone to further condensation generating water insoluble, resinous polymers. The molecular weight of the resulting polymers is predicted to be over 1000.

Since 3-aminopropyltriethoxysilane is completely consumed into the developing polymer matrix, it is assumed that the toxicological profile of Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine will be mainly determined by triethylene glycol and to a lesser extent by ethanol.

Several in vitro genotoxicity studies have been conducted which showed that triethylene glycol is devoid of any mutagenic and clastogenic potential. Triethylene glycol did not show genotoxic effects in an Ames Test, an SOS-chromotest, a gene mutation study (HGPRT locus) and chromosome aberration study in Chinese hamster ovary cells as well as a sister chromatid exchange assay in Chinese hamster ovary cells (Ballantyne and Snelligs, Appl. Toxicol. 27: 291–299, 2007).

The balance of evidence is that ethanol is not genotoxic in vitro. The results of bacterial mutagenicity assays have generally been negative for ethanol. Positive results are only found at ethanol concentrations higher than recommended for guideline testing. Ethanol is not therefore considered to be mutagenic in the Ames test (Phillips and Jenkinson, Mutagenesis 16: 91-101, 2001).

3-Aminopropyltriethoxysilane has been submitted to several Ames assays, in vitro V79 hamster lung cell and Chinese hamster fibroblast chromosome aberration assays, two Chinese hamster ovary cell HGPRT gene mutation assays, and an in vivo mouse micronucleus assay. Existing in vitro studies have not revealed any evidence of genotoxic potential (OECD SIDS Initial Assessment Report, 3-aminopropyltriethoxysilane, 2003). Since these tests are executed under conditions, which lead to formation of silanols and other oligomeric structures, these compounds are covered as well.

Existing data on the precursors of Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine clearly show that testing would not yield positive results in an Ames study. Furthermore, Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine will react upon contact with water to form poly silicic acids by releasing triethylene glycol and ethanol. The chemically stable reaction product is water insoluble, highly polymerized and would therefore not exhibit mutagenic effects. For the aforementioned reasons testing of Ethanol, 2,2'-[1,2-ethanediylbis(oxy)]bis-, reaction products with 3-(triethoxysilyl)-1-propanamine in the Ames test is scientifically not required.