3-(trimethoxysilyl)propylamine

Ecotoxicological Summary

Hazard for aquatic organisms

Freshwater

Hazard assessment conclusion:

PNEC aqua (freshwater)

PNEC value:

0.5 mg/L

Assessment factor:

50

Extrapolation method:

assessment factor

PNEC freshwater (intermittent releases):

2.05 mg/L

Marine water

Hazard assessment conclusion:

PNEC aqua (marine water)

PNEC value:

0.05 mg/L

Assessment factor:

500

Extrapolation method:

assessment factor

STP

Hazard assessment conclusion:

PNEC STP

PNEC value:

0.81 mg/L

Assessment factor:

10

Extrapolation method:

assessment factor

Sediment (freshwater)

Hazard assessment conclusion:

PNEC sediment (freshwater)

PNEC value:

1.8 mg/kg sediment dw

Extrapolation method:

equilibrium partitioning method

Sediment (marine water)

Hazard assessment conclusion:

PNEC sediment (marine water)

PNEC value:

0.18 mg/kg sediment dw

Extrapolation method:

equilibrium partitioning method

Hazard for air

Air

Hazard assessment conclusion:

no hazard identified

Hazard for terrestrial organisms

Soil

Hazard assessment conclusion:

PNEC soil

PNEC value:

0.069 mg/kg soil dw

Extrapolation method:

equilibrium partitioning method

Hazard for predators

Secondary poisoning

Hazard assessment conclusion:

PNEC oral

PNEC value:

11.1 mg/kg food

Assessment factor:

90

Additional information

The hydrolysis half-life of 3-(trimethoxysilyl)propylamine (CAS 13822-56-5, EC 237-511-5) is 2.6 hours at pH 7 and 25°C. The registered substance will hydrolyse in contact with water and atmospheric moisture to form 3-aminopropylsilanetriol and methanol.

3-Aminopropylsilanetriol and methanol are both miscible in water and have low log K_ow (-2.0 and -0.82, respectively).

As described in Section 4.8 of IUCLID and Section 1.5 of the CSR, condensation reactions of the silanetriol are possible.

REACH guidance (ECHA 2016, R.16) states that “for substances where hydrolytic DT₅₀ is less than 12 hours, environmental effects are likely to be attributed to the hydrolysis product rather than to the parent itself”. TGD and REACH guidance (EC 2003) and R.16 (2016) also suggest that when the hydrolysis half-life is less than 12 hours, the breakdown products, rather than the parent substance, should be evaluated for aquatic toxicity. Therefore, the environmental chemical safety assessment (aquatic, sediment and soil) is based on the properties of the silanol hydrolysis product, 3-aminopropylsilanetriol, in accordance with REACH guidance.

 

Amines are basic, therefore once dissolved they will increase the pH of the test media. In addition, the un-ionised form of the amine is more toxic than the ionised form. This pattern of toxicity is consistent with ammonia, where the un-ionised form, NH₃, is more toxic than the ionised form, NH₄+. The difference in toxicity is attributed to bioavailability, where the un-ionised form can cross cell membranes more readily than the ionised form. Many of the aquatic toxicity studies for amine-containing organosilicon substances were conducted at pH ~8 and in some cases the pH was not adjusted after the test substances were added to the test media. Therefore, for media and natural waters having a pH closer to 7 it is likely that ecotoxicity might be expected to be less severe than indicated by these test results (i.e. the value of E(L)C₅₀ may possibly be higher under pH-neutral conditions) (PFA 2013z). 

 

READ-ACROSS JUSTIFICATION

There are no reliable available measured data for 3-(trimethoxysilyl)propylamine (CAS 13822-56-5) for ecotoxicity. In order to reduce animal testing, the Annex requirements are fulfilled with data from substances that have similar structure and physicochemical properties. Ecotoxicological studies are conducted in aquatic medium or in moist environments; therefore the hydrolysis rate of the substance is particularly important since after hydrolysis occurs the resulting product has different physicochemical properties and structure.

The selection of substances used for read-across (source substances) is based on the silanol hydrolysis products, the groups present on the side chains, as well as their log K_ow.

The analogue approach for fulfilling the data requirement by read-across is discussed below, according to the Read-across Assessment Framework (RAAF).

 

The registered substance (target substance) 3-(trimethoxysilyl)propylamine (CAS 13822-56-5), and the following substances used as surrogates for read-across (source substances), (3-aminopropyl)triethoxysilane (CAS 919-30-2, EC 213-048-4) and (3-isocyanatopropyl)trimethoxysilane (CAS 15396-00-6, EC 239-415-9), are part of a class of amine and alkoxysilane compounds which hydrolyse rapidly or moderately rapidly to produce the same Si hydrolysis product, 3-aminopropylsilanetriol, and another non-Si hydrolysis product.

In the context of the RAAF, the basis of the read-across hypothesis is “(Bio)transformation to common compound(s)”; Scenario 1 applies. Both source substances rapidly hydrolyse to the same silicon containing hydrolysis product as the target substance, and the non-common hydrolysis products will not have an impact on the prediction of the ecotoxicological property.

 

Data have also been read-across from N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3, EC 217-164-6). In the context of the RAAF, the basis of the read-across hypothesis for this substance is “Different compounds have the same type of effect(s)”; Scenario 2 applies. Both the source and target substance hydrolyse to compounds with qualitatively similar properties. The non-common hydrolysis products will not have an impact on the prediction of the ecotoxicological property. 

 

Read-across from (3-aminopropyl)triethoxysilane (CAS 919-30-2) to 3-(trimethoxysilyl)propylamine (CAS 13822-56-5).

This scenario covers the analogue approach for which the read-across hypothesis is based on (bio) transformation to common compound(s). For the REACH information requirement under consideration, the effects obtained in a study conducted with one source substance are used to predict the effects that would be observed in a study with the target substance if it were to be conducted. The same type of effect(s) or absence of effect is predicted. The predicted strength of the effects may be similar or based on a worst-case approach.

AE A.1 Characterisation of source and target substances

The registered substance (target) and the substance used as surrogate for read-across (source) are part of a class of amine and alkoxysilane compounds which hydrolyse rapidly or moderately rapidly to produce 3-aminopropylsilanetriol and another non-Si hydrolysis product.

3-(Trimethoxysilyl)propylamine (CAS 13822-56-5) and (3-aminopropyl)triethoxysilane (CAS 919-30-2) share similar physicochemical structures and properties; they are alkoxysilanes with a 3-aminopropyl sidechain, therefore the main structural feature of a 3-aminopropyl sidechain is present in both substances. The difference between them is the nature of the three alkoxy groups present. 3-(Trimethoxysilyl)propylamine (CAS 13822-56-5) and (3-aminopropyl)triethoxysilane (CAS 919-30-2) have similar moderate molecular weight (179.29 and 221.37, respectively), low log K_ow (-2.8 and -1.3 at pH 7, respectively) and high water solubility (5.7E+05 mg/l and 5400 mg/l, respectively).

Both the substances hydrolyse rapidly, with half-lives of <12 hours at pH 7 and 25°C.

The hydrolysis half-life of the target substance 3-(trimethoxysilyl)propylamine (CAS 13822-56-5) at pH 7 and 25°C is predicted to be 2.6 hours; the substance will therefore undergo rapid hydrolysis in contact with water to form 3-aminopropylsilanetriol and methanol.

The hydrolysis half-life of (3-aminopropyl)triethoxysilane (CAS 919-30-2) is 8.5 hours at pH 7 and 25 °C; the substance will therefore undergo hydrolysis in contact with water to form 3-aminopropylsilanetriol and ethanol.

Both target and source substances share the same silicon containing hydrolysis product 3-aminopropylsilanetriol, which is the relevant silicon containing substance for environmental assessment.

 

AE A.2 Link of structural similarities and structural differences with the proposed prediction (presence of hypothesis)

During the ecotoxicity studies conducted with the source substance (3-aminopropyl)triethoxysilane (CAS 919-30-2), the media preparation and test conditions (mixing of the test solution for 18 hours prior to inclusion of test organisms, and minimum pH of 7.5) indicate that the organisms would have been exposed to the hydrolysis products 3-aminopropylsilanetriol and ethanol.

Due to the rapid hydrolysis of the target registration substance 3-(trimethoxysilyl)propylamine (CAS 13822-56-5), the hydrolysis product 3-aminopropylsilanetriol is the relevant silicon containing substance for environmental assessment. Therefore both source and target substances share identical substances upon which the chemical safety assessment is based.

Methanol and ethanol are the non-silanol compounds formed from hydrolysis of the target and source substances. They are both well-characterised in the public domain literature and are not hazardous at the concentrations relevant to the studies; the short-term EC₅₀ and LC₅₀ values for these substances are in excess of 1000 mg/l (OECD 2004a - SIDS for methanol, CAS 67-56-1 and (OECD 2004b - SIDS for ethanol, CAS 64-17-5).

 

AE A.3 Impact of impurities on the prediction

The source substance has a reported purity of 99%. There are no impurities described. The boundary composition of the target substance reports a purity of =95 % and =100 %. No impurities are described.

It is therefore concluded that the source and target substances do not contain impurities at concentrations that would influence the effects observed in the available tests with the source substance.

 

AE A.4 Consistency of properties in the data matrix

Short-term toxicity to fish, invertebrates and algae data are read-across from (3-aminopropyl)triethoxysilane (CAS 919-30-2) (data are presented here prior to molecular weight adjustment):

Short-term fish: 96-hour LC₅₀ >934 mg/l, Danio rerio.

Short-term toxicity to invertebrates: 48-hour EC₅₀ 331 mg/l, Daphnia magna (freshwater);

48-hour LC₅₀ 580 mg/l, Acartia tonsa (marinewater).

Algae: 72-hour ErC₅₀ >1000 mg/l and ErC₁₀ of 321 mg/l, Scenedesmus subspicatus (freshwater algae);

72-hour ErC₅₀ 863 mg/l and NOEC 40 mg/l, Skeletonema costatum (marine algae).

 

AE A.5 Reliability and adequacy of the source data

All key data included in the chemical safety assessment have been reviewed and assigned Klimish scores of 1 or 2.

 

AE A.6 Bias that influences the prediction

Data with the source substance, (3-aminopropyl)triethoxysilane (CAS 919-30-2), were selected because it hydrolyses to the same substance as the hydrolysis product of the target substance. Data have also been included with a second source substance which also hydrolyses to the same substance as that of the target substance. This is discussed further below.

The selection of the source study used as the basis for the prediction is the study that gives the lowest definitive effect result (marine algal NOEC of 40 mg/l corrected for molecular weight to 25 mg/l).

 

 

Read-across from N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) to 3-(trimethoxysilyl)propylamine (CAS 13822-56-5):

This scenario covers the analogue approach for which the hypothesis is based on different compounds with the same type of effect(s). For the REACH information requirement under consideration, the effects obtained in a study conducted with one source substance are used to predict the effects that would be observed in a study with the target substance if it were to be conducted. The same type of effect(s) or absence of effect is predicted. The predicted strength of the effects may be similar or based on a worst-case approach.

 

AE A.1 Characterisation of source and target substances

The registered substance (target) and the substance used as surrogate for read-across (source) are part of a class of alkoxysilane and silanol substances which contain one or more alkoxy (methoxy or ethoxy) groups or hydroxyl groups attached directly to silicon, and one to three N (amines) on one branch. The substances are susceptible to hydrolysis, producing either methanol or ethanol, and the corresponding silanol. For both the test undertaken with the source substance, and the chemical safety assessment of the target substance, the silanol hydrolysis product is the assessment entity of primary interest, as discussed below.

The hydrolysis half-life of the target substance 3-(trimethoxysilyl)propylamine (CAS 13822-56-5) at pH 7 and 25°C is predicted to be 2.6 hours; the substance will therefore undergo rapid hydrolysis in contact with water to form 3-aminopropylsilanetriol (one mole) and methanol (three moles).

The hydrolysis half-life of the source substance N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) at pH 7 and 25°C is predicted to be 0.025 hours; the substance therefore reacts very rapidly in water to produce N-(3-(trihydroxysilyl)propyl)ethylenediamine (one mole) and methanol (three moles).

The environmental chemical safety assessment of the registered (target) substance (aquatic, sediment and soil) is based on the properties of the silanol hydrolysis product, 3-aminopropylsilanetriol as the primary assessment entity. The considerations for the methanol hydrolysis product are discussed below (see AE A.2). The characterisation therefore focuses on the silicon containing hydrolysis products of the target substance, 3-aminopropylsilanetriol, and of the source substance, N-(3-(trihydroxysilyl)propyl)ethylenediamine. 

 

The un-ionised form of the amine is more toxic than the ionised form and more of the un-ionised form is present at higher pH. In addition, the amine can significantly increase the pH of the test media outside of the tolerable range of the test organisms.  If the test solution is adequately buffered, the additional amine is not expected to cause an increase in toxicity; at the test concentrations used in the source study pH adjustment was not necessary. Natural waters are effectively buffered due to the presence of minerals and naturally occurring organic compounds.

N-(3-(trihydroxysilyl)propyl)ethylenediamine and 3-aminopropylsilanetriol share similar physicochemical properties: very low log K_ow  (-4 (corrected for ionisation)), high water solubility (both very soluble) and moderate molecular weight (MW 180.28 and 137.21 g mol-1, respectively).

During the tests with the source substance, test organisms will have been exposed to the hydrolysis products of the test substance.

The common non-Si hydrolysis product is methanol.

 

AE A.2 Link of structural similarities and structural differences with the proposed prediction (presence of hypothesis)

N-(3-(trihydroxysilyl)propyl)ethylenediamine is a highly polar molecule with three electronegative/ electron-withdrawing structural features: two amino nitrogen atoms (which will be ionised in the environmental pH range) and a silanetriol group (silicon atom attached to three silanol hydroxy groups); while the silanols would not be expected to be ionised in the environmental pH range this is nevertheless a relatively polar structural feature. 3-Aminopropylsilanetriol has one amino nitrogen atom (ionised) and one silanetriol group.

The main significance of the presence of amine functional groups in the source and target substance structures is that amines are basic and are likely to elevate the pH of the test media. The pH influences the toxicity of the substance. In the available studies toxic effects are observed at high pH (pH >8.5). The source substance has two amine groups per molecule whereas the target substance has one. A diamine might be expected to increase the pH faster, making the effects more pronounced. When the pH of the test media is taken into account, there is no significant difference between monoamines, diamines and triamines.

Due to the rapid hydrolysis of the substance, during the long-term toxicity to invertebrates study conducted with the source substance N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3), the organisms would have been exposed to the hydrolysis products N-(3-(trihydroxysilyl)propyl)ethylenediamine and methanol.

The silanol hydrolysis products are structurally very similar, both with one silanetriol group, and either one or two amino nitrogen atoms in the alkyl chain.

 

Consideration of the non-Si hydrolysis product:

Methanol is formed as a by-product of the hydrolysis of both the target and source substances. Methanol is well-characterised in the public domain literature and is not hazardous at the concentrations relevant to the studies; the short-term EC₅₀ and LC₅₀ values are in excess of 1000 mg/l (OECD 2004a - SIDS for methanol, CAS 67-56-1). As such, no hazard is identified for the methanol assessment entity for the environment, and there is no reason to anticipate that it could have contributed to observations in the study with the source substance. 

 

AE A.3 Impact of impurities on the prediction

The source substance has a reported purity of =80 % to =99.9 %. There are no impurities described. The boundary composition of the target substance reports a purity of between =95 % and =100 %. No impurities are described.

It is therefore concluded that the source and target substances do not contain impurities at concentrations that would influence the effects observed in the available tests with the source substance.

 

AE A.4 Consistency of properties in the data matrix

Long-term toxicity to invertebrates data are read-across from N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) (data are presented here prior to molecular weight adjustment):

Long-term toxicity to invertebrates: 21-day NOEC =1 mg/l (highest concentration tested), Daphnia magna.

There are no other long-term toxicity to aquatic invertebrates data available with other structural analogues.

 

AE A.5 Reliability and adequacy of the source data

All key data included in the chemical safety assessment have been reviewed and assigned Klimisch scores of 1 or 2.

 

AE A.6 Bias that influences the prediction

Data with the source substance, N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3), were selected because it hydrolyses to a structurally similar substance to the hydrolysis product of the target substance. Both substances are within an analogue group of silicon-containing compounds with amine groups. Within this group it is generally true that when pH variation is managed by adjusting the test media pH, aquatic ecotoxic effects are limited or not observed (mainly based on short-term data).

There are no other long-term toxicity to aquatic invertebrates data available with other structural analogues.

 

 

Microorganisms toxicity data are read-across from (3-aminopropyl)triethoxysilane (CAS 919-30-2):

 

Read-across from (3-aminopropyl)triethoxysilane (CAS 919-30-2) to 3-(trimethoxysilyl)propylamine (CAS 13822-56-5)

Both the target substance and source substance hydrolyse rapidly (hydrolysis half-lives of <12 hours at pH 7) in contact with water to form the same silanol hydrolysis product, 3 -aminopropylsilanetriol. The other hydrolysis products are ethanol and methanol respectively.

 

See IUCLID Section 6.1.7 Toxicity to Microorganisms for further discussion.

Table. Overview of physico-chemical and ecotoxicity data for the registered substance and surrogate substances. 

CAS Number	13822-56-5	919-30-2	24801-88-5	15396-00-6	1760-24-3
Chemical Name	3-(Trimethoxysilyl)propylamine	(3-Aminopropyl)triethoxysilane	Triethoxy(3-isocyanatopropyl) silane	3-(Trimethoxysilyl)propyl isocyanate	N-(3-(trimethoxysilyl)propyl)ethylenediamine
-	-	-	Note, this substance reacts very rapidly in water generating (3-aminopropyl)triethoxysilane (CAS 919-30-2), see column to left	Note, this substance reacts very rapidly in water generating 3-(trimethoxysilyl)propylamine (CAS 13822-56-5), see column to left	-
Si hydrolysis product	3-aminopropylsilanetriol	3-aminopropylsilanetriol	3-aminopropyltriethoxysilane (CAS 919-30-2) and subsequently 3-aminopropylsilanetriol.See column to left for all properties of Si hydrolysis products.	3-(trimethoxysilyl)propylamine (CAS 13822-56-5) and subsequently 3-aminopropylsilanetriol.See column to left for all properties of Si hydrolysis products.	N-(3-(trihydroxysilyl)propyl)ethylenediamine
Molecular weight (parent) g/mol	179.29	221.37	247.37	205.29	222.36
Molecular weight (hydrolysis product) g/mol	137.21	137.21	See column to left	See column to left	180.28
log Kow  (parent)	0.2 (un-ionised); -2.8 at pH 7	1.7 (un-ionised); -1.3 (at pH 7)	n/a	n/a	-0.3 (un-ionised) (QSAR)
log Kow  (silanol hydrolysis product)	-2.9 (un-ionised); -4 (at pH 7)	-2.9 (un-ionised); -4 (at pH 7)	See column to left	See column to left	-3.4 (un-ionised); -4 (at pH 7)
Water sol (parent)	5.7E+05 mg/l	5400 mg/l	n/a	n/a	1.0E+06 mg/l (QSAR)
Water sol (silanol hydrolysis product))	1E+06 mg/l (but will be limited by condensation reactions)	1E+06 mg/l (but will be limited by condensation reactions)	See column to left	See column to left	1E+06 mg/l (but will be limited by condensation reactions)
Vapour pressure (parent)	18 Pa at 25°C	8 Pa at 25°C	2 Pa at 20°C	7.1 Pa	0.3 - 0.4 Pa at 20 °C
Vapour pressure (hydrolysis product)	2.5E-04 Pa at 25°C	2.5E-04 Pa at 25°C	See column to left	See column to left	6.8E-06 Pa at 25 °C (QSAR)
Hydrolysis t1/2 at pH 7 and 25°C	2.6 hours	8.5 hours	<5 minutes	<5 minutes	0.025 hours
Short-term toxicity to fish (LC50)	1264 mg/l (R4)	>934 mg/l	n/a	>100 mg/l	597 mg/l
Short-term toxicity to aquatic invertebrates (EC50)	302 mg/l (R4)	331 mg/l	n/a	>100 mg/l	81 mg/l
Algal inhibition (ErC50 and NOEC)	n/a	ErC50 values >1000 and 863 mg/l from two tests; ErC10 values 321 and 40 mg/l respectively	n/a	n/a	ErC50 8.8 mg/l; NOEC 3.1 mg/l
Long-term toxicity to invertebrates	No data	No data	No data	No data	=1 mg/l
Long-term toxicity to fish	No data	No data	No data	No data	No data

Conclusion on classification

Reliable short-term toxicity tests results are available with (3-aminopropyl)triethoxysilane (CAS 919-30-2, EC 213-048-4) as a surrogate substance. Read-across data are available for freshwater fish, invertebrates and algae. E(L)C₅₀ values for the three organisms were all >100 mg/l. A long-term invertebrate study is available for invertebrates: NOEC (21-day): >1 mg/l read-across from N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3). The registration substance hydrolyses rapidly to a silanetriol hydrolysis product, 3-aminopropylsilanetriol, which has a very low log K_ow, but may persist in the environment.

 

These data are consistent with the following classification under Regulation (EC) No 1272/2008 (as amended) (CLP):

Acute toxicity: Not classified.

Chronic toxicity: Not classified.

 

Methanol is included in the United Nations Environment Programme (UNEP) Chemicals Branch, OECD SIDS list of harmonised substances and does not require classification for the environment under the CLP Regulation (Regulation (EC) No. 1272/2008).