3-(trimethoxysilyl)propiononitrile

Ecotoxicological Summary

Hazard for aquatic organisms

Freshwater

Hazard assessment conclusion:

PNEC aqua (freshwater)

PNEC value:

110 mg/L

Assessment factor:

1 000

PNEC freshwater (intermittent releases):

1 100 mg/L

Marine water

Hazard assessment conclusion:

PNEC aqua (marine water)

PNEC value:

11 mg/L

Assessment factor:

10 000

STP

Hazard assessment conclusion:

PNEC STP

PNEC value:

0.76 mg/L

Assessment factor:

100

Extrapolation method:

assessment factor

Sediment (freshwater)

Hazard assessment conclusion:

PNEC sediment (freshwater)

PNEC value:

400 mg/kg sediment dw

Extrapolation method:

equilibrium partitioning method

Sediment (marine water)

Hazard assessment conclusion:

PNEC sediment (marine water)

PNEC value:

40 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:

15 mg/kg soil dw

Extrapolation method:

equilibrium partitioning method

Hazard for predators

Secondary poisoning

Hazard assessment conclusion:

no potential for bioaccumulation

Additional information

The hazard assessment for the environment is based on the properties of the silanol hydrolysis product, 3-(trihydroxysilyl)propiononitrile, because the hydrolysis half-life of the registered substance is predicted to be 1.1 hour at 20-25°C and pH 7. The substance will hydrolyse very rapidly in contact with water and atmospheric moisture. 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”. REACH guidance, (ECHA 2017, R.7b) also suggests 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 hazard assessment, including sediment and soil compartments due to water and moisture being present, is based on the properties of the silanol hydrolysis product, in accordance with REACH guidance. As described in Section 1.3, condensation reactions of the silanol are possible.

In order to reduce animal testing read-across is proposed to fulfil up to REACH Annex IX requirements for the registered substance 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 registered substance and the substance used as surrogate for read-across are part of a class of low functionality compounds acting via a non-polar narcosis mechanism of toxicity. The group of organosilicon substances in this group contain alkyl, aryl, alkoxy or hydroxy groups attached to the Si atom when present in aqueous solution. Secondary features may be present in the alkyl chain (e.g. halogen, nitrile, unsaturated bonds) that do not affect the toxicity of the substances. The registered substance hydrolyses rapidly in water and therefore the selection of surrogate substance is based on log K_ow of the resulting silanols and the chemical groups present in them. The side chain of the registered and read-across substance is propiononitrile.

Additional information is given in a supporting report (PFA 2016y) attached in Section 13 of the IUCLID dossier.

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)propiononitrile (CAS 2526-62-7), and the following substance used as surrogate for read-across (source substance), 3-(triethoxysilyl)propiononitrile (CAS 919-31-3), are part of a class of alkoxysilane compounds which hydrolyse rapidly or moderately rapidly to produce the same Si hydrolysis product, 3-(trihydroxysilyl)propiononitrile, 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. The source substance hydrolyses 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.

 

Read-across from 3-(triethoxysilyl)propiononitrile (CAS 919-31-3) to 3-(trimethoxysilyl)propiononitrile (CAS 2526-62-7).

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 alkoxysilane compounds which hydrolyse rapidly or moderately rapidly to produce 3-(triethoxysilyl)propiononitrile and another non-Si hydrolysis product.

3-(Trimethoxysilyl)propiononitrile (CAS 2526-62-7) (target substance) and 3-(triethoxysilyl)propiononitrile (CAS 919-31-3) (source substance) share similar physicochemical structures and properties; both substances are trialkoxysilanes with a propiononitrile side-chain. The difference between these substances is that the three alkoxy groups are ethoxy for the source substance and methoxy for the target substance.

The hydrolysis half-life of the target substance is predicted to be 1.1 hour at 20-25°C and pH 7. The hydrolysis half-life of the source substance is 6.5 hours at 20°C and pH 7. Both substances will hydrolyse to form 3-(trihydroxysilyl)propiononitrile, with non-si hydrolysis products of methanol and ethanol, respectively.

The nitrile group is expected to be stable except under conditions of high temperature and low or high pH and significant hydrolysis is not expected under environmentally-relevant conditions.

The target substance 3-(trimethoxysilyl)propiononitrile (CAS 2526-62-7) and the source substance 3-(triethoxysilyl)propiononitrile (CAS 919-31-3) have similar moderate molecular weight (175.26 and 217.34, respectively) and low vapour pressure (4.7 Pa (QSAR prediction) and 1.9 Pa at 20-25°C, respectively). They have low predicted log K_ow (0.2 and 1.7, respectively) and high water solubility (130000 and 4000 mg/l, respectively). Both the substances hydrolyse rapidly, with half-lives of <12 h at pH 7 and 25°C (1.1 h and 6.5 h, respectively). The table below presents relevant physicochemical properties.

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

3-(Trihydroxysilyl)propiononitrile is predicted to be very soluble in water (1E+06 mg/l), has low predicted log K_ow (-2.9) and low predicted vapour pressure (6.7E-05 Pa).

 

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

3-(Trimethoxysilyl)propiononitrile (CAS 2526-62-7) (target substance) and 3-(triethoxysilyl)propiononitrile (CAS 919-31-3) (source substance) share similar chemical structures; both substances are trialkoxysilanes with a propiononitrile side-chain. The difference between these substances is that the three alkoxy groups are ethoxy for the source substance and methoxy for the target substance. These differences in the alkoxy group are expected to slightly impact hydrolysis rate; the ethoxy group is expected to hydrolyse more slowly than the methoxy group. Therefore, the target and source substances are structurally similar and have similar physicochemical properties (see table below).

The hydrolysis half-life of the target substance is predicted to be 1.1 hour at 20-25°C and pH 7. The hydrolysis half-life of the source substance is 6.5 hours at 20°C and pH 7. Both substances will hydrolyse to form 3-(trihydroxysilyl)propiononitrile, with non-si hydrolysis products of methanol and ethanol, respectively.

During the short-term toxicity to fish and invertebrates ecotoxicity studies conducted with the source substance 3-(triethoxysilyl)propiononitrile (CAS 919-31-3), the test conditions (flow through regime at an approximate rate of 6 solution volume replacements per day) indicate that the organisms would have been exposed to a mixture of the parent substance and the hydrolysis products 3-(trihydroxysilyl)propiononitrile and ethanol, with the parent substance predominating.

The algal study was conducted as a static regime, therefore it is likely that the test organisms were exposed to a mixture of the parent substance and its hydrolysis products at the beginning of the test, but predominantly to the hydrolysis products towards the end of the test. Analysis of test substance concentrations of the parent substance support the expectation that degradation of parent substance occurred in the test solution, because recoveries of parent substance were low.

The fish and invertebrate tests resulted in exposure of the test organisms to the parent substance, with smaller amounts of the hydrolysis products. The parent substance is expected to be more likely to cause toxicity than its hydrolysis products due to its higher log K_ow (please refer to discussion in PFA 2016y). The hydrolysis half-life of the target substance is more rapid than the source substance and if tests were performed with the target substance, it is unlikely that organisms would be exposed to any significant amounts of parent substance. Read-across from the source substance is therefore considered to be conservative. However, no effects on the test organisms were reported in the fish or invertebrate studies, with the E(L)C₅₀ values reported as limit values, and the short-term EC₅₀ value in the algae test was also a limit value.

Due to the rapid hydrolysis of the registration substance 3-(trimethoxysilyl)propiononitrile (CAS 2526-62-7) (target substance), the hydrolysis product 3-(trihydroxysilyl)propiononitrile is the relevant silicon containing substance for environmental assessment. Both source and target substances produce the same hydrolysis product, 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, respectively. 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 96.8 – 98.5% in the studies that are read-across. There are no impurities described. The boundary composition of the target substance reports a purity of =95 %. The Substance Identification Profiles for both substances report impurities that are methanol/ethanol (hydrolysis products of the substances), siloxanes (products of hydrolysis and condensation of the substances) and structurally related alkoxysilanes. None of the impurities impact the classification and labelling of the substances.

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-(triethoxysilyl)propiononitrile (CAS 919-31-3) (data are presented here prior to molecular weight adjustment):

Short-term fish: 96-hour LC₅₀ >120 mg/l (nominal concentration), Oncorhynchus mykiss.

Short-term toxicity to invertebrates: 48-hour EC₅₀ >120 mg/l (nominal concentration), Daphnia magna (freshwater);

Algae: 72-hour ErC₅₀ >120 mg/l and NOEC 60 mg/l (nominal concentration), Pseudokirchneriella subcapitata (freshwater algae).

No aquatic toxicity data are available for the target substance.

 

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.

 

AE A.6 Bias that influences the prediction

Data with the source substance, 3-(triethoxysilyl)propiononitrile (CAS 919-31-3), were selected because it hydrolyses to the same substance as the hydrolysis product of the target substance.

The selection of the source studies used as the basis for the prediction are the only reliable studies available.

Table: Summary of physico-chemical and ecotoxicological properties of the registered and surrogate substance.

CAS Number	2526-62-7	919-31-3
Chemical Name	3-(trimethoxysilyl)propiononitrile	3-(triethoxysilyl)propiononitrile
Si hydrolysis product	3-(trihydroxysilyl)propiononitrile	3-(trihydroxysilyl)propiononitrile
Molecular weight (parent)	175.26	217.34
Molecular weight (hydrolysis product)	133.18	133.18
log Kow (parent)	0.2	1.7
log Kow (silanol hydrolysis product)	-2.9	-2.9
Water sol (parent)	1.3E+05 mg/l	1.3E+03 mg/l
Water sol (silanol hydrolysis product))	1.0E+06 mg/l	1.0E+06 mg/l
Vapour pressure (parent)	4.7 Pa	1.9
Vapour pressure (hydrolysis product)	6.7E-05 Pa	0.00007 Pa
Hydrolysis t1/2 at pH 7 and 25°C	1.1 hour (QSAR)	6.5 hours
Hydrolysis t1/2 at pH 4 and 25°C	0.1 hours	<0.5 hours
Hydrolysis t1/2 at pH 9 and 25°C	0.02 hours	<0.5 hours
Short-term toxicity to fish (LC50)	n/a	>110 mg/l
Short-term toxicity to aquatic invertebrates (EC50)	n/a	>100 mg/l
Algal inhibition (ErC50 and NOEC)	n/a	EC50 >3.6 mg/l and NOEC 1.8 mg/l (geom. mean) ErC50 >120 mg/l and NOEC 60 mg/l (nominal)
Long-term toxicity to fish (NOEC)	n/a	n/a
Long-term toxicity to aquatic invertebrates (NOEC)	n/a	n/a
Sediment toxicity (NOEC)	n/a	n/a
Terrestrial toxicity	n/a	n/a

n/a = no data

Conclusion on classification

The substance has reliable short-term E(L)C₅₀ values of >100 mg/l in fish, invertebrates and algae based on read-across from a structural analogue with a common silicon containing hydrolysis product. It has reliable NOEC of 60 mg/l in algae (effect concentrations are prior to molecular weight correction).

3-(Trimethoxysilyl)propiononitrile hydrolyses rapidly to 3-(trihydroxysilyl)propiononitrile and methanol. Based on a weight-of-evidence approach, no significant biodegradation is expected for 3-(trihydroxysilyl)propiononitrile. The log K_ow of 3-(trihydroxysilyl)propiononitrile is <3.

 

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.