hydrolysis products of 3-(triethoxysilyl)propan-1-amine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

47 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Modified dose descriptor starting point:

NOAEC

Value:

1 175 mg/m³

Explanation for the modification of the dose descriptor starting point:

NOAECcorr = NOAELoral*(1/0.38 m³/kg bw/day)*(ABSoral-rat/ABSinh-human)*(6.7 m³ (8h)/10 m³ (8h)) = 1333 mg/kg bw/day*(1/0.38 m³/kg bw/day)*0.67*(0.5/1) = 1175 mg/m³. It is assumed that oral absorption rate is 50% of that of inhalation absorption. ABSoral-rat=oral absorption rate in rats, ABSinh-human=inhalation absorption rate in humans.

AF for dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEL

AF for differences in duration of exposure:

2

Justification:

The DNEL is based on a subchronic study

AF for interspecies differences (allometric scaling):

1

Justification:

AF not used for inhalation route

AF for other interspecies differences:

2.5

Justification:

Default AF

AF for intraspecies differences:

5

Justification:

Default AF for workers

AF for the quality of the whole database:

1

Justification:

DNEL is based on a high-quality study

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

13.3 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEL

Value:

1 333 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

It is assumed that the dermal absorption rate is 100% of that of the oral absorption as no adequate information is available.

AF for dose response relationship:

1

Justification:

The dose descriptor starting point is based on a NOAEL

AF for differences in duration of exposure:

2

Justification:

The DNEL is based on a subchronic study

AF for interspecies differences (allometric scaling):

4

Justification:

The starting point has been derived in rats

AF for other interspecies differences:

2.5

Justification:

Default AF

AF for intraspecies differences:

5

Justification:

Default value for workers

AF for the quality of the whole database:

1

Justification:

DNEL is based on a high-quality study

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

There are no long term toxicity data available for “hydrolysis products of 3-(triethoxysilyl)propan-1-amine” (EC No. 939-125-9). In order to fulfil the standard information requirements set out in Annex VIII, read-across from a structurally related substance is conducted in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

The read-across is based on the hypothesis that the analogue substance, 3-(triethoxysilyl)propan-1-amine, hydrolyses rapidly in water resulting in the target substance. It can be expected that both the target and the source substance have similar behaviour under aqueous conditions. The target substance consists of 3-aminopropylsilanetriol and ethanol which are formed directly after hydrolysis and several condensation products such as dimers, trimers as well as polymers of siloxanes having similar functional groups (-O-Si- or HO-Si-). Therefore, it is considered that the target and the source substance are in one class of compounds and structural differences are not supposed to contribute to significant differences in activity with respect to eco- and human toxicological endpoints. A detailed analogue approach justification is provided in the technical dossier (Please refer to IUCLID Section 13 for further information).

The starting point for DNEL derivation is a no observed adverse effect level (NOAEL) of 200 mg/kg bw/day obtained from a repeated dose toxicity study according to OECD 408 (WIL Research Laboratories, 2001). The animals were treated at dose levels of 70, 200 and 600 mg/kg bw/day. At 600 mg/kg bw/day,pathological and histopathological findings were noted in the liver.Also an increase in the level of alanine aminotransferase and aspartate aminotransferase was observed in the high dose group. The animals showed labored respiration, gasping, partial closure of the eyes, general paleness, hypothermia, dermal atonia and/or tremors at 600 mg/kg bw/day. As the treatment-related effects were limited to the high dose group, the NOAEL was therefore 200 mg/kg bw/day. The study indicates that 3-(triethoxysilyl)propan-1-amine or its hydrolysis product is systemically bioavailable after repeated oral administration. Based on the fact that the hydrolysis product is formed in aqueous solutions of 3-(triethoxysilyl)propan-1-amine where the concentration range of 3-(triethoxysilyl)propan-1-amine is > 0.1 - < 16% (w/w), the available repeated dose toxicity study represents a worst case assumption. With respect to mixture rules, the NOAEL for hydrolysis products of 3-(triethoxysilyl)propan-1-amine (15%) is 1333 mg/kg bw/day (200 mg/kg bw/day x 100/15 = 1333 mg/kg bw/day).

According to the “Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of [concentration]-response for human health, Version 2.1, November, 2012”, the oral NOAEL needs to be converted into a NOAEC:the oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m³/kg for 8 h exposure). In addition, it should be taken into account that during 8 hours light activity at work the respiratory rate becomes higher (10 m³/person) than standard (6.7 m³/person). In the absence of route-specific information, a default factor of 2 (i.e. the absorption percentage for the starting route is half that of the end route) in case of oral-to-inhalation extrapolation is included. The inclusion of factor 2 means that 50% (instead of 100%) absorption is assumed for oral absorption, and 100% for inhalation(Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of [concentration]-response for human health, Version 2.1, November 2012).Considering these differences, the corrected starting point is a NOAEC of 1175 mg/m³.

The long-term worker DNEL for dermal systemic effects is again based on the repeated dose toxicity study (WIL Research Laboratories, 2001) as there is no dermal repeated dose toxicity study. To convert the oral NOAEL [mg/kg bw/day] into a dermal NOAEL [mg/kg bw/day], the differences in absorption between routes as well as differences in dermal absorption between rats and humans have to be accounted for (Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health, Version 2.1, December 2012). In the absence of any adequate information on dermal bioavailability, the bioavailability is expected to be in the same order of magnitude as oral absorption. This assumption results in the identical NOAEL for the oral and dermal exposure route.

In general, assessment factors (AF) recommended by ECHA (Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose[concentration]-response for human health. European Chemicals Agency, Version 2.1, November, 2012) were used when applicable to derive the DNEL. The difference in metabolic rate between humans and the test species has been taken into account, where relevant. An AF for exposure duration is applied to take into account the difference between experimental exposure duration and the exposure duration for the worker.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure

DNEL related information

Additional information - General Population

The general population is not exposed to the substance based on its identified uses.