N-(2-aminoethyl)-N'-[3-(trimethoxysilyl)propyl]ethylenediamine

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Screening study for reproductive/developmental toxicity (OECD 422, oral, rat with read across CAS 1760 -24 -3): NOAEL systemic toxicity and fertility >= 500 mg/kg bw/day

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Dose descriptor:

NOAEL

Effect level:

>= 500 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effects observed up to highest dose tested

Critical effects observed:

no

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

>= 500 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effects observed up to highest dose tested.

Critical effects observed:

no

Reproductive effects observed:

no

Conclusions:

In an oral gavage study conducted to OECD 422 and to GLP (reliability score 1) the NOAEL for the source substance N-(3-(trimethoxysilyl)propyl)ethylenediamine relating to repeated dose (parental systemic) effects and to reproductive toxicity was at least 500 mg/kg bw/day, as no significant adverse effects were observed up to the highest dose of 500 mg/kg bw/day tested in rats. As explained in the analogue justification, it is considered that the target and the source substances are unlikely to lead to differences in reproductive toxicity potential.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

500 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group and similarities in physico-chemical and toxicological properties (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

No data are available to assess the reproductive toxicity of N-(2-aminoethyl)-N'-[3-(trimethoxysilyl)propyl]ethylenediamine (CAS 35141-30-1). Therefore, the risk assessment was performed based on the available data from the source substance N-(3-trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3). In accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 “Grouping of substances and read across” and following the Read across assessment framework (RAAF, ECHA 2017) read across from an analogue substance has been applied to support the human health hazard assessment of N-(2-aminoethyl)-N'-[3-(trimethoxysilyl)propyl]-ethylenediamine (CAS 35141-30-1). Further details are provided in the analogue justification attached to the respective target entry.

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD guideline 422 and in compliance with GLP was performed with the source substance N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) in Sprague-Dawley rats (DCC, 2002). Ten male and 20 female rats (10 per reproductive and toxicity group each) were administered 25, 125 and 500 mg/kg bw/day of the test substance in corn oil by gavage, for 28 (males), 29 (toxicity group females) or 39-44 (reproductive group females) consecutive days. Control animals received the concurrent vehicle.

The dose selection was based on a 7-day range finding study where 3 Sprague-Dawlex rats per sex were dosed per gavage with 125, 250, 500 or 1000 mg/kg bw/day. Based on mortality observed in the high dose group (1 male and 1 female) and no further effects observed in all other dose groups a NOAEL of 500 mg/kg bw/day was derived and 500 mg/kg bw/day was chosen as the high dose in the main study.

In the main study no treatment-related deaths were observed and no other treatment-related adverse effects were observed. Functional observational battery revealed no treatment-related effects. There were no pathology or histopathology findings attributable to the test substance throughout the study period and no treatment-related effects on organ weights were observed.

Furthermore, no effects attributable to the test substance for any of the reproductive parameters examined were observed. Litter size, total implant sites and corpora lutea were not affected by the administration of the test item. At 500 mg/kg bw/day six of the eight surviving dams became pregnant and delivered litters that were not different from control litters in any parameters. Three rats were not found pregnant, two in the 500 mg/kg bw/day and one in the 25 mg/kg bw/day dose group, although all had evidence of copulation.

In conclusion, a NOAEL of 500 mg/kg bw/day for fertility and systemic toxicity was derived for the analogue substance N-(3-(triethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3).

Thus, a similar result is also considered for the target substance.

Effects on developmental toxicity

Description of key information

Screening study for reproductive/developmental toxicity (OECD 422, oral, rat with read across CAS 1760 -24 -3): NOAEL systemic toxicity and fertility >= 500 mg/kg bw/day

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

500 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group and similarities in physico-chemical and toxicological properties (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

No data are available to assess the reproductive toxicity of N-(2-aminoethyl)-N'-[3-(trimethoxysilyl)propyl]ethylenediamine (CAS 35141-30-1). Therefore, the risk assessment was performed based on the available data from the source substance N-(3-trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3). In accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 “Grouping of substances and read across” and following the Read across assessment framework (RAAF, ECHA 2017) read across from a analogue substance has been applied to support the human health hazard assessment of N-(2-aminoethyl)-N'-[3-(trimethoxysilyl)propyl]-ethylenediamine (CAS 35141-30-1). Further details are provided in the analogue justification attached to the respective target entry.

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test according to OECD guideline 422 and in compliance with GLP was performed with the source substance N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) in rats Sprague-Dawley rats (DCC, 2002). Ten male and 20 female rats (10 per reproductive and toxicity group each) were administered 25, 125 and 500 mg/kg bw/day of the test substance in corn oil by gavage, for up to 29 (males and toxicity group females) or 39-44 (reproductive group females) consecutive days. Control animals received the concurrent vehicle.

The dose selection was based on a 7-day range finding study where 3 Sprague-Dawlex rats per sex were dosed per gavage with 125, 250, 500 or 1000 mg/kg bw/day. Based on mortality observed in the high dose group (1 male and 1 female) and no further effects observed in all other dose groups a NOAEL of 500 mg/kg bw/day was derived and 500 mg/kg bw/day was chosen as the high dose in the main study.

In the main study no treatment-related deaths were observed and no other treatment-related adverse effects were observed. Functional observational battery revealed no treatment-related effects. There were no pathology or histopathology findings attributable to the test substance throughout the study period and no treatment-related effects on organ weights were observed.

Furthermore, pup survival and weight were not affected by the administration of the test item.

In conclusion, a NOAEL of 500 mg/kg bw/day for developmental and systemic toxicity was derived for the analogue substance N-(3-(triethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3).

Thus, a similar result is also considered for the target substance.

Justification for classification or non-classification

Data on fertility and developmental toxicity of a structural analogue substance indicate that N-(2-aminoethyl)-N'-[3-(trimethoxysilyl)propyl]ethylenediamine does not meet the criteria for classification according to Regulation (EC) 1272/2008 and according to Directive 67/548/EEC, and is therefore conclusive but not sufficient for classification.