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

Endpoint summary

Description of key information

OECD 422 (including FOB), oral (gavage), rat: NOAEL =500 mg/kg bw/day (RA from N-(3-(trimethoxysilyl)propyl) ethylenediamine, CAS 1760-24-3))

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

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 treatment-related adverse effects observed.

Remarks on result:

other: CAS 1760-24-3, Dow Corning Corporation, 2002

Critical effects observed:

no

Conclusions:

In an oral gavage study conducted to OECD 422 and to GLP (reliability score 1) the NOAEL for repeated dose toxicity was at least 500 mg/kg bw/day for the source substance N-(3-(trimethoxysilyl)propyl)ethylenediamine 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 repeated dose toxicity potential.

Endpoint conclusion

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. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.6, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No data are available to assess the repeated dose 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 422 and in compliance with GLP was performed with source substance N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) in Sprague-Dawley rats (Dow Corning Corporation, 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-Dawley rats per sex were dosed per gavage with 125, 250, 500 or 1000 mg/kg bw/day. One high dose female was found dead on study day 4. One high dose male was found moribund on study day 6 and was humanely sacrificed. All other animals survived until scheduled necropsy. Slight effects on body weight and food consumption were observed in the treatment groups. Increased breathing sounds recorded as rales and soiling and wetness around the muzzle were the most common clinical findings related to treatment. Both findings were most common and most persistent in the 1000 mg/kg bw/day group. Some animals in the lower dose groups exhibited rales or wetness around the nose and/or mouth or soiling of the muzzle. However, these clinical findings were detectable for only one or two days of the study. At the highest dose, the majority of the clinical signs were associated with the two mortalities. However, one of the surviving females from the high dose group exhibited rales, hunched posture and muzzle soiling. Both of the animals that died before scheduled sacrifice had gaseous distension of the gastrointestinal tract and small dark livers. There were no adverse findings in the necropsy examination of the surviving animals.

In the main study no treatment-related deaths were observed. Clinical signs as clear perioral soiling were slightly more common in the middle and high dose group. In the high dose groups there were increased nasal sounds, laboured breathing and/or soft squeaky vocalisation for one male and four toxicity and five reproductive group females. At 125 mg/kg bw/day, one toxicity group and one reproductive group female had increased nasal sounds. At 25 mg/kg bw/day, one toxicity group female exhibited soft squeaky vocalisation for three days of the study. The incidence of nasal sounds/squeaky vocalisation was noted in some animals and several times in others to a maximum of 18 days during the study. These findings were not observed in control rats.

Mean body weights in males and females in the 25, 125 and 500 mg/kg bw/day groups were comparable to the control group values throughout the study; no statistically significant differences were noted. There were no statistically significant differences in food consumption in any group throughout the study period.

There were no treatment-related effects on haematology parameters. However, in all toxicity group females there was a statistically-significant increase in platelet counts compared to controls. The counts for the treated groups were within published historical control ranges, whereas controls in the present study were somewhat below those ranges. No biological/toxicological significance is attributed to treatment.

In females, there was a statistically significant decrease in the chloride value (1.9%) in the high dose group, and a slight decrease (1.4%) in sodium in the middle and high dose groups compared to the control group. There was no dose-related trend in either parameter. Sodium values for all female groups, including controls, were within or slightly below published historical control ranges. Chloride values for all groups were slightly above published control ranges. There were no associated clinical or morphological findings, so the findings were not thought to be biologically or toxicologically significant.

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.

In conclusion, a NOAEL of =500 mg/kg bw/day 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

Based on reliable data from the analogue substance N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3), the registered substance N-(2-aminoethyl)-N'-[3-(trimethoxysilyl)propyl]ethylenediamine (CAS 35141-30-1) does not meet the criteria to be classified for specific target organ toxicity - repeated exposure (STOT RE) according to Regulation (EC) No 1272/2008 and Directive 67/548/EEC.