Registration Dossier

Administrative data

Description of key information

RDT oral (OECD 407), rat: NOAEL  = 1228 mg/kg bw/day (RA from CAS 116912-64-2)
RDT inhalation: no data available
RDT dermal: no data available

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
Key result
Dose descriptor:
NOAEL
Effect level:
1 228 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no adverse effects observed up to and including the highest dose tested
Key result
Critical effects observed:
no
Conclusions:
A 28-day repeated dose toxicity study with the source substance was perforemd according to OECD 407 and GLP. Administration of the test material up to and including the highest dose tested (1228 mg/kg bw/day) did not results in any substance-related adverse effects. Thus, a NOAEL of 1228 mg/kg bw/day is derived. As explained in the analogue justification, the differences in molecular structure between the target and the source are unlikely to lead to differences in the oral NOAEL.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 228 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(s), common precursors/breakdown products, similarities in PC/ECO/TOX 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, 8.6, 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 on repeated dose toxicity on 1-[3-(trimethoxysilyl)propyl]urea (CAS 23843-64-3) are available. Therefore, the risk assessment was performed based on the available data from the source substance ureidopropyltrialkoxysilane, mixed methoxy and ethoxy esters (CAS 116912-64-2). The source substance is the reaction mass of 1-[3-(trimethoxysilyl)propyl]urea, 1-[3-(dimethoxyethoxysilyl)propyl]urea, 1-[3-(methoxydiethoxysilyl)propyl]urea and 1-[3-(triethoxysilyl)propyl]urea and therefore contains the target substance as one of its components. In accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 “Grouping of substances and read across” and in accordance with the Read across assessment framework (RAAF, ECHA 2017) read across from the analogue substance has been applied to support the human health hazard assessment of 1-[3-(trimethoxysilyl)propyl]urea (CAS 23843-64-3).

Details on read across justifications can be found in the attached justification in the respective target entry and in the overall justification for grouping of substances attached in IUCLID Section 13.

 

Repeated dose toxicity: oral

A subacute repeated dose study performed according to OECD 407 and in compliance with GLP is available for ureidopropyltrialkoxysilane, mixed methoxy and ethoxy esters (CAS 116912-64-2) (NOTOX, 2000b). In this subacute toxicity study groups of five fasted Wistar rats of each sex per dose were administered nominal doses of 61, 184 or 1228 mg/kg bw/day once daily for 28 consecutive days via oral gavage. Appropriate control animals were administered water at a dose level of 1000 mg/kg bw/day in the same way. Dose selection of the test material was based on a previous 5-day pilot study. Animals were observed twice daily for mortalities and daily for clinical signs. Detailed clinical observations were performed before treatment and on days 8, 15, 22, and 28. Body weights, food consumption and neurobehavioural examination were recorded. No mortality and no severe clinical signs of toxicity were observed throughout the study period. Salivation was observed in the animals of the high dose group but was not considered to be a sign of adverse systemic toxicity. Slightly lower body weight gain was observed in the mid and high dose males, but was not statistically significant. No treatment related effects for haematology and clinical chemistry were observed. Furthermore, no severe neurobehavioural signs of toxicity were recorded. In two females of the mid-dose group the total motor activity was increased. Moreover, in one of these females the ratio between upper and lower sensor recordings was reverse to what is expected. These effects were considered to have occurred by chance because no corroborative findings in the animals and no dose-response relationship was observed. Moreover, no significant change in organ weights was recorded. Gross pathology and histopathology revealed thickening of the limiting ridge in the stomach of 2/5 females of the high dose group. Microscopically, a minimal squamous hyperplasia was observed. These effects were attributed to an irritating effect of the substance and are also commonly seen in gavage studies. In summary, the test substance did not result in any substance-related adverse effect. Thus, a NOAEL for males/females of =1228 mg/kg bw/day was derived.

Justification for classification or non-classification

The available data on repeated dose toxicity of the registered substance do not meet the criteria for classification according to Regulation (EC) No 1272/2008 and are therefore conclusive but not sufficient for classification.