N-[3-(trimethoxysilyl)propylcyclohexylamine]

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test (OECD 422), rat: NOAEL (reproduction P, F1) ≥500 mg/kg bw/day (RA from CAS 1760-24-3)

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:

reference to same study

Reason / purpose for cross-reference:

read-across source

Details on exposure:

VEHICLE
- Justification for use and choice of vehicle: Corn oil was dried and de-acidified to removal residual water before use as test substance hydrolyses in contact with moisture.
- Lot/batch no: 070K0127
- Purity: 100%

Key result

Dose descriptor:

NOAEL

Remarks:

systemic

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 on parent animals were observed.

Key result

Critical effects observed:

no

Key result

Dose descriptor:

NOAEL

Remarks:

reproduction/developmental

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 effects attributable to the test item were observed.

Critical effects observed:

no

Key result

Reproductive effects observed:

no

Conclusions:

In an oral gavage study conducted to OECD 422 the NOAEL for the structural analogue with CAS 1760-24-3 relating to repeated dose (parental systemic) effects and to reproductive/developmental toxicity was at least 500 mg/kg bw/day, as no adverse effects were observed up to the highest dose of 500 mg/kg bw/day tested in rats.
As explained in the analogue justification, the differences between the target and the source substance are unlikely to lead to differences in reproductive toxicity.

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(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, 8.7, 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 on toxicity to reproduction of N-[3 -(trimethoxysilyl)propylcyclohexylamine] (CAS 3068 -78-8) are available. However, an OECD 422 study with the registered substance is on-going, but the results will not be available before the REACh deadline in May. Therefore, as an interim measure, the hazard assessment was performed based on available data from the structural analogue 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 in accordance with 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-[3 -(trimethoxysilyl)propylcyclohexylamine] (CAS 3068 -78-8).

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.

 

A reliable key Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test with N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3) is available and was performed according to OECD 422 and in compliance with GLP (Health and Environmental Sciences, 2002). Groups of 10 Sprague-Dawley rats of each sex (toxicity group) were administered the test material at doses of 25, 125 and 500 mg/kg bw/day or vehicle alone (corn oil) via oral gavage on 7 consecutive days per week. 10 additional females (reproductive group) were administered the test material in a same manner and observed for reproductive parameters. Males and females of the toxicity group were treated for at least 28 days, starting from 2 weeks prior to mating, whereas females of the reproductive group were treated for 39 - 44 days starting from 2 weeks prior to mating, throughout mating and gestation until day 3 post-partum. Animals of the toxicity group were monitored for clinical signs, body weight, food consumption, haematology and clinical biochemistry parameters, organ weights and functional observations whereas females of the reproductive group were observed for clinical signs, body weight, food consumption and mating and litter performance. All animals were submitted to necropsy, which included weighing of testes and epididymides. Histopathology was conducted on male and female reproductive organs of the control and high dose group. 1/10 male of the 125 mg/kg bw/day dose group and 2/10 females of the 500 mg/kg bw/day dose group died due to renal disease and dosing errors, respectively. Clinical signs such as increased nasal sounds, laboured breathing and/or soft squeaky vocalisation were recorded in animals of all dose groups. Body weight changes, food consumption, haematology, clinical chemistry, functional observations, organ weights as well as gross pathology and histopathological examination revealed no treatment-related abnormalities or adverse effects. Furthermore, no effects attributable to the test substance for any of the reproductive parameters examined were observed. Litter size, sex ratio, pup survival and weight, total implantation sites and corpora lutea were not affected by the administration of the test item. No incidence of abnormal behavior was recorded for any of the pups. At 500 mg/kg bw/day 6/8 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, whereby all had evidence of copulation. Gross pathology performed with the offspring did not reveal any abnormalities. In conclusion, a NOAEL (systemic/developmental) of ≥500 mg/kg bw/day was derived for the N-(3-(triethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3).

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Reliable data from a structural analogue on toxicity to reproduction indicates that N-methyl-3-(trimethoxysilyl)propylamine do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and the available data are therefore conclusive but not sufficient for classification.