1-Butanamine, N-[3-(trimethoxysilyl)propyl]-, reaction products with (trimethoxysilyl)-N-[(trimethoxysilyl)propyl]-1-propanamine and 1,6-diisocyanatohexane homopolymer

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Additional information

iGloss Crosslinker (ZQ54-2211) was administered to male rats for 28 days and to female rats for 14 days prior to pairing, through the pairing and gestation periods until the F1 generation reached day 4 post partum. The study was conducted according to OECD 422 guideline and GLP (Harlan, 2013).

 

The following dose levels were applied:

Group 1: 0 mg/kg body weight/day (control group)

Group 2: 75 mg/kg body weight/day

Group 3: 250 mg/kg body weight/day

Group 4: 750 mg/kg body weight/day

A standard dose volume of 4 mL/kg body weight with a daily adjustment to the actual body weight was used. Control animals were dosed with the vehicle alone (olive oil).

 

The following results were obtained:

 

Parent Animals

General Tolerability

At 750 mg/kg bw/day, one female died spontaneously at the end of the gestation period. It showed a hunched posture and ruffled fur to a slight degree starting 14 days prior to the spontaneous death. This was accompanied by a weakened condition with increasing severity and visible body weight loss. Severe ulcerations/erosions of the forestomach were observed by histopathological examination. All these findings were considered to be test item-related.

No other test item-related clinical signs were noted in males or females at any dose level.

 

Food Consumption

No effects on food consumption of males and females were observed at any dose level.

Body Weights

In males, mean body weight gain was dose-dependently reduced during the pre-pairing period at 250 and 750 mg/kg bw/day. The reduction in mean body weight gain resulted in reduced absolute mean body weights in these dose groups until the end of the study. During the following pairing period, mean body weight gain remained reduced at 750 mg/kg bw/day.

 

In females, no test item-related effects on mean body weight and mean body weight gain were noted.

 

Clinical Laboratory Investigations

No test item-related findings were noted.

Reproduction and Breeding Data

Mean precoital time, fertility index and conception rate were not affected by the treatment with the test item.

No effects on implantation loss or postnatal loss were observed.

 

Organ Weights

No effects on organ weights were noted in any group.

 

Macroscopical Findings and Histopathological Examinations

There were no test item-related findings noted at necropsy.

 

The incidence and severity of the ulceration/erosion of the glandular and forestomach, squamous hyperplasia and/or inflammatory cell infiltration in the submucosa of the stomach were dose-dependently increased at 250 and 750 mg/kg bw/day.

Litter Data - F1 Pups

Findings at First Litter Check and during Lactation

The mean number of pups at first litter check was not affected by the treatment with the test item. The sex ratio was also not affected. No abnormal pup was noted at any dose level.

 

Pup Weights to Day 4 Post Partum

No effects on pup weight and pup weight gain were observed.

Macroscopical Findings

At necropsy of pups, there were no abnormal findings.

Conclusion

Based on these results a general NOAEL (No Observed Adverse Effect Level) was considered to be 75 mg/kg body weight/day. However, it should be noted that this NOAEL was primarily based on local irritation at the stomach, and the only additional effect was limited to a decreased body weight gain in males. No signs of systemic toxicity were evident by hematological and clinical chemistry examinations, organ weights, as well as macroscopic and microscopic examinations.

Therefore, the systemic NOAEL is set at 750 mg/kg body weight/day and 75 mg/kg body weight/day is considered as local NOAEL for irritation at the stomach.

 

The NOEL (No Observed Effect Level) for reproduction/developmental toxicity was considered to be 750 mg/kg body weight/day.

Short description of key information:
OECD 422: NOAEL (reproduction/development) = 750 mg/kg bw/day (Harlan, 2013)

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

Based on the available data, the test substance is not classified with regard to toxicity to reproduction according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP), respectively.