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Key value for chemical safety assessment

Effects on fertility

Description of key information

In the combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test conducted according to OECD Test Guideline 422 and in compliance with GLP, no reproductive or developmental toxicity was observed up to the maximum dose of 250 mg/kg bw/day. A NOAEL of ≥250 mg/kg bw/day Reaction mass of trimethoxy(aminoalkyl)-silanes and modified alkylether oligomers was established for reproductive toxicity (Charles River, 2018).

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
250 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Klimisch score of 1
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

In the key combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test for reaction mass of trimethoxy(aminoalkyl)-silanes and modified alkylether oligomers, undiluted test material was administered by oral gavage to 10 male and female Wistar Han rats respectively per dose groups. The administered concentrations were 25, 75 or 250 mg/kg bw/day with a treatment period for a minimum of 28 days. A control group was also included that received water. A 14-day recovery period was performed to 5 additional male and female rats respectively, from the high and low dose groups. The recovery animals (used to study the potential reversibility of possible toxic effects) were not mated and consequently were not used for the assessment of reproduction/ developmental toxicity.

Mortality/moribundity, clinical signs, functional observations, body weight and food consumption, oestrous cycle determination, clinical pathology, measurement of thyroid hormone T4 (F0-males), gross necropsy findings, organ weights and histopathologic examinations were performed. In addition, the following reproduction/developmental parameters were determined: mating and fertility indices, precoital time, number of implantation sites, gestation index and duration, parturition, maternal care, sex ratio and early postnatal pup development (mortality, clinical signs, body weights, sex, anogenital distance, areola/nipple retention and macroscopy, measurement of thyroid hormone T4.

No toxicological significant clinical signs were observed in male and female rats treated up to 250 mg/kg.  

The motor activity in male and female rats showed a large variation between the groups. Despite the fact that the motor activity recorded in the animals of all dose groups was within the historical control range, there was no indication of a treatment related change in males, but it could not be ruled out that the marked decrease in group mean values for total movements and ambulation in both main and recovery females at 250 mg/kg bw/day was a treatment related effect. Any corroborating evidence from other possibly related parameters was not observed in the current study, e.g. no other behavioural changes, no effects on grip strength and absence of histopathological alterations in nerve and muscle tissue in these females. Nevertheless, in case the changes in motor activity in females at 250 mg/kg bw/day were treatment related the magnitude of the decrease of approximately 40% lower group mean values for total movements and ambulation should be an indication of an adverse effect.

Slightly reduced body weight gain was observed in males at 250 mg/kg bw/day during treatment, resulting in approximately 4% lower group mean body weight compared to that of controls. During the recovery period, the body weight gain was similar between these two groups and the difference in body weight continued until termination of the recovery males. Based on the magnitude of the changes in body weight the effect of treatment was considered to be non-adverse.

At the end of treatment, lower mean levels for bile acids were observed in 250 mg/kg treated males and recovery females. These high dose animals had not recovered from this difference and the levels of bile acids remained lower at the end of the subsequent fourteen-day treatment free period in the recovery animals.

At the end of treatment, a dose related increase in splenic weight (in males) and decrease in adrenal weight (in females) was observed. The changes in weight of these organs in high dose animals were still within the historical control range and there were no microscopic correlates for these organ weight changes. In addition, the splenic weights in control and high dose recovery males and the adrenal weights in control and high dose recovery females were comparable at the end of the fourteen-day treatment free period. Therefore, these changes in organ weights at the end of treatment were considered to be non-adverse after treatment up to 250 mg/kg. 

No treatment-related changes were noted in the other parameters investigated in this study (i.e. food consumption, haematology, coagulation and (male) T4 thyroid hormone levels, macroscopic and microscopic examination) at the end of treatment.

Furthermore, the fourteen-day recovery period after cessation of treatment did not induce changes between the 250 mg/kg treated males and females compared to their concurrent controls in any of the parameters investigated. 

No reproduction toxicity was observed up to the highest dose level tested (250 mg/kg) and a NOAEL of 250 mg/kg bw/day was established for reproductive toxicity.

Effects on developmental toxicity

Description of key information

In the combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test conducted according to OECD Test Guideline 422 and in compliance with GLP, no reproductive or developmental toxicity was observed up to the maximum dose of 250 mg/kg bw/day. A NOAEL of ≥250 mg/kg bw/day Reaction mass of trimethoxy(aminoalkyl)-silanes and modified alkylether oligomers was established for developmental toxicity (Charles River, 2018).

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
250 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Klimisch score of 1
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

In the key combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test for reaction mass of trimethoxy(aminoalkyl)-silanes and modified alkylether oligomers, undiluted test material was administered by oral gavage to 10 male and female Wistar Han rats respectively per dose groups. The administered concentrations were 25, 75 or 250 mg/kg bw/day with a treatment period for a minimum of 28 days. A control group was also included that received water. A 14-day recovery period was performed to 5 additional male and female rats respectively, from the high and low dose groups. The recovery animals (used to study the potential reversibility of possible toxic effects) were not mated and consequently were not used for the assessment of reproduction/ developmental toxicity.

Mortality/moribundity, clinical signs, functional observations, body weight and food consumption, oestrous cycle determination, clinical pathology, measurement of thyroid hormone T4 (F0-males), gross necropsy findings, organ weights and histopathologic examinations were performed. In addition, the following reproduction/developmental parameters were determined: mating and fertility indices, precoital time, number of implantation sites, gestation index and duration, parturition, maternal care, sex ratio and early postnatal pup development (mortality, clinical signs, body weights, sex, anogenital distance, areola/nipple retention and macroscopy, measurement of thyroid hormone T4.

No toxicological significant clinical signs were observed in male and female rats treated up to 250 mg/kg.  

The motor activity in male and female rats showed a large variation between the groups. Despite the fact that the motor activity recorded in the animals of all dose groups was within the historical control range, there was no indication of a treatment related change in males, but it could not be ruled out that the marked decrease in group mean values for total movements and ambulation in both main and recovery females at 250 mg/kg bw/day was a treatment related effect. Any corroborating evidence from other possibly related parameters was not observed in the current study, e.g. no other behavioural changes, no effects on grip strength and absence of histopathological alterations in nerve and muscle tissue in these females. Nevertheless, in case the changes in motor activity in females at 250 mg/kg bw/day were treatment related the magnitude of the decrease of approximately 40% lower group mean values for total movements and ambulation should be an indication of an adverse effect.

Slightly reduced body weight gain was observed in males at 250 mg/kg bw/day during treatment, resulting in approximately 4% lower group mean body weight compared to that of controls. During the recovery period, the body weight gain was similar between these two groups and the difference in body weight continued until termination of the recovery males. Based on the magnitude of the changes in body weight the effect of treatment was considered to be non-adverse.

At the end of treatment, lower mean levels for bile acids were observed in 250 mg/kg treated males and recovery females. These high dose animals had not recovered from this difference and the levels of bile acids remained lower at the end of the subsequent fourteen-day treatment free period in the recovery animals.

At the end of treatment, a dose related increase in splenic weight (in males) and decrease in adrenal weight (in females) was observed. The changes in weight of these organs in high dose animals were still within the historical control range and there were no microscopic correlates for these organ weight changes. In addition, the splenic weights in control and high dose recovery males and the adrenal weights in control and high dose recovery females were comparable at the end of the fourteen-day treatment free period. Therefore, these changes in organ weights at the end of treatment were considered to be non-adverse after treatment up to 250 mg/kg. 

No treatment-related changes were noted in the other parameters investigated in this study (i.e. food consumption, haematology, coagulation and (male) T4 thyroid hormone levels, macroscopic and microscopic examination) at the end of treatment.

Furthermore, the fourteen-day recovery period after cessation of treatment did not induce changes between the 250 mg/kg treated males and females compared to their concurrent controls in any of the parameters investigated. 

No developmental toxicity was observed up to the highest dose level tested (250 mg/kg).

Higher pup weights in the litters at 250 mg/kg were observed at birth (+12%), for which the difference had slightly decreased on PND 13-15 (+8%) when compared to controls. Although a relation to treatment cannot be ruled out, this change in body weight was considered to be non-adverse based on the magnitude and direction of difference (a slight increase in pup weight compared to controls) and the fact that the overall development of the pups was normal. A NOAEL of 250 mg/kg bw/day was established for developmental toxicity.

Justification for classification or non-classification

Based on the available data for reaction mass of trimethoxy(aminoalkyl)-silanes and modified alkylether oligomers, no classification is required for reproductive or developmental toxicity according to Regulation (EC) No. 1272/2008.

Additional information