[No public or meaningful name is available]

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Description of key information

In an oral gavage study conducted, the NOAEL for N-(3-(trimethoxysilyl)propyl)ethylenediamine relating to repeated dose (parental systemic) effects and to reproductive toxicity was at least 500 mg/kg bw/day, as no significant adverse effects were observed up to the highest dose of 500 mg/kg bw/day tested in rats.

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Remarks:

Read across data

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from secondary source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

not specified

Limit test:

no

Specific details on test material used for the study:

Not specified

Species:

rat

Strain:

Sprague-Dawley

Details on species / strain selection:

Not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

Not specified

Details on mating procedure:

not specified

Duration of treatment / exposure:

39 days

Frequency of treatment:

Daily, 7 days per week for up to 39 days

Details on study schedule:

Not specified

Dose / conc.:

0 mg/kg bw/day (actual dose received)

Dose / conc.:

25 mg/kg bw/day (actual dose received)

Dose / conc.:

125 mg/kg bw/day (actual dose received)

Dose / conc.:

500 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

Not specified

Control animals:

yes, concurrent vehicle

Details on study design:

Not specified

Positive control:

Not specified

Parental animals: Observations and examinations:

The animals were observed twice daily (once daily on weekends) for mortality/viability

Oestrous cyclicity (parental animals):

Not specified

Sperm parameters (parental animals):

Not specified

Litter observations:

Not specified

Postmortem examinations (parental animals):

Not specified

Postmortem examinations (offspring):

Not specified

Statistics:

Data were analyzed by Bartlett's and Kolmogorov-Smirnov tests. Parametric data was tested by using ANOVA followed by Dunnett's test; Non-parametric data was analyzed by Kruskal-Wallis test followed by Wilcoxon test. Significance levels were either P<0.05 or P<0.01.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Endocrine findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

not specified

Not specified

Dose descriptor:

NOAEL

Effect level:

>= 500 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

food consumption and compound intake

Critical effects observed:

no

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Increased nasal sounds, labored respiration or soft vocalization

Mortality / viability:

mortality observed, treatment-related

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

no effects observed

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Sexual maturation:

not specified

Anogenital distance (AGD):

not specified

Nipple retention in male pups:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings:

not specified

Other effects:

not specified

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

>= 500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

clinical signs

mortality

body weight and weight gain

clinical biochemistry

urinalysis

organ weights and organ / body weight ratios

Critical effects observed:

no

Reproductive effects observed:

no

Conclusions:

In an oral gavage study conducted, the NOAEL for N-(3-(trimethoxysilyl)propyl)ethylenediamine relating to repeated dose (parental systemic) effects and to reproductive toxicity was at least 500 mg/kg bw/day, as no significant adverse effects were observed up to the highest dose of 500 mg/kg bw/day tested in rats.

Executive summary:

A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test study was performed with test chemical (CAS: 1760-24-3) in sprague dawley rats. Test chemical wass dissolved in corn oil at the doses of 25, 125, 500 mg/kg bw/day. Two females in the 500 mg/kg/day group were sacrificed or found dead in moribund condition. Both of these deaths were attributed to dosing-related errors. Clinical signs attributed to test substance included increased nasal sounds, labored respiration or soft vocalization. These signs were not seen in the control and infrequently seen in either of the two lower dose groups. There was no test substancerelated effects on body weight, body weight gain or food consumption. Observations recorded at dosing indicate a dose-related resistance to dosing. No test substance-related effects were observed in any of the reproductive parameters evaluated. Two high dose (500 mg/kg/day) and one low dose (25 mg/kg/day) females that did not produce litters had positive evidence of copulation. Six of the eight eight surviving high dose group females produced litters that were similar in all respects to control litters. Based on the results of this reproductive/developmental screening study, the NOAEL for maternal systemic toxicity of AEAPTMS in the rat via the oral dosing was considered to be 500 mg/kg/day.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

500 mg/kg bw/day

Species:

rat

Quality of whole database:

Data is from secondary source and klimisch 4.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Toxicity to reproduction:

 

Study 1: A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test study was performed with test chemical (CAS: 1760-24-3) in sprague dawley rats. Test chemical wass dissolved in corn oil at the doses of 25, 125, 500 mg/kg bw/day. Two females in the 500 mg/kg/day group were sacrificed or found dead in moribund condition. Both of these deaths were attributed to dosing-related errors. Clinical signs attributed to test substance included increased nasal sounds, labored respiration or soft vocalization. These signs were not seen in the control and infrequently seen in either of the two lower dose groups. There was no test substancerelated effects on body weight, body weight gain or food consumption. Observations recorded at dosing indicate a dose-related resistance to dosing. No test substance-related effects were observed in any of the reproductive parameters evaluated. Two high dose (500 mg/kg/day) and one low dose (25 mg/kg/day) females that did not produce litters had positive evidence of copulation. Six of the eight eight surviving high dose group females produced litters that were similar in all respects to control litters. Based on the results of this reproductive/developmental screening study, the NOAEL for maternal systemic toxicity of AEAPTMS in the rat via the oral dosing was considered to be 500 mg/kg/day.

 

Study 2: In a repertaed dsoe toxicity study,SPF male andfemale rats were treated with menthone in the concentration of 0, 200, 400 and 800 mg/kg bw/ day orally by gavage for 28 days. At 800 mg/kg bw,after 19 days of dosing female rats showed signs of toxic effects. They had pale mucous membranes and showed signs of pain prevent deaths in this group, the dose was reduced to 400 mg/kg.4 animals died during the study due to accidental intratracheal dosing.Decreased in body weight gain was observed in treated male and female rats at 200, 400 and 800 mg/kg bw as compared to control. Decreased in food consumption was observed in treated male rat at 800 mg/kg bw, and in female rats from 3rd week at400 mg/kg bwas compared to control. Decreased in food consumption was observed in female rat within the first 2 weeks at 200 and 400mg/kg bwas compared to control. Dose-dependent decrease in creatinine concentration and a dose dependent increase of both alkaline phosphatase activity and bilirubin content were observed in treated male and female rats at 800 mg/kg bw as compared to control. Similarly,statistically significant dose-related increase in relative weight of the spleen, liver and brain of the male rat at 800 mg/kg bw and kidneys, spleen, liver and brain of female rats at 400 mg/kg bw were observed as compare to control. In addition, Cyst-like spaces appeared scattered in the white matter of the cerebellum at 800 mg/kg bw. The findings resembled the changes found in rats dosed with peppermint oil. No histopathological changes were observed in reproductive organ of testis and ovary of treated rats as compared to control. Therefore, NOAEL was considered to be 800 mg/kg bw for male and 671 mg/kg bw for female when SPF male and female rats were treated with menthone orally by gavage for 28 days.

Justification for classification or non-classification

Thus based on the above annotation and CLP criteria the test chemical is not likely to exhibit reproductive toxicant substance. Hence the substance cannot be classified as reproductive toxicant.