Trimethoxy(2-methylpropyl)silane

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

08.12.1987 to 05.01.1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was well documented and meets generally accepted scientific principles, and conducted in compliance with GLP, and is therefore considered to be reliability 1. Read-across of the result is considered to be reliability 2. Further details on read-across are given in the endpoint summary.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

No urinalysis

GLP compliance:

yes

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

17980-47-1

EC Number:

605-871-6

Cas Number:

17980-47-1

IUPAC Name:

17980-47-1

Constituent 2

Reference substance name:

Triethoxyisobutylsilane

EC Number:

402-810-3

EC Name:

Triethoxyisobutylsilane

IUPAC Name:

Triethoxyisobutylsilane

Details on test material:

- Name of test material (as cited in study report): Isobutyltriethoxysilane (Dynasylan IBTEO)
- Substance type: Alkoxysilane
- Physical state: Colourless liquid
- Analytical purity: No data
- Stability under test conditions: No data
- Storage condition of test material: Closed bottles under ambient conditions in non-continuous artificial light.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Portage, Michigan, USA.
- Age at study initiation: 27-29 days
- Weight at study initiation: 72-95 g
- Fasting period before study: No
- Housing: Five/cage ( no other information)
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 22.2
- Humidity (%): 44.8 - 53.3
- Air changes (per hr): Approx. 19
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 08.12.1987 To: 05.01.1988

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: None, dosed undiluted.

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

Not required.

Duration of treatment / exposure:

28 days

Frequency of treatment:

Daily (seven days per week)

Doses / concentrations

Remarks:

Doses / Concentrations:
1000 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

Five

Control animals:

other: Distilled water

Details on study design:

- Dose selection rationale: Guideline limit dose
- Rationale for selecting satellite groups: No satellite groups
- Post-exposure recovery period in satellite groups: No recovery groups

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily (all animals were observed for signs of ill health, behavioural changes or toxicosis)

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: All rats were weighed prior to dosing and subsequently weekly intervals throughout the study.

FOOD CONSUMPTION: Yes
- Time schedule for examinations: The quantity of food consumed in each cage was measured at weekly intervals throughout the study.

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Prior to termination in week 4
- Anaesthetic used for blood collection: Yes (ether)
- Animals fasted: Yes
- How many animals: All
- Parameters checked in table 1 were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Prior to termination in week 4
- Animals fasted: Yes
- How many animals: All
- Parameters checked in table 1 were examined.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes (see table 2)
HISTOPATHOLOGY: Yes (see table 2)

Statistics:

All statistical analyses were carried out seperately for males and females. Bodyweight data were analysed using weight gains. The following sequence of statistical tests was used for bodyweight, organ weight and clinical pathology data: (i) If the data consisted predominently of one particular value (relative frequency of the mode exceeds 75%), the proportion of values different from the mode were analysed by appropriate methods. Otherwise: (ii) Bartlett's test (i) was applied to test for heterogeneity of variance between treatments. Where significant (at the 1% level) heterogeneity was found, a logarithmic transformation was tried to see if a more stable variance structure could be obtained. (iii) If no significant heterogeneity was detected (or if a satisfactory transformation was found), a one-way analysis of variance was carried out. If significant heterogeneity of variance was present, and could not be removed by a transformation, the Kruskal-Wallis analysis of ranks (2) was used. (iv) Analysis of variance were followed by Student's 't' test. The Kruskal-Wallis analyses were followed by the non-parametric equivalents of the 't' test. Where appropriate for organ weight data, analysis of covariance was used in place of analysis of variance in the above sequence. The final bodyweight was used as covariate in an attempt to allow for differences in bodyweight which have influenced the organ weights.

Results and discussion

Results of examinations

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 examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY: All rats survived the treatment period. There were no treatment-related clinical signs.

BODY WEIGHT AND WEIGHT GAIN: There were no differences in bodyweight gain between treated and control rats.

FOOD CONSUMPTION: There were no differences in food consumption between treated and control rats.

HAEMATOLOGY: There were no statistically significant differences in male animals. A single female rat among the controls had a low PCV, Hb and RBC values and raised MCV. As this was consistent with reaction to trauma, the data for this rat were excluded from the calculation of the group means and the statistical analyses.

The PCV values recorded for treated female rats tended to be slightly lower than those of the female controls (P>0.05). This was reflected by statistically significantly higher MCHC (P<0.001) and lower MCV (P<0.05) values for the treated female rats in comparison with the female controls. These small differences of erythron parameters between female rats of the control group and the treated group were considered to be of no toxicological importance.

CLINICAL CHEMISTRY: AST values of treated male rats and ALT values of treated females were slightly lower than in the corresponding control groups (P<0.05). These small differences in transaminase levels were not considered to be toxicologically important. Higher potassium levels were apparent in both male and female rats treated with IBTEO. The intergroup differences were small and achieved statistical significance only in the female rats (P<0.05). Although the possibility that this constituted a treatment-related effect cannot be completely discounted, the potassium levels of individual rats were consistent with the values expected for this parameter. Other electrolyte levels were not affected.

ORGAN WEIGHTS: Adjusted liver and kidney weights recorded in female rats receiving IBTEO were statistically higher than in the female controls (P<0.001 and P<0.01, respectively). However, no macroscopic abnormalities were observed in these organs at postmortem examination or at subsequent microscopic examination of tissues.

GROSS PATHOLOGY: No adverse findings.

HISTOPATHOLOGY: It was concluded by the study authors that there were no adverse findings. Regarding the liver, there were no findings in females. In two control and four test male animals minimal vacuolation of centrilobular hepatocytes was observed. Minimal vauolation of midzonal hepatocytes was observed in one test animal. Minimal focal periportal mononuclear cells were observed in one control male.

Regarding the kidney, occasional groups of basophilic cortical tubules were observed in one control and one animal from each group (control and test). There was a cyst in the medulla of one test male. Minimal focal mineralisation at the corticomedullary junction was observed in one control female.

Lymph nodes were only examined in male animals. Three of three test animals and one of two control animals examined had minimal reactive hyperplasia of the cervical area.

Effect levels

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: There were no toxicologically relevant findings.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In a 28-day oral gavage study conducted using a protocol similar to OECD 407 and to GLP (reliability score 1) the NOAEL for triethoxyisobutylsilane was at least 1000 mg/kg bw/day, as there were no adverse toxicological findings at this the only dose tested.