Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

sub-chronic toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
16.01.1992 to 16.04.1992
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
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 Type:
study report
Report date:

Materials and methods

Test guideline
according to guideline
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
No urinalysis
GLP compliance:
yes (incl. QA statement)
Limit test:

Test material

Constituent 1
Reference substance name:
EC Number:
Cas Number:
Constituent 2
Reference substance name:
EC Number:
EC Name:
Details on test material:
- Name of test material (as cited in study report): Dynasylan IBTEO (Isobutyltriethoxysilane)
- Substance type: Alkoxysilane
- Physical state: Colourless liquid
- Stability under test conditions: No data
- Storage condition of test material: Metal drum. Once dispensed, stored over silica gel in a cool place

Test animals

Details on test animals or test system and environmental conditions:
- Source: Charles River (UK) Limited, Manston, Kent.
- Age at study initiation: 6-7 weeks
- Weight at study initiation: Males: 174 - 235 g; Females: 148 - 198 g
- Fasting period before study: No
- Housing: 5/sex in polypropylene grid-floor cages (except during exposure)
- Diet (e.g. ad libitum): Ad libitum except during exposure
- Water (e.g. ad libitum): Ad libitum except during exposure
- Acclimation period: 14 days

- Temperature (°C): 19-24
- Humidity (%): 40-55
- Air changes (per hr): Approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 16.01.1992 To: 16.04.1992

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Remarks on MMAD:
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION: The test substance was aerosilised using glass concentric jet nebulisers located at the top of each exposure chamber. Each nebuliser was connected to a glass syringe attached to a modified infusion pump, which provided a continuous supply of test substance under pressure, and to a metered compressed air supply. The nature of the test substance was such that production of an aerosol into an exposure chamber at room temperature resulted in instantaneous vapourisation. The resulting atmosphere was shown, during an atmosphere characterisation phase, to be a vapour containing no aerosol particles.
- Exposure apparatus: During the daily exposure period each dose group was housed in a separate chamber.
- Method of holding animals in test chamber: Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber '0' ring. Only the noses of the animals were exposed to the test atmosphere.
- Source and rate of air:
- Method of conditioning air: Compressed air was supplied by means of a Gast 2HBB-10-P25Y oil free compressor and was passed through a water trap and respiratory quality filters which removed particulates over 0.005 µmbefore it was introduced to the nebulisers.
- Temperature, humidity, pressure in air chamber: The temperature and relative humidity inside the exposure chambers were measured in the animals' breathing zone and automatically recorded every thirty minutes wherever possible, throughout the daily six-hour exposure periods. Temperatures were all in the range 17-25, humidity in the range 27-88. No information on the pressure.
- Air flow rate: No data
- Treatment of exhaust air: No data

- Brief description of analytical method used: Gas chromatography
- Samples taken from breathing zone: yes
Analytical verification of doses or concentrations:
Details on analytical verification of doses or concentrations:
The chamber concentration of the test substance in each exposure chamber was measured, from a sampling point in the animals' breathing zone, by gas chromatography. Chamber air was continuously sampled through impinger bottles containing methanol over the entire six hour exposure period. The resulting samples were collected twice daily, at the middle and end of the exposure period, and were submitted for gas chromatographic analysis on a weekly basis.
Duration of treatment / exposure:
90 days (6 hours/day)
Frequency of treatment:
Daily (seven days per week)
Doses / concentrationsopen allclose all
Doses / Concentrations:
0.25, 0.8 and 2.5 mg/l
other: target
Doses / Concentrations:
0.22, 0.75 and 2.54 mg/l
analytical conc.
No. of animals per sex per dose:
Control animals:
other: air only
Details on study design:
- Dose selection rationale: Based on the results of a range-finding study
- Rationale for selecting satellite groups: No satellite group
- Post-exposure recovery period in satellite groups: No post-exposure recovery group


Observations and examinations performed and frequency:
- Time schedule: All animals were continuously monitored throughout the exposure period for any changes in appearance, respiratory and behavioural patterns. Clinical observations were recorded prior to the start of exposure, three hours after the start of exposure and on removal from the chamber at six hours.


- Time schedule for examinations: Individual body weights were recorded on the day before the start of treatment (day 0) and at weekly intervals thereafter. Bodyweights were also recorded at necropsy.

- Food consumption was recorded for each cage group at weekly intervals throughout the study.

- Time schedule for examinations: Group mean water consumptions were measured for a period of seven days during each of weeks 1, 6 and 12.

- Time schedule for examinations:Before start of treatment and at termination.
- Dose groups that were examined: High dose and control animals.

- Time schedule for collection of blood: Prior to necropsy
- Anaesthetic used for blood collection: Yes, halothane B.P.
- Animals fasted: No
- How many animals: All test and control animals
- Parameters checked in table 1 were examined.

- Time schedule for collection of blood: Prior to necropsy
- Animals fasted: No
- How many animals: All test and control animals
- Parameters checked in table 1 were examined.


Sacrifice and pathology:
GROSS PATHOLOGY: Yes (see table 2)
HISTOPATHOLOGY: Yes (see table 2)
Data were processed to give group mean values and standard deviations where appropriate. Absolute and relative organ weights, hematological and blood chemical data were analysed by one way analysis of variance incorporating 'F-max' test for homogeneity of variance. Data showing heterogeneous variances were analysed using Kruskal Wallis non-parametric analysis of variance and Mann Whitney U-test.
Histological data were analysed using the following methods to determine significant differences between control and treatment groups for the individual sexes: (i) Chi squared analysis for differences in the incidence of lesions occurring with an overall frequency of 5 or greater. (ii) Kruskal-Wallis one way non-parametric analysis of variance for the comparison of severity grades for the more frequently observed graded conditions.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
no mortality observed
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):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
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: There were no treatment-related deaths during the study, One low dose male was killed in extremis on day 49. No clinically observable signs of toxicity were detected in test or control animals throughout the study. Incidents of red/brown staining around the eyes, snout and of the fur, together with wet fur, were detected in all dose groups throughout the treatment period. These are typical findings associated with the restraint procedure and as such are not indicative of toxicity. One low dose male showed signs of hunched posture, piloerection and lethargy from dy 44 to day 49. This animal was later removed from the restraining cone during the exposure period on day 49 and killed in extremis. Other isolated signs were reported for the low and intermediate dose animals including hunched posture, lethargy, piloerection, decreased respiratory rate and ptosis. These were not dose-related and as such were not toxicologically significant.

BODY WEIGHT AND WEIGHT GAIN: No adverse effects on bodyweight were detected that could be considered attributable to treatment with the test substance. Slight reductions in bodyweight gain were noted in individual animals in all dose groups, including controls, throughout the latter part of the study. This was considered to be associated with the restraint procedure and since there were no intergroup differences in the incidence and severity of bodyweight changes, these were considered to be of no toxicological significance.

FOOD CONSUMPTION: There were no apparent adverse effects on food consumption.

FOOD EFFICIENCY: Food efficiency was comparable between test and control animals.

WATER CONSUMPTION: There were no apparent adverse effects on water consumption.

OPHTHALMOSCOPIC EXAMINATION: There were no treatment-related ocular effects.

HAEMATOLOGY: there were no treatment-related changes on haematological parameters. A statistically significant increase in mean corpuscular haemoglobin (MCH) was detected in mid and high dose females together with an increase in high dose female neutrophil counts. All values were entirely within the normal ranges for rats of this strain and age and in isolation the increases were considered fortuitous and of no toxicological significance. The other minor statistically significant difference detected between test and control groups was confined to the mid dose female mean corpuscular haemoglobin concentration (MCHC) and as such was not dose-related.

CLINICAL CHEMISTRY: there were no treatment-related changes on blood chemical parameters. A statistically significant increase in plasma urea was detected in mid and high dose males together with a reduction in high dose male glucose. All values were within the normal range and not considered to be toxicologically significant. A statistically significant reduction in alkaline phosphatase was observed in high dose animals of both sexes, but a reduction in the level of this enzyme alone was not considered toxicologically important. Inorganic phosphate was significantly reduced in all female test animals, however there was not a dose response. The other minor statistically significant differences detected between test and control groups were confined to low and intermediate group animals and were not dose related.

ORGAN WEIGHTS: A statistically significant reduction in absolute lung weight was detected in high dose females in comparison with controls. No change in relative weight was detected and consequently the reduction was considered to be of no toxicological significance.

High dose males showed a statistically significant increase in relative liver weight, however with no associated blood chemical or histopathological evidence to support an hepatic effect, the increase was considered unlikely to be of any toxicological importance.

GROSS PATHOLOGY: No treatment-related macroscopic abnormalities were detected. The decedent from day 49 showed accentuated lobular pattern and patchy pallor of the liver, unusually pink pancreas and epithelial sloughing and thickening of the forestomach. A large pus-filled mass was noted dorsal to the seminal vesicles and bladder which appeared to have caused an intestinal blockage. One intermediate dose male showed a similar, but smaller mass adjacent to the prostate gland at necropsy.

HISTOPATHOLOGY: The authors of the study reported that treatment-related changes were not observed.

Heart: 9/10, 1/10 and 7/10 animals (control, low and high dose groups, respectively) had minimal focal myocarditis, and 1/10 and 3/10 control and high dose animals had slight focal myocarditis. Focal myocardial necrosis was observed in no control animals, 1/1 low dose (only one animal examined) and 2/10 high dose animals.

Kidneys: 1/10, 1/1 (only one animal examined), and 3/10 animals (control, low and high dose groups, respectively) had groups of basophilic/dilated tubules.

Liver: minimal or slight mononuclear cell foci was observed in all control and high dose animals, and in the one low dose animal that was examined.

Lung: All animals, including those in the control group had peribronchiolar/perivascular lymphoid aggregates. The severity was not dose-related. Focal pneumonitis was observed in all test groups (2/10, 3/10, 3/10 animals in low, mid and high dose groups). Minimal/slight groups of alveolar macrophages were observed in 8/10, 7/10, 9/10 and 9/10 animals in the control, low, mid and high dose groups.

Nasal cavities: minimal inflammatory cell infiltrates were observed in 2/10 control and high dose animals. Focal epithelial hyperplasia was observed in 1/10 high dose animals. Inflammatory exudate was observed in 2/10 control and 2/10 high dose animals.

Prostate: chronic prostatitis was observed in 1/10 controls (severe), 1/1 low dose group (marked) and 1/10 high dose group (marked) animals. Abscess formation was observed in 1/10, and 1/1 control and low dose animals.

Testes: atrophy was observed in 3/10 controls and 2/10 high dose animals.

Urinary bladder: epithelial hyperplasia was observed in 1/10 controls and 1/10 low dose animals.

Effect levels

Dose descriptor:
Effect level:
>= 2.54 mg/L air (analytical)
Based on:
test mat.
Basis for effect level:
other: No treatment-related adverse effects observed.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

In a repeated nose-only inhalation study, conducted to OECD 413 and to GLP (reliability score 1) the NOAEC for triethoxyisobutylsilane was at least 2.54 mg/l in rats.