2,2,4-trimethyl-1-oxa-4-aza-2-silacyclohexane

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1969

Report date:

1969

Materials and methods

Principles of method if other than guideline:

- Principle of test: Vapourisation of the test substance in a 0.4 m³ vapourisation chamber. Animals (2 rabbits, 5 guinea pigs and 10 rats) were exposed to vapour of the test substance 4h/ day, 5 days/week for a total experimental time of 4 weeks. The mean concentration of the test item in the vapour was 2.475 mg/L.
- Parameters analysed / observed: At the beginning of the test and at the end of the experimental time Haemoglobin was determined with the cyanmethaemoglobin method, erythrocytes and leucocytes were counted and haematocrit as well as MCV and MCHC were determined. Additionally, GPT, GOT, bilirubin, urea and creatinine were detected in 5 male Wistar rats.

GLP compliance:

no

Remarks:

study conducted prior to implementation of GLP

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,2,4-trimethyl-1-oxa-4-aza-2-silacyclohexane

EC Number:

233-487-5

EC Name:

2,2,4-trimethyl-1-oxa-4-aza-2-silacyclohexane

Cas Number:

10196-49-3

Molecular formula:

C6H15NOSi

IUPAC Name:

2,2,4-trimethyl-1,4,2-oxazasilinane

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Wistar II

Sex:

male

Details on test animals or test system and environmental conditions:

not specified

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Remarks on MMAD:

MMAD was not determined

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 0.4m³ chambers

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

4 weeks total exposure time

Frequency of treatment:

4h/day, 5 days/week

Doses / concentrations

Dose / conc.:

2.475 mg/L air

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

not specified

Positive control:

no

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once daily

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: once per week for 6 weeks, i.e. during the exposure time and an additional 2 weeks observation period.

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the beginning and at the end of the experiment
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- How many animals: 5 rats
- Parameters checked in table [No.2] were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At the beginning and at the end of the experiment
- Animals fasted: Not specified
- How many animals: 5 rats
- Parameters checked in table [No.3] were examined.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

IMMUNOLOGY: No

Sacrifice and pathology:

GROSS PATHOLOGY: No
HISTOPATHOLOGY: No

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Normal weight gain was observed during the exposure and observation period

Food consumption and compound intake (if feeding study):

not examined

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:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Effect levels

Key result

Dose descriptor:

dose level: 2.475 mg/L

Effect level:

> 2.475 mg/L air

Based on:

test mat.

Sex:

male

Remarks on result:

other: no adverse effects observed at the highest dose/concentration tested

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 1: Body weights of treated rats during exposure and observation period

Species	Body weight in kg [weeks]
	exposure time				observation time
	1	2	3	4	5	6
Wistar rats	0.249	0.255	0.268	0.278	0.280	0.296
Rabbits	3.05	3.08	3.10	3.25	3.30	3.38
Guinea pigs	0.504	0.507	0.548	0.559	0.564	0.573

Table 2: Results of haematology: in Wistar rats/Rabbits

time point of determination	Hb [g%]	Erythrocytes [E+006]	HbE γγ	Leucocytes [E+003]	Haematocrit	EEV µm³
before exposure	16.6	9.32	17.8	13.4	51	55
after exposure	16.2	8.93	18.5	14.4	51	58
	Rabbits
before exposure	12.9	5.99	21.7	7.5	40	67
after exposure	12.7	5.87	22.8	8.2	38	66

Table 3: Results of clinical biochemistry in Wistar rats/Rabbits

Species	time point of determination	GOT	GPT	Bilirubin	Urea	Creatinine
		mU		mg%
rat	before exposure	51.6	20.8	0.20	28.3	0.85
	after exposure	51.5	14.8	0.18	33.4	0.98
rabbit	before exposure	8.2	11.0	0.20	32.4	1.44
	after exposure	6.9	8.0	0.24	35.1	1.67

Applicant's summary and conclusion

Conclusions:

The LC50 for repeated dose toxicity by inhalation was determined to be > 2.475 mg/L. Under the present test conditions, i.e. only one concentration tested, only the LC0 could be determined.

Executive summary:

In a repeated dose toxicity: inhalation study, male Wistar II rats were exposed by inhalation route to the test substance for 4 hours per day, 5 days per week for a total exposure time of 4 weeks. The whole body was exposed to a concentration of 2.475 mg/L. After the exposure period the animals were observed for additional 2 weeks. In rats no adverse effects were detected in the parameters observed at the concentration tested.

Other results are also available for rabbits and guinea pigs (see any other information on results). No change of general condition of the animals was detected. However, during the 3. and the 4. week of exposure slight irritation of the rabbits eye mucosa but not of the other species occurred.