Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
There are only limited details in study report, but this is consistent with other reports of this type from this period. Study was done before standardized test guidelines and GLP but was conducted using a standard and documented method at a reputable facility.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 433 draft (Acute Inhalation Toxicity: Fixed Concentration Procedure) (not officially approved)
Deviations:
not applicable
GLP compliance:
no
Test type:
fixed concentration procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: clear, colourless liquid
Details on test material:
The sample, received from the principal on June 13, was a colourless liquid, 95% of which consisted of 2,4,4-trimethylpentyl-2-hydroperoxide. The other components of the tes material were 2,4,4-trimethylpentane-2-ol, diisobutylene and water.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Young rats (Wistar-derived, and reared under S.P.F. conditions) were used for this experiment. The weight of the males varied from 189 to 192 g, that of the females from 133 to 138 g. The animals were obtained from the Central Institute for the Breeding of Laboratory Animals, TNO-Zeist, The Netherlands.

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Remarks:
Although not stated, exposure was probably whole-body.
Vehicle:
air
Details on inhalation exposure:
The exposure chamber consists of a horizontally placed glass cylinder (0.90 x 0.15 m) with sampling ports at both ends and contains a perforated stainless steel frame-work for separate accomodation of the rats.

Samples were analysed by means of gas-liquid chromatography, using an Intersmat gas-chromatograph loaded with a SE30 column (0.70 m, ø 1/2 cm), and detected with a flame ionisation detector.

Column-detection and injection temperatures were 75, 85 and 90 °C respectively.

The test compound was gauged by using a 4% solution in acetone.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
480 ppm (2.85 mg/l).
No. of animals per sex per dose:
five
Control animals:
no
Details on study design:
The dynamic atmosphere for the inhalation experiment was formed by passing air (relative humidity 50%) through various columns - airflow per column 1 l/min - containing chromosorb W, AW, saturated with the test substance. Five columns were used in parallel, giving an eventual airfow of 5 l/min (the minimum quantity required to prevent condensation of vapou (H2O)) through the exposure chamber. The temperature inside the cylinder was 24 °C.

A group of five male and five females rats was exposed to an atmosphere saturated with T.M.P.H. for four hours. After the exposure the rats were returned to their living-cages and provided with food and tap water ad libitum during an observation period of 14 days.
Statistics:
None

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
LC0
Effect level:
2.85 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Key result
Sex:
female
Dose descriptor:
LC0
Effect level:
2.85 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
None.
Clinical signs:
From the start of the exposure the animals were restless. After half an hour they closed their eyes and had wet noses. The severity of the effects increased during the exposure period. After two hours mouth breathing was observed as well as some incoordination of movement. The female rats have been recovered one day after the exposure; the males however, needed about two days before they behaved normally again.
Body weight:
No data.
Gross pathology:
No data.
Other findings:
The intoxication signs observed at 480 ppm, seem to justify the expectation that the 4-hour LC50 will not be very far above this level.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
From the results of the present study it can be concluded that the 4-hour LC50 of T.M.P.H. exceeds 480 ppm (2.85 mg/l) but is expected to be less than 10 mg/L.
Executive summary:

The acute inhalation toxicity of T.M.P.H. was studied in rats, by exposing them to an atmosphere saturated with the test material for a period of four hours.

The dynamic atmosphere for the inhalation experiment was formed by passing air (relative humidity 50%) through various columns - airflow per column 1 l/min - containing chromosorb W, AW, saturated with the test substance. Five columns were used in parallel, giving an eventual airfow of 5 l/min (the minimum quantity required to prevent condensation of vapou (H2O)) through the exposure chamber. The temperature inside the cylinder was 24 °C.

A group of five male and five females rats was exposed to an atmosphere saturated with T.M.P.H. for four hours. After the exposure the rats were returned to their living-cages and provided with food and tap water ad libitum during an observation period of 14 days.

Exposure of the rats to an atmosphere saturated with T.M.P.H. - viz. 480 ppm (2.85 mg/l) under the experimental conditions - caused no mortality. From the start of the exposure the animals were restless. After half an hour they closed their eyes and had wet noses. The severity of the effects increased during the exposure period. After two hours mouth breathing was observed as well as some incoordination of movement. The female rats have been recovered one day after the exposure; the males however, needed about two days before they behaved normally again.

Since no mortality occurred during the subsequent observation period of 14 days, no LD50 value could be determined. From the results of the present study it can be concluded that the 4-hour LC50 of T.M.P.H. exceeds 480 ppm (2.85 mg/l) but is expected to be less than 10 mg/L.