Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study acceptable for assessment. No data on analytical method was provided and there is no certificat of analysis.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
The test material, a clear colourless liquid, was received from the principal on 26th May 1981. It was stated to be Tert-Amylhydroperoxide.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Rats were obtained from the Central Institute for the Breeding of Laboratory Animals TNO, Zeist, The Netherlands.
Just prior to exposure the weight variation of the animals was smaller than ± 20% of the mean body weight.
The animals were housed 5 to a cage. The cages were suspended in an open rack in an animal room. The animals received ad libitum the Institute's
stock diet for rats and bottled unfluoridated water. The temperature and the relative humidity in the animal room were set and controlled at 21 ± I°C
and 50 - 60% respectively.


Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Tert-Amylhydroperoxide aerosol was generated from a stainless (steel/glass air nebulizer, which was fitted with a baffle to remove the large droplets by impaction. The aerosol generated was passed into the inhalation chamber were it was mixed with an additional airflow.
The stainless steel exposure chamber, having a capacity of 1.5 m3, was used. The chamber was operated under dynamic airflow conditions. The
total airflow through the chamber ranged from 11 to 16 m3/hour. Through a glass door at the front of the exposure chamber the animals could be observed continuously. The front door is provided with several openings for taking samples of the test atmosphere at different locations.

The nominal concentration was measured by dividing the total quantity of the test material used by the total quantity of air which had been passed through the inhalation chamber during the exposure period.

The actual concentrations were determined: A measured quantity of test atmosphere was passed through an impinger filled with an absorbent (xylene). The quantity of tert-amylhydroperoxide in the absorbent was analysed by method no. Jo/73.6, d.d.10.07.1975, provided by the sponsor. The actual concentration in the test atmosphere was calculated from the quantity of Tert- Amylhydro­peroxide in the absorbent and the total volume of air sampled.

Particle size determinations and counts were carried out in samples taken from the test atmosphere with a cascade impactor.


Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
1580, 2100, 2230, 2375 and 2890 mg/m3
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The animals were housed in wire mesh stainless steel cages which were located at one level in the exposure chamber. Individual housing was used to minimize filtration of inspired air by the animals fur as a result of crowding. During the exposure the animals were deprived of water and food.

After the exposure the survivals were returned to their living cages for an observation period of two weeks.

Observations:
During the exposure and the consecutive observation period all reactions to treatment or mortality were observed and recorded daily.
Body weights were recorded at days 1, 2, 4, 7 and 14. At the end of the
observation period the animals were killed by exsanquination of the abdominal aorta under ether anaesthesia, autopsied and examined for gross pathological changes.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
2 425 mg/m³ air (analytical)
Based on:
other: vapors of test mat.
95% CL:
2 100 - 2 750
Exp. duration:
4 h
Mortality:
All animals that died, died within a period of 2 days after starting the exposure, except for one male of the 2890 mg/m 3 air group, which died on day 3.
Clinical signs:
After about one hour of exposure the animals showed mouth breathing and after about 2 hours they showed also laboured respiration. Twelve hours after termination of the exposure all surviving animals showed normal respiration pattern.
Body weight:
Both males and females lost body weight during the first 24 hours after starting the exposure. Thereafter they gained weight in a normal way.
Gross pathology:
No abnormalities that were considered to be treatment-related, neither in died animal nor in no-died animals

Any other information on results incl. tables

Analytical data:

Exposure n° Nominal concentration (mg/m3) Actual concentration (mg/m3)* IC 95%
1 1620 1580 (1420 - 1740)
2 1990 2100 (1820 - 2260)
3 2240 2230 (1980 - 2360)
4 2320 2375 (2040 - 2660)
5 2520 2890 (2460 - 3120)

* All attempts to determine particle size distribution were unsuccesful most probably as a result of the relative high volatility of the test

material. Animals were most probably exposed to vapors.

Mortality:

Exposure n° Actual concentration (mg/m3) Mortality _
1 1580 0% _
2 2100 20% 10 % at the end of the exposure and 10% at the end of day 1
3 2230 60% 50 % at the end of day 1 and 10% at the end of day 2
4 2375 70% 10 % at the end of the exposure, 20% at the end of day 1, and 40% at the end of day 2
5 2890 50%  20% at the end of day 1, 20% at the end of day 2 and 10 % at the end of day 3

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The 4-hour LC 50 of tert-amylhydroperoxide in rats was calculated to be 2425 mg/m3 air with 2100 and 2750 mg/m3 air as the 95 % confidence limits.
Executive summary:

Five groups of 5 male and 5 female rats were whole-body exposed for 4 hours to vapors of ter-amyl hydroperoxide. Dermal exposure was minimized. The exposure concentrations were 1580, 2100, 2230, 2375 and 2890 mg/m3. Mortality occured mainly after the end of the exposure. At necropsy, no gross abnormality was observerd in any rats. The 4-hour LC50 of tert-amylhydroperoxide in rats, whole-body exposed, was calculated to be 2425 mg/m3 air with 2100 and 2750 mg/m3 air as the 95% confidence limits.