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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
30 May 1986
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
Test was conducted as limit study, but the results revealed an LC100 below the nominal test concentration of 4.5 mg/L. No further doses were tested. Moreover, the test material condensed on the surfaces of the delivery apparatus and inhalation chamber during delivery, so that the actual test concentration was unknown. It was estimated that the rats were exposed to vapor concentrations at least 10-fold less than the nominal concentration. The study was not conducted under GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Study was not condcuted under GLP.
GLP compliance:
no
Test type:
traditional method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2,6,6-tetramethylpiperidinooxy
EC Number:
219-888-8
EC Name:
2,2,6,6-tetramethylpiperidinooxy
Cas Number:
2564-83-2
Molecular formula:
C9H18NO
IUPAC Name:
2,2,6,6-tetramethylpiperidinooxy
Test material form:
solid
Remarks:
color: orange
Details on test material:
purchased from Sigma Chemical Company, Munich, Germany.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Species/Strain: Rat (Sprague-Dawley)
- Source: Charles River Breeding Laboratories, Inc., Portage, MI
- Body weigth: 220g mean males, 176 g mean females
- Housing: single housing in stainless steel cages
- Diet: Purina Rodent Chow 5001
- Water: Water supplied from a reverse-osmosis purifier, ad libitum
- Acclimation period: 7 days befor the first test-substance application

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 40 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: mixture of vapour and aerosol / mist
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
The test article was generated by heating it to 100°C and drawing the vapour/aerosol mixture into the exposure system. The flow system malfunctioned due to the corrosive nature of the test article so accurate flow readings could not be obtained during the exposure. However, testing showed that an adequate airflow was maintained during the exposure, and flowrates were estimated by calibrations after the exposure ended. The estimated nominal concentration was 4.5 - 6.8 mg/L. However, the test material condensed on the surfaces of the delivery apparatus and inhalation chamber during delivery, so that the actual test dose is unknown. It is estimated that the rats were exposed to vapor concentrations at least 10-fold less than the nominal concentration.
The average temperature of the inhalation chamber was 25°C with a relative humidity range of 78-87%.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
ca. 2 h
Remarks on duration:
Inhalation was terminated after all rats have died within the first 2 hours of exposure.
Concentrations:
Nominal concentration was 4.5 - 6.8 mg/L, but the test material condensed on the surfaces of the delivery apparatus and inhalation chamber so that the actual test dose is unknown.
No. of animals per sex per dose:
5M / 5F
Control animals:
no
Details on study design:
Rats were exposed for 2 hours to a vapour/aerosol mixture generated from a single batch of the test article at a temperture of 100°C. The nominal concentration was between 4.5 and 6.8 mg/L but the actual test dose is unknown..The average temperature of the inhalation chamber was 25°C with a relative humidity range of 78-87%.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC100
Effect level:
< 4.5 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
2 h
Remarks on result:
not determinable because of methodological limitations
Remarks:
The test material condensed on the surfaces of the delivery apparatus and inhalation chamber during delivery, so that the actual test dose is unknown. It is estimated that the rats were exposed to vapor concentrations at least 10-fold less than the nominal concentration. The test was set up as limit test, but further doses were not tested.
Mortality:
All test rats died within 2 hours of exposure to the test article.
Clinical signs:
other: breathing difficulty
Gross pathology:
All rats exhibited red lungs, while distended stomach/intestines and full urinary bladders were observed in the majority of the rats. One rat had red spots on the thymus, while another rat had mottled lungs.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Conclusions:
This study was considered to be invalid and was disregarded for classification due to major methodological deficiencies.
The study was set up as limit study, but the results revealed an LC100 below the test concentration (nominal test concentration of 4.5 mg/L), and no further doses were tested in order to characterize the toxic concentration range. Moreover, the test material condensed on the surfaces of the delivery apparatus and inhalation chamber during delivery, so that the actual test concentration is unknown. It is estimated that the rats were exposed to vapor concentrations at least 10-fold less than the nominal concentration. Since the test item is corrosive to the skin, corrosion to the respiratory tract might have been contributed to the lethal effect and hampered the investigation of inhalation toxicity.
Due to the corrosive nature of the test substance, risk management measures to avoid inhalation exposure (technical measures and use of personal protective equipment) are in place.


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