Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Single 4-hour exposure; 14-day observation period
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to generally accepted guidelines for acute inhalation toxicity study

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
Guideline:
other: The test report did not specifiy a guideline by name but the notation (EPA 8/78) was included as part of the test report name. The study method was similar to the current EPA OPPTS guideline 870.1300.
GLP compliance:
yes
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
2-methylpropan-2-ol
EC Number:
200-889-7
EC Name:
2-methylpropan-2-ol
Cas Number:
75-65-0
Molecular formula:
C4H10O
IUPAC Name:
2-methylpropan-2-ol
Constituent 2
Reference substance name:
tertiary butyl alcohol
IUPAC Name:
tertiary butyl alcohol
Details on test material:
-Identity (according to report): t-butyl alcohol, A-209412
-Purity: 99.9% per sponsor
-Appearance of test material: clear liquid
-Source of test material: ARCO Chemical Company, Glenolden, PA

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS:
-Source: The Charles River Breeding Laboratories, Portage, MI
-Animals: 5/sex
-Age at study initiation: male rats were 48 days old, female rats were 54 days old
-Quarantine period: rats were group-caged in suspended wire mesh cages, segregated by sex for an unspecified period of time
-Housing: during exposure and post-exposure, rats were caged individually
-Identification method: monel metal eartags
-Diet: Purina® Certified Pelleted Rodent Chow® #5002 provided ad libitum except during actual exposure
-Water: tap water provided ad libitum except during actual exposure

ENVIRONMENTAL CONDITIONS: during quarantine and post-exposure periods, rats were housed in rooms controlled for temperature and humidity with a 12-hour photoperiod in accordance with standards outlined in the “Guide for the Care and Use of Laboratory Animals” (DHEW No. N.I.H. 74-23, 1974)

IN-LIFE DATES:
-Date of study initiation: 16 April 1981
-Date of study termination: 30 April 1981

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: chamber ventilation air
Details on inhalation exposure:
A single group of 5 male and 5 female albino rats was exposed for approximately 4 hours to a vapor concentration of 10000 ppm tertiary butyl alcohol.

EXPOSURE GENERATION METHOD: A vapor atmosphere of tertiary butyl alcohol was generated using a counter-current vaporization system. This system operates as follows: A FMI fluid metering pump pumps the test material at a known and constant rate to the top of a glass bead column. Air, heated if necessary, by a cartridge heating element operated from an autotransformer, and monitored by an ammeter passes up the bead column in a counter-current manner relative to the liquid. Vaporization occurs on the bead column. The concentrated vapors are then piped to the exposure chamber air inlet where dilution with chamber ventilation air reduces the concentration to the desired level. For this study, the vapor generation system operating conditions were: Pump type: RPG-20-1/4; Pump setting: 3.0; Theoretical compound flowrate (mL/min): 1.9; Air flowrate (L/min): 30; Air temp °C: 55.

TEST MATERIAL ADMINISTRATION: Animals were exposed whole-body for 4 hours. Exposures were conducted in 160-liter glass and stainless steel chambers. Air used for chamber ventilation was supplied from an HVAC system separate from the general laboratory system. This air was particulate filtered and controlled for temperature and humidity. Exhaust air from the chamber was filtered prior to discharge into the chamber exhaust system. Chamber airflow rate was 40 L/min.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Please see further details in "Any other information on materials and methods" section.
Duration of exposure:
4 h
Concentrations:
Nominal concentration: 11880 ppm
Actual analytical concentration: 10000 ppm


No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
-Duration of observation period following exposure: 14 days
-Mortality/morbidity/clinical signs: at various times during the exposure and daily during the post-exposure observation period
-Body weights: individual body weights recorded on all animals prior to exposure and on all survivors at 7 and 14 days post-exposure
-Necropsy performed: all animals which died or were sacrificed at termination
-Gross pathology examination: all major organs in the abdominal and thoracic cavities were observed for macroscopic abnormalities by trained technicians; carcasses were then discarded
-Histopathology: none
Statistics:
Means and standard deviations were used to express the body weights.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 10 000 ppm
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Ocular discharge, dyspnea, prostration, ataxia were noted during exposure. These same signs along with generalized weakness were noted post-exposure. One death occurred post-exposure. Focal areas of redness on the lungs were noted at necropsy.
Mortality:
One female was found dead on study day 3.
Clinical signs:
other: The principal signs exhibited during the exposure were ocular discharge (1 male, 5 females), dyspnea (all animals), and prostration (all animals). One female also exhibited ataxia. These same signs, together with what appeared to be generalized weakness
Body weight:
Both male and female groups appeared to gain weight normally during the two week post-exposure observation period.
Gross pathology:
At necropsy, the most notable observation was that four of the ten animals (3 males, 1 female) in the study were observed to have focal areas of redness on the lungs. The only female rat that exhibited macroscopic abnormalities at necropsy was the animal which died on the third day of the post-exposure period.

Applicant's summary and conclusion

Interpretation of results:
other: Category 4 for Acute Toxicity; classified as Category 3 for Specific Target Organ Toxicity – Single Exposure.
Remarks:
Criteria used for interpretation of results: other: OECD GHS and EU
Conclusions:
Under the conditions of this study, the 4-hour inhalation LC50 of tertiary butyl alcohol in male and female Sprague-Dawley rats was greater than 10000 ppm (actual concentration) or 36 mg/L (nominal concentration). Exposure to high concentrations of tertiary butyl alcohol may cause reversible CNS effects and ocular irritation.

Based on an acute inhalation LC50 value of >10000 ppmV/4 hours in male and female rats, there are insufficient data to determine if tertiary butyl alcohol meets one of the classification categories for acute lethality by the inhalation route under UN GHS. However, tertiary butyl alcohol is classified as R20 – Harmful if Inhaled under the EU Dangerous Substances Directive (DSD). Annex VII to Regulation (EC) No. 1272/2008 on classification, labeling and packaging (CLP) of substances and mixtures contains translation tables to translate a classification derived in accordance with DSD into a CLP classification. Using the translation tables, tertiary butyl alcohol is classified as Category 4 for acute toxicity by the inhalation route according to EU CLP GHS. Based on clinical signs indicating reversible effects on the central nervous system, tertiary butyl alcohol is classified as Category 3 for classification and labeling under GHS for Specific Target Organ Toxicity – Single Exposure.
Executive summary:

In an acute inhalation study, a single group of 5 male and 5 female rats was exposed whole-body for 4 hours to a vapor concentration of 10000 ppmV tertiary butyl alcohol and observed for 14 days. One female was found dead on study Day 3. The principal signs observed during exposure were indicative of central nervous system depression and included dyspnea and prostration in all animals. These same signs, along with generalized weakness, appeared in several animals of each sex during the post-exposure period but were fully reversible by study termination. Gross pathological effects observed at necropsy were limited to focal areas of redness on the lungs.  Tertiary butyl alcohol is classified as Category 4 for acute lethality by the inhalation route.  Tertiary butyl alcohol is classified as Category 3 for Specific Target Organ Toxicity – Single Exposure.