Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
No GLP compliance statement was provided in the publication but the study was conducted according to generally accepted methods for pharmacokinetic studies. Study provides evidence of the clinical endpoints observed following a single intravenous (i.v.) dose administration of tertiary butyl alcohol. There are no regulatory guidelines for the conduct of an acute toxicity study by the intravenous route. The study lacks some of the elements and observations expected in an acute toxicity study.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1997

Materials and methods

Test guideline
Qualifier:
no guideline available
GLP compliance:
not specified
Limit test:
no

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
Details on test material:
-Name of test material (as cited in study report): tertiary butyl alcohol (TBA)
-Source of test material: Aldrich, Milwaukee WI
-Analytical purity: >99.5%

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
-Source: Charles River Laboratories, Raleigh, NC
-Age at receipt: 11 weeks
-Acclimation: 5 days
-Surgical procedure: Prior to receipt, each rat was surgically implanted with a cannula into the right jugular vein (cannulae made of Dow Corning silastic tubing)
-Cannulae patency: Cannulae were kept patent with daily flushings of heparinized saline that was sufficient to fill the cannula without administration to the rat (approximately 100 µL of 500 U/mL).
-No information was provided on feed/water, animal weights at start of study or post-exposure observation period. At various times after dosing, blood was withdrawn from the cannulae.

Administration / exposure

Route of administration:
intravenous
Vehicle:
other: sterile saline.
Details on exposure:
Animals were dosed intravenously by a bolus injection with 37.5, 75, 150 or 300 mg/kg bw tertiary butyl alcohol. Solutions were prepared in sterile saline so the total volume administered was 1 mL/kg. Following dose administration, cannulae were each flushed with 100 µL saline. Blood samples were withdrawn through the same cannulae into heparinized syringes at 5, 10, 20, 30, 40 and 60 min and 4, 8, 12, 16 and 24 h after tertiary butyl alcohol administration. The total amount of blood withdrawn at each sampling period was replaced with sterile sodium chloride (0.9%).
Doses:
37.5, 75, 150 or 300 mg/kg bw.
No. of animals per sex per dose:
4 males and 3 females.
Control animals:
no
Details on study design:
Animals received a single intravenous dose of tertiary butyl alcohol. Blood samples were withdrawn at various times over a 24-hour period. This was not intended to be an acute toxicity study and no information was provided on morbidity, body weights, clinical signs, necropsy or gross pathology.
Statistics:
No statistics conducted on mortality. Statistical analysis was limited to pharmacokinetic parameters. That information can be found in the section for toxicokinetics.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 300 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No deaths were observed by 24 hours following intravenous administration of TBA at doses up to 300 mg/kg bw.
Mortality:
No deaths occurred in either sex at any dose level.
Clinical signs:
not reported.
Body weight:
not reported.
Gross pathology:
not examined.

Applicant's summary and conclusion

Conclusions:
In a study to characterize the pharmacokinetics of tertiary butyl alcohol in male and female Fischer 344 rats, groups of 4 male and 3 female animals were administered a single intravenous dose of 37.5, 75, 150 or 300 mg/kg bw tertiary butyl alcohol. All data throughout the 24-hour study were reported as the means for 4 males and 3 females, indicating no deaths occurred during the study. Although this study was not intended to be an acute toxicity study, these results suggest that the intravenous LD50 in male and female rats is >300 mg/kg bw.
Executive summary:

In a study to examine the acute toxicity of tertiary butyl alcohol by the intravenous route, the LD50 of tertiary butyl alcohol was established to be >300 mg/kg bw in male and female Fischer 344 rats. No deaths occurred in either sex at any dose level.