Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June, 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 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Remarks:
Study performed before GLP regulations
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: clear, colourless liquid
Details on test material:
The test material was a clear colourless liquid, designated TMPH, chemical name: 2.4.4.-trimethylpentyl-2-hydroperoxide.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Young adult albino rats (Wistar-derived) from the Institute's colony were used. The body weights of males varied from 194 to 373 g, those of femals from 157 to 220 g.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
After some preliminary observations, the test material was give by gavage, as a 10% (v/v) dilution in propylen (sic) glycol.
Doses:
Single doses of 6.0, 7.2, 8.6, 10.3 or 12.4 ml per kg body weight.
No. of animals per sex per dose:
Five males and five females
Control animals:
no
Details on study design:
After treatment the rats received stock diet and tap water ad libitum. They were observed for signs of intoxication during a 14-day period, after which autopsies were carried out on the survivors. The LD50 was calculated according to the method of Weil (Biometrics 8 [1952] 249-263).
Statistics:
none

Results and discussion

Effect levels
Key result
Dose descriptor:
LD50
Effect level:
0.92 mL/kg bw
95% CL:
>= 0.87 - <= 0.96
Clinical signs:
Within a few hours after dosing the rats showed sluggishness and decreased activity. Thereafter, most of the rats lost consciousness. deaths occurred between 8 hours and 3 days after treatment. Thereafter, the survivors recovered gradually and looked quite healthy again at the end of the observation period.
Body weight:
no data
Gross pathology:
Macroscopic examination of the survivors at autopsy revealed rounded edges of the livers in some of the rats. No other treatment-related gross alterations were seen.

Any other information on results incl. tables

  Dose     Mortality    
  dilution (ml/kg)   test material (ml/kg)   number    %
   males  females  
   6.0   0.60  0/5  0/5  0

7.2

 0.72  1/5  0/5 10 
 8.6  0.86  1/5  0/5 10
 10.3  1.03  5/5  5/5  100
 12.4  1.24  5/5  5/5  100
         

Applicant's summary and conclusion

Interpretation of results:
sligthly toxic
Remarks:
Migrated information Criteria used for interpretation of results: other: conclusion in report
Conclusions:
From the mortality-figures the LD50 of TMPH was calculated to be 0.92 ml per kg body weight with 0.87 and 0.96 as the 95% confidence limits. Therefore, the material can be classified as slightly toxic.
Executive summary:

The acute oral toxicity of TMPH was determined by administration of graded doses of the test material. Young adult albino rats (Wistar-derived) from the Institute's colony were used. The body weights of males varied from 194 to 373 g, those of femals from 157 to 220 g.

After some preliminary observations, the test material was given by gavage, as a 10% (v/v) dilution in propylen (sic) glycol to groups of five male and five female rats in single doses of 6.0, 7.2, 8.6, 10.3 or 12.4 ml/kg body weight.

Within a few hours after dosing the rats showed sluggishness and decreased activity. Thereafter, most of the rats lost consciousness. deaths occurred between 8 hours and 3 days after treatment. Thereafter, the survivors recovered gradually and looked quite healthy again at the end of the observation period.

Macroscopic examination of the survivors at autopsy revealed rounded edges of the livers in some of the rats. No other treatment-related gross alterations were seen.

From the mortality-figures the LD50 of TMPH was calculated to be 0.92 ml per kg body weight with 0.87 and 0.96 as the 95% confidence limits. Therefore, the material can be classified as slightly toxic.