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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994-1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
t-Amyl Hydroperoxide,
Lot 5867422102
Receipt Date: October 3, 1994
Physical Description : Clear colorless liqui
Storage Conditions: Room temperature
Expiration Date:February 9, 1995
Density: 0.91 g/ml
Purity: 86.7 %

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Young adults rats were received at SLS from Charles River Laboratories, lnc., Portage, Michigan. 200 to 300 g prior to the study
Method of identification: Upon receipt, metal ear tags displaying unique identification numbers were used to individually identify the animais.
Housing: The animals were housed individually in suspended stainless steel cages.
Environment: The animal room temperature and relative humidity ranges were 63-71° F and 35-55%, respectively. Environmental control equipment was monitored and adjusted as necessary to minimize fluctuations in the animal room environment. Light timers were set to maintain a 12-hour light/12-hour dark cycle. There were ten to twelve air changes in the animal room per hour. The animal room temperature and relative humidity were recorded a minimum of once daily.
Food and water ad libitum
Quarantine: 5 days at minimum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
0.27, 0.55 and 1.10 ml/kg (equivalent to 250, 500 and 1000 mg test mat./kg bw/day based on a density of 0.91)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: two times on study day 0 (postdose) and daily thereafter (days 1- 14). A mortality check was performed twice daily, in the morning and afternoon.
- Weighing: prior to fasting (day -1), prior to dosing on day 0 and for all surviving animals on days 7 and 14 and at the time of death for any animal dying on study.
- All study animals which died spontaneously during the study or were euthanized (carbon dioxide inhalation) at study termination (day 14) were necropsied. Body cavities (cranial, thoracic, abdominal and pelvic) were opened and examined. No tissues were retained.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
500 mg/kg bw
Based on:
test mat.
95% CL:
418 - 598
Sex:
male
Dose descriptor:
LD50
Effect level:
518 mg/kg bw
Based on:
test mat.
95% CL:
383 - 700
Sex:
female
Dose descriptor:
LD50
Effect level:
483 mg/kg bw
Based on:
test mat.
95% CL:
357 - 652
Mortality:
Dose Males Females Males/females
250 0/5 0/5 0/10
500 2/5 3/5 5/10
1000 5/5 5/5 10/10

Rats died at day 1 or 2
Clinical signs:
Salivation was present in all groups on study day 0 only.
Abnormal breathing and urine stain were present in all groups on study days 0-2 (except for one animal in the 500 mg/kg dose group who had urine stain on study days.
Decreased activity, dehydration, reddish-colored urine, decreased/no defecation and dark material around the facial area were present in the 250 and 500 mg/kg dose groups on study days 0-3.
Rough hair coat was present in the 250 and 500 mg/kg dose groups on study days 0-6.
Hunched posture.
Piloerection and wobbly gait were present in the 500 mg/kg dose group on study days 0-2; partially closed eye lids was present in the 500 and
1000 mg/kg dose groups; tremors, lacrimation, apparent hypothermia, and prostration were only present in the animals that died during the study.
1-5)
Body weight:
No abnormal gain body weight.
Gross pathology:
The most notable gross internal findings were observed in the animals that died and included congested meningeal vessels in the brain, mottled livers, abnormal contents in the digestive tract, smooth mucosa, linear striations and dark red foci in the stomach, reddened mucosa in the small intestines, dark red and thickened serosa in the stomach, discolored thymus, abnormally colored fluid contents in the urinary bladder and thoracic cavity and musculature and viscera in the whole body stained orange.

Any other information on results incl. tables

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Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the conditions of this test, the acute oral LD50 of t-Amyl Hydroperoxide in the male rat was determined to be 518 mg/kg. ln the female rat, the oral LD50 was determined to be 483 mg/kg. ln the sexes combined, the oral LD50 was determined to be 500 mg/kg.
Executive summary:

The Acute oral toxicity of tert-amyl hydroperoxide was evaluated in rats according a method similar to OECD N°401 guideline (Acute Toxic Standard Method), GLP study compliant. Groups of 5 male and 5 female Sprague Dawley rats were given a single oral dose of tert-amyl hydroperoxide at doses of 0, 250, 500, 1000 mg/kg. Following treatment, rats were observed daily and weighted weekly. A gross necropsy examination was performed at the time of scheduled euthanasia (Day 14) or when animals were found dead.

No mortality occurred in the lowest dose group. 5 animals died before day 2 after administration of 500 mg/kg (2 males and 3 females). All animals of the highest dose group died one day after oral administration of the substance. Clinical signs observed were [hypoactivity, salivation, piloerection, abnormal breathing, urine stain, wobbly gate] for most of animals; and tremor, prostration, apparent hypothermia in animals who died.

The most notable gross internal findings were observed in the animals that died and included congested meningeal vessels in the brain, mottled livers, abnormal finding in the digestive tract, discolored thymus, abnormally colored fluid contents in the urinary bladder and thoracic cavity and musculature and viscera in the whole body stained orange.

Under these experimental conditions, the oral LD50 of tert-amyl hydroperoxide is 500 mg/kg in Sprague Dawley rats (517 mg/kg in males, 483 mg/kg in females).