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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline Study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Diisopropylamine
- Purity: no data
- Physical state: clear liquid
- Lot/batch No.: CCBX 2526
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. Wilmington Massachussets 01887
- Age at study initiation: 9-12 weeks old
- Weight at study initiation: 273-340 g (males) 232-263 g (females)
- Fasting period before study: yes (18 hours)
- Housing: 6/cage during acclimation; 1/cage during study
- Diet (e.g. ad libitum): ad libitum Purina Laboratory Chow 5001
- Water (e.g. ad libitum): ad libitum municipal water
- Acclimation period: 15-22 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24°C (67-76°F)
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Dose-Volume: 10 ml/kg
Doses:
50, 250, 500, 1000 mg/kg
No. of animals per sex per dose:
5 males and 5 females per group except the high dose group (5 males only)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were checked for viability twice daily. Pharmacologic and toxicologic signs were recorded approx. 1, 2 and 4 hours after dosing and daily thereafter. Animals were weighted prefast, post fast (just prior dosing) and on days 7 and 14.
- Necropsy of survivors performed: yes
Gross postmortem examination were performed on all animals.
Statistics:
LD50 and 95% confidence limits were calculated using Miller's method (1944)

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
420 mg/kg bw
95% CL:
277 - 563
Sex:
female
Dose descriptor:
LD50
Effect level:
310 mg/kg bw
95% CL:
198 - 422
Sex:
male
Dose descriptor:
LD50
Effect level:
540 mg/kg bw
95% CL:
242 - 838
Mortality:
See the table below
Clinical signs:
Signs seen during the 24 hours after dosing in groups receiving doses of 250, 500 and 1000 mg/kg included ataxia and/or tremors, hypoactivity, wet rales, food consumption decrease, dyspnea, hypopnea and ocular, oral and nasal discharge.
Some animals exhibited decreased food consumption and/or emiaciation for up to 8 days after dosing.
Animals in the 50 mg/kg group were generally free of abnormalities.
Body weight:
Females in the 250 mg/kg group and surviving males in the 500 mg/kg dose group exhibited substantial weight losses a t day 7 but gained weight between days 7 and 14. All animals in the 50 mg/kg group gained wieght at both days 7 and 14.
Gross pathology:
In animals found dead: changes in lungs and gastrointestinal tract.
Some animals exhibited changes in the stomach and intestine which were suggestive of an irritant effect (presence of red or black fluid, discoloration of walls).
Some animals were also noted to have red fluid in hte body cavity and urinary bladder.
One animal in the 500 mg/kg group which survived until study termination had adhesions of the stomach to the liver and abdominal walls.

Any other information on results incl. tables

Preliminary study mortality results
Dose level (mg/kg) Mortality
Male Female
80 1/1 1/1
120 1/1 1/1
170 1/1 1/1
250 1/1 1/1
350 1/1 1/1
500 0/1 1/1
710 1/1 1/1
1000 1/1 1/1
1420 1/1 1/1

Definitive study

Dose level (mg/kg) Mortality Time of death
Male Female Total
50 0/5 0/5 0/10  -
250 0/5 1/5 1/10 day 8
500 2/5 5/5 7/10 3hours, day 6
1000 5/5  - 5/5 1-3 hours

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Toxicity Category IV Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008
Conclusions:
Under these experimental conditions, rat oral LD50 is 420mg/kg.
Executive summary:

The Acute oral toxicity of Diisopropylamine (DIPA) was evaluated in rats according to the EPA OPP 81-1 guideline. After a preliminary dose range-finding test, groups of 5 male and 5 female Sprague Dawley rats (except the high dose group, constituted of 5 males only) were given a single oral dose of DIPA at doses of 0, 50, 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).

All animals died on day 1 after administration of 1000 mg/kg (5 males). 5/5 females and 2/5 males died after treatment with 500 mg/kg. 1/5 female only died in the 250 mg/kg group and no mortality was observed in the low dose group (50 mg/kg)

Signs seen during the 24 hours after dosing in groups receiving doses of 250, 500 and 1000 mg/kg included ataxia and/or tremors, hypoactivity, wet rales, food consumption decrease, dyspnea, hypopnea and ocular, oral and nasal discharge. Some animals exhibited decreased food consumption and/or emiaciation for up to 8 days after dosing. Animals in the 50 mg/kg group were generally free of abnormalities.

Under these experimental conditions, the oral LD50 of DIPA is 420 mg/kg (277-563 mg/kg) in Sprague Dawley rats with 95% confidence interval limits.