1,4-diazabicyclooctane

Endpoint summary

Description of key information

1,4-Diazabicyclo[2.2.2]octane is of low acute toxicity to animals following single oral, dermal or inhalation exposures.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study pre-dates GLPs Purity was not documented. Clinical signs were not reported.

Principles of method if other than guideline:

Method: other

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Sex:

male

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Concentration in vehicle: 25% weight to volume

Doses:

250, 500, 1000, 2000, and 4000 mg/kg (active ingredient)

No. of animals per sex per dose:

5

Sex:

male

Dose descriptor:

LD50

Effect level:

700 mg/kg bw

95% CL:

> 500 - < 1 100

Mortality:

At 250 mg/kg, no rats died.  At 500 mg/kg, one rat died.  At 1000 mg/kg four rats died.  At greater than or equal to 2000 mg/kg all of the rats died. The deaths occurred in three days or less.

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

700 mg/kg bw

Quality of whole database:

Five studies are available where the test material was administered using water as a vehicle. In these studies the LD50 in male rats ranged from 700 to 2260 mg/kg bw.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study pre-dates GLPs Test material purity was not documented.

Qualifier:

equivalent or similar to guideline

Guideline:

other: Evaluation and the scoring of the results was similar to that described in Section 1500.40 - Federal Hazardous Substances Act Regulations - 16 CFR - P o 123.

Principles of method if other than guideline:

One group of six (3 male & 3 female) albino rabbits weighing between 2.0 and 3.0 kg. each was employed i n t h i s study. A l l animals had their backs clipped free of hair 24 hours prior to testing. A l l of the animals had their backs abraded prior to dosing.
The animals were housed and maintained in compliance with the Animal Welfare Act (Pub. L-94-279) 9 CFR Part 3.
The sample was dosed as supplied.
The following dosage level was administered:
A l l rabbits were weighed and the correct amount of experimental material was applied to the back of each animal.
These treated areas were covered with large gauze patches and an impervious material was wrapped snugly around the trunk of
each animal. The dressings were removed after twenty-four hours and any excess material was removed and the approximate
amount remaining was noted.
The animals were observed for a 14 day period for signs of toxicity and for mortalities.Gross autopsies were performed on a l l animals which died
during the 14 day observation period and also on a l l survivors of the 14 day observation period.

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

yes

Species:

rabbit

Strain:

other: Albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

The animals were housed and maintained in compliance with the Animal Welfare Act (Pub. L-94-279) 9 CFR Part 3.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

experimental material was applied to the back of each animal.
These treated areas were covered with large gauze patches and an impervious material was wrapped snugly around the trunk of
each animal. The dressings were removed after twenty-four hours and any excess material was removed and the approximate
amount remaining was noted.

Duration of exposure:

24 h

Doses:

2 g/kg

No. of animals per sex per dose:

3

Control animals:

no

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No

Clinical signs:

other: Severe erythema lasting for several days.

Gross pathology:

Pathology revealed nothing remarkable.

All animals survived.  Severe erythema which lasted for
several days was the only finding of note.  Gross necropsy
did not reveal anything remarkable.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 dermal is > 2000 mg/kg for rabbit.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The dermal LD50 was >2000 mg/kg bw when the test material was administered as a crystalline solid or as a 50% aqueous solution to the abraded skin and >3200 mg/kg bw when a 25% solution was applied to the intact skin of rabbits. No deaths or signs of systemic toxicity were observed.

Additional information

Oral

In multiple non-guideline studies where the test material was administered as an aqueous solution, the oral LD₅₀in male rats ranged from 700 to 2260 mg/kg bw. At non-lethal doses transient depression and poor grooming were observed. At lethal doses, severe depression and ataxia rapidly progressed to coma and death within a few hours. 

Inhalation Under standard conditions 1,4-Diazabicyclo[2.2.2]octane is a crystalline solid with 99% particle size >100um and does not present an inhalation hazard.

In a non-guideline study, the inhalation LC₅₀ in male and female rats of a 20% solution of 1,4-Diazabicyclo[2.2.2]octane in water was >20 mg/L/1 hour. Clinical signs noted immediately after exposure included wet, ruffled appearance and slight depression. All animals survived the 1-hour exposure and appeared normal within 24 hours of exposure. In studies where rats were exposed to a saturated vapor of 1,4-Diazabicyclo[2.2.2]octane for 8 hours, all animals survived and exhibited only transitory irritation of the eyes and mucous membranes.

Dermal

In non-guideline studies, the dermal LD₅₀was >2000 mg/kg bw when 50% aqueous solution was applied to the abraded skin and >3200 mg/kg bw when 25% aqueous solution was applied to the intact skin of rabbits.  No signs of systemic toxicity were observed. The abraded application sites exhibited severe erythema and the intact application sites exhibited slight necrosis following 24 hours of occluded contact with the test material. Both the intact and abraded skin sites exhibited desquamation and some scab formation after 14 days of observation.

Justification for selection of acute toxicity – oral endpoint
Lowest reported LD50 value

Justification for selection of acute toxicity – inhalation endpoint
Under standard conditions 1,4-Diazabicyclo[2.2.2]octane is a crystalline solid with 99% particle size >100um and does not present an inhalation hazard.

The inhalation LC50 in male and female rats of a 20% solution of 1,4-Diazabicyclo[2.2.2]octane in water was >20 mg/L/1 hour. Clinical signs noted immediately after exposure included wet, ruffled appearance and slight depression. All animals survived the 1-hour exposure and appeared normal within 24 hours of exposure. In studies where rats were exposed to a saturated vapor of 1,4-Diazabicyclo[2.2.2]octane for 8 hours, all animals survived and exhibited only transitory irritation of the eyes and mucous membranes

Justification for selection of acute toxicity – dermal endpoint
Under standard conditions the test material is a crystalline solid.

Justification for classification or non-classification

Based on the lowest reported oral LD50 the material should be classified as harmful. Inhalation and dermal data is adequate and no classification is required for these routes of exposure.