4,4'-trimethylenedipiperidine

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Feb-July, 992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Justification for type of information:

Guideline study under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OTS 798.1100 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,1'-(1,3-Propanediyl)dipiperidine

Cas Number:

16898-52-5

Molecular formula:

C13H26N2

IUPAC Name:

1,1'-(1,3-Propanediyl)dipiperidine

Test material form:

solid

Details on test material:

Purity 100%, Brownish White Flaky Solid, Lot # 11202AB

Specific details on test material used for the study:

Brownish white flaked solid, Lot # 11202AB

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Ten healthy young adult New Zealand White rabbits, five of each sex, were used in the study.
Animals were purchased from a registered commercial breeding laboratory (Eastern Rabbit Breeding laboratory, Taunton, MA)
Animals were in the weight range between 2.0 and 3.0 kilograms at the start of the study
Animals were 10-12 weeks old at the start of the study. They were quarantined for 5 days prior to the study.

Animals were all housed individually using suspended stainless steel cages marked with the corresponding animal number.
Hardwood Sani-chips were used as non-contact bedding under the cages.
Animal rooms were maintained at 68±F at 30-70% Humidity
A minimum of 10-13 complete air exchanges per house occured
12 hour light/dark cycles using full spectrum fluorescent lights were used.

Animals were supplied with a commercial rabbit ration (Agway Prolab, Waverly, NY) and municipal tap water ad libitum.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Animals were weighed prior to testing and their fur clipped 24 h prior to adminstration of test material. The test substance was introduced under gauze patches two single layers thick and applied directly to the skin of the body surface (approximately 10%) of each of the ten animals. Animals were immobilized and the patches were secured in place by wrapping the entire trunk of the animal with an impervious bandaging.

Duration of exposure:

24 hours

Doses:

2 g/kg

No. of animals per sex per dose:

5 males
5 females

Control animals:

no

Details on study design:

After the exposure period, the wrapping was removed from the animals and the site rinsed gentily with USP water to remove remaining test material. Any skin lesions found were graded 30-60 minutes after bandage removal. Animals were observed for erythema and edema for a 24 h observation period. The animals were observed daily for 14 days. Any animal found dead was necropsied within 12 hours. All animals underwent a gross necropsy. Surviving animals were euthanised with an injectable barbiturate, Euthanasia-5 (Veterinary Laboratories Inc, Lenexa , KS, USA).

Statistics:

none

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other:

Remarks:

given as > 2 g/kg

Mortality:

No animals died during the 14 day observation period

Clinical signs:

other: There were no overt signs of toxicity exclusive of skin irritation noted in any test animal during the observation period. There was no evidence the animals experienced pain or suffering

Gross pathology:

Necrosis was observed in the skin in all animals. Gross necropsy showed that necrosis penetrated through the skin into the underlying muscle. It also showed atrophy of the spleen and discoloration of the liver and kidneys.

Any other information on results incl. tables

LD50 > 2 g/kg bw.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance is considered nontoxic in rabbits at a dose of 2000 mg/kg bw for 24 h, occlusive exposure, based upon the absense of mortality in a 14 day limit dose acute dermal toxicity study. Necrosis of the skin was observed in all animals at necropsy but no other clinical signs were reported.