Enbucrilate

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented medical guideline study with GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: ISO 10993-11 (1993), Biological Evaluation of Medical Devices Part 11: Test for Systemic Toxicity

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: ISO 10993-12 (1997), Biological Evaluation of Medical Devices Part 12: Sample Preparation and Reference Materials

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Enbucrilate

EC Number:

229-552-2

EC Name:

Enbucrilate

Cas Number:

6606-65-1

Molecular formula:

C8H11NO2

IUPAC Name:

butyl 2-cyanoprop-2-enoate

Test material form:

other: extract

Details on test material:

(1) POLYMERISED INDERMIL (n-butylcyanoacrylate, CAS 6606-65-1) DISK (Area 64.7cm2 approx, 4g weight - 2 pieces):
- Lot/Batch #: U02B51, Lab Book Refs: 2696/75-85; 2696/75-86
- Physical State: Solid
- Color: Amber
- Stability: Highly Stable
- Solubility: Practically Insoluble

(2) CONTROL ARTICLE 1:
- 0.9% USP Sodium Chloride for Injection (NaCl)
- QC Inventory #: CSC-02-01-002-VIV
- Physical State: Liquid
- Color: Clear

(3) CONTROL ARTICLE 2:
- Cottonseed Oil (CSO)
- QC Inventory #: CSC-02-03-003-VIV
- Physical State: Liquid
- Color: Yellow

Test animals

Species:

mouse

Strain:

Swiss

Sex:

male

Details on test animals or test system and environmental conditions:

ANIMALS
- 20 Albino Swiss mice (Mus musculus)
- Sex: male
- Weight/Age range: 17.2 - 20.6 grams / at least 34 days old (adult)
- Health Status: healthy, not previously used in other experimental procedures
- Animal Identification: ear punch
- Animal Purchase: Harlan, Indianapolis, IN.

CARE AND MAINTANANCE
- Housing: group housed (5 mice of same sex)
- Bedding: hardwood chips, (contact), P.W.I. Industries, St-Hyacinthe, Quebec, Canada
- Acclimatization: minimum 5 days under the same conditions as for the actual test
- Animal room temperature: 68±5°F
- Animal room relative humidity: 30-70%
- Air exchanges per hour: 10 to 15
- Lights: 12-hour light/dark cycle, full spectrum fluorescent lights
- Animal rations: TEK 7012, Rodent Diet, Harlan Teklad, Madison, WI, ad libitum
- Water: tap water, ad libitum
- The laboratory and animal rooms were maintained as limited-access facilities
- Animal Selection: chosen from larger pool and examined for lack of adverse clinical signs
- There were no known contaminants present in the feed, water, or bedding expected to interfere with the test data.

Administration / exposure

Route of administration:

other: intravenous or intraperitoneal

Vehicle:

other: physiol. saline or cotton seed oil

Doses:

50 mL/kg bw of Extract of 0.2g Polymerised Indermil per 1 mL vehicle (24h at 70±2°C)

No. of animals per sex per dose:

5

Control animals:

yes

Results and discussion

Any other information on results incl. tables

RESULTS

Animal Weights

All of the test and control animals increased in weight.

Clinical Observations

None of the test or control animals exhibited overt signs of toxicity at any of the observation points.

The test is considered negative because none of the animals injected with the extracts of the test article showed a significantly greater biological reaction than the animals treated with the control articles.

Group	Animal (Sex)	Weight change (g)	Signs of Toxicity
NaCl / Test	1 (m)	2.2	none
NaCl / Test	2 (m)	2.2	none
NaCl / Test	3 (m)	1.8	none
NaCl / Test	4 (m)	2.4	none
NaCl / Test	5 (m)	2.3	none
NaCl / Control	6 (m)	2.3	none
NaCl / Control	7 (m)	2.5	none
NaCl / Control	8 (m)	1.8	none
NaCl / Control	9 (m)	2.6	none
NaCl / Control	10 (m)	2.3	none
CSO / Test	11 (m)	2.5	none
CSO / Test	12 (m)	1.8	none
CSO / Test	13 (m)	2.4	none
CSO / Test	14 (m)	1.6	none
CSO / Test	15 (m)	2.4	none
CSO / Control	16 (m)	1.8	none
CSO / Control	17 (m)	1.7	none
CSO / Control	18 (m)	1.7	none
CSO / Control	19 (m)	2.2	none
CSO / Control	20 (m)	2.3	none

Applicant's summary and conclusion

Conclusions:

This test is considered negative.

Executive summary:

SUMMARY

The 0.9% USP Sodium Chloride for Injection (NaCl) and Cottonseed Oil (CSO) extracts of the test article, Polymerised Indermil (n-butylcyanoacrylate) Disk, did not induce a significantly greater biological reaction than the control articles, when tested in Albino Swiss mice.

This test is considered negative based on standards set by the study protocol.