Mecrilate

Carcinogenicity

Administrative data

Endpoint:

carcinogenicity

Remarks:

other: in vitro - direct exposure to cell medium

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented medical guideline study with GLP

Justification for type of information:

Justification: Butylcyanoacrylate (BUCA) is a structural homologue

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: ISO 10993-3 (1992), Biological Evaluation of Medical Devices Part 3: Tests for Genotoxicity, Carcinogenicity and Reproductive 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-cyanoacrylate

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, 4 pieces)
- Physical State: Solid
- Color: Amber
- Stability: Highly Stable
- Solubility: Practically Insoluble

(2) NEGATIVE CONTROL ARTICLE
- DMEM Complete
- QC #: LPR-02-10-009-CC
- Physical State: Liquid
- Color: Pink

(3) POSITIVE CONTROL ARTICLE (non-activated assay)
- 3-Methylcholanthrene (3-MCA)
- QC #: CSC-94-03-001-CC
- Physical State: Solid
- Color: Yellow

(4) POSITIVE CONTROL ARTICLE (activated assay)
- N-Nitrosodimethylamine (DMN)
- QC #: CSC-01-08-010-CC
- Physical State: Liquid
- Color: Clear

Test animals

Species:

other: not applicable

Strain:

other: not applicable

Sex:

not specified

Details on test animals or test system and environmental conditions:

in vitro test

Administration / exposure

Route of administration:

other: in vitro - direct exposure to cell medium

Type of inhalation exposure (if applicable):

other: not applicable

Vehicle:

other: cell culture medium

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

5-72 h

Frequency of treatment:

once

Post exposure period:

4 w

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.2 other: g per 1 mL culture medium

Remarks:

Extract

Doses / concentrations 2

Dose / conc.:

5 other: µg/mL

Remarks:

3-Methylcholanthrene (positive control), non-activated assay

Doses / concentrations 3

Dose / conc.:

0.5 other: µL/mL

Remarks:

N-Nitrosodimethylamine (positive control), activated assay

No. of animals per sex per dose:

not applicable

Control animals:

other: not applicable

Results and discussion

Any other information on results incl. tables

RESUL TS

The number of foci in the test article groups was not significantly different from the corresponding negative control groups in both non-activated and activated conditions (p>0.05). Cultures exposed to positive control article exhibited a significant increase in the frequency of foci in both activated and non-activated conditions (p<0.05), thus validating the assay.

Parallel Cytotoxicity Assay

	Non-activated Assay	Activated Assay
	Mean Colonies / Plate	Mean Colonies / Plate
Negative Control	85	86
Positive Control *	1	0
Test Article	91	97

Morphological Cell Transformation Assay Summary

	Non-activated Assay			Activated Assay
	Total Plates	Total Foci	Average Foci	Total Plates	Total Foci	Average Foci
Negative Control	15	14	0.93	15	16	1.07
Positive Control *	15	233	15.53	15	250	16.67
Test Article	15	14	0.93	15	15	1.00

* Non-activated Assay: 3 -MCA / Activated Assay: DMN

Applicant's summary and conclusion

Conclusions:

The test article is considered to have no significant carcinogenic potential, under the experimental conditions employed.

Executive summary:

SUMMARY

The test article, Polymerised Indermil (n-butylcyanoacrylate) Disk (Area 64.7cm² approx, 4g weight, 4 pieces), was tested for its ability to cause morphological transformation of BALB/c-3T3 cells, an indicator of carcinogenic potential. The cell culture medium extract of the test article was tested at the neat concentration in the presence and absence of mammalian metabolic activation (S9). Negative controls (cell culture medium) and appropriate positive control articles (3-Methylcholanthrene (3-MCA): Non-Activated Assay; Nitrosodimethylamine (DMN): Activated Assay) were also tested.

The results indicated that the positive control articles caused a statistically significant increase in the number of morphologically transformed cell foci as compared to their concurrent negative controls validating the functioning of the assay. The number of foci in the test article cultures was not statistically significant compared to the concurrent negative control cultures in the presence and absence of metabolic S9 liver microsomal enzyme activation. Based on these results, the test article is considered to have no significant carcinogenic potential, under the experimental conditions employed.