Enbucrilate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented study with GLP, comparable to OECD-guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Irritation and Sensitization Test, EN/ISO 10993-10 (1996)

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Test performed prior to OECD 429 guideline; standard prodecure for testing of medical devices.

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:

TEST ARTICLE:
- Polymerised Indermil (n-butylcyanoacrylate, CAS 6606-65-1) - Disk (Area 64.7cm2 approx, 4g weight - 8 pieces)
- Lot/Batch: U02B41 (Lab Book Refs: 2696/73-21;2696/73-22; 2696/73-23; 2696/73-24; 2696/73-26; 2696/73-27; 2696/73-28; 2696/73-29)
- Physical State: Solid
- Color: Amber
- Stability: Highly Stable
- Solubility: Practically Insoluble
- Storage Conditions: Room Temperature

NEGATIVE CONTROL ARTICLE (Toxikon Supplied):
- Cottonseed Oil (CSO)
- QC Inventory #: CSC-02-03-003-VIV
- Physical State: Liquid
- Color: Yellow
- Storage Conditions: Room Temperature

POSITIVE CONTROL ARTICLE (Toxikon Supplied):
- Dinitrochlorobenzene (DNCB)
- Physical State: Solid
- Color: Yellow
- Storage Conditions: Room Temperature

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

ANIMALS:

- 7 males, 10 females
- Weight/Age range: 374.3 - 432.6 grams, at least 26 days old (adult)
- Health status: healthy, not previously used in other experimental procedures
- Animal purchase: Elm HilI Breeding Labs, Inc., Chelmsford, MA
- Animal identification: ear punch
- Acclimatization: minimum 5 days under the same conditions as for the actual test
- Animal selection: chosen from larger pool and examined for lack of adverse clinical signs

CARE & MAINTANANCE:

- 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
- Housing: group housed
- Cages: suspended stainless steel
- Bedding: hardwood chips, P.W.L Industries, St-Hyacinthe, Quebec, Canada (non-contact)
- Animal rations: TEK Hi-Fiber Guinea Pig Diet 2041, Harlan Teklad, Madison, WI, ad libitum
- Water: tap water, ad libitum
- There were no known contaminants present in the feed, water, or bedding expected to interfere with the test data.
- The laboratory and animal rooms were maintained as limited-access facilities.

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal and epicutaneous

Vehicle:

cotton seed oil

Concentration / amount:

- Article extract: 3 cm2 per 1 mL CSO
- Primary irritation test: Article extract 100% and 75% (diluted in CSO)
- Application: Article extract 100%

Challenge

Route:

epicutaneous, occlusive

Vehicle:

cotton seed oil

Concentration / amount:

- Article extract: 3 cm2 per 1 mL CSO
- Primary irritation test: Article extract 100% and 75% (diluted in CSO)
- Application: Article extract 100%

No. of animals per dose:

5 males, 5 females

Positive control substance(s):

yes

Remarks:

Dinitrochlorobenzene (DNCB)

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100% Test article extract in CSO

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Results 2

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100% Test article extract in CSO

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Results 3

Key result

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

100% Test article extract in CSO

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Results 4

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100% CSO

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Results 5

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100% CSO

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Results 6

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

negative control

Dose level:

100% CSO

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Any other information on results incl. tables

RESULTS

- Animal Weights: All animals gained in body weight.

- Clinical Observations: No systemic signs of toxicity were observed in treated or control animals.

- Sensitization: None of the treated (CSO extract) or negative control animals (CSO) exhibited any reaction to the challenge (0% sensitized).

- Historical positive control: animals have exhibited skin reactions of 1, 2 or 3 at each observation point (100% sensitized).

Primary Irritation Test - Reactions

Animal #	Dose	Erythema/Edema Day 0	Erythema/Edema 24 h	Signs of toxicity
16/F	100% intradermal	0/0	0/0	none
16/F	75% intradermal	0/0	0/0	none
17/F	100% topical	0/0	0/0	none
17/F	75% topical	0/0	0/0	none

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the standards set by the study protocol, the Cottonseed Oil (CSO) extract of the test article, Polymerised Indermil (n-butylcyanoacrylate), elicited no reaction at the challenge (0% sensitization), following an induction phase. Therefore, as defined by the scoring system of Kligman, this is a Grade I reaction and the test article is classified as having weak allergenic potentiaL. A Grade I sensitization rate is not considered significant according to Magnusson and Kligman (1969, 1970).