Carbamic acid, N-butyl-, 2-propyn-1-yl ester

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002-02-05 until 2002-03-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well documented GLP study according 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:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Version / remarks:

EPA 712-C-98-197, August 1998

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: EC Guideline 96/54/EC (22nd Adaptation of 67/548/EEC), Method "Skin Sensitisation" B.6

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

Propargyl-N-butylcarbamat

IUPAC Name:

Propargyl-N-butylcarbamat

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Propargyl-N-butylcarbamat
- Chemical name: Carbamic acid, butyl-, 2-propynyl ester
- Physical state: clear, yellowish liquid
- Analytical purity: 98.8%
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Lot/batch No.: H 0012
- Expiration date of the lot/batch: 2002-06-04
- Storage condition of test material: room temperature

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Hsd Poc:DH

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, D-33176 Borchen
- sex: female
- Weight at study initiation: 341 - 440 g
- Age at study begin: 4 - 5 weeks
- Housing: in groups of 5 during the adaptation period and groups of 2 - 3 per cage throughout the study period
- Diet: ad libitum, PROVIMI KLIBA 3420 - Maintenance Diet for Guinea Pigs, supplied by PROVOMI KLIBA AG
- Tab water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 3 °C
- Humidity (%): 40 - 60 %
- Air changes (per hr): 10 times per hour
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

polyethylene glycol

Induction 2

Concentration / amount:

5%, 100%

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

polyethylene glycol

Challenge 2

Concentration / amount:

5%, 100%

No. of animals per dose:

5 male, 5 female, additional 2 animals were used for dose-finding.

Details on study design:

RANGE FINDING TESTS:

Intradermal:
1 animal: intradermal injections twice with o.1 ml test item concentrations: 0%, 1%, 2.5%, 5%
topical induction:
4 test animals with 0%, 25, 50 and 100 %
Challenge:
2 female guinea pigs, dermal application of 0.1 ml of a 0, 25, 50 and 100 % formulation in polyethylene glycol 400.

MAIN STUDY
A. INDUCTION EXPOSURE
Intradermal induction:
- No. of injections: 6
- administration volume: 0.1 ml
- Test groups: 10 female
- Control group: 5 female animals
- Site: back, 3 injections on each side of the spinal column (injection site 1: complete Freund's adjuvant 1:1 diluted with sterile physiological saline solution, injection site 2: 5 % test item formulated in polyethylene glycol 400, injection site 3: 5 % test item formulated at equal parts in polyethylene glycol 400 and complete Freund's adjuvant)
- Frequency of applications: single
- Concentrations: 5% formulated in polyethlene glycol 400

Topical Induction (7 days later): occlusive
- application volume: 0.5 ml
- Test groups: 10 female
- Control group: 5 female animals
- Site: back
- Frequency of applications: single
- Concentrations: 100 % (applied volume: 0.5 mL)
- at the end of the 48 hour exposure period, the remaining test item was removed with sterile physiological saline solution.

B. CHALLENGE EXPOSURE
- No. of exposures: single
- Challenge was performed 3 weeks after the intradermal induction.
- Day(s) of challenge: day 14 after the intradermal induction
- Exposure period: 24 h
- Test groups: 10 female
- Control group: 5 female animals
- Site: back
- Application volume: 0.5 ml
- Concentrations: 100%
- At the end of exposure period: the remaining test item was removed with sterile physiological saline solution and 21 hours later the skin was shorn in the zone of the challenge area.

- Evaluation (hr after the end of challenge): 48 and 72 hs

Challenge controls:

test on male guinea pigs using alpha-Hexylzimtaldehyd formulated in sterile physiological saline solution intradermal induction with 5%, topical induction with 12% and challenge with 25%. 100% of the test animals exhibited dermal reactions.

Positive control substance(s):

yes

Results and discussion

Positive control results:

Expected positive reaction was demonstrated.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

intradermal induction: 0.1 ml 5% formulation in polyethylene glycol 400, topical induction: 0.5 ml 100% test article, topical challenge: 0.5 ml 100% test article (= 500 mg test item/ animal)

No. with + reactions:

6

Total no. in group:

10

Clinical observations:

slight localized up to moderate confluent redness

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: intradermal induction: 0.1 ml 5% formulation in polyethylene glycol 400, topical induction: 0.5 ml 100% test article, topical challenge: 0.5 ml 100% test article (= 500 mg test item/ animal). No with. + reactions: 6.0. Total no. in groups: 10.0. Clinical observations: slight localized up to moderate confluent redness.

Results 2

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

intradermal induction: 0.1 ml 5% formulation in polyethylene glycol 400, topical induction: 0.5 ml 100% test article, topical challenge: 0.5 ml 100% test article (= 500 mg test item/ animal)

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

slight localized redness

Remarks on result:

other: see Remark

Remarks:

Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: intradermal induction: 0.1 ml 5% formulation in polyethylene glycol 400, topical induction: 0.5 ml 100% test article, topical challenge: 0.5 ml 100% test article (= 500 mg test item/ animal). No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: slight localized redness.

Any other information on results incl. tables

After the intradermal induction the animals n the control group and in the test item group showed strong effects up to encrustation at the injection sites.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Propargyl-N-butylcarbamat exhibits a skin-sensitizing potential. Propargyl-N-butylcarbamat is classified as skin sensitiser CAT 1 B, H317 according to EU-CLP-criteria 3.4.2.2.3 table 3.4.4.

Executive summary:

Propargyl-N-butylcarbamat was tested in a guinea pig maximisation test according to OECD 406 for its sensitising properties.

In a pilot study with 2 female animal the effects of an topical application of 0.5 ml of a 0, 25, 50 and 100% formulation in polyethylene glycol 400 were tested.

Based on the results of the dose range-finding studies the following concentrations were selected:

Intradermal induction: 5%

Topical induction: 100%

Topical challenge: 100%

In the main study with 10 female animals a first induction was started with the intradermal injection of 0.1 ml of a 5 % formulation in polyethylene glycol 400 with Freund's complete adjuvans.

The second induction was done 7 days later by an occlusive dermal application of 0.5 ml of the pure test article.

21 days after the intradermal induction the challenge was done by an occlusive dermal application of 0.5 ml of the pure test article.

The effect was controlled 48 and 72 hours after the end of the application.

The challenge using the pure test article led to skin effects in 6 of 10 animals. No skin effects were observed in the control group.

Therefore under the conditions of the maximization test and with respect to the evaluation criteria the test item therefore exhibits a skin-sensitization potential.