Acrylamide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented guideline study conducted to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

Acrylamide

EC Number:

201-173-7

EC Name:

Acrylamide

Cas Number:

79-06-1

Molecular formula:

C3H5NO

IUPAC Name:

prop-2-enamide

Details on test material:

- Name of test material (as cited in study report): Acrylamide, 50 % aqueous. Source: Cytec Industries B. V., Rotterdam, The Netherlands
- Physical state: clear, colourless to pale yellow liquid
- Analytical purity: 50.2%
- Impurities (identity and concentrations): soluble polymer 52 ppm
- Composition of test material, percentage of components: 50 % aqueous solution
- Purity test date: 19 January 1995
- Lot/batch No.: MC91-1938
- Expiration date of the lot/batch: 19 July 1995
- Storage condition of test material: room temperature
- pH 5.7

In vivo test system

Test animals

Species:

guinea pig

Strain:

Pirbright-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann, Borchen, Germany
- Age at study initiation: -9 weeks
- Weight at study initiation: males = mean 353.9+/-33.5; female= mean 343.4 +/-16.3
- Housing:2 or 3 animals in Makrolonll-cages of appropriate size
- Diet (e.g. ad libitum): food "3022" from Altromin International Lage, Germany batch n° 1115 and 0808
- Water :ad libitum: Drinking water for the animals consisted of normal tap water from municipal sources Städtische Werke Krefeld AG
- Acclimation period:at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature : 20°C (17 - 23 °C)
- Humidity : 30-70 %
- Air changes (per hr): 8 times/hour
- Photoperiod (hrs dark / hrs light): 12-hour

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

water

Induction 2

Concentration / amount:

Intradermal:0.1 ml of 3.5% (v/v) solution
Dermal: soaked patch with undiluted test substance (50 % (vlv))
Challenge: Duhring chamber with soaked patch of 25 % (vlv) solution

Challenge

Challenge 1

Route:

epicutaneous, semiocclusive

Vehicle:

water

Challenge 2

Concentration / amount:

Intradermal:0.1 ml of 3.5% (v/v) solution
Dermal: soaked patch with undiluted test substance (50 % (vlv))
Challenge: Duhring chamber with soaked patch of 25 % (vlv) solution

No. of animals per dose:

20 test and 10 control

Details on study design:

RANGE FINDING TESTS:
Intradermal: 0.1 ml of 0.5, 2.0, 3.5 and 5.0 % (v/v) solution
Dermal: soaked patch with undiluted test substance (50 % (v/v)), 35, 20 and 5.0 % (v/v) solution
Challenge: Duhring chamber with soaked patch of undiluted test substance and 25 % (vlv) solution

MAIN STUDY
Intradermal: 0.1 ml of 3.5 % (v/v) solution
Dermal: soaked patch with undiluted test substance (50 % (vlv))
Challenge: Duhring chamber with soaked patch of 25 % (vlv) solution

Adjuvant: Freund's Adjuvant complete (FCA), Behringwerke AG, Marburg, Germany, No. OREC 20/21, Batch No. 377010 A.
Due to strong skin reactions and heavy crust formation with this batch in former experiments FCA was diluted 1 + 2 with sesame oiL.

VALIDATION:
Reference substance: Neomycintrisulfate trihydrate, Fluka Chemie AG, Buchs, Switzerland, No. 72133, Batch No. 299279 1090
Concentrations:
Intradermal: 0.1 ml of 2.0 % (w/v) solution
Dermal: soaked patch with 20 % (wlv) solution
Challenge: Duhring chamber with soaked patch of 2.0 % (wlv) solution

Challenge controls:

Duhring chamber with soaked patch of 25 % (v/v) aquaous solution

Positive control substance(s):

not required

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

25 % (v/v) solution

No. with + reactions:

17

Total no. in group:

20

Clinical observations:

discrete to intense erythema and edema

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25 % (v/v) solution. No with. + reactions: 17.0. Total no. in groups: 20.0. Clinical observations: discrete to intense erythema and edema.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

25 % (v/v) solution

No. with + reactions:

17

Total no. in group:

20

Clinical observations:

discrete to intense erythema and edema

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25 % (v/v) solution. No with. + reactions: 17.0. Total no. in groups: 20.0. Clinical observations: discrete to intense erythema and edema.

Any other information on results incl. tables

Systemic toxic symptoms after application were not observed at any time during the study. Body weight development was positive and within normal ranges. No erythema and edema were observed at any time point after the challenge application in the control group. There were apparently no skin reactions in control animals but 85% of test animals gave a positive response.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information

Conclusions:

On the basis of these results, acrylamide should be considered as a skin sensitiser in animals.