N-(butoxymethyl)acrylamide

Endpoint summary

Description of key information

The skin sensitisation potential of the read-across material, acrylamide, was assessed according to OECD Test Guideline 406 using a guinea pig maximisation test. The read-across material is considered sensitising.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

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:

guideline study

Justification for type of information:

See the Analogue Approach Report attached in Section 13 of the IUCLID dossier.

Reason / purpose for cross-reference:

other: Read across to target substance

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Existing non-LLNA data avaliable

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 Makrolon ll-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

Route:

intradermal and epicutaneous

Vehicle:

water

Route:

other:

Vehicle:

other:

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

Route:

epicutaneous, semiocclusive

Vehicle:

water

Concentration / amount:

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

MAIN STUDY
Intradermal: 0.1 mL of 3.5 % (v/v) solution
Dermal: soaked patch with undiluted test substance (50 % (v/v))
Challenge: Duhring chamber with soaked patch of 25 % (v/v) 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 % (w/v) solution
Challenge: Duhring chamber with soaked patch of 2.0 % (w/v) solution

Challenge controls:

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

Positive control substance(s):

not required

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.

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.

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.

Interpretation of results:

sensitising

Remarks:

Migrated information

Conclusions:

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

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The skin sensitisation potential of the read-across material, acrylamide, was assessed according to OECD Test Guideline 406 using a guinea pig maximisation test. The sensitisation potential was assessed using intradermal application of 0.1 mL of a 3.5 % (v/v) solution, the dermal application of a soaked patch with undiluted test substance (50 % v/v) and challenge with a soaked patch of 25 % (v/v). At a dose level of 25 % (v/v) solution of the read-across substance 17 of the 20 animals had a positive reaction with discrete to intense erythema and oedema. Systemic toxic symptoms after application were not observed at any time during the study. Body weight development was positive and within normal ranges. The read-across material, acrylamide, is therefore considered sensitising.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The read-across material, acrylamide, elicited a sensitisation reaction in 17 out of 20 guinea pigs tested and is therefore considered as a Category 1 skin sensitiser.