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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
This key study was conducted to an acceptable study design (guinea pig maximation test) is already available. The existing data are of good quality and provides clear negative response. There is also a supporting Buehler assay showing no evidence of skin sensitisation potential. These data preclude the need for further in vivo testing.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): furfural
- Physical appearance: colourless to dark brown liquid
- Analytical purity: 99.62%
- Lot/batch No.: 5371
- Expiration date of the lot/batch: 10 October 2003
- Storage condition of test material: Stored in the original container as supplied by the Sponsor (i.e., glass bottle), at room temperature.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Mahaveera Enterprises, Hyderabad, India
- Weight at study initiation: males 257-412 g, females 272-429 g
- Housing: 2 to 3 animals of the same sex per cage
- Diet: Guinea pig pellet diet (Amrut brand) (Pranav Agro Industries Ltd., Pune, Maharashtra, India) ad libitum
- Water: Charcoal filtered and UV sterilised water with vitamin-C (1 g/L) ad libitum
- Acclimation period: 6 days prior to dosing

ENVIRONMENTAL CONDITIONS
- Temperature: 19-24°C
- Humidity: 63-66%
- Air changes: 18 air changes per hour
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 28 February 2003 To: 24 March 2003

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: induction intradermal = propylene glycol, induction epicutaneous = no vehicle, challenge = acetone
Concentration / amount:
induction intradermal: 5% furfural in propylene glycol
induction epicutaneous: undiluted
challenge: 0.2 mL of 25% furfural in acetone
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: induction intradermal = propylene glycol, induction epicutaneous = no vehicle, challenge = acetone
Concentration / amount:
induction intradermal: 5% furfural in propylene glycol
induction epicutaneous: undiluted
challenge: 0.2 mL of 25% furfural in acetone
No. of animals per dose:
5 males and 5 females in control group
10 males and 10 females treated group
Details on study design:
RANGE FINDING TESTS:
2 males and 2 females (clipped skin) injected intradermally with 0.1 mL of 0.5, 1, 2.5 and 5% in propylene glycol
2.5% = very slight erythema observed at 24 and 48 hours
5% = very slight erythema and oedema at 24 and 48 hours
The 5%, being mild to moderate irritant dose was selected for intradermal injection for the main study.

2 males and 2 females were epicutaneous (clipped skin) exposed to 0.2 mL of 25, 50, 75 and 100% for 24 hours. (Vehicle = 80% ethanol)
100% was selected for the epicutaneous induction, based on very slight erythema and oedema at 24 hours as well as 48 hours
25% was selected as non-irritant concentration for the challenge phase

MAIN STUDY
A. INDUCTION EXPOSURE
INTRADERMAL INDUCTION
- No. of exposures: 3 pairs of injections at a single timepoint
- Test groups:
1:1 mixture (v/v) of Freud's Complete Adjuvant (FCA) with distilled water
5% furfural in propylene glycol
5% Furfural in propylene glycol formulated in a 1:1 mixture (v/v) FCA with distilled water
- Control group: propylene is injected in the place of Furfural
- Site: scapular region each three injections on both sites of the back of the animal
TOPICAL INDUCTION (no pre-treatment with sodium lauryl sulphate required)
- No. of exposures: 1
- Exposure period: 48 hours
- Test groups: 0.2 mL furfural
- Concentrations: undiluted
- Control group: 0.2 mL distilled water
- Site: left flank
- Frequency of applications: single

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 21
- Exposure period: 24 hours
- Test groups and control groups: 0.2 mL 25% furfural in acetone
- Site: right flank
- Evaluation (hr after challenge): 24 and 48 hours after patch removal
Challenge controls:
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 21
- Exposure period: 24 hours
- control groups: 0.2 mL 25% furfural in acetone
- Site: right flank
- Evaluation (hr after challenge): 24 and 48 hours after patch removal
Positive control substance(s):
yes
Remarks:
2-mercaptobenzothiazole (reliability check JRF 4125)

Results and discussion

Positive control results:
24 hours after challenge, 12/20 test and 0/10 controls had discrete or patchy erythema. 48 hours after challenge, 7/20 and 0/10 controls had discrete or patchy erythema. The results of this study confirmed the skin sensitisation potential of 2-mercaptobenzothiazole and thereby the sensitivity and reliability of the study. 2-mercaptobenzothiazole is a moderate skin sensitiser.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25%
No. with + reactions:
3
Total no. in group:
20
Clinical observations:
no
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25%. No with. + reactions: 3.0. Total no. in groups: 20.0. Clinical observations: no.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25%
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
no
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 2.0. Total no. in groups: 20.0. Clinical observations: no.

Any other information on results incl. tables

Grade of eryththema in the test animals which responded = grade1 discrete or patchy erythema

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Furfural is not a skin sensitiser in the Guinea Pig maximisation test
Executive summary:

Since a sensitization rate of only 15% was observed in the present study using an adjuvant (guinea pig maximisation test) furfural is classified as a non-sensitiser as per OECD Harmonised System for Classification of Chemicals (2001)