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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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study undertaken prior to the introduction of the LLNA (OECD TG 429 originally adopted April 2002)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
- Manufacturing date: 22 Aug 1988
- Storage condition of test material: Protected from light and humidity

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, D-4799 Borchen, Germany
- Weight at study initiation: 303 - 359 g
- Housing: Up to 5 animals / cage in Makrolon Type IV cages
- Diet (e.g. ad libitum): G4 guinea pig diet, Ssniff spezialfutter GmbH D-4770 Soest, Germany, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 4 - 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21 deg C
- Humidity (%): 55 - 65 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hour light / 12 hour dark

IN-LIFE DATES: From: 1988-09-20 To: 1988-10-14

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
maize oil
Concentration / amount:
Induction, injection: 0.5% in maize oil and o.5% in FCA emulsion
Induction, epicutaneous: 100%
Challenge, epicutaneous: 100%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
maize oil
Concentration / amount:
Induction, injection: 0.5% in maize oil and o.5% in FCA emulsion
Induction, epicutaneous: 100%
Challenge, epicutaneous: 100%
No. of animals per dose:
Test 20
Control: 10
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: Single intradermal injection on Day 1; 48 hour epicutaneous exposure over injection sites one week later
- Test groups:
Induction, injection - 2 x 0.1 mL FCA emulsion + 2 x 0.1 mL 0.5% substance in maize oil + 2 x 0.1 mL 0.5% substance in FCA emulsion
Induction, epicutaneous - 100% substance spread over 2 x 4 cm area
- Control group:
Induction, injection - 2 x 0.1 mL FCA emulsion + 2 x 0.1 mL maize oil + 2 x 0.1 mL maize oil in FCA emulsion
Induction, epicutaneous - Maize oil spread over 2 x 4 cm area
- Site: Scapular region
- Frequency of applications: 1 x injection + 1 x epicutaneous
- Duration: Single intradermal injection on Day 1; 48 hour epicutaneous exposure over injection sites one week later

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2 weeks after end of induction
- Exposure period: 24 hours
- Test groups: 100% substance spread over 2 x 2 cm area
- Control group: 100% substance spread over 2 x 2 cm area
- Site: left flank
- Evaluation (hr after challenge): 24 and 48 hours after end of challenge exposure
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
No. with + reactions:
19
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 19.0. Total no. in groups: 20.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
16
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 16.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Group:
positive control
Remarks on result:
not measured/tested

Applicant's summary and conclusion

Interpretation of results:
sensitising
Conclusions:
Hexahydrophthalic anhydride causes delayed dermal sensitisation in the guinea pig maximisation test of Magnusson and Kligman
Executive summary:

Dermal sensitisation has been investigated in a maximisation test according to OECD test methods. A marked sensitisation response was observed to hexahydrophthalic anhydride following a period of induction exposure.