Registration Dossier

Administrative data

Description of key information

Skin sensitisation: sensitising

Respiratory sensitisation: 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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)
Specific details on test material used for the study:
- Manufacturing date: 22 Aug 1988
- Storage condition of test material: Protected from light and humidity
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
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%
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
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
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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

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


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Allergic reactions of the skin and allergic respiratory reactions are known effects of occupational exposure to cyclic acid anhydrides (Concise International Chemical Assessment Document 75 - Cyclic Acid Anhydrides: Human Health Aspects,World Health Organization, 2009).

 

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Allergic reactions of the skin and allergic respiratory reactions are known effects of occupational exposure to cyclic acid anhydrides (Concise International Chemical Assessment Document 75 - Cyclic Acid Anhydrides: Human Health Aspects,World Health Organization, 2009). This is reflected in current classification and labelling of the substance.
Based on available data on sensitisation, the test item is to be classified as Skin Sens. 1, H317 and as Resp. Sens. 1, H334 according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.