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Diss Factsheets

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar 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:
A Guinea Pig Maximization Test (M&K method ) was already available before the LLNA test became available.

Test material

Constituent 1
Chemical structure
Reference substance name:
Glutaric anhydride
EC Number:
203-593-6
EC Name:
Glutaric anhydride
Cas Number:
108-55-4
Molecular formula:
C5H6O3
IUPAC Name:
glutaric anhydride
Test material form:
solid: crystalline
Specific details on test material used for the study:
Test Material : Glutaric Anhydride
- Lot/Batch No.: Truck #2
- Description: White solid
- Date of Receipt: November 1, 1991
- Expiration Date: Not provided
- Received from : Union Carbide
- Storage: Room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
Test animals

- Age: approximately 2-3 weeks at receipt, approximately 4-5 weeks old at study initiation.

Observations: All animals were checked for viability twice daily. Prior to assignment to study a1 1 animals received a physical examination to ascertain suitability for study.
- Husbandry: Currently acceptable practices of good animal husbandry were followed, e.g., Guide for the Care and Use of Laboratory Animals; NIH Publication No. 86-23, revised 1985.
- Housing : Individually, in suspended, stainless steel cages with wire mesh bottoms.
- Environmental conditions:
1. Temperature: monitored and recorded twice daily.
2. Humidity: monitored and recorded daily
3. Light Cycle: 12 hours light, 12 hours dark (controlled by an automatic timer).
- Food : Agway Purina Guinea Pig Diet, ad libitum
- Water: Automatic watering system, gSd libitum. Municipal water supply (El izabethtown Water Company, Westfield, New Jersey).
- Contaminants: There were no known contaminants reasonably expected to be found in food or water which would interfere with the results of this study.
- Animal Identification: Each animal was identified with a ear tag, bearing a unique animal number, prior to testing.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: ethanol (70%)
Concentration / amount:
intradermal induction - 5%
topical induction and challenge - 50% test substance
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol (70%)
Concentration / amount:
intradermal induction - 5%
topical induction and challenge - 50% test substance
No. of animals per dose:
Range Finding study: 8 animals (4/sex)

Sensitisation study:
20 animals (10 per sex) for sensitisation
10 animals (5 per sex) for irritation control - 1st challenge
10 animals (5 per sex) for irritation control - Re-challenge

Main study: positive control:
10 animals (5 per sex); irritation control for positive control group - 10 animals (5 per sex)

68 animals in total
Details on study design:
RANGE-FINDING STUDY
1. Intradermal
To confirm that the concentration proposed for intradermal injection (5.0%) did not produce extensive necrosis or ulceration or severe systemic toxicity, two animals were administered intradermal injections (2 sites per animal) of a 5.0% v/v concentration of the test material in propylene glycol. Injections of 0.1 ml per site were made intradermally using a 1.0 cc syringe and a 25 gauge 5/8" needle. Observations were made at 24- and 48-hours for necrosis and ulceration. Results indicated that a 5.0% concentration produced no necrosis or only local necrosis, no extensive necrosis or
ulceration occurred). Therefore, this concentration was used for the intradermal induction administration.

2. Topical
A topical range-finding study was performed as follows to determine the lowest concentration which produced mi ld irritation (to be used for induction) and the highest concentration which did not produce irritation (to be used for chal lenge) . Number of Animals: 6 (3/sex) Vehicle: 70% ethanol
Concentrations: 10, 25 and 50% w/v; 100%, moistened with 0.9% sterile saline. Based on the results of this study, the test material was found to be essentially non-irritating. Although Magnusson and Kligman (1970) suggest dosing solids at a maximum concentration of 25%, a 50% concentration in 70% ethanol was selected for topical induction and both challenges, to maximize the response. A dose of 100% moistened with saline was not selected, due to a concern there may be poor absorption.

MAIN STUDY
1. Induction, intradermal :
Site One: Adjuvant: 10 or 3 ml of FCA was added to 10 or 3 ml of deionized water and mixed, to produce a 0.5 ml/ml (50% v/v) mixture).
Site Two: Positive Control: 0.01 g of DNCB was added to propylene glycol which was brought to a total volume of 10 ml to produce a 0.001 g/ml (0.1% w/v) mixture. Test Material: 0.5 g of Glutaric Anhydride was added to propylene glycol which was brought to a total volume of 10 ml to produce a 0.05 g/ml (5% w/v) mixture. Irritation Controls : Propylene glycol was administered as received.
Site Three: Positive Control: 0.01 g of DNCB was added to a 50% mixture of FCA in deionized water which was brought to a total volume of 10 ml to produce a 0.001 g/ml (0.1% w/v) mixture. Test Material: 0.5 g of Glutaric Anhydride was added to a 50% mixture of FCA in deionized water, which was brought to a total volume of 10 ml, to produce a 0.05 g/ml (5% w/v) mixture. Irritation Controls: Site Three dosed with same mixture as site one.

2. Induction, topical
Positive Control: 0.01 g of DNCB was added t o 70% ethanol which was brought t o a t o t a l volume of 10 ml t o produce a 0.001 g/ml (0.1% w/v) mixture. Test Material: 5 g of Glutaric Anhydride was added to 70% ethanol, which was brought to a total volume o f 10 ml , to produce a 0.5 g/ml (50% w/v) mixture. Irritation Controls: 70% ethanol as prepared. Enhancer: 4 g of sodium lauryl sulfate was added to petrolatum, which was brought to a total weight of 40 g, to produce a 0.1 g/g (10% w/w) mixture.

Challenge/Rechallenge:
Test material and irritation control animals both received a 50% concentration prepared in the same manner as for the induction exposure.

Challenge controls:
Test material and irritation control animals both received a 50% concentration prepared in the same manner as for the induction exposure.
Positive control substance(s):
yes
Remarks:
2,4-dintrochlorobenzene

Results and discussion

Positive control results:
Nine of the ten animals treated with 0.1% DNCB exhibited clear dermal responses (scores of 1 or greater) at challenge, as confirmed by a lack of response by control animals (Group IB) to the same concentration. This 90% response would categorize this material as an extreme sensitizer (Grade V) .This positive response to a known sensitizer demonstrates the susceptibility of this group of animals to sensitization in the guinea pig maximization test.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1%
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1%
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
other: DNCB, irritation contriol
Dose level:
0.1% DNCB
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
other: DNCB, irritation control
Dose level:
01.%% DNCB
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under conditions of this study, glutaric anhydride exhibited no potential to produce dermal sensitization in the guinea pig. Based on the 0% incidence of sensitization, glutaric anhydride would not be categorized as a sensitizer.
Executive summary:

This study was conducted in order to evaluate the allergic contact sensitization potential of glutaric anhydride in guinea pigs. This study was performed, using procedures based on the method described by Bertil Magnusson, M.D., and Albert M. Kligman, M.D., Ph.D. in "The Identification of Contact Allergens by Animal Assay. The Guinea Pig Maximization Test", Journal of Investigative Dermatology, 57: 268-276 and in Allergic Contact Dermatitis in the Guinea Pig, Identification of Contac Allergens, Thomas, Springfield, IL, 1970.

Under conditions of this study, glutaric anhydride exhibited no potential to produce dermal sensitization in the guinea pig. Based on the 0% incidence of sensitization, glutaric anhydride would not be categorized as a sensitizer.