A mixture of: bis(1S,2S,4S)-(1-benzyl-4-tert-butoxycarboxamido-2-hydroxy-5-phenyl)pentylammonium succinate; isopropyl alcohol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 11 to Jun 03, 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: done under GLP and OECD method

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

92/69/EEC Part B Acute Toxicity

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study carried out in 1994

Test material

Test material information

Constituent 1

Reference substance name:

A mixture of: bis(1S,2S,4S)-(1-benzyl-4-tert-butoxycarboxamido-2-hydroxy-5-phenyl)pentylammonium succinate; isopropyl alcohol

EC Number:

414-810-0

EC Name:

A mixture of: bis(1S,2S,4S)-(1-benzyl-4-tert-butoxycarboxamido-2-hydroxy-5-phenyl)pentylammonium succinate; isopropyl alcohol

Cas Number:

144163-85-9

Molecular formula:

Empirical formula: C25H35N2O5

IUPAC Name:

butanedioic acid; propan-2-ol; bis(tert-butyl N-[(4R)-5-amino-4-hydroxy-1,6-diphenylhexan-2-yl]carbamate)

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Crl:(HA)BR Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Inc, Portage, Michigan
- Age at study initiation: 1 month approximately
- Weight at study initiation: 250 - 350gram
- Housing: Individual Stainless Steel ventilated cages
- Diet: Certified Guinea Pig Chow®
- Water: ad libitum
- Acclimation period: 5 days followed by an 9 day pretreatment period.

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 69 - 74
- Humidity (%): Ambient
- Photoperiod (hrs dark / hrs light): 12hr daily light cycle

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: 1st induction: 0.2% HPMC. 2nd induction and challenge: Petrolatum

Induction 2

Concentration / amount:

Concentration of test material at First Induction (Intradermal injection): 3% in 0.2% HPMC.
Concentration of test material at Second Induction (topical application): 50% in petrolatum
Concentration of test material used for challenge (topical applications): 25% and 50% in petrolatum

Challenge

Challenge 1

Route:

other: Topically

Vehicle:

other: 1st induction: 0.2% HPMC. 2nd induction and challenge: Petrolatum

Challenge 2

Concentration / amount:

Concentration of test material at First Induction (Intradermal injection): 3% in 0.2% HPMC.
Concentration of test material at Second Induction (topical application): 50% in petrolatum
Concentration of test material used for challenge (topical applications): 25% and 50% in petrolatum

No. of animals per dose:

10 animals assigned to the negative control group.
20 animals assigned to treatment group.

Details on study design:

MAIN STUDY

An approximate 40 x 60mm area of dorsal skin on the scapular region was clipped free of hair prior to treatment

A. INDUCTION EXPOSURE
- No. of exposures: 2 - intadermal and topical
- Exposure period: 7 days for first induction and 14 days for second induction.
- Observations: 24hrs after the intradermal injections and once daily for 5 days. 24 and 48hrs after patch removal for the second induction.
- 0.05ml injection vol.
- Site for 2nd induction was pre-treared by massaging 0.3ml of 10% sodium dodecyl sulphate in water into the skin of animals in both groups on the day prior to topical inductionto illicit an inflammatory reaction.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: Day 21
- Exposure period: 24hr occlusive bandage
- Site: right flank; patch saturated with 50% Abbott-88820 succinate in petrolatum.
left flank; patch saturated with 25% Abbott-88820 succinate in petrolatum.
- Evaluation (hrs after challenge):24 and 48 hr after patch removal.

Body weights were measuredc twice during the pretreatment period, on the day of the first and second induction, on the day of the challenge and on the final day of the observations

Challenge controls:

10 animals with 0.2% Hydroxypropyl methylcellulose for the 1st induction, petrolatum for the 2nd induction. Challenge: 25% Abbott-88820 succinate in petrolatum.

Positive control substance(s):

not required

Remarks:

Sensitivity tested periodically with 1-chloro-2,4-dinitrobenzene.

Results and discussion

Positive control results:

n/a

In vivo (non-LLNA)

Results

Reading:

other:

Hours after challenge:

24

Group:

test chemical

Dose level:

25% in petrolatum

No. with + reactions:

1

Total no. in group:

19

Clinical observations:

slightly patchy erythema

Remarks on result:

other: Reading: other:. . Hours after challenge: 24.0. Group: test group. Dose level: 25% in petrolatum. No with. + reactions: 1.0. Total no. in groups: 19.0. Clinical observations: slightly patchy erythema.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Abbott-88820 succinate did not induce delayed contact hypersensitivity in guinea pigs in this study. Criteria used for interpretation of results: EU

Conclusions:

Abbott-88820 succinate did not induce delayed contact hypersensitivity in guinea pigs in this study.