Registration Dossier

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: EPA Health Effects Test Guidelines, 40 CFR 798.4100 (1985)

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: EPA Health Effects Test Guidelines, 40 CFR 798.4100 (1985)
GLP compliance:
yes
Remarks:
OECD GLP
Type of study:
Buehler test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Biphenol Dianhydride (BPA-DA); from GE Company; Purity: >99%

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
Male and female albino Hartley guinea pigs were received from Hazleton Dutchland, Inc. They were ordered to be between 300 and 350 g (males) and 350 to 400 g (females) approximately 4-6 weeks of age. They were housed individually upon arrival in stainless steel suspended cages. The animals were acclimated for approximately two weeks prior to dosing. Water (municipal) and feed were provided ad libitum. The temperature and humidity were monitored continuously and during the test period, included temperatures of 65-73 degrees F and a relative humidity range of 42-60%. Room lights were on a 12-hour cycle.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: aqueous methyl cellulose
Concentration / amount:
25% BPA-DA
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: aqueous methyl cellulose
Concentration / amount:
25% BPA-DA
No. of animals per dose:
5/sex BPA-DA Group
5/sex Naïve BPA-DA group
5/sex DNCB group (Positive Control)
5/sex Naïve DNCB group (Positive Control)
Details on study design:
A preliminary irritancy test was conducted, in which it was determined that 25% BPA-DA in aqueous methyl cellulose was the highest non-irritating dose that could be technically dosed.

For the main study, fur was clipped from the dose site the day before application. For topical induction and challenge, the test material was placed in a Hill Top Chamber®, an adhesive patch was placed over the chamber and the chamber was placed securely on the animal. A rubber dental dam was then tightly wrapped over the animal’s dorsal surface. The animals were restrained for the dosing and subsequent 6-hour contact period. Once the exposure was complete, the animals were removed from the restrainer, all coverings taken off and any residual material was wiped off. Warm tap water was used to wash the dosed area, as necessary.

Two groups were exposed to either BPA-DA (25%) or DNCB (0.3%) for 3 induction doses, spaced one week apart, followed by a two week rest period. A single challenge application of either BPA-DA (25%) or DNCB (0.1%) was then applied. Additionally, at this time, two groups of naïve (previously untreated) animals (5/sex/group) received the single application of either BPA-DA (25%) or DNCB (0.1%).

For BPA-DA, the three induction applications were made to the left scapular area, while a new, previously unexposed site, the right scapular area, was selected for the challenge application. For DNCB, the first induction dose was made to the left scapular area, but subsequent induction applications were applied to other previously unexposed posterior area sites due to staining, scaliness and/or scabs being present at the initial site. The challenge doses and single application doses to naïve animals were applied on the right scapular region.

The animals were examined frequently during the induction phase of the study. At 24 and 48 hours post-induction application, the fur was removed from the dose site, when necessary, and the dose site evaluated for erythema (as per the scale below). At 24 and 48 hours post-challenge application and at least two hours after depilation, each dose site was examined and graded as per the scale below. Any grade of 1 or more was considered positive as there were no reactions on the naïve animals greater than 0.

0 = No reactions
0+ (0.5) = slight patchy erythema
1 = slight, solid erythema or moderate patchy erythema
2 = moderate erythema
3 = severe erythema (with or without edema)
Challenge controls:
1 Naïve BPA-DA Group: 5 animals/sex
1 Naïve DNCB Group: 5 animals/sex
Positive control substance(s):
yes
Remarks:
2,4-Dinitro-1-chlorobenzene, CAS No. 97-00-7, Lot No. A11L.

Results and discussion

Positive control results:
Following the challenge application of 0.1% DNCB to the test animals, 10 of 10 animals developed moderate erythema within 24 hours. All animals continued to exhibit moderate erythema through 48 hours. Red to brown scab-like areas, scratches or foci were evident on four animals at 24 and/or 48 hours following the challenge application of DNCB. The challenge application of 0.1% DNCB to naïve control animals produced no significant irritation on any animal. Two animals exhibited slight, patchy erythema (score of 0.5) at 24 hours which is not considered a positive response.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
other: Naive test group
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Naive test group
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, BPA-DA is not a skin sensitiser.