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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Conducted under OECD Guidelines, OECD Good Laboratory Practices

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Solid white powder, 99.36 % pure.

In vivo test system

Test animals

Species:
mouse
Strain:
NMRI
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Animal strain: Specific pathogen-free female NMRI mice of the strain Hsd Win:NMRI were obtained from Harlan Winkelmann GmbH, 33176 Borchen, Germany.
- Housing: During the adaptation period, animals were housed in conventional Makrolon type III cages with up to 10 mice per cage. During the study period, animals were housed in type II cages with one mouse per cage. The cages were changed at least twice a week. Low-dust wood granulate type S 8/15 from J. Rettenmaier & Sohne Fullstoff-Fabriken, 7092 Ellwangen-Holzmuhle, was used as bedding. The wood granulate was analysed at random for contaminants.
-Diet: Ad libitum. Feed was PROVIMI KLIBA SA 3883 maintenance diet for rats and mice (from Provimi Kliba SA, CH-4303 Kaiseraugst, Switzerland). Contaminant content and nutritive composition was analysed routinely in random samples.
-Drinking water. Ad libitum. Tap water of drinking water quality was provided in polycarbonate bottles.
-Acclimation period: At least 7 days, during which the state of health of the animals was monitored.

ENVIRONMENTAL CONDITIONS
-Temperature: 20-24 degrees C
-Relative humidity: About 30%
-Photoperiod: 12 hours light/12 hours dark

Study design: in vivo (LLNA)

Vehicle:
other: DAE 433
Concentration:
25 µl of a 0%, 3%, 10%, or 30% solution of BPA in DAE 433
No. of animals per dose:
6
Details on study design:
Female NMRI mice were treated epicutaneously on the dorsal part of both ears with 25 µl per ear of a solution containing 0%, 3%, 10%, or 30% BPA in DAE 433 (6 animals per dose group). Treatments were given once per day for three consecutive days (day 0, day 1, and day 2). On day 0 and day 3 (one day after last application), the ear swelling of the animals was measured using a spring-loaded micrometer and mean ear swelling was calculated. Ear weight was measured on day 3 using a punch to cut off a piece of each ear with an 8 mm diameter. Also on day 3, animals were sacrificed by inhalation of carbon dioxide and lymphatic organs (the auricular lymph nodes) were transferred to PBS. Lymph nodes (LNs) were weighed and then crushed through a plastic sieve into 12-well plates and cell counts per ml were determined using a Coulter counter. The stimulation index was calculated by dividing the absolute number of the weight or cell counts of the treated lymph nodes by the vehicle lymph nodes.
Statistics:
When statistically reasonable, the values from treated groups were compared with those from controls by the Mann-Whitney or the Wilcoxon significance test (Rank Sum Test or One-Way ANOVA or Kruskal-Wallis ANOVA) at significance levels of 5% (one-tailed for LLNA/ear swelling). Outlying values in the LN/ear weights or LN cell counts were eliminated at a probability level of 99% by Nalimov's method. For the LLNA/ear swelling, the smallest significant differences in the means were calculated by Scheffe's method. For indices, only the standard deviations between groups and difference analysis of the mean values (Scheffe's method) were used in the evaluation of the biological relevance.

Results and discussion

Positive control results:
No positive control was used.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: see Remark
Remarks:
Lymph node stimulation was measured by cell counts instead of radioactive labelling. Lymph node weight index at 0, 3%, 10%, and 30%: 1.00, 0.85, 1.07, and 0.93, respectively. LN cell count index at 0, 3%, 10%, and 30%: 1.00, 1.25, 1.35, and 1.24, respectively. Ear swelling index on day 3 at 0, 3%, 10%, and 30%: 1.00, 1.02, 1.04, and 0.99, respectively.
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: Lymph node stimulation was measured by cell counts instead of radioactive labelling, as authorised in OECD Guideline No. 429.

Any other information on results incl. tables

The authors stated that compared to vehicle-treated animals, none of the measured parameters reached or exceeded the "positive levels" defined for the assay.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
The authors concluded that BPA has neither an irritating nor a sensitising potential in mice after dermal application.
Executive summary:

Female NMRI mice were treated epicutaneously on the dorsal part of both ears with 25 µl per ear of a solution containing 0%, 3%, 10%, or 30% BPA in DAE 433 (6 animals per dose group). Treatments were given once per day for three consecutive days (day 0, day 1, and day 2). On day 0 and day 3 (one day after last application), the ear swelling of the animals was measured using a spring-loaded micrometer and mean ear swelling was calculated. Ear weight was measured on day 3 using a punch to cut off a piece of each ear with an 8 mm diameter. Also on day 3, animals were sacrificed by inhalation of carbon dioxide and lymphatic organs (the auricular lymph nodes) were transferred to PBS. Lymph nodes (LNs) were weighed and then crushed through a plastic sieve into 12-well plates and cell counts per ml were determined using a Coulter counter. The stimulation index was calculated by dividing the absolute number of the weight or cell counts of the treated lymph nodes by the vehicle lymph nodes. Compared to vehicle-treated animals, none of the measured parameters reached or exceeded the "positive levels" defined for the assay. The authors concluded that BPA has neither an irritating nor a sensitising potential in mice after dermal application.