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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Nov 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
yes
Remarks:
- modification: in addition, measurements of ear swelling and ear weight were done to discriminate the irritating potential from the sensitizing potential of the test substance (Integrated Model for the Differentiation of Skin reactions (IMDS))
Principles of method if other than guideline:
Modified LLNA (IMDS; Integrated Model for the Differentiation of Skin Reactions). Modifications are authorised in the OECD TG 429 and in the Note for Guidance SWP/2145/00 of the CPMP (2001). Information on validation of IMDS and scientific justification is given in: Vohr HW et al., Arch. Toxicol., 73, 501-509 (2000); Ehling G et al., Toxicology 212, 60-68 and 69-79 (2005).
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymphnode assay (LLNA)
Test material information:
Composition 1
Species:
mouse
Strain:
NMRI
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Strain: Hsd Win:NMRI (SPF)
- Age at study initiation: 10-11 weeks
- Weight at study initiation: 26-33 g
- Housing: individual
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 40-70
- Air changes (per hr): about 10
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
dimethylformamide
Concentration:
0, 2, 10, 50 %
No. of animals per dose:
6
Details on study design:
TREATMENT PREPARATION AND ADMINISTRATION:
The test item in the formulation or the vehicle were applied epicutaneously onto the dorsal part of both ears of the animals. This  treatment was repeated on three consecutive days (d1, d2 and d3). The volume administered was 25µl/ear. The used concentrations were based on the experiences with the test system and the toxic properties of the test substance.
The animals were anaesthetized by inhalation of carbon dioxide and sacrificed one day after the last application (d4). The appropriate organs were then removed. Lymphatic organs (the auricular lymph nodes) were transferred into physiological saline (PBS).
Investigations:
- weight of draining lymph nodes (given as weight index compared to vehicle controls)
- cell counts in draining lymph nodes (given as cell count index compared to vehicle controls)
Stimulation indices were calculated by dividing the absolute weight or number of cell counts of the substance treated lymph nodes by the vehicle treated ones.
- ear swelling (given in 0.01 mm and as index)
- ear weight (given in mg/8 mm diameter punch and as index)
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
When it was statistically reasonable, the values from treated groups were compared with those from the control group by the Mann-Whitney or the Wilcoxon signigicance test (Rank Sum Test or One Way ANOVA or Kruskal-Wallis ANOVA) at significance levels of 5 % (one-tailed for LLNA/IMDS or PNLA (larger)). Outlying values in the LN/ear weights or LN cell counts were eliminated at a probability level of 99% by Nalimov's method. In addition, for the LLNA/IMDS the smallest significant differentes in the means were calculated by Scheffels method, which according to Sachs can be used for both equal and unequal sample sizes.
Positive control results:
Alpha hexyl cinnamic aldehyde showed a clear sensitizing potential in the local lymph node assay (IMDS).
Parameter:
SI
Remarks on result:
other: No significant dose-dependent increase in the stimulation indices for the weight or cell counts as well as for ear swelling or ear weights.

Table 1: Summary of the LLNA/IMDS results (means of 6 animals per group)

Parameter investigated

Vehicle

control

Dose 2 %

Dose 10 %

Dose 50 %

Stimulation index:

weight of draining lymph nodes

1.00

0.84

0.88

0.83

Stimulation index:

cell count in draining lymph nodes

1.00

0.87

0.93

0.79

Ear swelling in 0.01 mm on day 4 (index)

18.17

(1.00)

17.92

(0.99)

18.00

(0.99)

17.92

(0.99)

Ear weight in mg / 8 mm diameter punch on day 4 (index)

12.54

(1.00)

12.73

(1.02)

12.80

(1.02)

13.18

(1.05)

The mice did not show any significant dose-dependent increase in the stimulation indices for the weight or cell counts as well as for ear swelling or ear weights. Slight significant decrease compared to vehicle treated animals regarding cell counts was detected in the highest dose group. This decrease is in the normal range of variance for these parameters and is such of no biological relevance. The reason for this decrease is not known but could be due to osmosis in the tissues and/or cytotoxicity induced by a relative high local concentration of the test item.

Interpretation of results:
not sensitising
Remarks:
Migrated information
Executive summary:
BAY 43-9006 was investigated in the modified local lymph node assay (LLNA-IMDS) on female mice according to OECD TG 429. Concentrations of 0 (vehicle control), 2, 10 and 50 % formulated in dimethylformamide were tested. The results show that the test item has neither an irritating nor a sensitizing potential in mice after dermal application.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

BAY 43-9006 was investigated in the modified local lymph node assay (LLNA-IMDS) on female mice according to OECD TG 429 (Vohr, 2004). Concentrations of 0 (vehicle control), 2, 10 and 50 % formulated in dimethylformamide were tested. The results show that the test item has neither an irritating nor a sensitizing potential in mice after dermal application.


Migrated from Short description of key information:
BAY 43-9006 has no skin sensitizing potential.

Justification for selection of skin sensitisation endpoint:
Only one study available

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the study results a classification according to Regulation (EC) No.1272/2008 (CLP) is not required.