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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Valid and conclusive guideline study under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: 4,4’-Dichlorodiphenylsulfone (DCDPS)
- Physical state: solid
- Analytical purity: 99.15 %
- Purity test date: 2009-07-15
- Batch No.: LP090404 (Solvay Advanced Polymers LLC)
- Expiration date: 2009-04-21 plus 2 years (according to section 4.18)
- Stability: stable under storage conditions
- Storage: at room temperature, moisture protected

In vivo test system

Test animals

Species:
mouse
Strain:
other: CBA/CaOlaHsd
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V., Postbus 6174, 5960 AD Horst, The Netherlands
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: 17.8-20.6 g, mean 19.5 ± 0.9 g
- Housing: individually, in Makrolon Type II cages, with wire mesh top (Ehret GmbH, 79302 Emmendingen, Germany)
- Diet: pelleted standard diet (Harlan Laboratories B.V., 5960 AD Horst, The Netherlands), ad libitum
- Water: tap water (Gemeindewerke, 64380 Rossdorf, Germany), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2°C
- Humidity: 25-66 %
- Photoperiod: 12 hours dark / 12 hours light

Study design: in vivo (LLNA)

Vehicle:
dimethylformamide
Concentration:
Pre-test: 10 and 25 % (w/v)
Main study: 0, 5, 10, and 25 % (w/v)
No. of animals per dose:
4 females
Details on study design:
RANGE FINDING TESTS:
- Compound solubility: the highest test item concentration, which could be technically used was a 25 % (w/v) solution in dimethylformamide.
- Irritation: the animals did not show any signs of irritation or systemic toxicity.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response:
(1) Exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the stimulation index.
(2) The data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression.

TREATMENT PREPARATION AND ADMINISTRATION:
The test item was placed into a volumetric flask on a tared balance and dimethylformamide was quantitatively added. The different test item concentrations were prepared serially. The preparations were made freshly before each dosing occasion.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
The mean values and standard deviations were calculated in the body weight tables.

Results and discussion

Positive control results:
The EC3 value determined in the positive control experiment with hexyl cinnamic aldehyde (0, 5, 10, and 25 % w/v) was 12.9 % (w/v).

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: see Remark
Remarks:
Stimulation index (S.I.) values of 1.62, 0.83, and 1.00 were determined for the 5, 10 and 25 % (w/v) dose groups, respectively. The S.I. for the high dose group was derived from 3 animals only due to one premature decedent (day 6) in this dose group. However, the result obtained for the high dose group was considered as clearly negative. In this assay, the EC3 value could not be calculated, since all S.I. values were below 3.
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: The measured DPM and background DPM values (in brackets) were as follows: 0 %: 2781 (2762) 5 %: 4504 (4485) 10% : 2299 (2280) 25%: 2099 (2080)

Any other information on results incl. tables

Mortality:

One animal of the high dose group (25 % w/v) was moribund on day 6 and died prior to the application of 3H-methyl thymidine.

 

Clinical Signs:

During the course of the study, no signs of local irritation were noted on the ears of treated mice. The animals of the low and mid dose groups (5 and 10 % w/v) showed no signs of systemic toxicity. In the high dose group (25 % w/v), one animal died. The remaining animals showed no symptoms of systemic toxicity.

 

Body Weights:

The body weights were within the range commonly recorded for mice of this strain and age.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Under the conditions of this study, DCDPS was not a dermal sensitiser.
Executive summary:

In a dermal sensitisation study (Harlan CCR, 2010) with DCDPS (99.15 %) in dimethylformamide, young adult CBA/CaOlaHsd mice (4 females/dose level) were tested at concentrations of 0, 5, 10, or 25 % (w/v) by means of the local lymph node assay (LLNA).

During the course of the study, no signs of local irritation were noted on the ears of treated mice. Low and mid dose group animals (5 and 10 %) showed no signs of systemic toxicity. In the high dose group (25 %), one animal died. The remaining animals at this dose level showed no symptoms of systemic toxicity. There was no effect of treatment on the body weights. In this assay, the stimulation indices were 1.62 (n=4), 0.83 (n=4) and 1.00 (n=3) at dose levels of 5, 10 and 25 %, respectively. No EC3 value was established.

Hexyl cinnamic aldehyde in acetone:olive oil (4 +1) was used as positive control item and induced the appropriate response over background. Using the same dose levels as in the main assay, the EC3 value for the positive control item was 12.9 %.

 

In this study, DCDPS was not a dermal sensitiser.