Mono- and/or di- and/or tri(1-phenylethyl)-m-cresol and p-cresol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Atlen SK

IUPAC Name:

Atlen SK

Details on test material:

- Name of test material (as cited in study report): Atlen SK
- Substance type: organic, UVCB
- Physical state: liquid
- Lot/batch No.:proba of 24/07/2009
- Expiration date of the lot/batch: 2010-07-24
- Stability under test conditions: stable

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/Ca

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Velaz s.r.o., Lysolaje 15, 165 00 Praha 6
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 18-20 g
- Housing: the animals were housed individually in plastic cages T I
- Diet (e.g. ad libitum): ad libitum, the animals were given standard fodder MP (TOP DOVO)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: qnimals were quarantined before the start of the experiement

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 45-65
- Air changes (per hr): min. 10
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

the test item was administered at 10, 25 and 50% concentrations

No. of animals per dose:

5 animals per dose

Details on study design:

RANGE FINDING TESTS: range finding test was not performed.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: pooled approach
- Criteria used to consider a positive response: SI ≥ 3 and dose dependece of increase in lymph node weight and in DPM

TREATMENT PREPARATION AND ADMINISTRATION:
On day 1 the dorsum of each ear of each animal was treated with 25 µl of appropriate dilution of the test item, positive control or vehicle only. The treatment was repeated on days 2 and 3. No treatment was performed on days 4 and 5. On day 6 250 µl of phosphate buffered saline (PBS) containing 20 µCi of 3H-methyl thymidine (3H-TdR) was made into the tail vein of each experimental mouse. Five hours later the animals were sacrificed. The draining Auricular lymph node of each ear was excised into PBS for each experimental group and weighted.
Cell suspension of lymph node cells from pooled treatment groups was prepared by gentle mechanical desagregation in glass homogenizer. lymph node cells were washed with an excess of PBS and centrifuged by 600 g at 4 °C for 10 min. Suspension of cells was precipitated with 5 % trichloroacetic acid (TCA) at 4 °C for 18-20 hrs. Pellets were centrifuged by 2000 g at 4 °C for 5 min., re-suspended in 1 ml TCA and transferred into scintillation vials containing 10 ml of scintillation fluid for 3H-counting.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: Pos. Control 4.46 Atlen SK 10% 2.87 Atlen SK 25% 3.13 Atlen SK 50% 4.18

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Control 1067.21 Pos. Control 4760.68 Atlen SK 10% 3084.38 Atlen SK 25% 3342.82 Atlen SK 50% 4487.57

Any other information on results incl. tables

EC3 calculated on the basis of the aforementioned results amounted to 17.5% (moderate sensitizer).

According to ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health:

LOAEL = EC3 [%]*250 [μg/cm2/% ] = EC3 [μg/cm2]

Calculated LOAEL: 4375 μg/cm²

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information

Conclusions:

Results of the LLNA study indicate that Atlen SK is a skin sensitiser.

Executive summary:

Presented results originate from a guideline study conducted in accordance with the requirements of the GLP. Hence, this information can be considered reliable and suitable for use as the key study for this endpoint.