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

Endpoint summary

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

Reliability:

1 (reliable without restriction)

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)

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

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)

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

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

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin sensitising potential of Atlen SK was tested in vivo.

Atlen SK was tested in LLNA study on mice at concentrations 10, 25 and 50%. Statistically significant and dose dependend increase in the lymph node weight and number of measured disintegrations per second was found. This indicated that Atlen SK was positive in the test.

EC3 value obtained in this test (17.5%) was converted to μg/cm² using the equation given in the document 'Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health' (May 2008, p. 128) in order to obtain the LOAEL value. The obtained LOAEL value of 4375 μg/cm² was next used as the key value in the Chemical Safety Assessment.

Migrated from Short description of key information:
Atlen SK was found to be a skin sensitizer in LLNA test.

Justification for selection of skin sensitisation endpoint:
One study available.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Evaluation of this endpoint is not required under REACH.

Justification for classification or non-classification

Available data is conclusive and sufficient for the classification of Atlen SK as skin sensitiser of category 1 under the CLP regulation and skin sensitiser with assigned phrase R43 and the symbol Xi - 'Irritant' - under the DSD.