Oligomeric reaction products of 4,4'-propane-2,2-diyldiphenol and 2-methyloxirane and 2-(chloromethyl)oxirane

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 July 2012 - 21 August 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant study conducted in accordance with international guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (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

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Name of test material (as cited in study report): EP-4000S, Chemical name: Phenol, 4-4’-(1-methylethylidene)bis-, polymer with 2-(chloromethyl)oxirane and 2- methyloxirane
- Physical state: Light yellow liquid
- Analytical purity: 89.52%
- Lot/batch No.: 902Y1
- Expiration date of the lot/batch: 07 December 2012
- Storage condition of test material: Ambient temperature in the dark

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 17.7 to 22.9 g
- Housing: Animals were housed inside a barriered rodent facility and were allocated without conscious bias to cages within the treatment groups.
They were housed two animals per cage, in solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved wood flake bedding, additionally Nestlets and a plastic shelter were included for environmental enrichment.
- Diet (e.g. ad libitum): standard rodent diet
- Water (e.g. ad libitum): Portable water taken from the public supply was freely available via polycarbonate bottles
fitted with sipper tubes.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12hrs dark/12hrs light

Study design: in vivo (LLNA)

Vehicle:

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

Concentration:

25, 50% w/v and 'as supplied'

No. of animals per dose:

2 mice in the preliminary investigations and 4 female mice in each of the three treated groups

Details on study design:

TREATMENT PREPARATION AND ADMINISTRATION: The mice were treated by daily application of 25 µL of the appropriate concentration or control (vehicle or positive), to the dorsal surface of both ears for three consecutive days.

The proliferative response of the lymph node cells (LNC) from the draining auricular lymph nodes was assessed five days following the initial application, by measurement of the incorporation of 3H-methyl Thymidine (3HTdR) by B-scintillation counting of LNC suspensions.
The response was expressed as radioactive disintegrations per minute per lymph node (dpm/node) and as the ratio of 3HTdR incorporation into LNC
of test nodes relative to that recorded for control nodes (test/control ratio), termed as Stimulation Index (SI).

Positive control substance(s):

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

Results and discussion

Positive control results:

The SI for the positive control substance hexyl cinnamic aldehyde was 4.0, which demonstrates the validity of this study.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: 3.8 (for 25% w/v) 6.3 (for 50% w/v) 9.3 (for 'As supplied)

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Concentration Disintegrations per minute 25% w/v 37484.5 50% w/v 61784.4 'As supplied' 55089.9

Any other information on results incl. tables

Preliminary investigation:

There were no deaths and no signs of ill health or toxicity were observed during this study.

No erythema was observed on the ears of either mouse on Days 1 to 6.

There was no evidence of an effect of treatment on ear thickness.

There was no indication of an overt effect of treatment on bodyweight gain.

Main phase:

There were no deaths and no signs of ill health or toxicity were observed during this study.

No signs of dermal irritation were seen on the ear during the study.

There was no indication of an effect of treatment on bodyweight gain.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

EP-4000S is regarded as a potential skin sensitizer. The EC3 value was calculated to be 20% w/v.