2,2-dimethylpropane-1,3-diyl cyclohex-4-ene-1,2-dicarboxylate

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)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

1,2,3,6-Tetrahydrophthalic anhydride, oligomeric reaction products with 2,2-dimethylpropane-1,3-diol

EC Number:

500-091-1

EC Name:

1,2,3,6-Tetrahydrophthalic anhydride, oligomeric reaction products with 2,2-dimethylpropane-1,3-diol

Cas Number:

36621-20-2

Molecular formula:

(C8H8O3.C5H12O2)x

IUPAC Name:

1,2,3,6-Tetrahydrophthalic anhydride, oligomeric reaction products with 2,2-dimethylpropane-1,3-diol

Constituent 2

Reference substance name:

1,3-Isobenzofurandione, 3a,4,7,7a-tetrahydro-, polymer with 2,2-dimethyl-1,3-propanediol

IUPAC Name:

1,3-Isobenzofurandione, 3a,4,7,7a-tetrahydro-, polymer with 2,2-dimethyl-1,3-propanediol

Details on test material:

As per IUCLID Sections 1.1. 1.2. and 4.1.

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

The test animals were acquired from Harlan Sprague-Dawley; Indianapolis, IN and were acclimated five days before being placec on study. The animal weight range the day of experimental initiation was 18.9 - 22.2 gm. The animals were housed in Polycarbonate boxes with bedding. There were 10-12 air changes/hour and a 12-hour lightJdark cycle. in the animal room. The temperature range was 18-22°C and the relative humidity ranged 26-89%. The animals were maintained on PMI Feeds Jnc.TM Formulab #5 008; available ad libitum and Sugar Land Texas Municipal water supply analyzed by TCEQ Water Utilities Division; available ad libitum from automatic water system.

Study design: in vivo (LLNA)

Vehicle:

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

Concentration:

The concentrations of the test substance were 25, 50 and 100% (neat).

No. of animals per dose:

5

Details on study design:

Five female mice were selected for each of three Test groups. On Days 1, 2 and 3, each Test animal in its group received an open application of 25 uL of an appropriate dilution (25% or 50%) of the test substance, or 100% test substance.undiluted, to the dorsum of both ears. The Vehicle Control group (5 females) was treated in the same way as test animals, but with vehicle alone. The Positive Control group (5 females) was treated with 80% alpha-hexylcinnamaldehyde in.acetone:olive oil. All Test and Control animals were given a two-day rest period on Days 4 and 5.

On Day 6 of the study, all Test and Control animals were injected in the tail vein with 250 uL of 0.01 M phosphate-buffered saline (PBS) pH 7.4, containing 20 uCi of {methyl-3Hj Thymidine. Five hours after the injection, the animals were sacrificed with an overdose of CO2, the draining auricular lymph nodes were excised and pairs from each individual animal were processed.

A single cell suspension was prepared by gentle mechanical disintegration through 200 mesh stainless steel gauze. The cells were washed twice with an excess of PBS and precipitated with 5% trichloroacetic acid (TCA) at 4°C for 18 hours. The pellets were resuspended in 1 mL of TCA and transferred to 10 mL of scintillation fluid. Incorporation of tritiated thymidine was measured by liquid scintillation counting as disintegrations per minute (DPM) from the paired lymph nodes of each animal, and mean DPM/animal was calculated for each group.

Positive control substance(s):

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

Statistics:

None

Results and discussion

Positive control results:

The positive control, 80% alpha-hexylcinnamaldehyde induced a Stimulation Index of 5.5 relative to mean concurrent control DPM value.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

3.3

Test group / Remarks:

25% concentration

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: The mean DPM counts were as follows: Control-5469, 25%-17652, 50%-26126, 100%-27925

Results 3

Parameter:

SI

Value:

4.36

Test group / Remarks:

50% concentration

Results 4

Parameter:

SI

Value:

5.5

Test group / Remarks:

100% concentration

Any other information on results incl. tables

The Stimulation Index values for the test substance were: 25%-3.3, 50%-4.38, 100%-5.5.  

Applicant's summary and conclusion

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Remarks:

Migrated information

Conclusions:

Based upon a Stimulation Index of > 3 at all concentration of the test substance, the test substance is a skin sensitizer under the conditions of the study.

Executive summary:

The test substance, 1,2,3,6 -Tetrahydrophthalic anhydride, oligomeric reaction products with 2,2 -dimethylpropane-1,3 -diol, was accessed for skin sensitization potential in an O.E.C.D. test guideline 429 mouse LLNA study. Based upon a Stimulation Index of > 3 at all concentration of the test substance, the test substance is a skin sensitizer under the conditions of the study.