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Description of key information

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)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)
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.



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
Positive control results:
The positive control, 80% alpha-hexylcinnamaldehyde induced a Stimulation Index of 5.5 relative to mean concurrent control DPM value.
Parameter:
SI
Value:
3.3
Test group / Remarks:
25% concentration
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
Parameter:
SI
Value:
4.36
Test group / Remarks:
50% concentration
Parameter:
SI
Value:
5.5
Test group / Remarks:
100% concentration

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

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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Based upon a stimulation index of >3 at all concentrations tested (25%, 50% and 100%), the test substance is considered to be a skin sensitizer under the conditions of the study.


Migrated from Short description of key information:
A local lymph node assay was performed according to OECD 429 on 1,2,3,6-tetrahydrophthalic anhydride, oligomeric reaction products with 2,2-dimethylpropan-1,3-diol used as read-across chemical. The substance is considered to be a skin sensitizer.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

- skin sensitisation:

Based on the above stated assessment of the skin sensitisation potential, the substance needs to be classified as R43 (May cause sensitisation by skin contact) according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and Skin Sens Cat 1 according CLP (Regulation (EC) No 1272/2008 Of The European Parliament And Of The Council)as implementation of UN-GHS in the EU.

- respiratory sensitisation:

As no data on respiratory sensitization is available for the substance a classification is not possible according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according CLP (Regulation (EC) No 1272/2008 Of The European Parliament And Of The Council)as implementation of UN-GHS in the EU.