Registration Dossier

Administrative data

Description of key information

Skin irritation of 4,4’-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with 3-aminopropyldiethylamine and 2-piperazin-1-ylethylamine was determined to ce GHS category 2 in study with rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
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 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Animals were received from Covance Research Products Inc., Denver, PA, on 28 Jun 2017. Following
an acclimation period of at least five days, three healthy New Zealand White rabbits (two males - one
female) were selected from a larger group without conscious bias.
The animals were born on 28 Jan 2017 and 11 Feb 2017. The pre-test body weight range was
2.9 - 3.2 kg.
The animals were identified by cage notation and a uniquely numbered metal ear tag and individually
housed in suspended wire-bottom cages. Absorbent paper bedding was placed beneath the cages and
changed at least three times per week. Fresh PMI Rabbit Chow (Diet No. 5321) was provided daily.
Water was available ad libitum. The animal room, reserved exclusively for rabbits on acute tests, was
temperature controlled, had a 12-hour light/dark cycle, and was kept clean and vermin free.
Type of coverage:
open
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml ot test material
Duration of treatment / exposure:
1h and 4 h
Observation period:
14 days
Number of animals:
4
Details on study design:
Site Preparation
Approximately 24 hours prior to application of the test article, the dorsal area of the trunk of each animal
was clipped free of hair. The prepared site was approximately 10% of the body surface and remained
intact.
Dosing
Initially, one rabbit was dosed on Site 1. The test article was dosed by volume, 0.5 ml per site and placed
on top of a 2 x 3 cm gauze patch. Gentle pressure was applied to aid in the distribution of the test article
over the prepared site. The dose patch was secured with non-irritating tape and the rabbit was gently held
in place. The dose patch was removed at 3 minutes post-exposure and the test site was gently washed
with gauze saturated with distilled water following patch removal. The outline of the dose site was
marked using an indelible marker.
Since no evidence of a corrosive or severely irritating effect was observed in the initial animal, two
additional animals were added to the study. All three animals were dosed at Site 2 for an exposure
period of one hour and Site 3 for an exposure period of four hours. The clipped area of the torso was
covered with a piece of porous dressing large enough to cover all dose sites with at least 5 cm2 to spare
on all sides of the gauze patch. Porous, non-irritating tape was used to encircle the trunk of the animal.
After the exposure period, the wrappings and patches were removed and the sites gently washed with
gauze saturated with distilled water. The outline of the dose site was marked using an indelible marker.
Type and Frequency of Observations
Exposure Site 1 of the initial animal was scored for dermal irritation immediately post-exposure and at
one hour post-exposure. Sites 2 (one-hour exposure) and 3 (four-hour exposure) were scored for dermal
irritation at 1, 24, 48 and 72 hours and again on Day 7 after patch removal. Reactions were scored again
on Day 14 for the four-hour exposure. Erythema and edema were scored according to the numerical
Draize1 scale. The skin was also evaluated for ulceration and necrosis or any evidence of tissue
destruction. Additional signs were described.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 h
Score:
0
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 1 h exposure
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 1 h exposure
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 1 h exposure
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 1 h exposure
Irritation parameter:
erythema score
Basis:
mean
Time point:
7 d
Score:
> 0 - < 1
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other:
Remarks:
1 h exposure
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 1 h exposure
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 1 h exposure
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 1 h exposure
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 1 h exposure
Irritation parameter:
edema score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 1 h exposure
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 4 h exposure
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 4 h exposure
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 4 h exposure
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
> 1 - < 3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 4 h exposure
Irritation parameter:
erythema score
Basis:
mean
Time point:
7 d
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 4 h exposure
Irritation parameter:
erythema score
Basis:
mean
Time point:
14 d
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 4 h exposure
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 h
Score:
0
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other:
Remarks:
4 h exposure
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
> 1 - < 2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 4 h exposure
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 4 h exposure
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 4 h exposure
Irritation parameter:
edema score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 4 h exposure
Irritation parameter:
edema score
Basis:
mean
Time point:
14 d
Score:
> 0 - < 1
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: 4 h exposure
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Skin irritation of 4,4’-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with 3-aminopropyldiethylamine and 2-piperazin-1-ylethylamine was determined to ce GHS category 2 in study with rabbits.
Executive summary:

Skin irritation of 4,4’-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with 3-aminopropyldiethylamine and 2-piperazin-1-ylethylamine was determined to ce GHS category 2 in study with rabbits.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Justification for classification or non-classification