Reaction products of 4,4'-methylenebis(cyclohexylamine) and 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane

Endpoint summary

Description of key information

The test substance was tested in vivo on the skin of rabbits according to OECD 404. Based on results the test material is corrosive to skin (MB Research, 2016).

The test substance was found to be non-corrosive in Corrositex study, however, the method is not considered suitable for the tested substance (MB research 2016).

The study "eye irritation" needs not be conducted because the available information indicates that the criteria are met for classification as corrosive to the skin or irritating to eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin corrosion: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Reference 2

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

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animals were received from Covance Research Products Inc., Denver, PA, on 06 Apr 2016. Following an
acclimation period of at least five days, one healthy New Zealand White rabbit (male) was selected from a
larger group without conscious bias.
The animal was born on 21 Nov 2015. The pre-test body weight was 3.2 kg.
The animal was 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 #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:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 g per site

Duration of treatment / exposure:

Site 2 - 1 h, Site 3 - 4 h,

Observation period:

14 day

Number of animals:

1

Details on study design:

Site Preparation
Approximately 24 hours prior to application of the test article, the dorsal area of the trunk of the animal
was clipped free of hair. The prepared site was approximately 10% of the body surface and remained
intact.
Dosing
One rabbit was dosed on Site 2 for an exposure period of one hour and Site 3 for an exposure period of
four hours. The test article was individually weighed, 0.5 g per site and applied over a 2 x 3 cm gauze
patch at which time the test article solidified. Gentle pressure was applied to aid in the distribution of the
test article over the prepared site. The clipped area of the torso was covered with a piece of porous
dressing large enough to cover both 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
periods, the wrapping and patches were removed and the sites were gently washed with gauze saturated
with 70% isopropyl alcohol. The outline of the dose sites were marked using an indelible marker.
Type and Frequency of Observations
Site 2 (one-hour exposure) and 3 (four-hour exposure) were scored for dermal irritation at 1, 24, 48 and
72 hours after patch removal and again on Days 7 and 14. 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:

animal #1

Time point:

other: 1 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: One hour exposure site

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: One hour exposure site

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: One hour exposure site

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: One hour exposure site

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

7 d

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: One hour exposure site

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

14 d

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: One hour exposure site

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 1 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: 1 hour exposure site

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: 1 hour exposure site

Irritation parameter:

edema score

Basis:

animal #1

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: 1 hour exposure site

Irritation parameter:

edema score

Basis:

animal #1

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: 1 hour exposure site

Irritation parameter:

edema score

Basis:

animal #1

Time point:

7 d

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: 1 hour exposure site

Irritation parameter:

edema score

Basis:

animal #1

Time point:

14 d

Score:

0

Max. score:

4

Remarks on result:

other: 1 hour exposure site

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 1 h

Score:

0

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: 4 hour exposure site

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: 4 hour exposure site

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: 4 hour exposure site

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: 4 hour exposure site

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

7 d

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: 4 hour exposure site

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

14 d

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: 4 hour exposure site

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 1 h

Score:

0

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: 4 hour exposure site

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: 4 hour exposure site

Irritation parameter:

edema score

Basis:

animal #1

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: 4 hour exposure site

Irritation parameter:

edema score

Basis:

animal #1

Time point:

72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: 4 hour exposure site

Irritation parameter:

edema score

Basis:

animal #1

Time point:

7 d

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: 4 hour exposure site

Irritation parameter:

edema score

Basis:

animal #1

Time point:

14 d

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: 4 hour exposure site

Other effects:

No abnormal physical signs were observed. The animal gained body weight by study termination.

Conclusions:

Corrosivity of PACM BADGE was tested on rabbit using one test animal. Based on results the test material is corrosive to skin meeting criteria of catagory Corr 1C.

Executive summary:

Corrosivity of PACM BADGE was tested on rabbit using one test animal. Based on results the test material is corrosive to skin meeting criteria of catagory Corr 1C.

Reference 3

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Method is not suitable for the test material.

Qualifier:

according to guideline

Guideline:

other:

Version / remarks:

The Corrositex® - InVitro International, Placentia, CA

Principles of method if other than guideline:

The Corrositex® (InVitro International, Placentia, CA) test is a standardized and reproducible method that can be employed to determine the potential corrosivity and the Packing Group classification of specified
categories of chemical compounds under the hazardous materials transportation regulations administered by the U.S. Department of Transportation (DOT) and international dangerous goods codes. The
Corrositex® test predicts1,2 the in vivo corrosive potential of a chemical compound or mixture by using as an endpoint the amount of time it takes for a chemical to permeate or destroy a synthetic biobarrier.
A color change in a proprietary liquid Chemical Detection System (CDS) is used to indicate that the chemical has passed through the biobarrier. This assay system is depicted below.

The Corrositex® test is a three step procedure. First, each test article was qualified to ensure that it was compatible with the Corrositex® system, and then it was categorized according to pH to determine cut-off
times. Finally, they were classified based on the mean time each test article took to penetrate the biobarriers.
Qualification
For each test article, 150 μl or 100 mg of the test article were added to the CDS reagent in a Qualify vial, and the vial was observed for any notable color change. An observable color change indicates that the
test article is compatible with the Corrositex® system.
Categorization
Next, each test article was categorized, which determined cut-off times for the Packing Group designations. A 10% formulation of each test article was prepared and its pH was measured. If the pH of the 10%
formulation was  7.0, 150 μl or 100 mg of the neat test article were added to Tube A. The pH of Tube A was then measured, and if it was  5.0, the test article was assigned to Category 1, and if it was  5.0, the
test article was assigned to Category 2. If the pH of the 10% formulation was  7.0, 150 μl or 100 mg of the neat test article were added to Tube B. The pH of Tube B was measured, and if the final pH was  9.0, the
test article was Category 1, and if it was  9.0, the test article was Category 2.
Classification
Finally, each test article was classified by adding 500 μl or 500 mg of the test article to four test vials containing biobarriers to determine the Packing Group. If the test article mixture permeates or destroys
the biobarrier, it will come in contact with the CDS reagent in the vial and induce a color change similar to that observed in the Qualify tube. The amount of time required for the test article to permeate or destroy
each biobarrier was recorded and the mean time of the four replicates is used to designate the United Nations (U.N.) Packing Group classification. Classifications are as follows: Packing Group I (severe
corrosivity), Packing Group II (moderate corrosivity), Packing Group III (mild corrosivity), or Non-Corrosive. A positive control was performed using 1.0 N Sodium Hydroxide . The result for the Positive
Control is considered valid if it falls within the range of the MB Research historical mean ± 2 standard deviations. A negative control was performed using 1% citric acid; the result is considered valid if the
breakthrough time is greater than 60 minutes.

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Lot# 20160226-PDU-PACM-828

Test system:

artificial membrane barrier model

Vehicle:

unchanged (no vehicle)

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

The crushed test article was used neat.

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

1

Value:

> 66

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

2

Value:

> 65.75

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

3

Value:

> 66.5

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Irritation / corrosion parameter:

penetration time (in minutes)

Run / experiment:

4

Value:

65.25

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Interpretation of results:

GHS criteria not met

Conclusions:

4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with 4,4'-methylenebis(cyclohexylamine) was found to be non-corrosive in Corrositex study however method is not considered suitable for the tested substance.

Executive summary:

4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with 4,4'-methylenebis(cyclohexylamine) was found to be non-corrosive in Corrositex study however method is not considered suitable for the tested substance.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Justification for classification or non-classification

Based on the in vivo skin irritation test according to OECD 404, the test substance has to be classified according to CLP regulation 1272/2008 as skin corrosive Cat 1 C.