Reaction products of amines, polyethylenepoly-, triethylenetetramine fraction and 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental start 13th September 2017 Experimental completion 31 October 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

3,3'-[propane-2,2-diylbis(benzene-4,1-diyloxy)]bis(1-{[2-({2-[(2-aminoethyl)amino]ethyl}amino)ethyl]amino}propan-2-ol)

Molecular formula:

C33H60N8O4

IUPAC Name:

3,3'-[propane-2,2-diylbis(benzene-4,1-diyloxy)]bis(1-{[2-({2-[(2-aminoethyl)amino]ethyl}amino)ethyl]amino}propan-2-ol)

Constituent 2

Reference substance name:

1,16-bis(4-{2-[4-(3-{[2-({2-[(2-aminoethyl)amino]ethyl}amino)ethyl]amino}-2-hydroxypropoxy)phenyl]propan-2-yl}phenoxy)-4,7,10,13-tetraazahexadecane-2,15-diol

Molecular formula:

C60H102N12O8

IUPAC Name:

1,16-bis(4-{2-[4-(3-{[2-({2-[(2-aminoethyl)amino]ethyl}amino)ethyl]amino}-2-hydroxypropoxy)phenyl]propan-2-yl}phenoxy)-4,7,10,13-tetraazahexadecane-2,15-diol

Constituent 3

Reference substance name:

3-(4-{2-[4-(3-{[2-({2-[(2-aminoethyl)amino]ethyl}amino)ethyl]amino}-2-hydroxypropoxy)phenyl]propan-2-yl}phenoxy)propane-1,2-diol

Molecular formula:

C27H44N4O5

IUPAC Name:

3-(4-{2-[4-(3-{[2-({2-[(2-aminoethyl)amino]ethyl}amino)ethyl]amino}-2-hydroxypropoxy)phenyl]propan-2-yl}phenoxy)propane-1,2-diol

Constituent 4

Reference substance name:

Polymeric adducts of 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bis-oxirane and N1,​N2-​bis(2-​aminoethyl)​-​2-​ethanediamine

IUPAC Name:

Polymeric adducts of 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bis-oxirane and N1,​N2-​bis(2-​aminoethyl)​-​2-​ethanediamine

Constituent 5

Reference substance name:

Unknown components

IUPAC Name:

Unknown components

Specific details on test material used for the study:

Identification: 4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with triethylenetetramine
Batch: #01725
Purity: 100% UVCB
Description: pale yellow extremely viscous liquid
Expiry date: 1st September 2021
Storage: room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Two New Zealand White rabbits were supplied from Envigo RMS Limited, Leicestershire UK. At the start of the study the animals weighted 3.55 or 3.42 kg and were 12 to 52 weeks old. After an acclimatization period of at least 5 days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.

Animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Animals were individually housed in suspended cages. Free access to mains drinking water and food was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 17 to 23 degrees C and 30 to 70 % respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Test system

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

A volume of 0.1 mL of the test item, found to weigh approximately 92.7 mg was placed into the conjunctival sac of the right eye.

Observation period (in vivo):

Immediately after administration of the test item, an assessment of the initial pain reaction was made.
Assessment of ocular damage/administration was made approximately 1 hour and 24, 48 and 72 hours following treatment.

Additional observations were made on days 7, 14 and 21 to assess the reversibility of the ocular effects.

Number of animals or in vitro replicates:

2

Details on study design:

Occular damage/irritation was observed alongside any other ocular effects. Examination of the eye was facilitated by the use of the light source from a standard opthalmoscope.
Any other clinical signs of toxicity were also recorded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

1

Reversibility:

not specified

Results 2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

48 h

Score:

1

Reversibility:

not reversible

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The test item produced irreversible ocular damage and was considered to be corrosive to the rabbit eye. The test item was classified as Category 1 (irreversible effects on the eye) according to the Globally Harmonized system of classification and labelling of Chemicals.