4,4'-Isopropylidenediphenol, polymer with 1-chloro-2,3-epoxypropane, propane-1,2-diol acrylate and succinic anhydride

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 22 March, 2004 to 2 April, 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Few deviation in maximum weight level of the test substance (exceeded), relative humidity and temperature were observed, however these deviations was considered not to have affected the study integrity

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Few deviation in maximum weight level of the test substance (exceeded), relative humidity and temperature were observed, however these deviations was considered not to have affected the study integrity

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

yes

Remarks:

Few deviation in maximum weight level of the test substance (exceeded), relative humidity and temperature were observed, however these deviations was considered not to have affected the study integrity

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000.

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-Isopropylidenediphenol, polymer with 1-chloro-2,3-epoxypropane, propane-1,2-diol acrylate and succinic anhydride

EC Number:

500-240-0

EC Name:

4,4'-Isopropylidenediphenol, polymer with 1-chloro-2,3-epoxypropane, propane-1,2-diol acrylate and succinic anhydride

Cas Number:

68958-77-0

Molecular formula:

UVCB, major component represented by di-functionalised BADGE (HPA-SA-BADGE-SA-HPA): C41H52O16 Other constituents present at >10%: Mono-functionalised BADGE (BADGE-SA-HPA): C35H44O14 Dimers (HPA-SA-BADGE-SA-BADGE-SA-HPA): C66H82O24

IUPAC Name:

2-Propenoic acid, monoester with 1,2-propanediol, polymer with 2-(chloromethyl)oxirane, dihydro-2,5-furandione and 4,4'-(1-methylethylidene)bis[phenol]

Test material form:

liquid

Test animals / tissue source

Species:

rabbit

Strain:

other: Albino Rabbit, New Zealand White, (SPF-Quality)

Details on test animals or tissues and environmental conditions:

Age and body weight: Animals used within the study were at least 6 weeks old and body weights were at least 1000 mg
Identification: Earmark
Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approx 15 air changes/h, a temperature of 21.0 ± 3.0°C (actual range: 16.6 - 24.3°C), a relative humidity of 30-70% (actual range: 29 78%) and 12 h artificial fluorescent light and 12 h darkness per day. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.
Accommodation: Individually in labeled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm). Acclimatization period was at least 5 d before start of treatment under laboratory conditions.
Diet: Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany) approx. 100 g/day. Certificates of analysis were examined and retained in the NOTOX archives. In addition, pressed hay (BMI, Helmond, the Netherlands) was provided at least three times a week.
Water: Free access to tap-water. Certificates of quarterly analysis were examined and retained in the NOTOX archives.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

100.4 mg (100.3 - 100.5)

Duration of treatment / exposure:

24 h

Observation period (in vivo):

Observations were made 1, 24, 48 and 72 h after exposure.

Number of animals or in vitro replicates:

3

Details on study design:

-Treatment: Each animal was treated by instillation of 100.4 mg (100.3-100.5) of the test substance as the maximum required amount, in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about 1 sec to prevent loss of the test substance. The other eye remained untreated and served as the reference control. Immediately after the 24 h observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage.
-Observation:
Mortality/viability: Twice daily.
Toxicity: At least once daily.
Body weight: Day of treatment (prior to instillation) and at termination.
Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 h after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hrs

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hrs

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hrs

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

positive indication of irritation

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Irritation: Instillation of approx 100 mg of the test substance into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 48 h. No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein, 24 h after test substance instillation revealed no corneal epithelial damage.
Corrosion: There was no evidence of ocular corrosion.
Colouration/Remnants: Remnants of the test substance were present on the outside of the eyelids on days 1 and 2.

Other effects:

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Draize score calculation:

Animal#	Tissue	Time after application
		1 h	24 h	48 h	72 h
	Cornea	0	0	0	0
	Iris	0	0	0	0
	Conjuctivae	4	2	0	0
878	Subtotal	40	0	0	0
Animal#	Tissue	Time after application
		1 h	24 h	48 h	72 h
	Cornea	0	0	0	0
	Iris	0	0	0	0
	Conjuctivae	6	2	0	0
917	Subtotal	6	2	0	0
Animal#	Tissue	Time after application
		1 h	24 h	48 h	72 h
	Cornea	0	0	0	0
	Iris	0	0	0	0
	Conjuctivae	6	2	0	0
923	Subtotal	6	2	0	0
Total		16	6	0	0
Mean		5	2	0	0

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the overall mean Draize score for the substance was calculated to be 0.7 /110.

Executive summary:

A study was performed to assess the eye irritation potential of the substance ‘4,4’-Isopropylidenediphenol, polymer with 1-chloro-2,3-epoxypropane, propane-1,2-diol acrylate and succinic anhydride’in New Zealand White rabbits according to OECD Guideline 405 and EU Method B.5, in compliance with GLP. Approximately 100 mg of the test substance was instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 h after instillation. Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 48 h. Remnants of the test substance were present on the outside of the eyelids on Days 1 and 2. Under the test conditions, the overall mean Draize score for the test substance was calculated to be 0.7 /110. Therefore, under the conditions of the study, the test substance was considered to be non-irritating to eyes (Huygevoort, 2004).