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

Endpoint summary

Description of key information

Based on the available reliable in vivo skin irritation and eye irritation study results, the test substance was determined to be non-irritating to the rabbit skin and eyes.

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

Study period:

From 18 March, 2004 to 26 March, 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Deviations from the minimum and maximum level of temperature occurred however, these deviations were considered not to have affected the study integrity.

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Deviations from the minimum and maximum level of temperature occurred however, these deviations were considered not to have affected the study integrity.

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

yes

Remarks:

Deviations from the minimum and maximum level of temperature occurred however, these deviations were considered not to have affected the study integrity.

Qualifier:

according to guideline

Guideline:

other: JMAFF, Japanese Test Guidelines (2000)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

other: New Zealand White, (SPF-Quality)

Details on test animals or test system and environmental conditions:

Age and body weight: Animals used within the study were at least 6 week 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: 17 - 24.1⁰C), a relative humidity of 30-70% (actual range: 33 - 66%) and 12 h artificial fluorescent light and 12 h darkness per day.
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 wk.
Water: Free access to tap-water. Certificates of quarterly analysis were examined and retained in the NOTOX archives.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 h

Observation period:

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

Number of animals:

3

Details on study design:

-Treatment: Approx 24 h before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approx 150 square centimeters (10x15 cm2). Whenever considered necessary the treated skin areas were re-clipped at least 3 h before the observations, to facilitate scoring. A health inspection was performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities. Each animal was treated by dermal application of 500 mg of the test substance. The test substance was applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage. 4 h after the application, the dressing was removed and the skin cleaned of residual test substance using water and watery ethanol (50% v/v).
-Observation:
Mortality/Viability: Twice daily.
Toxicity: At least once daily.
Body Weight: Day of treatment (prior to application) and at termination.
Irritation: The skin reactions were assessed at approximately 1, 24, 48 and 72 h after the removal of the dressings and test substance.The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hrs

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 24hrs

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hrs

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema 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: 4 h exposure to 500 mg of the test substance resulted in very slight erythema in the treated skin-areas of the three rabbits. No oedema was noted. The skin irritation had resolved within 48 h after exposure in all animals.
Corrosion: There was no evidence of a corrosive effect on the skin.
Colouration/remnants: No staining of the treated skin by the test substance was observed. Sticky remnants of the test substance were present on the skin on Day 1.

Other effects:

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

Mean value irritation scores (24, 48 and 72 h):

Animal #	Mean 24-72 h
	Erythema	Oedema
899	0.3	0
938	0.3	0
948	0.3	0
Primary irritation index: 0.3

 

Mean value irritation scores (24 and 72 h):

Animal #	Mean 24-72 h
	Erythema	Oedema
899	0.5	0
938	0.5	0
948	0.5	0
Primary irritation index: 0.5

Interpretation of results:

other: CLP criteria not met (not irritating)

Conclusions:

Under the conditions of the study, the test substance was considered to be non-irritating to skin.

Executive summary:

A study was performed to assess the skin irritation potential of the substance '4,4'-Isopropylidenediphenol, polymer with 1-chloro-2,3-epoxypropane, propane-1,2-diol acrylate and succinic anhydride'according to OECD Guideline 404, EU Method B.4, US EPA, OPPTS 870.2500 and JMAFF Guidelines, in compliance with GLP. Three rabbits were exposed to 500 mg of the test substance, applied onto clipped skin for 4 h using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 h after exposure. Exposure to the test substance resulted in very slight erythema in the treated skin areas of the rabbits. No oedema was noted. The skin irritation had resolved within 48 h after exposure in all animals. Sticky remnants of the test substance were present on the skin, 1 h after exposure only. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. Based on the 24, 48 and 72 h readings, the primary irritation index was calculated to be 0.3. Based on the 24 and 72 h readings, the primary irritation index was calculated to be 0.5. Under the conditions of the study, the test substance was considered to be non-irritating to skin (Huygevoort, 2004).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

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

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

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

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)

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.

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.

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

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

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

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

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

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

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

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

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

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

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

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.

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

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin:

A study was performed to assess the skin irritation potential of the substance '4,4'-Isopropylidenediphenol, polymer with 1-chloro-2,3-epoxypropane, propane-1,2-diol acrylate and succinic anhydride' according to OECD Guideline 404, EU Method B.4, US EPA, OPPTS 870.2500 and JMAFF Guidelines, in compliance with GLP. Three rabbits were exposed to 500 mg of the test substance, applied onto clipped skin for 4 h using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 h after exposure. Exposure to the test substance resulted in very slight erythema in the treated skin areas of the rabbits. No oedema was noted. The skin irritation had resolved within 48 h after exposure in all animals. Sticky remnants of the test substance were present on the skin, 1 h after exposure only. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. Based on the 24, 48 and 72 h readings, the primary irritation index was calculated to be 0.3. Based on the 24 and 72 h readings, the primary irritation index was calculated to be 0.5. Under the conditions of the study, the test substance was considered to be non-irritating to skin (Huygevoort, 2004).

Eye:

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).

Justification for classification or non-classification

Based on the results of in vitro skin and eye irritation studies, the test substance is not required to be classified for skin and eye irritation according to EU CLP (EC 1272/2008) criteria.