Registration Dossier

Administrative data

Description of key information

An eye irritation study according to OECD guidelines and GLP principles is available. A skin irritation study with exposure during 24h under occlusion on intact and abraded skin is available. Both showed that the substance is not irritating for skin and eye.

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:
not indicated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed in 1975, non-GLP, but appropriate for this endpoint.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Patch-test technique on the intact and abraded skin of albino rabbits.
GLP compliance:
no
Remarks:
test was performed before GLP principles were in place.
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Preparation of test site:
other: shaved or shaved and abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 grams
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
12
Details on study design:
TEST SITE
- Area of exposure: not indicated
- % coverage: 1 inch x 1 inch
- Type of wrap if used: impervious tape to retard evaporation.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: at 24h and 48 hours later (72 hours after application)

SCORING SYSTEM:Draize
Irritation parameter:
other: mean of erythema and edema score
Basis:
mean
Time point:
24 h
Score:
0.8
Max. score:
2
Remarks on result:
other: intact skin; edema score is 0 in all animals
Irritation parameter:
other: probably mean of erythema and edema score
Basis:
mean
Time point:
72 h
Score:
0.7
Max. score:
1
Remarks on result:
other: intact skin
Irritation parameter:
other: mean of erythema and edema score
Basis:
mean
Time point:
24 h
Score:
1.8
Max. score:
2
Remarks on result:
other: abraded skin
Irritation parameter:
other: probably mean of erythema and edema score
Basis:
mean
Time point:
72 h
Score:
1
Max. score:
1
Remarks on result:
other: abraded skin
Irritant / corrosive response data:
The available in vivo test on skin irritation for Dianol 33 is not according to current guidelines. Exposure was during 24 h on intact and abraded skin under occlusion. See included table for results.

Intact skin

Abraded skin

Rabbit nr

24h erythema

24h edema

72h

Rabbit nr

24h erythema

24h edema

72h

1

0

0

0

7

2

0

1

2

0

0

1

8

2

1

1

3

1

0

0

9

1

0

1

4

1

0

1

10

1

0

1

5

2

0

0

11

2

0

1

6

1

0

1

12

2

0

1

average

0.8

0.7

 

1.8

1.0

 24 h reading is directly after removal of the patches (with 24 h exposure), 72 h reading is 48 hours after first reading.

Interpretation of results:
GHS criteria not met
Remarks:
Not skin irritating.
Conclusions:
Dermal exposure of Dianol 33 was tested during 24h under occlusive conditions on both intact and abraded skin. Although this study was not performed according to current guidelines, the exposure conditions are more worst case than required by guidelines and are considered acceptable for conclusion on skin irritating properties of Dianol 33. Based on the observed slight irritation of exposed abraded skin after 24h of exposure, which effect was decreased after another 48h (mean score is 1 at 72h ), Dianol 33 does not have to be classified and has no obligatory labelling requirement for dermal irritation according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.
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:
23 November - 02 December 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan, Belton, Leics, England
- Age at study initiation: Animals used within the study were at least 6 weeks old *
- Weight at study initiation: body weights were at least 1.0 kg *.
- Housing: Individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).
- Diet (e.g. ad libitum): Pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Uden, The Netherlands) were available during the study period.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimatization period: at least 5 days before start of treatment under laboratory conditions.

* Animal specifications (sex, age and body weight) are specified in the attached table.

A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the eyes, which were free from any abnormality.

Results of analysis for diet (nutrients and contaminants), hay and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.6 – 19.8ºC
- Humidity (%): 38 - 68%
Temporary deviations from the minimum level of relative humidity occurred. Laboratory historical data do not indicate an effect of the deviations.
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day

IN LIFE DATES: From: 23 November - 02 December 2010
Vehicle:
unchanged (no vehicle)
Controls:
other: One eye of each animal remained untreated and served as the reference control.
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 48.4 mg (range 47.8 – 48.8 mg)
Duration of treatment / exposure:
Single instillation on Day 1.
Observation period (in vivo):
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance
Number of animals or in vitro replicates:
3 males
Details on study design:
STUDY DESIGN
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner one week later, after considering the degree of eye irritation observed in the first animal.

TREATMENT
Animals were treated by instillation of, on average, 48.4 mg (range 47.8 – 48.8 mg) of the test substance (a volume of approximately 0.1 mL), 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 one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control. Immediately after the 24-hour observation, a solution of 2% fluorescein (Merck, Darmstadt, Germany) in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area. After the final observation, the animals were sacrificed by intra-venous injection of Euthasol® 20% (AST Farma BV, Oudewater, The Netherlands).

REMOVAL OF TEST SUBSTANCE
-Washing (if done): No

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to instillation) and after the final observation.
- Necropsy: No necropsy was performed according to protocol.
- Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded.The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:

CORNEAL IRRITATION
Opacity: degree of density (area most dense taken for reading)
0: No ulceration or opacity (may include slight dulling of normal luster)
1: Scattered or diffuse areas of opacity, details of iris clearly visible
2: Easily discernible translucent area, details of iris slightly obscured
3: Nacreous area, no details of iris visible, size of pupil barely discernible
4: Opaque cornea, iris not discernible through the opacity

Area of cornea involved:
0: No ulceration or opacity
1: One quarter or less but not zero
2: Greater than one quarter, but less than half
3: Greater than half, but less than three quarters
4: Greater than three quarters, up to whole area

IRIS
0: Normal
1: Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination thereof, iris still reacting to light (sluggish reaction is positive)
2: No reaction to light, hemorrhage, gross destruction (any or all of these)

CONJUNCTIVAL IRRITATION
Redness (refers to palpebrae and sclera, excluding cornea and iris):
0: Blood vessels normal
1: Some blood vessels definitely hyperaemic (injected)
2: Diffuse, crimson color, individual vessels not easily discernible
3: Diffuse beefy red

Chemosis (refers to lids and/or nictitating membranes):
0: No swelling
1: Any swelling above normal (includes nictitating membranes)
2: Obvious swelling with partial eversion of lids
3: Swelling with lids about half closed
4: Swelling with lids more than half closed

Discharge:
0: No discharge (may include small amounts observed in inner canthus of normal animals)
1: Any amount different from normal and/or lacrimation
2: Discharge with moistening of the lids and hairs just adjacent to lids
3: Discharge with moistening of the lids and hairs (considerable area around the eye)

Where standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp.
In cases of equivocal results when comparing the treated and untreated eyes, the illustrated guide from the Consumer Product Safety Commission, Washington, D.C. 20207 was used for additional control purposes.
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
animal: #1, #2 and #3 (mean)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: Remnants of test substance in the eye at 1 h after instillation.
Irritation parameter:
iris score
Basis:
animal: #1, #2 and #3 (mean)
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Remarks:
(mean)
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Remarks:
(mean)
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: 1 h after instillation: Score 2
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Remarks:
(mean)
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: 1 h after instillation: Score 2
Irritation parameter:
chemosis score
Basis:
animal: #1, #2 and #3 (mean)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Instillation of approximately 48 mg of LIN10001:4,4’-Isopropylidenediphenol, propoxylated (BPA+2PO) (a volume of approximately 0.1 mL) into one eye of each of three rabbits resulted in redness of the conjunctivae. The irritation had completely resolved within 24 hours in two animals and within 48 hours in the other animal.

No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.

Individual and mean eye irritation scores are specified in the attached table.
Other effects:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

A small lump of test substance was present in the corner of the eye of all animals on Day 1. These remnants were manually removed immediately after observing these.

Interpretation of results:
GHS criteria not met
Remarks:
not eye irritating
Conclusions:
Based on these results 4,4’-Isopropylidenediphenol, propoxylated (BPA+2PO) does not have to be classified and has no obligatory labelling requirement for eye irritation according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

In an in vivo skin irritation study, rabbits were exposed to 0.5 g of 1,1'-isopropylidenebis(p-phenyleneoxy)dipropan-2 –ol on intact or abraded skin for 24 h under occlusion. Some slight irritation due to effects on erythema is observed directly after exposure. This effect was decreased after 48 hours, mean score of 1. Therefore, it was concluded that the substance does not have to be classified for skin irritation.

Eye

An in vivo eye irritation study is performed according to OECD, EC, EPA and JMAFF test guidelines. Instillation of approximately 48 mg of 1,1'-isopropylidenebis(p-phenyleneoxy)dipropan-2 –ol (a volume of approximately 0.1 mL) into one eye of each of three rabbits resulted in redness of the conjunctivae. The irritation had completely resolved within 24 hours in two animals and within 48 hours in the other animal. No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage. Therefore, the substance is considered to be not irritating to the eyes.

Justification for classification or non-classification

Based on the observed slight irritation of exposed abraded skin after 24h of exposure, which effect was decreased after another 48h (mean score is 1 at 72h ),1,1'-isopropylidenebis(p-phenyleneoxy)dipropan-2 –oldoes not have to be classified and has no obligatory labelling requirement for dermal irritation according to the:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007),

- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.

 

Based on these results, 1,1'-isopropylidenebis(p-phenyleneoxy)dipropan-2 –ol does not have to be classified and has no obligatory labelling requirement for eye irritation according to the:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007),

- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.