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Description of key information

Due to the results of in vitro skin corrosion and irritation studies on reconstructed human epidermis (EST-1000) the substance should be regarded as skin irritant.
As a consequence of read-across from a study performed with Bisphenol A, the substance has to be considered as inducer of irreversible effects to the eyes of rabbits and as irritating to the respiratory tract.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
GLP compliance:
yes
Test system:
human skin model
Source species:
human
Cell source:
other: in vitro reconstructed human epidermis EST-1000 (Cell Systems, St. Katharinen, Germany)
Details on test system:
The model used for this study has a functional statum corneum with an underlying layer of living cells. The barrier function of the stratum corneum is adequate, as has been shown by the supplier.
Control samples:
yes, concurrent vehicle
yes, concurrent positive control
Amount/concentration applied:
30 mg per insert, moistened with 50 µL physiological saline
Duration of treatment / exposure:
20 min
Duration of post-treatment incubation (if applicable):
42 hours
Number of replicates:
3
Irritation / corrosion parameter:
% tissue viability
Value:
1.83
Vehicle controls validity:
valid
Positive controls validity:
valid

Bisphenolharz spezial was characterised by a significant impact on cell viability. Thus, Bisphenolharz spezial should be regarded as skin irritant according to UN GHS category 2.

 Sample No.  Test item  % Viability
 1 -3  Negative Control (0.9% NaCl)  100.00
 4 -6  Positive Control (0.5% SDS)  1.71
 7 -9  Bisphenolharz spezial  1.83
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Remarks:
Migrated information
Executive summary:

The test item was tested in an in vitro skin irritation test on reconstructed human epidermis (EST-1000) according to EU method B.46 (Skin Irritation). The EST-1000 model provides a functional stratum corneum with an underlying layer of living cells. The test item was applied pure as powder, moistened with physiological saline, for 20 min followed by a 42 hour incubation time. Cell viability was determined by the MTT method. The test item was characterised by a significant impact on cell viability in this in vitro skin irritation study. Cell viability was reduced to 1.83% compared to negative control cultures (100%). Thus, the test item should be regarded as skin irritant according to UN GHS category 2.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline Study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
-General information: Three male animals approximately 7-9 months of age with initial body weights of 2.3-2.4 kg were used.
-Diet: Ad libitum before and after the exposure period. Standard rabbit diet of Altromin 2023 (ALTROMIN GmbH, D-32791 Lage/Lippe). Food was analysed at least twice per year for contaminants.
-Drinking water: Water was offered ad libitum before and after the exposure period. Water samples were analysed twice per year for contaminants and once per year for a bacteriological investigation.
-Housing: Before the exposure period and 8 hours after the exposure period, animals were kept singly in cages measuring 425 mm x 600 mm x 380 mm (manufacturer: Dipl. Ing. W. EHRET GmbH, D-16352 Schonwalde). During the exposure period and for 8 hours afterwards, animals were kept singly in restrainers which allowed free movement of the head but prevented a complete body turn and wiping of the eyes by the paws and excluded irritation of the eye by excrement and urine.
-Acclimation period: At least 20 days.

ENVIRONMENTAL CONDITIONS
-Temperature: 17-23 degrees C
-Humidity: 30-70%
-Photoperiod: 12 hours light (150 lux at approximately 1.5 meter room height)/12 hours dark
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
The test material was ground to a fine dust and 100 mg were applied per animal.
Duration of treatment / exposure:
Single instillation into the conjunctival sac, after which the lids were gently held together for one second.
Observation period (in vivo):
28 days
Number of animals or in vitro replicates:
3 males
Details on study design:
Three male Himalayan rabbits were treated with 100 mg BPA by a single instillation into the conjunctival sac of the right eye. The eye lids were then gently held together for one second to prevent loss of the material. The left eye, which remained untreated, served as a control. The eyes of the animals were not rinsed. The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1, 24, 48, and 72 hours and 4 to 28 days after administration. The eye reactions were observed and registered. At 24 hours, 7, 14, and 28 days after administration, the eyes were treated with Fluorescein SE Thilo eye drops (Alcon Pharma GmbH, D-79108, Freiburg, Germany) and examined.
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #1
Time point:
other: until day
Score:
9
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #2
Time point:
other: until day
Score:
13
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #3
Time point:
other: until day
Score:
28
Max. score:
1
Reversibility:
not fully reversible within: 28 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: until day
Score:
11
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: until day
Score:
28
Max. score:
1
Reversibility:
not fully reversible within: 28 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
other: until day
Score:
1
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
other: until day
Score:
4
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
other: until day
Score:
6
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal: #1 and #2
Time point:
other: day
Score:
1
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: until day
Score:
4
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: until day
Score:
6
Max. score:
1
Reversibility:
fully reversible
Irritant / corrosive response data:
Corneal opacity (grade 1) was observed in all three animals 1 hour to 9 days after instillation; in animal #2 until 13 days; and in animal #3 until 28 days after instillation. The fluorescein test performed after 24 hours revealed corneal staining in all 3 rabbits (whole surface). The fluorescein test performed after 7 days revealed corneal staining in animal #1 and animal #2 (3/4 of the corneal surface) and in animal #3 (whole surface). The fluorescein tests performed after 14 and 21 days revealed corneal staining in animal #3 (1/2 of the corneal surface). An irritation of the iris (grade 1) was observed in all three animals one hour to 9 days after instillation, and in animal #2 until 11 days and in animal #3 until 28 days after instillation. Conjunctival redness (grade 1) was observed in all animals one to 24 hours after instillation, in animal #2 until 4 days and in animal #3 until 6 days after instillation. Conjunctival chemosis (grade 1) was observed in animal #1 and animal #2 24 hours after instillation and in animal #3 one hour to 4 days (grade 2) and 5 and 6 days (grade 1) after instillation. Whitish deposits in the conjunctival sac (probably pus) were observed in animal #2 and animal #3 from 72 hours to 5 days after instillation.
Other effects:
There were no systemic intolerance reactions.
Interpretation of results:
other: irreversible effects: corneal opacity (grade 1) and iris irritation (grade 1) in 1 of 3 animals within an observation period of 28 days
Conclusions:
The authors concluded that Bisphenol A induced grade 1 corneal opacity, corneal staining, grade 1 iris irritation, grade 1 conjunctival redness, and grades 1 and 2 conjunctival chemosis. Although the irritating effects were only slight to moderate, Bisphenol A induced irreversible effects in 1 of 3 animals (corneal opacity grade 1, and iris irritation grade 1) within an observation period of 28 days.
Executive summary:

In an eye irritation study with Bisphenol A performed according to OECD 404 on three rabbits, the test substance induced grade 1 corneal opacity, corneal staining, grade 1 iris irritation, grade 1 conjunctival redness, and grades 1 and 2 conjunctival chemosis. Although the irritating effects were only slight to moderate, the effects (corneal opacity grade 1, and iris irritation grade 1) were not reversible in 1 of 3 animals within the observation period of 28 days. Therefore, Bisphenol A has to be considered as inducing irreversible effects to the eyes of rabbits.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

The test substance was investigated in an in vitro skin irritation test on reconstructed human epidermis (EST-1000) according to EU method B.46 (Skin Irritation). The EST-1000 model provides a functional stratum corneum with an underlying layer of living cells. The test item was applied pure as powder, moistened with physiological saline, for 20 min followed by a 42 hour incubation time. Cell viability was determined by the MTT method. The test substance was characterised by a significant impact on cell viability in this in vitro skin irritation study. Cell viability was reduced to 1.83% compared to negative control cultures (100%). Thus, the product should be regarded as skin irritant.

The test substance did not show corrosive properties in an in vitro skin corrosion test on reconstructed human epidermis according to OECD TG 431.

The substance contains up to 50% Bisphenol A (4,4'-isopropylidenediphenol). Bisphenol A is classified as an inducer of irreversible damage to eyes. Due to animal welfare reasons no eye irritation study was initiated for the substance but a read-across of results out of the key Bisphenol A eye irritation study was done. In an eye irritation study with Bisphenol A performed according to OECD TG 404 on three rabbits, the test substance induced grade 1 corneal opacity, corneal staining, grade 1 iris irritation, grade 1 conjunctival redness, and grades 1 and 2 conjunctival chemosis. Although the irritating effects were only slight to moderate, the effects (corneal opacity grade 1, and iris irritation grade 1) were not reversible in 1 of 3 animals within the observation period of 28 days. Therefore, Bisphenol A has to be considered as inducing irreversible effects to the eyes of rabbits. As a consequence of read-across, the registered substance has to be considered as inducer of irreversible effects to the eyes of rabbits.

No data is available for inhalation toxicity of the substance. Based on read-across with 4,4’isopropylidenediphenol (Bisphenol A), the main constituent of the registered substance, the substance should be considered as irritating to the respiratory tract.

Justification for classification or non-classification

Due to the results of in vitro skin corrosion and irritation studies on reconstructed human epidermis (EST-1000) the registered substance should be regarded as skin irritant category 2 according to 1272/2008 EC (Skin Irrit 2; H315).

As a consequence of read-across from a study performed with Bisphenol A, the main constituent of the registered substance, the registered substance has to be considered as inducer of irreversible effects to the eye Category 1 according to 1272/2008 EC (Eye Damage 1, H318).

No data are available for respiratory tract irritation of the substance. Based on read-across with 4,4’isopropylidenediphenol (Bisphenol A), the main constituent of the registered substance, the substance can be considered as not toxic after inhalative exposure but as irritating to the respiratory tract and classified accordingly with STOT SE 3 (H335) according to 1272/2008 EC.

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