Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Irritation:
- Skin irritation in vivo: not irritating (OECD404; Rosin, maleated)
- Skin corrosion in vitro: not corrosive (OECD 431; TOFA, maleated)
- Skin irritation in vitro: irritating (OECD 439; TOFA, maleated)
- Skin irritation in vivo: not irritating (EPA 560/6-82-001 and EPA 540/9-82-025; TOFA, maleated)
- Eye irritation in vivo: not irritating (EPA 560/6-82-001 and EPA 540/9-82-025; TOFA, maleated)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
9-6-1992 to 26-6-1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test according to guideline under GLP tested with the source substance CAS 68139-89-9. As the tested substance is a component of the target substance, this study is considered valid for read-across.
Qualifier:
according to guideline
Guideline:
other: EPA 560/6-82-001 and EPA 540/9-82-025
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
test on 6 animals
Principles of method if other than guideline:
according to EPA 560/6-82-001 and EPA 540/9-82-025
GLP compliance:
yes
Species:
rabbit
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: not indicated
- Weight at study initiation: 2.5 to 3.0 kg
- Housing: individual
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
other: coverlet
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
10 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 5X5 cm
- Type of wrap if used: elastic bandage and tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water or IPA
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72
Score:
>= 1 - <= 2
Max. score:
3
Reversibility:
fully reversible within: 10 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 h
Score:
>= 0.2 - <= 1
Max. score:
2
Reversibility:
fully reversible within: 10 days

Animal/scoring

1 h

24 h

48 h

72 h

 

E

O

E

O

E

O

E

O

1

0

0

2

1

0

0

0

0

2

0

0

3

3

1

0

2

2

3

0

0

2

1

1

0

1

2

4

0

0

3

0

2

0

2

0

5

0

0

0

0

1

0

1

1

6

0

0

2

1

2

1

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance is not irritant to skin
Executive summary:

Application of 0.5 mL of the test substance on the rabbit's skin during 4 hours led to slight erythema and oedema. These effects were fully reverible after 10 days. The test substance is considered not irritating to the skin.

Endpoint:
skin irritation / corrosion
Remarks:
in vitro
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
06 November 2012 - 09 November 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test according to guideline under GLP tested with the source substance CAS 68139-89-9. As the tested substance is a component of the target substance, this study is considered valid for read-across.
Qualifier:
according to guideline
Guideline:
OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.40 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Department of Health of the Government of the United Kingdom, 2012
Species:
other: EPISKIN (TM) in vitro Reconstructed Human Epidermis
Type of coverage:
other: in vitro system
Preparation of test site:
other: not applicable
Vehicle:
unchanged (no vehicle)
Controls:
other: 0.9% w/v sodium chloride solution was used as negative control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 µL
- Concentration (if solution): 100%
Duration of treatment / exposure:
2, 60 and 240 min
Details on study design:
APPLICATION
Duplicate tissues were treated with the test item for an exposure period of 3, 60 and 240 minutes minutes. The test item was applied topically to the corresponding tissues ensuring uniform covering. 50 μl of the test item was applied to the epidermis surface. Duplicate tissues treated with 50 μl of 0.9% w/v sodium chloride solution served as the negative controls and duplicate tissues treated with 50 μl of glacial acid served as the positive controls. The plate(s) were kept in the biological safety cabinet at room temperature for 15 minutes.
Cell viability was measured using the MMT assay.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Rinsing was achieved by filling and emptying each tissue insert for approximately 40 seconds using a constant soft stream of PBS to gently remove any residual test item.
- Time after start of exposure: 3, 60 and 240 minutes

SCORING SYSTEM:
For the test item the relative mean tissue viabilities obtained after the 3, 60 and 240 minutes exposure period were compared to the mean of the negative control treated tissues (n=3). The relative mean viabilities were calculated in the following way: Relative mean viability (%) = 100 x mean OD540 of test item/mean OD540 of negative control.
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
mean 240 min
Value:
96.4
Negative controls validity:
valid
Positive controls validity:
valid
Remarks:
mean viability 3.8%
Remarks on result:
no indication of irritation
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
mean 60 min
Value:
96.5
Negative controls validity:
valid
Positive controls validity:
valid
Remarks:
viability 3.8%
Remarks on result:
no indication of irritation
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
mean 3 min
Value:
103.5
Negative controls validity:
valid
Positive controls validity:
valid
Remarks:
viability 3.8%
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
The mean OD540 for the negative control treated tissues was 0.722.
The relative mean tissue viability for the positive control treated tissues was 3.8% relative to the negative control treated.

Results:

Item Exposure time OD540 of
tissues
Mean OD540
of duplicate
tissues
Relative
mean
viability (%)
Negative
Control Item
240 min 0.779 0.772 100*
0.765
Positive
Control Item
240 min 0.028 0.029 3.8
0.029
Test Item 240 min 0.724 0.744 96.4
0.763
60 min 0.815 0.745 96.5
0.674
3 min 0.193 0.799 103.5
0.805

* The mean viability of the negative control tissues is set at 100%

Interpretation of results:
GHS criteria not met
Conclusions:
Fatty acids, tall-oil, maleated did not show corrosive properties in the EPISKIN in vitro test system.

Executive summary:

Fatty acids, tall-oil, maleated was tested in an in vitro study performed according to OECD 431 and GLP using the EPISKIN ™ test system. After a 3, 60 and 240 min exposure time, the resulting relative tissue viability, by measurement of the OD540, was found to be 96.4 – 103.5% compared to values from the untreated control tissues. Therefore, Fatty acids, tall-oil, maleated can be regarded as not corrosive to skin under the conditions of this test.

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
06 February 2013 - 11 February 2013
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test according to guideline under GLP tested with the source substance CAS 68139-89-9. As the tested substance is a component of the target substance, this study is considered valid for read-across.
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Department of Health of the Government of the UK, 2012
Species:
other: EPISKIN (TM) reconstructed human epidermis
Type of coverage:
other: in vitro system
Preparation of test site:
other: not applicable
Vehicle:
unchanged (no vehicle)
Controls:
other: Dulbecco’s Phosphate Buffered Saline (DPBS) with Ca++ and Mg++ was used as the negative control. Sodium Dodecyl Sulphate (SDS) 5% w/v was used as the positive control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 μL
- Concentration (if solution): 100%
Duration of treatment / exposure:
15 min
Details on study design:
TEST SYSTEM
The EPISKINTM model is a three-dimensional reconstructed human epidermis model consisting of adult human-derived epidermal keratinocytes seeded on a dermal substitute consisting of a collagen type I matrix coated with type IV collagen. A highly differentiated and stratified epidermis model is obtained after a 13-Day culture period comprising of the main basal, supra basal, spinous and granular layers and a functional stratum corneum.

APPLICATION
Triplicate tissues were treated with the test item for an exposure period of 15 minutes. The test item was applied topically to the corresponding tissues ensuring uniform covering. 10 μl of the test item was applied to the epidermis surface. Triplicate tissues treated with 10 μl of DPBS served as the negative controls and triplicate tissues treated with 10 μl of SDS 5% w/v served as the positive controls. To ensure satisfactory contact with the positive control item the SDS solution was spread over the entire surface of the epidermis using a pipette tip (taking particular care to cover the centre). After 7-Minutes contact time the SDS solution was re-spread with a pipette tip to maintain the distribution of the SDS for the remainder of the contact period. The plate(s) were kept in the biological safety cabinet at room temperature for 15 minutes.

Cell viability was measured using the MMT assay.

REMOVAL OF TEST SUBSTANCE
- Washing (if done):Rinsing was achieved by filling and emptying each tissue insert for approximately 40 seconds using a constant soft stream of DPBS to gently remove any residual test item. The rinsed tissues were transferred to the second column of 3 wells containing 2 mL of maintenance medium in each well. The rinsed tissues were incubated at 37ºC, 5% CO2 in air for 42 hours.
- Time after start of exposure: 15 min

SCORING SYSTEM:
For the test item the relative mean tissue viabilities obtained after the 15-Minute exposure period followed by the 42-Hour post-exposure incubation period were compared to the mean of the negative control treated tissues (n=3). The relative mean viabilities were calculated in the following way: Relative mean viability (%) = 100 x mean OD540 of test item/mean OD540 of negative control
Irritation / corrosion parameter:
% tissue viability
Value:
33.1
Other effects / acceptance of results:
The standard deviation calculated from individual percentage tissue viabilities of the three identically treated tissues was 2.5%.
The mean OD540 for the negative control treated tissues was 0.822 and the standard deviation value of the percentage viability was 6.9%.
The relative mean tissue viability for the positive control treated tissues was 7.8% relative to the negative control treated tissues and the standard deviation value of the percentage viability was 0.6%.

Results:

Item OD540 of
tissues
Mean OD540
of triplicate
tissues
± SD of
OD540
Relative
individual
tissue
viability (%)
Relative
mean
viability (%)
± SD of
Relative
mean
viability (%)
Negative
Control Item
0.868 0.822 0.056 105.6 100* 6.9
0.759 92.3
0.839 102.1
Positive
Control Item
0.069 0.064 0.005 8.4 7.8 0.6
0.059 7.2
0.065 7.9
Test Item 0.263 0.272 0.021 32 33.1 2.5
0.296 36
0.258 31.4

SD Standard deviation

* The mean viability of the negative control tissues is set at 100%

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Fatty acids, tall-oil, maleated showed irritant properties in the EPISKIN in vitro test system.
Executive summary:

Fatty acids, tall-oil, maleated was tested in an in vitro study performed according to OECD 439 and GLP using the EPISKIN ™ test system. After a 15-min exposure time, the resulting relative tissue viability, by measurement of the OD450, was found to be 33.1% compared to values from the untreated control tissues. Therefore, Fatty acids, tall-oil, maleated can be regarded as irritating to skin under the conditions of this test.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study to OECD protocol and subject to GLP audit tested with the source substance CAS 8050-28-0. Based on the structural similarities and the fact that the target substance is an adduct of the source substance, this study is considered valid for read-across.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ranch Rabbits, Crawley Down, Sussex, UKr
- Age at study initiation:
- Weight at study initiation: 2.55-2.96 kg
- Housing: suspended stainless steel cages
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum):ad lib
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-19 deg C
- Humidity (%): 45-61%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 28-31 May 1991
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Remarks:
Test site moistened with approx. 0.2 mL water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 3x2 cm
- Type of wrap if used: gauze patch, Blendermstrips and and elasticated bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water
- Time after start of exposure: 4 h

SCORING SYSTEM:
Standard EU Erythema/Eschar formation - scale 0-4
Oedema - scale 0-4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 h
Score:
ca. 0.3
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 h
Score:
ca. 0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
No irritant or corrosive response
Interpretation of results:
GHS criteria not met
Conclusions:
Mean erythema score (24 to 72 hours) was 0.1 and mean oedema score (24 to 72 hours) was 0. In this study, rosin, maleated is not a dermal irritant.


Therefore, rosin, maleated is not classified for corrosion/ irritation in Annex I of Directive 67/548/EEC. Based on the absence of any signs of irritation during the study, this material is not classifiable for skin irritation according to UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) or EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.
Executive summary:

In a primary dermal irritation study, three New Zealand White rabbits were dermally exposed to 0.5 grams of rosin, maleated (CAS 8050 -28 -0) for 4 hours using a semi-occlusive dressing. Animals then were observed for 72 hours. Mean erythema and oedema scores were calucated for the 24 to 72 hour time period.Mean erythema score (24 to 72 hours) was 0.1 and mean oedema score (24 to 72 hours) was 0. In this study, rosin, maleated is not a dermal irritant.

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:
weight of evidence
Study period:
7-7-1992 to 17-7-1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test similar to guidance under GLP tested with the source substance CAS 68139-89-9. As the tested substance is a component of the target substance, this study is considered valid for read-across.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
6 animals used
Qualifier:
according to guideline
Guideline:
other: EPA 560/6-82-001 and EPA 540/9-82-025
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: not indicated
- Weight at study initiation: 2.3 to 3.5 kg
- Housing: individual
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
not specified
Controls:
other: untreated eyes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
single application, flushing of the eyes after 24 h observation
Observation period (in vivo):
10 days
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): after 24 h observation

SCORING SYSTEM: Draize

Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 10 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 10 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24-72 h
Score:
1.8
Max. score:
3
Reversibility:
fully reversible within: 10 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-72 h
Score:
1.8
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
other: discharge
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 10 days

Results:

Animal 1 h 24 h 48 h 72 h
  C I Conj Ch Dis C I Conj Ch Dis C I Conj Ch Dis C I Conj Ch Dis
1 0 0 1 2 0 0 0 2 3 0 0 0 2 3 0 0 0 2 2 0
2 0 0 1 2 0 0 0 2 4 0 0 0 2 2 0 0 0 1 0 0
3 0 0 1 2 0 0 0 2 2 0 0 0 1 1 0 0 0 1 0 0
4 0 0 1 2 0 0 0 2 2 0 0 0 1 1 0 0 0 1 0 0
5 0 0 1 2 0 0 0 2 2 0 0 0 1 1 0 0 0 1 0 0
6 0 0 1 2 0 0 0 2 3 0 0 0 1 2 0 0 0 1 0 0
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance is considered not irritating to eyes
Executive summary:

Application of 0.1 mL of the test substance in the rabbit's eye led to redness of the conjunctivae and chemosis. These effects were fully reversible after 10 days. The test substance is considered not irritating to the eyes.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

Data on skin irritation by the compounds Rosin, maleated (CAS 8050-28-0) and TOFA, maleated (CAS 68139-89-9) are used for assessment.

In a primary dermal irritation study performed according to GLP and OECD guideline 404, three New Zealand White rabbits were dermally exposed to 0.5 g of Rosin, maleated for four hours using a semi-occlusive dressing (Life Science Research, 1991). Animals were then observed for 72 hours. Mean erythema and oedema scores were calculated for the 24 to 72 hour time period. The resulting mean erythema and oedema scores were 0.1 and 0, respectively. Thus, rosin, maleated was not found to be irritating to skin.

Fatty acids, tall-oil, maleated was tested according to OECD 431 and GLP using the EPISKIN ™ test system. After a 3, 60 and 240 min exposure time, the resulting relative tissue viability, by measurement of the OD540, was found to be 96.4 – 103.5% compared to values from the untreated control tissues. The same batch of the substance was tested also in an in vitro study performed according to OECD 439 and GLP using the EPISKIN ™ test system. After a 15-min exposure time, the resulting relative tissue viability, by measurement of the OD450, was found to be 33.1% compared to values from the untreated control tissues. Therefore, Fatty acids, tall-oil, maleated can be regarded as not corrosive, but irritating to skin under the conditions of this test.

In an in vivo test TOFA, maleated was tested in accordance with GLP and EPA 560/6-82-001 and EPA 540/9-82-025 (US Testing Company, 1992).Application of 0.5 mL of the test substance on the skin of six New Zealand White rabbits for four hours led to slight erythema and oedema. As these effects were fully reversible after 10 days,TOFA, maleated was considered to be not irritating to the skin in vivo.

As the available in vivo data on the compounds Rosin, maleated and TOFA, maleated did not indicate any irritation properties, the same result could be also expected for the substance Reaction products of tall oil fatty acids and tall oil rosin with maleic anhydride.

 

Eye

Eye irritation by Reaction products of tall oil fatty acids and tall oil rosin with maleic anhydride is evaluated based on the data of the major compound TOFA, maleated, which was tested in accordance with EPA 560/6-82-001 and EPA 540/9-82-025 and GLP (US Testing Company, 1992). 0.1 mL of the test substance was instilled into the eyes of six New Zealand White rabbits and washed away after 24 h. The observation period was 10 days. The resulting mean reading scores for cornea, iris, conjunctivae, chemosis and discharge were 0, 0, 1.8, 1.8 and 0, respectively. Therefore,TOFA, maleated is not found to be an eye irritant and consequently the same result could be also expected for the substance Reaction products of tall oil fatty acids and tall oil rosin with maleic anhydride.


Justification for classification or non-classification

The available data on skin and eye irritation of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.