Registration Dossier

Administrative data

Description of key information

OECD 431 and 439 (BASF SE, 2015): not corrosive but skin irriation potential 
EpiOcular(TM) test (BASF SE, 2015): no potential for eye irriation

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion
Remarks:
in vitro
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP- and guideline-conformant study
Qualifier:
according to guideline
Guideline:
OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Qualifier:
according to guideline
Guideline:
OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)
GLP compliance:
yes (incl. QA statement)
Remarks:
testing lab
Species:
other: not applicable (in vitro test system)
Strain:
other: not applicable (in vitro test system)
Type of coverage:
other: not applicable (in vitro test system)
Preparation of test site:
other: not applicable (in vitro test system)
Controls:
other: not applicable (in vitro test system)
Duration of treatment / exposure:
see "Any other information on materials and methodes incl. tables"
Observation period:
see "Any other information on materials and methodes incl. tables"
Number of animals:
not applicable (in vitro test system)
Irritation parameter:
other: mean tissue viability
Basis:
other: corrosion test
Time point:
other: 3 min
Score:
105
Remarks on result:
other: CV 10.4%
Irritation parameter:
other: mean tissue viability
Basis:
other: corrosion test
Time point:
other: 1 hour
Score:
94.6
Remarks on result:
other: CV 5.9%
Irritation parameter:
other: mean tissue viability
Basis:
other: irritation test
Time point:
other: 1 hour + 42 hours recovery
Score:
44.1
Remarks on result:
other: high variation (27.6%), therefore repetition
Irritation parameter:
other: mean tissue viability
Basis:
other: irritation test
Time point:
other: 1 hour + 42 hours recovery
Score:
32.1
Remarks on result:
other: value for inter-tissue variance was out of acceptance range, therefore repetiton
Irritation parameter:
other: mean tissue viability
Basis:
other: irritation test
Time point:
other: 1 hour + 42 hours recovery
Score:
9.8
Remarks on result:
other: CV 54.9%, however study was considered acceptable

The test substance was not able to reduce MTT directly.

No reduction of viability was observed in the corrosion test. The irritation test was conducted as four separate tests, one of which was disregarded due to a technical error. The viability of test substance treated samples was 44.1±27.6%, 32.1± 59.7%, and 9.8 ± 54.9%. Although the coefficient of variation is high, overall the data are sufficient to assess the irritation potential of the test substance.

The following data were obtained from the corrosion test:

exposure period 3 min

Test substance

 

tissue 1

tissue 2

mean

OD

CV [%]

NC

mean OD570

1.891

1.837

1.864

0.038

 

Viability

101.4

98.6

100.0

2.0

2.0

1,3,5-Benzenetricarboxylic accid, copper (2+) salt (2:3)

mean OD570

1.827

2.117

1.972

0.205

 

Viability

98.0

113.6

105.8

11.0

10.4

PC

mean OD570

0.246

0.265

0.255

0.013

 

Viability

13.2

14.2

13.7

0.7

5.3

 

exposure period 1 hour

Test substance

 

tissue 1

tissue 2

mean

OD

CV [%]

NC

mean OD570

2.189

2.266

2.227

0.054

 

Viability

98.3

101.7

100.0

2.4

2.4

1,3,5-Benzenetricarboxylic accid, copper (2+) salt (2:3)

mean OD570

2.195

2.018

2.107

0.125

 

Viability

98.6

90.6

94.6

5.6

5.9

PC

mean OD570

0.237

0.138

0.187

0.070

 

Viability

10.6

6.2

8.4

3.1

37.4

 

The following data were obtained from irritation testing:

1sttest run

Test substance

 

tissue 1

tissue 2

tissue 3

mean

OD

CV [%]

NC

mean OD570

2.158

2.139

2.157

2.151

0.011

 

Viability

100.3

99.4

100.3

100.0

0.5

0.5

1,3,5-Benzenetricarboxylic accid, copper (2+) salt (2:3)

mean OD570

0.653

1.151

1.041

0.948

0.262

 

Viability

30.3

53.5

48.4

44.1

12.2

27.6

PC

mean OD570

0.092

0.072

0.077

0.080

0.010

 

Viability

4.3

3.4

3.6

3.7

0.5

13.0

 

4thtest run

Test substance

 

tissue 1

tissue 2

tissue 3

mean

OD

CV [%]

NC

mean OD570

2.070

1.918

1.962

1.983

0.078

 

Viability

104.4

96.7

98.9

100.0

3.9

3.9

1,3,5-Benzenetricarboxylic accid, copper (2+) salt (2:3)

mean OD570

0.071

0.258

0.252

0.193

0.106

 

Viability

3.6

13.0

12.7

9.8

5.4

54.9

PC

mean OD570

0.068

0.065

0.061

0.065

0.004

 

Viability

3.4

3.3

3.1

3.3

0.2

5.5

Viability is depicted as [% of NC]

NC, negative control

PC, positive control

CV, coefficiton of variation

 

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP- and guideline-conformant study
Qualifier:
according to guideline
Guideline:
other: OECD (2014a) Draft Proposal for a New Test Guideline (EpiOcular(TM))
Qualifier:
according to guideline
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
Principles of method if other than guideline:
EpiOcular(TM): The objective of this in vitro test is to assess the eye irritation potential of the test substance using the reconstructed human ocular model EpiOcular(TM). The test is based on the experience that irritant chemicals produce cytotoxicity in human reconstructed cornea after a short term topical exposure. After application of the test material to the surface of the EpiOcularTM tissue the induced cytotoxicity (= loss of viability) is measured by a colorimetric assay.
GLP compliance:
yes (incl. QA statement)
Remarks:
testing lab.
Species:
other: not applicable (in vitro test)
Strain:
other: not applicable (in vitro test)
Vehicle:
unchanged (no vehicle)
Controls:
other: not applicable (in vitro test)
Duration of treatment / exposure:
see "Any other information on materials and methods incl. tables"
Observation period (in vivo):
see "Any other information on materials and methods incl. tables"
Number of animals or in vitro replicates:
not applicable (in vitro test)
Irritation parameter:
in vitro irritation score
Run / experiment:
mean viability of three tissues [%]
Value:
82.7
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid

The test substance was not able to reduce MTT directly.

Only a slight reduction of viability was observed in the EpiOcularTM test. Since the data from the EpiOcularTM test alone were sufficient for assessment of the eye irritation potential of the test substance, no further tests were conducted.

The following data were obtained from the EpiOcularTMtest:

Test substance

 

tissue 1

tissue 2

mean

CV [%]

NC

mean OD570

1.476

1.518

1.497

 

Viability

98.6

101.4

100.0

2.8

1,3,5-Benzenetricarboxylic accid, copper (2+) salt (2:3)

mean OD570

1.268

1.207

1.237

 

Viability

84.7

80.7

82.7

4.0

PC

mean OD570

0.296

0.352

0.324

 

Viability

19.7

23.5

21.6

3.8

Viability is depicted as [% of NC]

NC, negative control

PC, positive control

CV, coefficiton of variation

 

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In vitro skin irritation and corrosion testing was performed with a turnkey strategy. Corrosivity and potential for irritation were assessed as ability of the test substance to decrease tissue viability. While the test substance was not corrosive (tissue viability >90%) , it was irritating in the EpiDerm(TM) assay under the test conditions chosen (tissue viability <50%).

Eye irritation testing was performed in vitro with the EpiOcular(TM) test, in which the irritation potential of the test substance is assessed as its ability to decrease tissue viability. The mean tissue viability was >80%, therefore the test substance did not show potential for eye irriation in the EpiOcular(TM) test under the test conditions chosen.


Justification for selection of skin irritation / corrosion endpoint:
GLP- and guideline-conformant study

Justification for selection of eye irritation endpoint:
GLP- and guideline-conformant study

Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

1,3,5-Benzenetricarboxylic acid, copper(2+) salt showed a skin irritation potential in the EpiDerm(TM) test in vitro. Therefore, according to Regulation (EU) 1272/2008 (CLP) classification as irritating to skin (Cat. 2, H315) is justified.

1,3,5-Benzenetricarboxylic acid, copper(2+) salt did not show eye irriation potential. Therefore, non-classification for eye damage is warranted.