Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Read-across: OECD 471, GLP, Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 102 (+/- S9), negative

Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Please refer to the Read-across statement attached under section 13.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This Read-Across is based on the hypothesis that the target and the source substances have similar environmental fate and (eco)toxicological properties, because both substances have the same common compound octyl sulfonate while another main constituent of the target substance octyl disulfonate is considered to have similar level of toxicity as octyl sulfonate. Other non-common compounds represented by impurities are considered not to influence the read-across validity because they are either structurally identical in the target and in the source substances or, if different, do not contribute to the toxicity effects because they are also anionic sulfonates with the same functional groups and their content is very low.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to the Read-across statement attached under section 13.

3. ANALOGUE APPROACH JUSTIFICATION
PAS category members are predicted to be non-mutagenic based on structural and chemical similarity with the other two sub-groups of ANS category - alkyl sulfates and the α-olefin sulfonates (SIDS, 2007). All ANS category members were non-mutagenic in numerous in vitro and in vivo studies. The source chemical was also non-mutagenic in the bacterial mutagenicity test.
Since the main constituents and most of the impurities of the target substance are also anionic surfactants with the same functional groups and the same length of hydrophobic carbon octyl chain, the same mode of toxicological action is expected for the target and the source substances. The constituents of the target substance do not possess functional groups associated with other modes of action or toxicity effects. Toxicokinetic behavior of the constituents of the target substance is expected to be essentially the same as that of the source substance. The second main constituent octyl disulfonate does not bear mutagenicity potential because it has no functional groups associated with binding to DNA. There are no structural alerts responsible for DNA binding and leading to mutations as profiled by the general mechanistic profiling methods “DNA binding by OECD” and by “DNA binding by OASIS” and by all endpoint specific methods related to DNA binding included into the OECD QSAR Toolbox. Thus, mutagenicity is not likey. The impurities are also structurally similar to the main constituents with octyl rest and sulfonate groups at different positions. They have also no functional groups leading to DNA binding and subsequently to mutations or chromosome aberrations. The minor amounts of other impurities (hexadecyl sulfonate, octyl sulfinosulfonate, benzoic acid and tert-butyl alcohol) are not expected to induce mutagenicity because they have no functional groups participating in DNA binding as well.
Therefore, it is predicted that the target substance would not possess mutagenic activity if it was tested in a bacterial mutagenicity test.

4. DATA MATRIX
Please refer to the Read-across statement attached under section 13.
Reason / purpose:
read-across source
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
not applicable
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
not applicable
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
not applicable
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
not applicable
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
not applicable
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: Not examined
- Effects of osmolality: Not examined
- Evaporation from medium: Not examined
- Water solubility: Not examined
- Precipitation: No precipitation of the test item was observed in any tester strain used in experiment I and II (with and without metabolic activation).
- Definition of acceptable cells for analysis: N/A
A test is considered acceptable if for each strain:
- the bacteria demonstrate their typical responses to ampicillin (TA 98, TA 100, TA 102)
- the negative control plates (A. dest.) with and without S9 mix are within the historical control data range outliend by Eurofins
- corresponding background growth on negative control, solvent control and test plates is observed
- the positive controls show a distinct enhancement of revertant rates over the control plate
- at least five different concentrations of each tester strain are analysable.

- Other confounding effects: N/A

RANGE-FINDING/SCREENING STUDIES: N/A

NUMBER OF CELLS WITH MICRONUCLEI : N/A

HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data:
Historical Laboratory Control Data of the Positive Control (in 2014 - 2016) without S9 (-S9):
TA 98 TA 100 TA 1535 TA 1537 TA 102
Substance 4-NOPD NaN3 NaN3 4-NOPD MMS
Conc./plate 10 µg 10 µg 10 µg 40 µg 1 µL ≙ 1.3 mg
Mean 430.7 612.1 792.0 94.5 1729.2
SD 155.5 220.0 299.5 22.7 518.8
Min 141 132 38 35 272
Max 1830 1423 1854 273 3321
RSD [%] 36.1 35.9 37.8 24.0 30.0
n 971 1188 931 929 682

Historical Laboratory Control Data of the Positive Control (in 2014 - 2016) with S9 (+S9)
TA 98 TA 100 TA 1535 TA 1537 TA 102
Substance 2-AA 2-AA 2-AA 2-AA MMS
Mean 1880.5 1727.7 133.9 234.1 801.2
SD 708.5 522.0 134.9 101.4 223.7
Min 70 169 22 26 137
Max 3606 3132 1954 682 3588
RSD [%] 37.7 30.2 100.8 43.3 27.9
n 966 1184 927 925 678

- Negative (solvent/vehicle) historical control data:
Historical Laboratory Control Data of the Negative Control (in 2014 - 2016) without S9 (-S9):
TA 98 TA 100 TA 1535 TA 1537 TA 102
Mean 24.2 90.7 13.8 8.2 270.4
SD 6.7 15.6 6.7 2.9 55.0
Min 11 49 4 3 141
Max 58 155 41 35 472
RSD [%] 27.7 17.2 48.6 35.3 20.3
n 972 1191 929 931 682

Historical Laboratory Control Data of the Negative Control (in 2014 - 2016) with S9 (+S9):
TA 98 TA 100 TA 1535 TA 1537 TA 102
Mean 29.0 96.4 10.5 8.3 339.7
SD 6.8 14.1 4.5 3.1 71.3
Min 15 62 3 3 157
Max 59 160 38 36 586
RSD [%] 23.4 14.6 42.7 37.4 21.0
n 967 1189 925 926 676

ADDITIONAL INFORMATION ON CYTOTOXICITY:
No toxic effects of the test item were noted in tester strain TA 102 up to the highest dose group evaluated (with and without metabolic activation) in experiment I and II.
Toxic effects of the test item were noted in all other tester strains evaluated in the pre-experiment, experiment I and II.
In the pre-experiment toxic effects of the test item were observed in tester strain TA 98 at concentrations of 2000 µg/plate and higher (without metabolic activation) and at a concentration of 4000 µg/plate (with metabolic activation). In tester strain TA 100 toxic effects of the test item were noted at concentrations of 800 µg/plate and higher (without metabolic activation) and at a concentration of 4000 µg/plate (with metabolic activation).
In experiment I toxic effects of the test item were seen in tester strain TA 1535 at a concentration of 5000 µg/plate (without metabolic activation). In tester strain TA 1537 toxic effects of the test item were observed at a concentration of 5000 µg/plate (with and without metabolic activation).
In experiment II toxic effects of the test item were noted in tester strain TA 98 at a concentration of 5000 µg/plate (with and without metabolic activation). In tester strain TA 100 toxic effects of the test item were seen at concentrations of 2500 µg/plate and higher (without metabolic activation) and at a concentration of 5000 µg/plate (with metabolic activation). In tester strains TA 1535 and TA 1537 toxic effects of the test item were observed at concentrations of 2500 µg/plate and higher (with and without metabolic activation).
Remarks on result:
other: predicted result from the source substance

Table 1: Pre-experimental Results (Plate-incorporation Test)

Treatment

Dose (µg/plate)

Mutation factor (toxicity)

 

 

Without S9

 

 

With S9

TA 98

Test item

2.53

1.1

1.1

8.00

1.0

0.8

25.3

1.2

1.1

80

1.4

0.8

253

1.2

0.6

800

1.5

0.8

2000

0.4 [B]

0.7

4000

0.6 [B]

0.5

A dest.

-

1.0

1.0

4-NOPD

10

21.2

-

NaN3

10

-

-

2-AA

2.5

-

54.4

TA 100

Test item

2.53

1.0

0.8

8.00

1.1

1.0

25.3

1.2

0.9

80

1.0

0.9

253

0.8

0.8

800

0.6 [B]

1.0

2000

0.6 [B]

1.0

4000

0.4 [B]

0.8 [B]

A dest.

-

1.0

1.0

4-NOPD

10

-

-

NaN3

10

7.2

-

2-AA

2.5

-

24.1

*(toxicity parameter): B = Background lawn reduced; N = No background lawn

Dose refers to concentration of main constituent.

Table 2: Experiment I Results (Plate-incorporation Test)

Treatment

 Dose

(µg/plate)

Revertant colonies per plate

Mutation factor

Without S9 (mean)

SD

With S9 (mean)

SD

-S9

+S9

TA 98

Test item

2.53

25

2.6

28

9.1

1.1

1.1

8.00

23

6.8

22

6.7

1.0

0.8

25.3

27

4.6

27

0.6

1.2

1.1

80

31

4.4

21

7.5

1.4

0.8

253

26

1.2

15

4.0

1.2

0.6

800

33

2.1

22

7.2

1.5

0.8

2000

9 [B]

8.5

18

7.9

0.4

0.7

4000

13 [B]

2.5

13

6.7

0.6

0.5

A dest.

-

22

8.5

26

4.0

1.0

1.0

4-NOPD

10

466

77.5

/

/

21.2

/

2-AA

2.5

/

/

1415

333.4

/

54.4

TA 100

Test item

2.53

116

15.7

69

5.5

1.0

0.8

8.00

133

2.5

86

3.5

1.1

1.0

25.3

141

12.5

83

17.9

1.2

0.9

80

126

8.6

77

13.1

1.0

0.9

253

94

5.0

73

4.6

0.8

0.8

800

68 [B]

18.8

90

17.9

0.6

1.0

2000

72 [B]

5.5

91

12.9

0.6

1.0

4000

47 [B]

2.5

75 [B]

3.1

0.4

0.8

A dest.

-

121

4.0

89

19.6

1.0

1.0

NaN3

10

874

81.1

/

/

7.2

/

2-AA

2.5

/

/

2152

201.3

/

24.1

TA 1535

Test item

10

19

5.1

17

1.7

1.1

1.1

31.6

16

2.9

16

1.0

0.9

1.0

100

18

6.1

15

5.9

1.1

1.0

316

22

3.5

13

3.1

1.3

0.8

1000

17

0.0

12

3.5

1.0

0.8

2500

17

2.6

14

4.0

1.9

0.9

5000

4 [B]

1.0

14

4.7

0.2

0.9

lA dest.

-

17

46.5

16

4.4

1.0

1.0

NaN3

10

1010

46.5

/

/

60.6

/

2-AA

2.5

/

/

110

13.9

/

6.9

TA 1537

Test item

10

11

1.5

9

1.2

1.0

1.0

31.6

10

0.6

9

0.6

0.9

1.0

100

12

0.6

8

1.2

1.1

0.9

316

13

1.2

8

0.6

1.1

1.0

1000

12

1.0

8

1.2

1.0

1.0

2500

11

1.0

6

0.6

0.9

0.7

5000

2 [B]

1.5

1 [B]

1.0

0.2

0.1

A dest.

-

12

0.6

9

0.6

1.0

1.0

4-NOPD

40

100

15.4

/

8.6

8.6

0

2-AA

2.5

/

/

268

/

/

31.0

TA 102

Test item

10

303

13.0

353

43.7

0.9

0.9

31.6

319

11.9

366

5.1

0.9

0.9

100

332

16.8

352

31.4

1.0

0.9

316

313

44.3

355

47.2

0.9

0.9

1000

349

45.7

394

13.2

1.0

1.0

2500

356

44.0

400

54.2

1.0

1.0

5000

294

17.6

369

11.1

0.9

1.0

A dest.

-

340

28.6

388

35.0

1.0

1.0

MMS

1.3 (mg/plate)

1342

62.6

/

/

3.9

/

2-AA

10

/

/

972

62.1

/

2.5

SD = standard deviation; P = precipitation; B = background lawn reduced; N = no background lawn; C contamination

Mutation factor = mean revertants (test item) / mean revertants (vehicle control)

Table 3: Experiment II Results (Pre-incubation Test)

Treatment

 Dose

(µg/plate)

Revertant colonies per plate

Mutation factor

Without S9 (mean)

SD

With S9 (mean)

SD

-S9

+S9

TA 98

Test item

10

23

6.4

20

0.0

0.9

0.7

31.6

21

1.2

29

8.7

0.9

1.0

100

25

9.1

26

7.2

1.0

1.0

316

28

4.4

25

2.1

1.1

0.9

1000

23

6.1

25

2.3

0.9

0.9

2500

18

2.1

26

4.5

0.7

1.0

5000

5 [B]

2.5

13 [B]

3.1

0.2

0.5

A dest.

-

25

6.0

27

4.5

1.0

1.0

4-NOPD

10

441

94.5

/

/

17.9

/

2-AA

2.5

/

 

1027

 

/

37.6

TA 100

Test item

10

83

11.0

79

6.1

0.9

0.8

31.6

95

4.9

89

5.1

1.0

0.9

100

94

16.0

81

6.4

1.0

0.9

316

92

10.1

93

9.0

1.0

1.0

1000

81

8.5

72

3.2

0.9

0.8

2500

42 [B]

4.9

68

7.8

0.4

0.7

5000

20 [B]

16.1

48 [B]

18.4

0.2

0.5

A dest.

-

94

3.157.8

95

13.1

1.0

1.0

NaN3

10

587

57.8

/

/

6.3

/

2-AA

2.5

/

/

814

142.8

/

8.6

TA 1535

Test item

10

22

0.6

13

2.0

1.1

0.8

31.6

22

2.3

14

0.6

1.2

0.9

100

20

2.1

14

2.0

1.0

0.9

316

19

2.1

15

0.6

1.0

0.9

1000

23

3.2

15

2.1

1.2

0.9

2500

3 [B]

1.5

4 [B]

1.0

0.1

0.3

5000

2 [B]

0.6

1 [B]

0.6

0.1

0.1

A dest.

-

19

1.7

16

 

1.0

1.0

NaN3

10

250

13.1

/

/

13.2

/

2-AA

2.5

/

/

684

85.9

/

42.8

TA 1537

Test item

10

11

1.2

8

1.0

0.9

1.0

31.6

13

1.5

8

1.5

1.1

1.0

100

12

0.6

8

2.3

1.0

1.0

316

12

2.6

8

0.6

1.0

1.0

1000

11

0.6

9

0.6

0.9

1.1

2500

5 [B]

0.6

4 [B]

3.1

0.4

0.5

5000

2 [B]

1.0

0 [B]

1.5

0.2

0.0

A dest.

-

12

2.0

8

0.6

1.0

1.0

4-NOPD

40

111

8.6

/

/

9.3

/

2-AA

2.5

/

/

87

4.0

/

10.9

 

TA 102

Test item

10

268

5.5

359

39.2

1.0

0.9

31.6

281

23.9

379

12/1

1.0

1.0

100

262

17.4

359

6.7

1.0

0.9

316

243

14.0

329

31.0

0.9

0.8

1000

308

25.4

354

30.1

1.1

0.9

2500

308

16.3

391

21.0

1.1

1.0

5000

193

12.1

385

16.5

0.7

1.0

A dest.

-

275

27.5

389

2.5

1.0

1.0

MMS

1.3 (mg/plate)

744

78.4

/

/

2.7

/

2-AA

10

/

/

866

95.6

/

2.2

SD = standard deviation; P = precipitation; B = background lawn reduced; N = no background lawn; C contamination

Mutation factor = mean revertants (test item) / mean revertants (vehicle control)

No biologically relevant increases in revertant colony numbers of any of the five tester strains were observed following treatment with the test item at any concentration level, neither in the presence nor absence of metabolic activation in experiment I and II.

All criteria of validity were met. The negative control plates (A. dest.) with and without S9 mix are within the historical control data range.The reference mutagens induced a distinct increase of revertant colonies indicating the validity of the experiments.

Conclusions:
The source substance sodium octane-1-sulfonate is considered to be non-mutagenic under the experimental conditions of this bacterial reverse mutation assay. The substance does not meet the criteria for classfication in accordance with GHS or Regulation (EC) No 1272/2008 (CLP). The same result is predicted for the target substance.
Executive summary:

In accordance with OECD 471, the source substance sodium octane-1-sulphonate was tested for it's potential to induce gene mutations. A plate incorporation test and pre-incubation test was conducted with the Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 102.

In three independent experiments several concentrations of the test item were used. Each assay was conducted with and without metabolic activation. The concentrations, including the controls, were tested in triplicate.

The following concentrations referring to the main constituent of the test item were prepared and used in the experiments:

Pre-Experiment (Part of Experiment I):

2.53, 8.00, 25.3, 80.0, 253, 800, 2000 and 4000 µg/plate (TA 98 and TA 100)

Experiment I:

10.0, 31.6, 100, 316, 1000, 2500 and 5000 µg/plate (TA 1535, TA 1537 and TA 102)

Experiment II:

10.0, 31.6, 100, 316, 1000, 2500 and 5000 µg/plate (TA 98, TA 100, TA 1535, TA 1537 and TA 102)

These concentrations correspond to the following concentrations of the test item:

Pre-Experiment (Part of Experiment I):

3.16, 10.0, 31.6, 100, 316, 1000, 2500 and 5000 µg/plate (TA 98 and TA 100)

Experiment I:

12.5, 39.5, 125, 395, 1250, 3125 and 6250 µg/plate (TA 1535, TA 1537 and TA 102)

Experiment II:

12.5, 39.5, 125, 395, 1250, 3125 and 6250 µg/plate (TA 98, TA 100, TA 1535, TA 1537 and TA 102).

No precipitation of the test item was observed in any tester strain used in experiment I and II (with and without metabolic activation).

No toxic effects of the test item were noted in tester strain TA 102 up to the highest dose group evaluated (with and without metabolic activation) in experiment I and II.

Toxic effects of the test item were noted in all other tester strains evaluated in the pre-experiment, experiment I and II.

In the pre-experiment toxic effects of the test item were observed in tester strain TA 98 at concentrations of 2000 μg/plate and higher (without metabolic activation) and at a concentration of 4000 μg/plate (with metabolic activation). In tester strain TA 100 toxic effects of the test item were noted at concentrations of 800 μg/plate and higher (without metabolic activation) and at a concentration of 4000 μg/plate (with metabolic activation).

In experiment I toxic effects of the test item were seen in tester strain TA 1535 at a concentration of 5000 μg/plate (without metabolic activation). In tester strain TA 1537 toxic effects of the test item were observed at a concentration of 5000 μg/plate (with and without metabolic activation).

In experiment II toxic effects of the test item were noted in tester strain TA 98 at a concentration of 5000 μg/plate (with and without metabolic activation). In tester strain TA 100 toxic effects of the test item were seen at concentrations of 2500 μg/plate and higher (without metabolic activation) and at a concentration of 5000 μg/plate (with metabolic activation). In tester strains TA 1535 and TA 1537 toxic effects of the test item were observed at concentrations of 2500 μg/plate and higher (with and without metabolic activation).

No biologically relevant increases in revertant colony numbers in any of the five tester strains were observed following treatment with the test item at any concentration level, neither in the presence nor absence of metabolic activation in experiment I and II.

In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item did not cause gene mutations by base pair changes or frameshifts in the genome of the tester strains used. All criteria of validity were met. Therefore, the test item is considered to be non-mutagenic in this bacterial reverse mutation assay.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In accordance with OECD 471, the source substance sodium octane-1-sulphonate was tested for it's potential to induce gene mutations. A plate incorporation test and pre-incubation test was conducted with the Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537 and TA 102.

In three independent experiments several concentrations of the test item were used. Each assay was conducted with and without metabolic activation. The concentrations, including the controls, were tested in triplicate.

The following concentrations referring to the main constituent of the test item were prepared and used in the experiments:

Pre-Experiment (Part of Experiment I):

2.53, 8.00, 25.3, 80.0, 253, 800, 2000 and 4000 µg/plate (TA 98 and TA 100)

Experiment I:

10.0, 31.6, 100, 316, 1000, 2500 and 5000 µg/plate (TA 1535, TA 1537 and TA 102)

Experiment II:

10.0, 31.6, 100, 316, 1000, 2500 and 5000 µg/plate (TA 98, TA 100, TA 1535, TA 1537 and TA 102)

These concentrations correspond to the following concentrations of the test item:

Pre-Experiment (Part of Experiment I):

3.16, 10.0, 31.6, 100, 316, 1000, 2500 and 5000 µg/plate (TA 98 and TA 100)

Experiment I:

12.5, 39.5, 125, 395, 1250, 3125 and 6250 µg/plate (TA 1535, TA 1537 and TA 102)

Experiment II:

12.5, 39.5, 125, 395, 1250, 3125 and 6250 µg/plate (TA 98, TA 100, TA 1535, TA 1537 and TA 102).

No precipitation of the test item was observed in any tester strain used in experiment I and II (with and without metabolic activation).

No toxic effects of the test item were noted in tester strain TA 102 up to the highest dose group evaluated (with and without metabolic activation) in experiment I and II.

Toxic effects of the test item were noted in all other tester strains evaluated in the pre-experiment, experiment I and II.

In the pre-experiment toxic effects of the test item were observed in tester strain TA 98 at concentrations of 2000 μg/plate and higher (without metabolic activation) and at a concentration of 4000 μg/plate (with metabolic activation). In tester strain TA 100 toxic effects of the test item were noted at concentrations of 800 μg/plate and higher (without metabolic activation) and at a concentration of 4000 μg/plate (with metabolic activation).

In experiment I toxic effects of the test item were seen in tester strain TA 1535 at a concentration of 5000 μg/plate (without metabolic activation). In tester strain TA 1537 toxic effects of the test item were observed at a concentration of 5000 μg/plate (with and without metabolic activation).

In experiment II toxic effects of the test item were noted in tester strain TA 98 at a concentration of 5000 μg/plate (with and without metabolic activation). In tester strain TA 100 toxic effects of the test item were seen at concentrations of 2500 μg/plate and higher (without metabolic activation) and at a concentration of 5000 μg/plate (with metabolic activation). In tester strains TA 1535 and TA 1537 toxic effects of the test item were observed at concentrations of 2500 μg/plate and higher (with and without metabolic activation).

No biologically relevant increases in revertant colony numbers in any of the five tester strains were observed following treatment with the test item at any concentration level, neither in the presence nor absence of metabolic activation in experiment I and II.

In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item did not cause gene mutations by base pair changes or frameshifts in the genome of the tester strains used. All criteria of validity were met. Therefore, the test item is considered to be non-mutagenic in this bacterial reverse mutation assay.

Justification for classification or non-classification

Based on the available data on the source substance the registered substance does not need to classified according to Regulation (EC) no 1272/2008.