Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Bacterial gene mutation (OECD 471): negative

Gene mutation in mammalian cells (equivalent to OECD 476): negative

DNA damage repair (equivalent to OECD 482): negative

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
7 - 21 May 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
adopted in 1983
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Version / remarks:
adopted in 1984
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
adopted in 1997
Deviations:
yes
Remarks:
only four S. typhimurium strains (additional E. coli WP2 strains or S. typhimurium TA 102 is missing)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Target gene:
his operon
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254
Test concentrations with justification for top dose:
First experiment: 8, 40, 200, 1000 and 5000 µg/plate with and without metabolic activation
Second experiment: 50, 100, 200, 240, 400 and 800 µg/plate with and without metabolic activation
Vehicle / solvent:
- Vehicle/solvent used: water
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: sodium azide (10 µg/plate, -S9, TA 1535), nitrofurantoin (0.2 µg/plate, -S9, TA 100), 4-nitro-1,2-phenylene diamine (10 µg/plate, -S9, TA 1537 and 0.5 µg/plate, -S9, TA 98), 2-aminoanthracene (3 µg/plate, +S9, all strains)
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 h

NUMBER OF REPLICATIONS: 4 replications each in 2 independent experiments

DETERMINATION OF CYTOTOXICITY
- Method: background growth; cloning efficiency; other: titer
Evaluation criteria:
A reproducible and dose-related increase in mutant counts of at least one strain is considered to be a positive result. For TA 1535, TA 100 and TA 98 this increase should be about twice the amount of negative controls, whereas for TA 1537, at least a threefold increase should be reached. Otherwise, the result is evaluated as negative. However, these guidelines may be overruled by good scientific judgement. In case of questionable results, investigation should continue, possibly with modifications, until a final evaluation is possible.
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 800 µg/plate and above
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 400 µg/plate and above
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 800 µg/plate and above
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 800 µg/plate and above
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Water solubility: The test substance was soluble in water.

HISTORICAL CONTROL DATA
Summaries of historical negative and positive controls of experiments performed within 6 months each from January 1987 to June 1991 are provided. Please refer to Table 1 under "Any other informations on results incl. tables" for the summarized historical control data of January to June 1991.

Table 1: Summary of historical negative and positive controls of experiments performed from January to June 1991

Compound

S9 mix

Strain

TA 1535

TA 100

TA 1537

TA 98

median

semi-Q range

median

semi-Q range

median

semi-Q range

median

semi-Q range

water

-

12

3

111

10

9

2

28

5

Na azide

-

623

102

 

 

 

 

 

 

NF

-

 

 

398

56

 

 

 

 

4-NPDA

-

 

 

 

 

49

10

89

20

30% water

+

16

3

252

15

12

2

38

7

2-AA

+

182

33

800

163

86

24

472

105

Na azide = sodium azide, NF = nitrofurantoin, 4-NPDA = 4-nitro-1,2-phenylenediamine

 

Table 2: First experiment - Average revertants per plate in tester strains TA98, TA 100, TA 1535 and TA 1537 without S9-mix

Concentration [µg/plate]

Revertants/plate [mean]

TA 1535

TA 100

TA 1537

TA 98

0

10

130

11

27

8

12

140

13

32

40

11

135

11

29

200

11

128

10

31

1000

6

44

2

19

5000

0

0

0

0

Na-azide1

479

 

 

 

NF2

 

8

 

 

4-NPDA3

 

 

55

146

Positive controls:

 1Sodium-azide, 10 µg/plate (only TA 1535)

2Nitrofurantoin, 0.2 µg/plate (only TA 100)

34-nitro-1,2-phenylenediamine, 10 µg/plate (only TA 1537), 0.5 µg/plate (only TA 98)

 

Table 3: First experiment - Average revertants per plate in tester strains TA98, TA 100, TA 1535 and TA 1537 with S9-mix

Concentration [µg/plate]

Revertants/plate [mean]

TA 1535

TA 100

TA 1537

TA 98

0

18

156

13

37

8

15

143

12

38

40

21

161

18

32

200

16

162

12

40

1000

11

102

5

25

5000

0

0

0

0

2-AA4

306

959

121

713

Positive controls:

42-aminoanthracene, 3 µg/plate

 

Table 4: Second experiment - Average revertants per plate in tester strains TA98, TA 100, TA 1535 and TA 1537 without S9-mix

Concentration [µg/plate]

Revertants/plate [mean]

TA 1535

TA 100

TA 1537

TA 98

0

16

121

11

27

50

20

114

13

32

100

15

117

11

29

200

17

118

10

31

400

19

111

2

19

800

12

76

0

0

Na-azide1

809

 

 

 

NF2

 

512

 

 

4-NPDA3

 

 

55

146

Positive controls:

1Sodium-azide, 10 µg/plate (only TA 1535)

2Nitrofurantoin, 0.2 µg/plate (only TA 100)

34-nitro-1,2-phenylenediamine, 10 µg/plate (only TA 1537), 0.5 µg/plate (only TA 98)

 

Table 5: Second experiment - Average revertants per plate in tester strains TA98, TA 100, TA 1535 and TA 1537 with S9-mix

Concentration [µg/plate]

Revertants/plate [mean]

TA 1535

TA 100

TA 1537

TA 98

0

20

172

16

48

50

26

176

13

41

100

2

 

185

15

36

200

25

188

15

44

400

1

176

15

40

800

17

121

6

30

2-AA4

295

1498

100

828

Positive controls:

42-aminoanthracene, 3 µg/plate

Executive summary:

The mutagenic potential of the test substance was tested in the Salmonella/Microsome test according to OECD Guideline 471 (1983) and in compliance with GLP. Tester strains used were the Salmonella typhimurium histidine auxotrophs TA98, TA100, TA 1535 and TA 1537. Liver microsomal enzymes were prepared from at least 6 male Sprague-Dawley or male Wistar rats which had received a peritoneal injection of Aroclor 1254 at 500 mg/kg bw (S9 mix). The test substance was solved in water. In a first experiment, 6 dose levels from 0 - 5000 µg/plate were plated with overnight cultures of TA 98, TA 100, TA 1535 and TA 1537 in the presence or absence of rat S9 mix. As a result, the appropriate maximum dose to be plated in the second experiment was determined to be 800 µg/plate with and without metabolic activation, respectively. In the second experiment the test substance was tested at 5 dose levels (50, 100, 200, 400, 800 µg/plate) along with vehicle control (water) and appropriate positive controls in the absence or presence of rat microsomal enzymes. DMSO was used as vehicle for positive controls. 0.1 mL of test-substance in water or positive control in DMSO were added to 0.1 mL of bacteria solution (grown for 17 hours at 37 °C at 90 rpm) and 0.5 mL S9 mix or buffer (for non-activating tests) were added to 2.0 mL molten top-agar. After incubation for a maximum of 30 s at 45 °C in a water bath and mixing, this solution was poured onto solid agar plates. Four replicates were plated for all dose levels and controls. The plates were incubated at 37 °C for 48 h, before the colonies were counted. A result was evaluated as positive when it caused a doubling in the mean number of revertants per plate in at least one tester strain. This increase must be accompanied by a positive dose response. There was no indication of bacteriotoxic effects of the test substances at doses of up to and including 200 µg/plate. Total bacteria counts were comparable to or only slightly different from the negative controls. No inhibition of growth was noted. Doses at and above 400 µg/plate caused bacteriotoxic effects. None of the four strains tested showed a dose-related and biologically relevant increase in mutant counts over those of the negative controls, with and without metabolic activation. The respective positive controls caused an increase in the number of revertants which proved the sensitivity of the test. Therefore, under the conditions of this study, no indications of mutagenic effects of the test substance could be found at doses up to 800 µg/plate in any of the S. typhimurium strains tested.

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:
Refer to analogue justification document provided in IUCLID section 13
Reason / purpose:
read-across source
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 480 µg/plate and above
Vehicle controls validity:
not examined
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 480 µg/plate and above
Vehicle controls validity:
not examined
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 480 µg/plate and above
Vehicle controls validity:
not examined
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 240 µg/plate and above
Vehicle controls validity:
not examined
Untreated negative controls validity:
valid
Positive controls validity:
valid
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Cytogenicity / micronucleus test in mice (OECD 474): negative

Link to relevant study records
Reference
Endpoint:
genetic toxicity in vivo, other
Remarks:
mammalian somatic cell studies: cytogenicity / bone marrow chromosome aberration and erythrocyte micronucleus
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
key study
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Remarks on result:
other: source, CAS 59-50-7, key rel.2, Herbold 1990
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Remarks on result:
other: source, CAS 59-50-7, rel.2, Herbold 1981
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

A reliable study regarding gene mutation in bacteria is available for the target substance sodium p-chloro-m-cresolate (CAS 15733-22-9); no data are available regarding gene mutation in mammalian cells and in vitro cytogenicity. The assessment was therefore based on studies conducted with the analogue substance p-chloro-m-cresol (CAS 59-50-7) as part of a read across approach, which is in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

 

In vitro:

- Gene mutation in bacteria:

CAS 15733-22-9

The mutagenic potential of the target substance sodium p-chloro-m-cresolate in bacteria was tested in the Salmonella/Microsome test according to OECD Guideline 471 (1983) and in compliance with GLP (Gahlmann, 1991). Tester strains used were the Salmonella typhimurium histidine auxotrophs TA98, TA100, TA 1535 and TA 1537. Liver microsomal enzymes were prepared from at least 6 male Sprague-Dawley or male Wistar rats which had received a peritoneal injection of Aroclor 1254 at 500 mg/kg bw (S9 mix). The test substance was solved in water. In a first experiment, 6 dose levels from 0 - 5000 µg/plate were plated with overnight cultures of TA 98, TA 100, TA 1535 and TA 1537 in the presence or absence of rat S9 mix. As a result, the appropriate maximum dose to be plated in the second experiment was determined to be 800 µg/plate with and without metabolic activation, respectively. In the second experiment the test substance was tested at 5 dose levels (50, 100, 200, 400, 800 µg/plate) along with vehicle control (water) and appropriate positive controls in the absence or presence of rat microsomal enzymes. DMSO was used as vehicle for positive controls. 0.1 mL of test-substance in water or positive control in DMSO were added to 0.1 mL of bacteria solution (grown for 17 hours at 37 °C at 90 rpm) and 0.5 mL S9 mix or buffer (for non-activating tests) were added to 2.0 mL molten top-agar. After incubation for a maximum of 30 s at 45 °C in a water bath and mixing, this solution was poured onto solid agar plates. Four replicates were plated for all dose levels and controls. The plates were incubated at 37 °C for 48 h, before the colonies were counted. A result was evaluated as positive when it caused a doubling in the mean number of revertants per plate in at least one tester strain. This increase must be accompanied by a positive dose response. There was no indication of bacteriotoxic effects of the test substances at doses of up to and including 200 µg/plate. Total bacteria counts were comparable to or only slightly different from the negative controls. No inhibition of growth was noted. Doses at and above 400 µg/plate caused bacteriotoxic effects. None of the four strains tested showed a dose-related and biologically relevant increase in mutant counts over those of the negative controls, with and without metabolic activation. The respective positive controls caused an increase in the number of revertants which proved the sensitivity of the test. Therefore, under the conditions of this study, no indications of mutagenic effects of the test substance could be found at doses up to 800 µg/plate in any of the S. typhimurium strains tested.

 

CAS 59-50-7

The mutagenic potential of the source substancep-chloro-m-cresolwas tested in the Salmonella/Microsome test according to OECD Guideline 471 (1983) and in compliance with GLP. Tester strains used were the Salmonella typhimurium histidine auxotrophs TA98, TA100, TA 1535 and TA 1537. Liver microsomal enzymes were prepared from at least 6 male Sprague-Dawley or male Wistar rats which had received a peritoneal injection of Aroclor 1254 at 500 mg/kg bw (S9 mix). The test substance was solved in ethanol. In a first experiment, 6 dose levels from 0 - 5000 µg/plate were plated with overnight cultures of TA 98, TA 100, TA 1535 and TA 1537 in the presence or absence of rat S9 mix. As a result, the appropriate maximum dose to be plated in the second experiment was determined to be 960 µg/plate with and without metabolic activation, respectively. In the second experiment the test substance was tested at 5 dose levels (30, 60, 120, 240, 480, 960 µg/plate) along with negative control and appropriate positive controls in the absence or presence of rat microsomal enzymes. DMSO was used as vehicle for positive controls. 0.1 mL of test-substance in ethanol or positive control in DMSO were added to 0.1 mL of bacteria solution (grown for 17 hours at 37 °C at 90 rpm) and 0.5 mL S9 mix or buffer (for non-activating tests) were added to 2.0 mL molten top-agar. After incubation for a maximum of 30 s at 45 °C in a water bath and mixing, this solution was poured onto solid agar plates. Four replicates were plated for all dose levels and controls. The plates were incubated at 37 °C for 48 h, before the colonies were counted. A result was evaluated as positive when it caused a doubling in the mean number of revertants per plate in at least one tester strain. This increase must be accompanied by a positive dose response. There was no indication of bacteriotoxic effects of the test substances at doses of up to and including 200 µg/plate. Total bacteria counts were comparable to or only slightly different from the negative controls. No inhibition of growth was noted. Doses at and above 240 µg/plate caused bacteriotoxic effects. None of the four strains tested showed a dose-related and biologically relevant increase in mutant counts over those of the negative controls, with and without metabolic activation. The respective positive controls caused an increase in the number of revertants which proved the sensitivity of the test. Therefore, under the conditions of this study, no indications of mutagenic effects of the test substance could be found at doses up to 960 µg/plate in any of the S. typhimurium strains tested.

 

- Gene mutation in mammalian cells:

The potential of the source substance p-chloro-m-cresol to induce gene mutations at the HPRT locus in Chinese hamster ovarian (CHO; subclone CHO-K1-BH4) cells was assessed in a study performed equivalent to OECD Guideline 476 (2016) and in compliance with GLP (forward mutation assay; Lehn, 1989). The test substance was suspended in DMSO. In a dose range-finding test (cytotoxicity test), 9 dose levels from 1.25 - 320 µg/mL were tested in the presence or absence of rat microsomal enzymes. As a result, the appropriate maximum dose to be plated in the main study would be 300 µg/mL with and without metabolic activation, respectively. The main study for evaluation of mutagenic effects was performed in two independent experiments, using two parallel cultures each. In both experiments cells were treated with concentrations of 50, 100, 150, 200, 250 and 300 µg/mL test substance in the presence in the absence of S9 mix for 6 h. Dimethylbenzanthracene (DMBA) and ethylmethanesulfonate (EMS) were used as positive controls in activation and non-activation assays, respectively. Negative controls included both untreated controls and vehicle (DMSO) controls. Cytotoxic effects were noted at doses of 200 µg/mL and above without metabolic activation and at 100 µg/mL and above with metabolic activation. There was no statistically significant increase in mutant frequency noted at any of the dose levels, under both activating and non-activating conditions. The positive controls EMS and DMBA showed a clear mutagenic effect. According to the results of the study and the relating evaluation criteria, the test substance is considered to be non-mutagenic in the CHO-HGPRT Forward Mutation Assay.

- DNA repair study:

The source substance p-chloro-m-cresol was evaluated for unscheduled DNA synthesis (UDS) in cultured primary rat hepatocytes equivalent to OECD Guideline 482 (1986) and in compliance with GLP (Cifone, 1988). Freshly prepared hepatocytes from male Fischer 344 rats were exposed to 6 concentrations of the test substance ranging from 0.25 to 20 µg/mL in two trials (trial 2: 0.25, 0.5, 2.5, 7.5, 10, 20 µg/mL and trial 3: 2.53, 5.06, 7.58, 10.1, 15.2, 20.2 µg/mL; the first trial was discarded due to extensive cytotoxicity). The test substance as well as the positive control (2-acetylaminofluorene) was solved in DMSO as vehicle. DMSO was used as vehicle control. In addition to the test substance 5 µCi/mL ³H-thymidine was present in the cell culture medium and cells were exposed for 18-19 h in medium with reduced serum content (1% FCS). Three replications were conducted for the UDS assay and duplicate cell cultures were treated for determination of cytotoxicity via trypan blue exclusion. The cells were fixed, washed and air-dried prior to coating in the dark with photographic emulsion. The coated slides were stored at 4°C for 4-10 days and then developed. The slides were then rinsed and stained with haematoxylin/eosin. Grain counting was done manually using a microscope. Selected concentrations represented a good range of cytotoxicity (100.6 - 43% relative survival). High toxicities were observed at dose levels from 20.0 μg/mL to 10.0 μg/mL in the second trial. In the third trial moderate toxicity was observed at 20.2 µg/mL which was the highest concentration chosen for nuclear grain counting. None of the treatments with the test substance in both trial 2 and trial 3 caused nuclear labeling significantly different from the solvent control. Furthermore, no dose-related trend was evident. Thus, under the conditions of the study, the test substance evaluated as inactive in the Rat Primary Hepatocyte UDS Assay.

In vivo:

CAS 59-50-7

- Cytogenicity / micronucleus test in mice:  

The potential of the source substance p-chloro-m-cresol to induce micronuclei in polychromatic erythrocytes (PCE) in the bone marrow of the mouse was assessed in a study performed according to OECD Guideline 474 (1983) and in compliance with GLP (Herbold, 1990). The test substance was suspended in polyethylene glycol 400, which was also used as vehicle control. Five male and five female Bor: NMRI mice per test group received a single intraperitoneal injection of 125 mg/kg bw. The mice were sacrificed at 24, 48 and 72 h after treatment and the bone marrow cells were collected for micronuclei analysis. Animals administered the positive control (20 mg/kg bw cyclophosphamide) or the vehicle were sacrificed at 24 h after treatment. Per animal 1000 polychromatic erythrocytes (PCEs) were scored for micronuclei. The ratio between PCEs and normochromatic erythrocytes (NCEs) was determined in the same sample and expressed in NCEs per 1000 PCEs. Animals treated with 125 mg/kg bw test substance showed symptoms of toxicity which comprise apathy, roughened fur, staggering gait, prone position, spasm, twitching and diarrhoea. The symptoms lasted until sacrifice. 4/40 mice treated with the test substance died during the study period. The ratio of PCEs to NCEs was not altered in the groups which received the test substance. In comparison to the corresponding vehicle controls there was no biologically relevant or statistically significant enhancement in the frequency of the detected micronuclei at any preparation interval after administration of the test item and with any gender used. The positive control caused a clear clastogenic effect which is shown by the significant increase of PCEs with micronuclei. Thus, under the conditions of this study, the test substance is considered to be non-mutagenic.

 

With respect to in vivo genotoxicity, an additional micronucleus test conducted with the source substance is considered for support (Herbold, 1981). In fact, this study was performed to assess the potential of the source substance p-chloro-m-cresol to induce micronuclei in polychromatic erythrocytes (PCE) in the bone marrow of the mouse. The test substance was suspended in Lutrol, which was also used as vehicle control. Five male and five female Bor NMRI mice per test group received the test substance at 200 and 400 mg/kg bw orally via gavage two times 24 h apart. Two groups (5 animals per sex) received the vehicle or the positive control (100 mg/kg bw cyclophosphamide) accordingly. The mice were sacrificed at 6 h after the second treatment and the bone marrow cells were collected for micronuclei analysis. Per animal 1000 polychromatic erythrocytes (PCEs) were scored for micronuclei. The ratio between PCEs and normochromatic erythrocytes (NCEs) was determined in the same sample and expressed in NCEs per 1000 PCEs. The ratio of PCEs to NCEs was not altered in the groups which received the test substance. In comparison to the corresponding vehicle controls there was no biologically relevant or statistically significant enhancement in the frequency of the detected micronuclei at any test substance concentration and with any gender used. The positive control caused a clear clastogenic effect which is shown by the significant increase of PCEs with micronuclei.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No 1907/2006, information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to sodium p-chloro-m-cresolate, data will be generated from data of the reference source substance to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

                                                                   

The available data on genetic toxicity for both the source and the target substance do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.

This is in line with the existing harmonised classification of the source substance according to Annex VI of Regulation (EC) 1272/2008 as well as with the Opinion of the Committee for Risk Assessment (RAC), adopted 10 March 2016.