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EC number: 202-433-2 | CAS number: 95-57-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
Ames test (OECD 471): negative in S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvrA with and without metabolic activation
Chromosome aberration test (similar to OECD 473): negative in CHL/IU cells without metabolic activation; inconclusive with metabolic activation
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 23 Mar - 2 Apr 1999
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- no data on historical controls provided
- GLP compliance:
- yes
- Remarks:
- according to the Japanese GLP Standard (as described on JECDB)
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in closed bottle at room temperature
- Solubility and stability of the test substance in the solvent/vehicle: water solubility 2.71%, easily soluble in DMSO and acetone - Target gene:
- his operon, trp operon
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix, prepared from the livers of rats treated with phenobarbital and 5-6-benzoflavone
- Test concentrations with justification for top dose:
- TA100 and TA1535, with and without metabolic activation: 39.1, 78.1, 156, 313, 652, 1250 and 2500 μg/mL (tested up to cytotoxic concentrations)
WP2uvrA, TA98 and TA1537, with and without metabolic activation: 156, 313, 652, 1250, 2500 and 5000 μg/mL (tested up to the limit dose) - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: Due to the limited solubility of the test substance in water, DMSO was selected as the vehicle. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- sodium azide
- other: aminofluorene for TA100 and TA98, N-ethyl-N'-nitrosogunanidine for WP2uvrA, 2-aminoanthracene for strains with S9
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: preincubation
DURATION
- Preincubation period: 20 minutes
- Exposure duration: 48 h
NUMBER OF REPLICATIONS:3 replications each in 2 independent experiments - Evaluation criteria:
- Evaluation:
A test substance was considered positive in the Ames test if:
a) a more than 2-fold increase in the number of revertants was observed
b) the increase was dose-related
c) the positive result was reproducible.
A test substance was considered negative in the Ames test if none of the above criteria were observed under all experimental conditions. - Statistics:
- Mean values and standard deviations were calculated.
- Key result
- Species / strain:
- S. typhimurium TA 98
- Remarks:
- TA100/ TA1535/ TA1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- starting at 1250 µg/mL +/-S9 in TA 100 and TA 1535; starting at 2500 µg/mL +/- S9 in WP2 uvrA, TA 98 and TA 1537
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- RANGE-FINDING/SCREENING STUDIES:
A preliminary test was performed with test concentrations ranging from 1.22 - 5000 μg/mL with/without S9. No increase in the number of revertants was observed. Furthermore, cytotoxicity was observed starting at 1250 μg/mL in TA100 and TA1535, and at 5000 μg/mL in WP2urvA, TA98 and TA1537 with and without metabolic activation.
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: number of revertant colonies - Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- no data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- 200 metaphases scored, evaluation criteria differ from OECD TG 473 (no statistical analysis performed); limited data on historical data provided, cell proliferation used as parameter for cytotoxicity, no C-charts or X-bar charts provided
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- Deviations:
- no
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- yes
- Remarks:
- 200 metaphases scored, evaluation criteria differ from OECD TG 473 (no statistical analysis performed), limited data on historical data provided (no values/range given), no RPD or RICC values given, no C-charts or X-bar charts provided
- GLP compliance:
- yes
- Remarks:
- according to the Japanese GLP Standard (as described on JECDB)
- Type of assay:
- in vitro mammalian cell micronucleus test
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in a closed bottle at room temperature
- Solubility and stability of the test substance in the solvent/vehicle: water solubility 2.71%, easily soluble in DMSO and acetone - Target gene:
- Not applicable
- Species / strain / cell type:
- other: CHL/IU
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: Dainippon Pharmaceutical Co., Ltd.
- Suitability of cells: yes
- Cell cycle length, doubling time or proliferation index: no data given
MEDIA USED
- Type and identity of media including CO2 concentration if applicable: Eagle MEM supplemented with 10% fetale calf serum, 0.02% L-glutamine, 0.12% NaHCO3
- Properly maintained: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix prepared from the livers of rats treated with phenobarbital and 5,6-benzoflavone
- Test concentrations with justification for top dose:
- Experiment I: with and without metabolic activitaion: 62.5, 125, 250 and 500 μg/mL (tested up to cytotoxic concentrations)
Experiment II: without metabolic activation: 200, 300, 400 and 500 μg/mL (tested up to cytotoxic concentrations) - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: Due to the limited solibility of the test substance in water, DMSO was selected as the vehicle. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- mitomycin C
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
- Cell density at seeding (if applicable): 4 * 10000 cells/mL. After 3 days of culture, the medium was changed and the cells were exposed to the test substance.
DURATION
- Exposure duration: 6 h
- Fixation time (start of exposure up to fixation or harvest of cells): 24 h (harvest time: 18 h)
h
SPINDLE INHIBITOR (cytogenetic assays): 0.1 µg/mL Colcemid in medium
STAIN: Giemsa
NUMBER OF REPLICATIONS: duplicates each; +S9 one experiment (Experiment I), -S9: 2 independent experiments (Experiment I and II)
NUMBER OF METAPHASE SPREADS ANALYSED PER DOSE (if in vitro cytogenicity study in mammalian cells): 200 - Rationale for test conditions:
- The test concentrations were selected based on the results of the preliminary tests.
- Evaluation criteria:
- A test substance is considered positive in the chromosome aberration test if it induced an increase in the aberration frequency of at least 10% . A test substance was considered false positive if it induced an increase in the frequency of aberrant cells in the range of 5 - 10%. A test substance was considered negative if it induced an increase in the aberration frequency of < 5%.
- Key result
- Species / strain:
- other: CHL/IU
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Remarks:
- no increase in the aberration frequency in non-cytotoxic concentrations (< 55% cytotoxicity) - S9; inconclusive + S9 (missing statistics and historical data)
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- all experimental parts: at the highest tested concentration (MT1, +/- S9: at 500 µg/mL; MT2, -S9: 500 µg/mL) (> 55% cytotoxicity)
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- RANGE-FINDING/SCREENING STUDIES:
Three range-finding tests were performed to evaluate cytotoxicity of the test material. In the first pre-test, concentrations of 50, 500 and 5000 μg/mL were applied with and without S9 mix. Based on the results in the first test, concentrations of 500, 1000, 2000, 3000, 4000 and 5000 μg/mL were tested in the second pre-test with and without S9 mix. In the second pre-test, reduced cell proliferation > 50% was observed starting at 500 µg/mL with and without S9 mix supplementation. To verify the observed results, a third pre-test was conducted with test concentrations of 12.6, 31.1, 62.5, 125, 250 and 500 µg/mL (no information on results provided).
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: cell profilferation (mitotic index)
TEST-SPECIFIC CONFOUNDING FACTORS
- Other confounding effects: Toxicity
In all experimental parts without S9 mix supplementation, an increase in the aberration frequency was observed at the highest concentration tested. Due to the observed excessive cytotoxicity at these concentrations, chromosomal damage is considered as artefactual positive result.
Referenceopen allclose all
Table 1. Test results for 2 -chlorphenol (Trial 1)
With or without S9-Mix |
Test substance concentration (μg/plate) |
Mean number of revertant colonies per plate ± standard deviation |
||||
Base-pair substitution type |
Frameshift type |
|||||
TA100 |
TA1535 |
WP2urvA |
TA98 |
TA1537 |
||
– |
0 |
112 ± 7 |
10 ± 3 |
24 ± 2 |
22 ± 5 |
7 ± 2 |
– |
39.1 |
123 ± 5 |
8 ± 1 |
- |
- |
- |
– |
78.1 |
104 ± 18 |
12 ± 1 |
- |
- |
- |
– |
156 |
116 ± 15 |
11 ± 5 |
22 ± 3 |
24 ± 2 |
6 ± 2 |
– |
313 |
103 ± 12 |
8 ± 2 |
33 ± 3 |
21 ± 3 |
7 ± 2 |
– |
625 |
101 ± 12 |
12 ± 4 |
22 ± 2 |
23 ± 4 |
7 ± 2 |
– |
1250 |
84 ± 9* |
7 ± 2* |
22 ± 2 |
20 ± 2 |
5 ± 1 |
– |
2500 |
0 ± 0* |
0 ± 0* |
0 ± 0* |
0 ± 0* |
0 ± 0* |
– |
5000 |
- |
- |
0 ± 0* |
0 ± 0* |
0 ± 0* |
– |
Positive controls |
AF-2 |
NaN3 |
ENNG |
AF-2 |
9-AA |
Mean No. of colonies/plate ± SD |
541 ± 38 |
377 ± 12 |
821 ± 29 |
375 ± 29 |
351 ± 39 |
|
+ |
0 |
113 ± 4 |
7 ± 2 |
27 ± 5 |
26 ± 4 |
13 ± 5 |
+ |
39.1 |
111 ± 9 |
8 ± 1 |
- |
- |
- |
+ |
78.1 |
110 ± 15 |
11 ± 3 |
- |
- |
- |
+ |
156 |
122 ± 6 |
9 ± 2 |
25 ± 4 |
28 ± 3 |
10 ± 2 |
+ |
313 |
117 ± 9 |
7 ± 2 |
29 ± 9 |
29 ± 10 |
12 ± 3 |
+ |
625 |
109 ± 11 |
9 ± 2 |
32 ± 7 |
28 ± 7 |
14 ± 3 |
+ |
1250 |
85 ± 5* |
12 ± 3* |
31 ± 4 |
27 ± 6 |
12 ± 4 |
+ |
2500 |
0 ± 0* |
0 ± 0* |
0 ± 0* |
0 ± 0* |
0 ± 0* |
+ |
5000 |
- |
- |
0 ± 0* |
0 ± 0* |
0 ± 0* |
+ |
Positive controls |
2-AA |
2-AA |
2-AA |
2-AA |
2-AA |
Mean No. of colonies/plate ± SD |
1161 ± 32 |
168 ± 7 |
1313 ± 38 |
443 ± 9 |
140 ± 6 |
AF-2= 2 -aminofluorene
NaN3 = sodium azid
ENNG = N-ethyl-N'-nitro-N'-nitrosogunanidine
9-AA = 9-aminoacridine
2AA = 2-aminoanthracene
SD = standard deviation
* = growth inhibition/cytotoxicity
Table 2. Test results for 2 -chlorphenol (Trial 2)
With or without S9-Mix |
Test substance concentration (μg/plate) |
Mean number of revertant colonies per plate ± standard deviation |
||||
Base-pair substitution type |
Frameshift type |
|||||
TA100 |
TA1535 |
WP2urvA |
TA98 |
TA1537 |
||
– |
0 |
105 ± 4 |
8 ± 2 |
20 ± 5 |
23 ± 3 |
13 ± 1 |
– |
39.1 |
106 ± 3 |
8 ± 2 |
- |
- |
- |
– |
78.1 |
103 ± 9 |
7 ± 1 |
- |
- |
- |
– |
156 |
103 ± 5 |
8 ± 2 |
29 ± 2 |
23 ± 2 |
15 ± 4 |
– |
313 |
108 ± 11 |
11 ± 1 |
26 ± 4 |
18 ± 2 |
12 ± 2 |
– |
625 |
94 ± 2 |
8 ± 1 |
23 ± 4 |
18 ± 2 |
15 ± 1 |
– |
1250 |
87 ± 15* |
8 ± 2* |
19 ± 3 |
15 ± 2 |
14 ± 4 |
– |
2500 |
0 ± 0* |
0 ± 0* |
0 ± 0* |
0 ± 0* |
0 ± 0* |
– |
5000 |
- |
- |
0 ± 0* |
0 ± 0* |
0 ± 0* |
– |
Positive controls |
AF-2 |
NaN3 |
ENNG |
AF-2 |
9-AA |
Mean No. of colonies/plate ± SD |
524 ± 14 |
514 ± 46 |
843 ± 33 |
505 ± 21 |
430 ± 34 |
|
+ |
0 |
105 ± 3 |
10 ± 2 |
25 ± 5 |
25 ± 5 |
19 ± 2 |
+ |
39.1 |
101 ± 6 |
9 ± 1 |
- |
- |
- |
+ |
78.1 |
108 ± 10 |
8 ± 2 |
- |
- |
- |
+ |
156 |
95 ± 8 |
11 ± 3 |
28 ± 5 |
25 ± 4 |
18 ± 5 |
+ |
313 |
96 ± 6 |
10 ± 1 |
27 ± 4 |
25 ± 6 |
16 ± 3 |
+ |
625 |
108 ± 10 |
9 ± 2 |
28 ± 6 |
26 ± 2 |
21 ± 3 |
+ |
1250 |
96 ± 5* |
8 ± 3* |
29 ± 3 |
23 ± 0 |
19 ± 2 |
+ |
2500 |
0 ± 0* |
0 ± 0* |
0 ± 0* |
0 ± 0* |
0 ± 0* |
+ |
5000 |
- |
- |
0 ± 0* |
0 ± 0* |
0 ± 0* |
+ |
Positive controls |
2-AA |
2-AA |
2-AA |
2-AA |
2-AA |
Mean No. of colonies/plate ± SD |
1010 ± 58 |
210 ± 9 |
1477 ± 47 |
424 ± 12 |
192 ± 7 |
AF-2= 2 -aminofluorene
NaN3 = sodium azido
ENNG = N-ethyl-N'-nitro-N'-nitrosogunanidine
9-AA = 9-aminoacridine
2AA = 2-aminoanthracene
SD = standard deviation
* = growth inhibition/cytotoxicity
Table 1 Test results of Experiment I.
Test item | Concentration | Mitotic Index | Aberrant cells | ||
[µg/mL] | [%] | with gaps (cells) | without gaps (%) | ||
structural aberrant cells | numerical aberrant cells | ||||
Exposure period 6 h, fixation time 18h, without S9 mix | |||||
DMSO | 0.5% (v/v) | 100 | 1 | 3.5 | 0.5 |
MMC | 0.1 | 53 | 15 | 95.5 | 0 |
Test substance | 62.5 | 97 | 2 | 3 | 0.5 |
125 | 75 | 0 | 4.5 | 0 | |
250 | 67 | 0 | 2 | 2 | |
500 | 30 T | 3 | 25.5 | 0 | |
Exposure period 6h, fixation time 18h, with S9 mix | |||||
DMSO | 0.5% (v/v) | 100 | 2 | 1.5 | 0 |
BP | 20 | 75 | 7 | 89.5 | 0 |
Test substance | 62.5 | 105 | 0 | 1.5 | 1 |
125 | 104 | 1 | 6 | 2 | |
250 | 90 | 3 | 12 | 0 | |
500 | 30 T | 1 | 38.6 | 0 |
MMC: mitomycin C, BP: benzo(a)pyrene, T: toxicity
Table 2. Test result of Experiment II.
Test item | Concentration | Mitotic Index |
Aberrant cells | ||
[µg/mL] | [%] | with gaps (cells) | without gaps (%) | ||
structural aberrant cells | numerical aberrant cells | ||||
Exposure period 6 h, fixation time 18h, without S9 mix | |||||
DMSO | 0.5% (v/v) | 100 | 1 | 0 | 0 |
MMC | 0.1 | 72 | 9 | 61.5 | 0.5 |
Test substance | 200 | 69 | 0 | 2.5 | 1.5 |
300 | 59 | 1 | 1 | 2.5 | |
400 | 52 | 1 | 2.5 | 0 | |
500 | 25 T | 5 | 34 | 0 |
MMC: mitomycin C, T: toxicity
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
SCE (in vivo, integrated in a 14 day RDT study): negative in testes and bone marrow cells (limited data, SS)
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Remarks:
- (limited details on study design and results provided)
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- - Principle of test: A 14-day repeat dose toxicity study with 2-chlorophenol was performed including evaluation of sister chromatid exchanges. Groups of 12 male and female CD-1 mice were exposed to 2-chlorophenol at dose levels of 35, 69 and 175 mg/kg bw/day by oral gavage once daily for 14 consecutive days. Vehicle control animals received the vehicle, corn oil, only. In addition a treatment naive and a positive control group (cyclosphosphamide, 25 mg/kg bw) were included.
- Parameters analysed / observed: SCE (testes and bone marrow). - GLP compliance:
- not specified
- Type of assay:
- sister chromatid exchange assay
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Assigned to test groups randomly: yes
- Housing: individually in plastic shoebox cage with hardwood sawdust bedding
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22° +/- 2°C
- Humidity (%): relative humidity 40-60%
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: corn oil
- Amount of vehicle: 10 mL/kg bw
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: prepared on day of administration
- Duration of treatment / exposure:
- 14 days
- Frequency of treatment:
- Once daily
- Post exposure period:
- none
- Dose / conc.:
- 35 mg/kg bw/day
- Remarks:
- Doses tested were 35, 69 and 175 mg/kg bw/day. All animals at 175 mg/kg bw/day died and could not be evaluated. Highest evaluated dose was 69 mg/kg bw/day.
- Dose / conc.:
- 69 mg/kg bw/day
- Remarks:
- Doses tested were 35, 69 and 175 mg/kg bw/day. All animals at 175 mg/kg bw/day died and could not be evaluated. Highest evaluated dose was 69 mg/kg bw/day.
- No. of animals per sex per dose:
- 12
- Control animals:
- yes, concurrent no treatment
- yes, concurrent vehicle
- other: yes, positive control
- Positive control(s):
- cyclophosphamide
- Route of administration: oral gavage
- Doses / concentrations: 25 mg/kg bw - Tissues and cell types examined:
- testes and bone marrow
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- not specified
- Negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Additional information on results:
- Mortality was observed in the highest dose group. In the mid-dose group, a decrease in body weight was observed. Administration of the low and mid-dose caused hyperactivity in the test animals. No alterations on clinical or haematological parameters were observed. Females revealed reduced liver, brain and spleen weights. No gross anomalies were observed. No biologically or statistically significant compound-related effects on DNA repair were observed in the examined tissues.
- Conclusions:
- Interpretation of results: negative
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
2-Chlorophenol was tested for its mutagenic properties in bacterial cells. Furthermore, data on the clastogenic properties were obtained based on in vitro and in in vivo studies.
Gene mutation in bacteria
Mutagenicity of 2-chlorophenol was tested in a GLP-conform bacterial reverse mutation assay equivalent to OECD TG 471 performed with a standard battery of Salmonella typhimurium tester strains including TA 1535, TA 1537, TA 98 and TA 100 and WP2uvrA bacterial cells (reference 7.6.1-1). Based on the results of a preliminary cytotoxicity test, concentrations of up to 2500 or 5000 µg/plate were tested in TA 100 and TA 1535 or WP2uvrA and, TA 98 and TA 1537, respectively. 2-chlorophenol did not exhibit mutagenic properties in the absence or presence of metabolic activation. Toxicity indicated by reduced number of revertants was observed in all strains at least at the highest applied dose. Positive control substances induced a distinct increase in the number of revertants in all strains with and without metabolic activation thereby proving validity of the assay. Based on the results of the conducted study, 2-chlorophenol is not considered to exhibit mutagenic properties in bacterial cells.
Cytogenicity in vitro
An in vitro mammalian chromosome aberration test was performed with the test substance in Chinese hamster lung cells (CHL/IU) similar to the current OECD TG 473 and GLP (reference 7.6.1-2). Duplicate cultures were evaluated for chromosome aberrations in the presence and absence of metabolic activation (rat liver S9-mix). Based on the results of two range-finding studies, concentrations of 62.5, 125, 250 and 500 μg/mL were applied for 6 h in the first experiment with and without metabolic activation. In the second experiment cells were exposed to 200, 300, 400 and 500 μg/mL without S9 mix for 6 h. Mitomycin C and Benzo(a)pyrene were used as positive control substances, which validated the test conditions and/or the activity of the metabolizing system. Evaluation of 200 well-spread metaphases per concentration revealed no biologically relevant increase in the frequency of chromosome aberrations at non-cytotoxic concentrations without metabolic activation in comparison to the negative controls. The observed increase in the aberration frequency at clearly cytotoxic concentrations determined in every experimental part without metabolic activation is considered as artefactual positive result due to excessive cytotoxicity > 55% as defined in OECD TG 473. In the presence of S9 mix, a dose-dependent increase in the frequency of aberrant cells was observed exceeding the defined threshold level (10%) at a non-cytotoxic concentration. However, due to missing historical data and statistical analysis, this result has to be considered as inconclusive. Thus, based on the results of this study taking into consideration the observed excessive cytotoxicity, 2-chlorophenol is considered to be non-clastogenic to Chinese hamster lung cells in vitro without metabolic activation, whereas no conclusive decision on the clastogenic properties in the presence of metabolic activation can be drawn.
Cytogenicity in vivo
In addition to the in vitro data on cytogenicity, supporting data from a 14-day repeat dose toxicity study including evaluation of sister chromatid exchanges in testes and bone marrow is available for 2-chlorophenol (reference 7.6.2-1). Groups of 12 male and 12 female CD-1 mice were exposed to the test item at dose levels of 35, 69, and 175 mg/kg bw/day by oral gavage once daily for 14 consecutive days. Vehicle control animals received the vehicle, corn oil, only. In addition a treatment naive and a positive control group (cyclosphosphamide, 25 mg/kg bw) were included. Observations and examinations of the animals included clinical signs, body weight, food consumption, haematology, clinical chemistry, liver microsomal activities, immune response, genetic toxicology, certain reproductive toxicology endpoints, activity and behavioral measurements, gross necropsy and organ weights. Mortality was observed in the highest dose group. In the mid-dose group, a decrease in body weight was observed. Administration of the low and mid-dose caused hyperactivity in the test animals. No alterations on clinical or haematological parameters were observed. Females revealed reduced liver, brain and spleen weights. No gross anomalies were observed. No biologically or statistically significant compound-related effects on DNA repair were observed in the examined tissues. Thus, the available data indicate that 2-chlorophenol does not exhibit DNA damaging properties and hence, support the in vitro data, that 2-chlorophenol does not exhibit clastogenic properties.
In summary, based on the available data on genetic toxicity, there is no clear evidence that 2-chlorophenol induces genetic toxicity in bacteria or clastogenic properties in vitro and in vivo. The in vivo data are considered as sufficiently reliable to enable a conclusive decision on the clastogenic properties as basic data are provided which support the inclonclusive finding in the available cytogenicity study.
Justification for classification or non-classification
Based on the available data on genetic toxicity, there is no indication that 2-chlorophenol induces genetic toxicity in bacteria or clastogenic properties in vitro and in vivo. Taking into consideration the harmonized classification, 2-chlorophenol is not expected to exhibit hazardous properties in regard to genetic toxicity. Thus, 2 -chlorophenol does not meet the classification criteria according to Regulation (EC) 1272/2008.
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