Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 412-050-4 | CAS number: 125109-85-5 FLORHYDRAL
- 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
The test substance has proven not genotoxic in several in 2 Ames tests, 2 Chromosomal aberration tests in vitro and 1 Micronucleus test in vivo.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2006
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- Only the E. coli strain was tested, as the other TA strains were already tested in a pre-existing study.
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- Batch number 9000631236
Purity 99.3%
Expiration date: August 28, 2006 - Target gene:
- Trp
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- 3; 10; 33; 100; 333; 1000; 2500 and 5000 microg per plate
- Vehicle / solvent:
- Ethanol
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- without S9
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- with S9
- Key result
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- The test item was found negative in this bacterial revers mutation assay in E. coli WP2.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1989
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- yes
- Remarks:
- Strain E. Coli or TA 102 missing. The strain was tested in another study provided in this dossier.
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- Batch number 8906-87
- Species / strain / cell type:
- other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- 0.0005µL - 0.500 mL (background lawn reduction at highest doses)
- Vehicle / solvent:
- DMSO
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- TA 1535 and 100 (without S9)
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- TA 1538 and 98 (without S9)
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: quinacrine mustard
- Remarks:
- TA1537 (without S9)
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-anthramine
- Remarks:
- all strains with S9
- Species / strain:
- other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Conclusions:
- The test item was found negative in this bacterial revers mutation assay in S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2005
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian chromosome aberration test
- Specific details on test material used for the study:
- Batch number 1100017369
Purity 98.8%
Expiration date January 26, 2005 - Species / strain / cell type:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9
- Test concentrations with justification for top dose:
- Scored up to:
50µg/mL (4hrs -S9)
1.88µg/mL (18hrs -S9)
7.50µg/mL (28hrs -S9)
150µg/mL (4hrs +S9)
100µg/mL (4hrs +S9)
High toxicity observed at higher doses. - Vehicle / solvent:
- Ethanol was used as solvent
- Untreated negative controls:
- yes
- Remarks:
- Culture medium
- Negative solvent / vehicle controls:
- yes
- Remarks:
- Ethanol
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Untreated negative controls:
- yes
- Remarks:
- Culture medium
- Negative solvent / vehicle controls:
- yes
- Remarks:
- Ethanol
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- ethylmethanesulphonate
- Key result
- Species / strain:
- Chinese hamster lung fibroblasts (V79)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- In conclusion it can be stated that under the experimental conditions reported, the test item did not induce structural chromosome aberrations in V79 cells when tested up to cytotoxicity.
However, it is suspected to inhibit mitotic processes and to induce numerical chromosome aberrations (increased rate of polyploid cells), and to inhibit cell cycle progression (increased rate of cells with endoduplicate chromosome) in this chromosome aberration test in the absence of metabolic activation. - Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2014-2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Specific details on test material used for the study:
- Batch no. VE00340722
Expiry date 25 July 2015 - Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Details on mammalian cell type (if applicable):
- Chinese hamster ovary cells were obtained from Dr. A.T. Natarajan (State
University of Leiden). This cell line derives from the CHO isolate originally
described by Kao and Puck (1968).
The karyotype, generation time and plating efficiency have been checked in
this laboratory. The cells are checked at regular intervals for the absence of
mycoplasmal contamination.
Permanent stocks of CHO cells are stored in liquid nitrogen, and subcultures
are prepared from the frozen stocks for experimental use. - Metabolic activation:
- with and without
- Metabolic activation system:
- One batch of S9 tissue fraction, provided by Trinova Biochem GmbH, was used in this study and had the following characteristics:
Species: Rat
Strain: Sprague Dawley
Tissue: Liver
Inducing Agents: Phenobarbital – 5,6-Benzoflavone
Producer: MOLTOX, Molecular Toxicology, Inc.
Batch Number: 3350 - Test concentrations with justification for top dose:
- In the absence of S9 metabolic activation, using the short treatment time,
the experimental series considered valid was that performed as experiment
two using the following dose levels: 0.626, 0.501, 0.401, 0.321, 0.257, 0.205,
0.164, 0.131, 0.105, 0.0841 and 0.0673 mM.
In the presence of S9 metabolism, the experimental series considered valid
was that performed as experiment four using the following dose levels: 1.09,
0.952, 0.828, 0.720, 0.626, 0.544, 0.473, 0.412, 0.358 and 0.311 mM.
Cytotoxicity occured at higher doses. - Vehicle / solvent:
- Solutions of the test item, as received, were prepared immediately before
use in DMSO. - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- mitomycin C
- Details on test system and experimental conditions:
- Two main experiments were performed. In the first experiment, the cells were treated for 3 hours in the presence and absence of S9 metabolism, respectively.
The harvest time of 20 hours, corresponding to approximately 1.5 cell cycle, was used. Two previous experiments were performed in the absence and/or presence of S9 metabolism, where no adequate cell growth nor adequate toxicity was found and no dose level could be selected for the scoring of chromosomal aberrations. As negative results were obtained in the first main experiment, a second experiment was performed in the absence of S9 metabolism using approximately the same harvest time. A continuous treatment until harvest at 20
hours was used. Solutions of the test item were prepared in dimethylsulfoxide (DMSO).
For the first main experiment, the maximum dose level for treatment was selected in agreement with the Study Protocol and on the basis of the toxicity observed in the previous experiments. Dose levels of 0.626, 0.501, 0.401, 0.321, 0.257, 0.205, 0.164, 0.131, 0.105, 0.0841 and 0.0673 mM were used in the absence of S9 metabolism. Dose levels of 1.09, 0.952, 0.828, 0.720, 0.626, 0.544, 0.473, 0.412, 0.358 and 0.311 mM were used in the presence of S9 metabolism.
On the basis of results obtained in the first main experiment, dose levels of 0.320, 0.213, 0.142, 0.0948, 0.0632, 0.0421, 0.0281, 0.0187, 0.0125, 0.00832, 0.00554, 0.00370, 0.00247, 0.00164 and 0.00110 mM were used for the second main experiment.
Each experiment included appropriate negative and positive controls. Two replicate cell cultures were prepared at each test point.
Dose levels were selected for the scoring of chromosomal aberrations on the basis of the cytotoxicity of the test item treatments as determined by the reduction of population doubling and mitototic index if considered necessary. - Rationale for test conditions:
- According to guideline
- Evaluation criteria:
- In this assay, the test item is considered as clearly positive if the following criteria are met:
– Significant increases in the proportion of cells bearing aberrations (excluding gaps) over the concurrent controls occur at one or more concentrations.
– Any increases observed must be present in both replicate cultures.
– The proportion of aberrant cells exceeds the historical control range. If the increases fall within the range of values normally observed in the negative control cultures, the test item can not be classified as
positive. Any significant increases over the concurrent negative controls are therefore compared with historical control values derived from recent studies. - Statistics:
- For the statistical analysis, Fisher’s Exact Test was used to compare the number of cells bearing aberrations (assumed to be Poisson distributed) in control and treated cultures. Bonferroni’s correction was applied for multiple comparisons. The analysis was performed using sets of data either including or excluding gaps. The results are presented in Table 4.
Following treatment with the test item, no statistically significant increase in the incidence of cells bearing aberrations (including or excluding gaps) over the control values, was observed at any dose level, in any experiment, in the absence or presence of S9 metabolism.
Incidences in endoreduplicated cells were significantly increased (at statistical analysis) both in the absence and presence of S9 metabolism. In addition, using the continuous treatment time, a statistically significant increase of polyploid cells was observed. - Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Conclusions:
- On the basis of the above mentioned results and in accordance with the criteria for outcome of the study, the test item was not considered to induce structural chromosomal aberrations in mammalian cells cultured in vitro.
The test item was considered to induce numerical changes of chromosomes. - Executive summary:
The test item FLORHYDRAL was assayed for the ability to induce chromosomal aberrations in Chinese hamster ovary cells, following in vitro treatment in the presence and absence of S9 metabolic activation. Two main experiments were performed. In the first experiment, the cells were treated for 3 hours in the presence and absence of S9 metabolism, respectively. The harvest time of 20 hours, corresponding to approximately 1.5 cell cycle, was used. Two previous experiments were performed in the absence and/or presence of S9 metabolism, where no adequate cell growth nor adequate toxicity was found and no dose level could be selected for the scoring of chromosomal aberrations. As negative results were obtained in the first main experiment, a second experiment was performed in the absence of S9 metabolism using approximately the same harvest time. A continuous treatment until harvest at 20 hours was used. Solutions of the test item were prepared in dimethylsulfoxide (DMSO). For the first main experiment, the maximum dose level for treatment was selected in agreement with the Study Protocol and on the basis of the toxicity observed in the previous experiments. Dose levels of 0.626, 0.501, 0.401, 0.321, 0.257, 0.205, 0.164, 0.131, 0.105, 0.0841 and 0.0673 mM were used in the absence of S9 metabolism. Dose levels of 1.09, 0.952, 0.828, 0.720, 0.626, 0.544, 0.473, 0.412, 0.358 and 0.311 mM were used in the presence of S9 metabolism. On the basis of results obtained in the first main experiment, dose levels of 0.320, 0.213, 0.142, 0.0948, 0.0632, 0.0421, 0.0281, 0.0187, 0.0125, 0.00832, 0.00554, 0.00370, 0.00247, 0.00164 and 0.00110 mM were used for the second main experiment. Each experiment included appropriate negative and positive controls. Two replicate cell cultures were prepared at each test point. Dose levels were selected for the scoring of chromosomal aberrations on the basis of the cytotoxicity of the test item treatments as determined by the reduction of population doubling and mitototic index if considered necessary.
On the basis of the obtained results, dose levels selected for scoring were as follows:
Experiment No.: S9 Treatment time (hours) Harvest time (hours) Dose level (mM)
1 − 3 20 0.401, 0.321 and 0.257
+ 3 20 0.828, 0.720 and 0.626
2 − 20 20 0.0632, 0.0421 and 0.0281
For the three selected doses, for the solvent and for the untreated controls, 100 metaphase spreads per cell culture were scored to assess the frequency of aberrant cells. Following treatment with the test item, no statistically significant increase in the incidence of cells bearing structural aberrations, including or excluding gaps, over the control value was observed at any dose level in any treatment series. Increases of cells bearing chromosomal numerical changes (mainly polyploid cells) over the control were observed. Statistically significant increases in the number of cells bearing aberrations (including and excluding gaps) were observed following treatments with the positive controls Cyclophosphamide and Mitomycin-C, indicating the correct functioning of the test system.
It is concluded that FLORHYDRAL does not induce structural chromosome aberrations in Chinese hamster ovary cells after in vitro treatment, under the reported experimental conditions.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
The substance was found not clastogenic and non aneugenic in a micronucleus test in vivo.
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1991
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- mammalian erythrocyte micronucleus test
- Specific details on test material used for the study:
- Batch number 185809
Purity 97.9% - Species:
- mouse
- Strain:
- other: Fullinsdorf Moro Albino mice
- Sex:
- male/female
- Route of administration:
- oral: gavage
- Vehicle:
- Standard Suspension Vehicle (SSV)
- Details on exposure:
- Once by oral gavage
- Duration of treatment / exposure:
- Once by oral gavage, exanimations at 24, 48 and 72 hours for the high dose and 24 hours only for the low dose
- Frequency of treatment:
- Single treatment
- Post exposure period:
- Up to 72 hours
- Dose / conc.:
- 1 000 mg/kg bw/day
- Dose / conc.:
- 2 000 mg/kg bw/day
- No. of animals per sex per dose:
- 18 Males and 18 Females for the negative control
6M and 6F at 1000mg/kg -> 5M+5F were evaluated
18M and 18F at 2000mg/kg -> 15M and 15F were evaluated
6M and 6F for the positive control -> 5M and 5F were evaluated - Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Positive control: Procarbazine hydrochloride
- Tissues and cell types examined:
- Erythrocytes of the bone marrow of mice
- Details of tissue and slide preparation:
- Sampling times at 24, 48 and 72 hours for the high dose and 24 hours only for the low dose.
2 slides per animal treated were made.
1000 PCE were per animal. - Evaluation criteria:
- The ratio of PCE/NCE was determined on 1000 counts of erythrocytes.
- Statistics:
- The observed yields of MN-PCE were evaluated by means of the Mann-Whitney-U-test.
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Conclusions:
- Under the experimental conditions described in this report, the test item did not show any genotoxic activity in the mouse bone marrow cells.Thus the test item is is considered to show no genotoxic effects under the described experimental conditions..
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Justification for classification or non-classification
According to the available test results, the substance does not need any classification for genotoxicity under CLP.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.