Registration Dossier
Registration Dossier
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EC number: 292-427-6 | CAS number: 90622-27-8
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2010-02-01 to 2010-02-12
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 enzymes from the livers of Aroclor 1254-treated adult, male Fisher rats
- Test concentrations with justification for top dose:
- Toxicity test: 17 / 50 / 167 / 500 / 1667 / 5000 µg/plate
Main tests: 17 / 50 / 167 / 500 / 1667 / 5000 µg/plate - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Acetone
- Justification for choice of solvent/vehicle: Initial solubility tests showed that acetone was a suitable solvent. Examination of the test item showed it to be a turbid liquid and it was normal for the suspended solid to separate from the liquid fraction at room temperature (confiremd by the Sponsor). The test item was thoroughly stirred before samples were taken for testing to ensure homogeneity. When the acetone was added, a clear, homogenous solution was obtained (both the solid and liquid components were fully in solution) - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: Sodium azide, 1 µg/plate with S. typhimurium TA 1535 and TA100; 9-Aminoacridine, 80 µg/plate with S. typhimurium TA 1537; 2-Nitrofluorene, 1 µg/plate with S. typhimurium TA 98; N-Ethyl-N-nitro-N-nitrosoguanidine, 2 µg/plate with E. coli WP2uvrA
- Remarks:
- without metabolic activation
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-Aminoanthracene, 2 µg/plate with S. typhimurium TA 1535 and TA 1537, 0.5 µg/plate with S. typhimurium TA 98 and TA 100, 20 µg/plate with E. coli WP2uvrA
- Remarks:
- with metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (direct plate method) in the first test; pre-incubation in the second (repeat) test
DURATION
- Preincubation period: 20 min (only in the repeat test)
- Exposure duration: 2 days in the toxoicity test; 3 days in the mutation tests
NUMBER OF REPLICATIONS: 3
DETERMINATION OF CYTOTOXICITY:
- Method: Plates were microscopically examined for thinning of background lawn, condition of background lawn was assessed as normal, slightly thin lawn, thin lawn, very thin lawn or lawn absent.
OTHER EXAMINATIONS:
- The numbers of mutant colonies on each plate were determined using a Sorcerer Colony Counter (Perceptive Instruments) and captured electronically in a validated software system (Ames Study Manager, Perceptive Instruments), the plates were also examined microscopically for precipitates and for microcolony growth (condition of backgroun lawn was assessed as in the toxicity test).
- Quality control of bacterial strains: All bacterial strains were tested for ampicillin resistence, crystal violet and ultraviolett radiation sensitivity and for essential animo acid requirement.
OTHER:
To establish suitable exposure levels for the first mutation test an initial dose-finding test in the presence and absence of S9 mix with a single strain of bacteria, S. typhimurium TA 100 and one plate per exposure level was conducted (Toxicity test). - Evaluation criteria:
- Interpretation of mutagenicity:
- doubling of the mean concurrent vehicle control value for S. typhimurium strains TA 1535, TA 1537 and TA 98 and for E. coli WP2uvrA, resp. 1.5-fold increase over the control value for S. typhimurium strain TA 100
- if the mean colony count on the vehicle control plates was less than 10, then a value of 10 was assumed for assessment purposes (in such cases a minimum count of 20, representing a 2-fold increase over 10, was required before a response was registered)
- concentration-related response, at high concentration, this relationship may be reversed
- a response should be reproducible in the independent test
Acceptance criteria:
- each bacterial strain demonstrated typical responses to crystal violet, ampicillin and ultralviolet radiation
- at least 2 of the 3 vehicle control plates were within the historical vehicle control data
- at least 2-fold increases over the mean vehicle control values in at least 2 of the 3 positive control plates for each strain and activation state were obtained (in the case of TA 100, at least 1.5-fold was obtained)
- no toxicity or contamination was observed in at least 4 concentration levels
- in cases where a mutagenic response was observed, no more than one exposure level was discarded below the concentration that gave the highest mean colony number - Statistics:
- not performed
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- slight toxicity was observed at the highest concentration of 5000 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- other: not tested
- Positive controls validity:
- valid
- 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:
- other: not tested
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no data
- Effects of osmolality: no data
- Evaporation from medium: not applicable
- Water solubility: no data
- Precipitation: Precipitation at 1667 and 5000 µg/plate in both absence and presence of S9 mix.
- Other confounding effects: nothing mentioned
RANGE-FINDING/SCREENING STUDIES: Slight toxicity was observed as a thinning of the background lawn of microcolonies at the highest concentration in both the absence and the presence of S9 mix.
COMPARISON WITH HISTORICAL CONTROL DATA: The vehicle control values were within the normal/historical ranges recorded in the testing laboratory and reported in the literature with these strains of S. typhimurium and E. coli (Ames et al, 1975; Gatehouse et al, 1994). The positive control values were also within the normal/historical ranges for each bacterial strain and activation condition. - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
No evidence of mutagenic activity was obtained with any strain in either test.
In the direct plate incorporation test, toxicity was encountered in all stains at the highest concentration or 2 highest concentrations in the absence of S9 mix and in 3 of 5 strains at the highest concentration in the presence of S9 mix. In the pre-incubation test, toxicity was encountered at the 2 highest concentrations in all strains in the absence of S9 mix, and in 4 of the 5 strains at the highest concentration or 2 highest concentrations in the presence of S9 mix. The test item precipitated at concentration s 1667 and 5000 µg/plate in all tests. In addition, the test substance precipitated at 1667 and 5000 µg/plate. - Executive summary:
Alkenes, C11 -12 hydroformylation products, distn. residues was tested for mutagenic activity in Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA100 and in Escherichia coli WP2uvrA according to OECD guideline 471and the European Commision Annex V Test Method B13 and B14.
The test item was dissolved and diluted in Acetone. Two independent tests were conducted on agar plate in triplicate in the absence and presence of an Aroclor 1254 -induced rat liver S9 preparation and co-factors required for mixed function oxidase activity (S9 mix). The first test was conducted by the direct plate incorporation method, while the second test was conducted by the pre-incubation method. The test item was dosed at concentrations ranging from 17 to 5000 µg/plate in both assays. The highest concentration was the predetermined maximum, as recommended by relevant guidelines, but was in addition both toxic to the bacteria and above the limit of solubility of the tes item in the test system.
Concurrent positive controls demonstrated the sensitivity of the assay and the metabolising activity of the S9 mix.
No evidence of mutagenic activity was obtained with any strain in either test.
In the direct plate incorporation test, toxicity was encountered in all stains at the highest concentration or 2 highest concentrations in the absence of S9 mix and in 3 of 5 strains at the highest concentration in the presence of S9 mix. In the pre-incubation test, toxicity was encountered at the 2 highest concentrations in all strains in the absence of S9 mix, and in 4 of the 5 strains at the highest concentration or 2 highest concentrations in the presence of S9 mix. The test item precipitated at concentration s 1667 and 5000 µg/plate in all tests.
It was concluded that Alkenes, C11 -12, hydroformylation products, distn. residues was not mutagenic in strains of Salmonella typhimurium and Escherichia coli when tested in acetone in the absence and presence of metabolic activation. The test item was tested to the predetermined maximum of 5000 µg per plate, at which concentration toxicity was encountered. In addition, the test item was tested up to and beyond its limits of solubility in the test system.
The study was performed in accordance with the principles of Good Laboratory Practice.
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Remarks:
- Type of genotoxicity: chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- fro 2010-02-08 to 2010-04-05
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Well-documented guideline study according to GLP
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian chromosome aberration test
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Details on mammalian cell type (if applicable):
- - Type and identity of media: Ham's F-10 containing HEPES buffer and supplemented with minocycline (basic medium, medium for treatment in the presence of S9 mix and for washing cultures before or after treatment), basic medium with 10% (v/v) foetal bovine serum (medium for cell growth and treatment in the absence of S9 mix)
- Periodically checked for Mycoplasma contamination: yes - Additional strain / cell type characteristics:
- other: Generation time: 12 - 14 h; modal chromosome number: 21
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix prepared from S9 fraction obtained from male rats dosed with Arochlor 1254
- Test concentrations with justification for top dose:
- First test:
1. Experiment: 20, 39, 78, 156, 313, 625, 1250, 2500 and 5000 µg/mL
2. Experiment: 25, 50, 100, 150, 200, 250, 300,325 and 350 µg/ml with metabolic activation; 6.25, 12.5, 25, 50, 75, 100, 150 and 200 µg/mL without metabolic activation - Vehicle / solvent:
- - Vehicle/solvent used: ethanol
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: with S9 mix: cyclophosphamid (CP), concentration range 20 - 50 µg/mL; without S9 mix: methyl methanesulphonate (MMS), concentration range 10 - 40 µg/mL
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration:
1. Experiment: -S9/+S9: 6 hours
2. Experiment: -S9: 22 hours; +S9: 6 hours
- Fixation time (start of exposure up to fixation or harvest of cells):
1. Experiment: -S9/+S9: 24 hours
2. Experiment: -S9: 24 and 48 hours; +S9: 24 hours
SPINDLE INHIBITOR (cytogenetic assays): Colcemid (0.1 µg/mL)
STAIN (for cytogenetic assays): 5% Giemsa
NUMBER OF REPLICATIONS: two cultures per dose level, controls and vehicle control
NUMBER OF CELLS EVALUATED: 200 metaphases per dose level (100 per replicate)
DETERMINATION OF CYTOTOXICITY
- Method: Slides were examined for evidence of metaphase cells and signs of cellular necrosis. From the cell counts, the number if cells recovered per culture, was calculated. This was then compared with the number of cells (mean of 2 cultures) recovered from the vehicle control cultures.
OTHER EXAMINATIONS:
- Determination of polyploidy: Yes
- Other: During the first test, the osmotic pressure of selected concentrations of the test substance was measured; observations of precipitation were made at the end of the treatment period. - Evaluation criteria:
- The results for test item and positive control treated cultures are evaluated by comparison with the concurrent vehicle control cultures and with historical negative control data. A negative response was recorded if responses from the test item treated cultures are within the 95% confidence limits for the historical negative control data.
The response at a single dose was classified as significant if the percent of aberrant cells is consistently greater than the 99% confidence limits for the historical negative control data or greater than double the frequency of an elevated vehicle or untreated control culture if appropriate.
A test was positive if the response in at least one acceptable dose level was significant by the criterion described above.
A test item was positive if Test 1 was positive, as described above or if one of the tests was positive and the other test gave indications of activity. These indications may be suspicious levels of aberrant cells (between 95% and 99% confidence limits).
Experiments that met in part the criteria for a positive response, or marginally met all the criteria, were classed as inconclusive. - Statistics:
- not performed
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- see "additional information on results" below
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: the colour of the medium was not changed by the test substance indicating no change of the pH
- Effects of osmolality: no effect on osmotic pressure at selected concentrations tested
- Precipitation: Precipitation was noted in cultures treated with 39-5000 µg/mL in the presence and in cultures with 78-5000 µg/mL in the absence of S9 mix.
RANGE-FINDING/SCREENING STUDIES:
Test #1 with metabolic activation: toxicity was noted in 156-5000 µg/mL, with no metaphases cells for assessment in 625-2500 µg/mL. 313 and 5000 µg/mL had reduced cell counts (below 50% of the vehicle controls) and 156 µg/mL was deemed toxic to the cells from slide observations.
Test #1 without metabolic activation: toxicity was noted in 78-5000 µg/mL, with no metaphase cells for assessment in 313-2500 µg/mL. 78,156 and 5000 µg/mL had reduced cell counts.
Test #2 with metabolic activation: toxicity was noted in 100-350 µg/mL, with too few metaphases cells for assessment in 300-350 µg/mL. 250 µg/mL had reduced cell counts and 100-200 µg/mL were deemed toxic to the cells from slide observations.
Test #2 without metabolic activation, 24 hour harvest: toxicity was noted in 25-200 µg/mL, with no metaphase cells for assessment in 200 µg/mL, 25 and 50 µg/mL had reduced cell counts.
Test #2 without metabolic activation, 48 hour harvest: toxicity was noted in 25-200 µg/mL, with no metaphase cells for assessment in 200 µg/mL, 50-150 µg/mL had reduced cell counts and 25 µg/mL was deemed toxic to the cells from slide observation.
The following dose levels were selected for assessment of chromosomal aberrations:
Test #1, presence of metabolic activation: 20, 78 and 156 µg/mL
Test #1, absence of metabolic activation: 39, 78 and 156 µg/mL
Test #2, presence of metabolic activation: 25, 150, 200 and 250 µg/mL
Test #2, absence of metabolic activation: 12.5, 25 and 50 µg/mL
COMPARISON WITH HISTORICAL CONTROL DATA: The vehicle control cultures had levels of structural and numerical aberration within the 95% confidence limits of the historical negative control data. - Conclusions:
- Interpretation of results (migrated information):
negative with and without metabolic activation
It was concluded that Alkenes, C11-12, hydroformylation products, distn. residues was not clastogenic when tested with Chinese hamster ovary cells in vitro. - Executive summary:
All cultures treated with Alkenes, C11-12, hydroformylation products, distn. residues had levels of structural aberrations within the 95% confidence limits for a negative response. An extra assessment of polyploidy was carried out on the cultures treated in the absence of S9 mix and harvested at 48 h. All the cultures treated with Alkenes, C11-12, hydroformylation products, distn. residues had levels of polyploidy within the 95% confidence limits for a negative response.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- February 2 to June 17, 2010
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: well documented study performed according to OECD Guideline and GLP
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- mammalian cell gene mutation assay
- Target gene:
- thymidine kinase locus
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- - Type and identity of media: RPMI 1640 medium supplemented with penicillin, streptomycin, sodium bicarbonate and pluronic acid (basic culture medium), R0P supplemented with 5% v/v heat-inactivated horse serum (R5P) (medium used during treatment for 4 h), R0P supplemented with 10% v/v heat-inactivated horse serum (R10P) (medium used during treatment for 24h), R0P supplemented with heat-inactivated horse serum (20% v/v), sodium pyruvate, and amphotericin B (fungizone) (cloning medium), cloning medium supplemented with trifluorothymidine (FT) (medium for selection of tk-tk- cells)
- Periodically checked for Mycoplasma contamination: yes
- Periodically "cleansed" against high spontaneous background: yes - Additional strain / cell type characteristics:
- other:
- Metabolic activation:
- with and without
- Metabolic activation system:
- liver S9 mix of Arochlor 1254-induced male rats
- Test concentrations with justification for top dose:
- Toxicity test (range finding): 0.5, 1.5, 5, 15, 50, 150, 500, 1500 and 5000 µg/mL in the absence and presence of S9 mix
Mutation assays:
Assay 1 (in the absence of S9 mix*): 20, 40, 80, 140, 220, 320, 440 and 580 µg/mL
Assay 2 (in the presence of S9 mix*): 20, 40, 80, 140, 220, 320, 440 and 580 µg/mL
Assay 3 (in the absence of S9 mix**): 25, 40, 70, 115, 175, 250, 340 and 445 µg/mL
Assay 4 (in the presence of S9 mix*): 60, 130, 200, 270, 340, 410, 480 and 550 µg/mL
Assay 5 (in the absence of S9 mix**): 120, 140, 160, 180, 200, 220, 240 and 260 µg/mL
Assay 6 (in the absence of S9 mix**: 130, 145, 160, 175, 190, 205, 220 and 235 µg/mL
* Experiment using a 4 h exposure period
** Experiment using a 24 h exposure period - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: acetone
- Justification for choice of solvent/vehicle: The test substance consisted of a liquid mixture containing a small proportion of suspended solids (turbid appearance). When diluted in acetone, a clear solution resulted, and it was therefore concluded that the test item was fully soluble in acetone. - Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: in the absence of metabolic activation (4 h/24h exposure): ethyl methanesulphonate (EMS, 250/150 µg/ml) and methyl methanesulphonate (MMS, 10/5 µg/ml); in the presence of metabolic activation: 3-methylcholanthrene (3-MC, 2.5 and 10 µg/ml)
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration:
Experiment 1: 4 h
Experiment 2: 24 h (without metabolic activation) and 4 h (with metabolic activation)
- Expression time (cells in growth medium): 2 days
- Selection time (if incubation with a selection agent): at least 12 days (mutation selection assay), at least 9 days (cloning efficienty assay)
SELECTION AGENT (mutation assays): trifluorothymidine (TFT)
NUMBER OF REPLICATIONS: 2 (test item and positive control, 4 (vehicle control)
NUMBER OF CELLS EVALUATED: mutation selection assay: 2000 per well (1x10E4 cells/mL); cloning efficiency assay: 1.6 cells per well (8 cells/mL)
DETERMINATION OF CYTOTOXICITY
- Method: relative suspension growth, recorded over 2 days following treatment using a haemocytometer
OTHER EXAMINTATIONS
- Colony sizing: ratio of small to large type mutants
- Observations on precipitation of the test substance: after dosing and at the end of the exposure period
- Observations of pH: colour change in indicator in medium - Evaluation criteria:
- Criteria for a positive result:
-one or more concentrations were biologically significant and there was a significant linear trend
-in the absence of a linear trend if there was mitigating evidence ( e.g. presence of similar level of toxicity at all concentrations; in such a case, the confirmatory experiment would have been expected to assess concentrations covering different levels of toxicity, to establish a linear trend.
Additional comparisons that can aid interpretation of results include:
-comparison of the induced mutant fraction with the historical maximum for difference between vehicle controls (No Effect Maximum)
-comparison of the mutant fraction of a treated group with the historical range of vehicle control values
A test item was positive if 2 positive experiments out of 2 were recorded within the same activation condition. Test items that gave a negative response in the standard exposure in the absence of S9 mix, but gave a positive response in the extended exposure, were liable to a confirmatory experiment with the extended exposure.
Criteria for a negative result:
In the absence of any significant findings or other criteria for a positive response, a test item was defined as non-mutagenic, provided data were obtained in both the absence and the presence of S9 mix that accompanied one or more of the following:
- the predetermined maximum concentration of 5000 µg/mL or 10 mM, whichever is lower
- the highest practical concentration limited by the solubility or pH of the test item
- RTG in the range 10-20%
A chemical may be determined to be non-mutagenic when there was no treatment showing an RTG value between 10 and 20%. These situations are as follows:
- no evidence of mutagenic activity in a series of data points within 100% to 20% RTG and there was at least one data point between 20% and 25% RTG
- no evidence of mutagenic activity in a series of data points between 100% to 25% RTG and there was also a data point between 10 and 1% RTG - Statistics:
- Data were analysed using methods outlined in Robinson et al (1989).
The analyses comprised the following:
1. Determination of the heterogeneity factor for each dose level.
2. Comparison of the heterogeneity factor with the historical control. Any dose levels with heterogeneity factor statistically higher than the historical control were excluded from all statistical analysis.
3. Determination of the heterogeneity factor for the experiment.
4. Calculation of a new historical control heterogeneity factor.
5. Calculation of the log mutant fraction.
6. Comparison of the log mutant fraction between the control and each treatment dose (at P<0.05).
7. Test for linear increasing trend of mutant fraction with increasing dose of test item (at P<0.05).
The term 'heterogeneity factors' is defined separately for survival (Hs) and mutant (Hm) data. - Species / strain:
- mouse lymphoma L5178Y cells
- 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:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: no
- Effects of osmolality: no data
- Precipitation: yes, at concentrations of 150 µg/mL and above
- Other confounding effects: Two isolated cultures in Assay 1 were affected by abnormal cell suspension growth between Day 1 and Day 2 of the experiment. The 2 cultures were the first replicate at 80 µg/mL and the second replicate at 320 µg/mL. Further instances of this phenomenon occurred in Assay 5 and Assay 6. The reason for the abnormal growth was not identified. The affected cultures had the following in common:
only cultures treated with Alkenes, C11-12, hydroformylation products, distn. residues were affected - no vehicle or positive control cultures were affected
only cultures in the absence of S9 mix were affected - no cultures dosed with S9 mix were affected
only one replicate in any duplicate pair was affected - on no occasion were both cultures from the same treatment affected
the occurrence was seen only between Day 1 and Day 2 - all Day 1 cell counts were normal
RANGE-FINDING/SCREENING STUDIES: When exposed to the cells for a period of 4 h in the absence of S9 mix (see Table 1a), a concentration of 500 µg/mL reduced relative suspension growth to 1.4% of the vehicle control value. Higher concentrations killed all the exposed cells. In the presence of S9 mix (Table 1b), 500 µg/mL reduced relative suspension growth to 5%. Higher concentrations killed all the exposed cells.
When the exposure period in the absence of S9 mix was increased to 24 h (Table 1c), 150 µg Alkenes, C11-12, hydroformylation products, distn. residues/mL reduced suspension growth to 47.2% of the vehicle control value. Higher concentrations killed all the exposed cells.
COMPARISON WITH HISTORICAL CONTROL DATA: The solvent control mean mutant fractions were within the normal ranges experienced in the testing laboratory and reported in the literature with the used cell line (Mitchell et al (1997)).
ADDITIONAL INFORMATION ON CYTOTOXICITY: Of the 3 assays conducted with an extended exposure period in the absence of S9 mix, only Assay 6 gave a definitive data set fully meeting acceptance criteria and demonstrating that results had been obtained at a sufficiently toxic concentration of test item. - Conclusions:
- Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation
No significant increase in mutant numbers was obtained when Alkenes, C11-12, hydroformylation products, distn. residues was tested in acetone with a 4 h exposure period in the absence and presence of S9 mix at concentrations extending into the toxic range.
One statistically significant but biologically irrelevant increase in mutant numbers was obtained when Alkenes, C11-12, hydroformylation products, distn. residues was tested with a 24 h exposure period in the absence of S9 mix at concentrations extending into the toxic range.
It is therefore concluded that Alkenes, C11-12, hydroformylation products, distn. residues is not mutagenic in mouse lymphoma L5178Y cells, in either the absence or the presence of S9 mix, when tested in acetone at concentrations extending into the toxic range. - Executive summary:
Alkenes, C11-12, hydroformylation products, distn. residues (CAS No. 90622-27-8) was assayed for mutagenic potential in the mouse lymphoma L5178Y cell line, clone 3.7.2C, scoring for forward mutations at the thymidine kinase locus: tk+tk- to tk tk . Alkenes, C11-12, hydroformylation products, distn. residues was formulated in acetone. Tests were conducted both in the absence and in the presence of a post mitochondrial supernatant fraction obtained from Aroclor 1254 induced livers of adult male rats and the co-factors required for mixed-function oxidase activity (S9 mix). The study was designed to be consistent with ICH Guidelines, OECD Guideline No. 476 and EC Directive 2000/32/EC B.17. The study also meets the requirements of the United States and Japan.
In preliminary cytotoxicity tests, Alkenes, C11-12, hydroformylation products, distn. residues was shown to be of a low to moderate order of toxicity. When exposed to the cell cultures for 4 h, a concentration of 500 µg/mL reduced cell growth to 1.4% and 5.0% of vehicle control values in the absence and presence of S9 mix, respectively. When the exposure period was increased to 24 h, a concentration of 150 µg/mL reduced cell growth to 47.2% of the control value. Alkenes, C11-12, hydroformylation products, distn. residues precipitated at concentrations of 150 µg/mL and above.
Six independent mutation assays were conducted, as follows:
Assay No. Presence or absence of S9 Treatment time (hours) Final concentrations* (µg/mL)
1 Absence 4 40, 80, 140, 220, 320 and 440
2 Presence 4 80, 140, 220, 320 and 440
3 Absence 24 40, 70, 115, 175 and 250
4 Presence 4 130, 200, 270, 340 and 410
5 Absence 24 120, 140, 160, 180 and 200
6 Absence 24 175, 190, 205, 220 and 235
* Concentrations taken through to final assessment
Positive control cultures were included, and the resultant mutant fractions from these provided the expected increase and proof of adequate recovery of 'small' type colonies. Duplicate cultures were carried through the experiments for each treatment point. Vehicle control cultures were also included and were tested in quadruplicate.
Biological relevance was given to any increase in mutant fraction greater than 126 mutants per million above the concurrent control value. In addition, the results were analysed for comparison of the log mutant fraction between the vehicle controls and each concentration of Alkenes, C11-12, hydroformylation products, distn. residues. In addition, all the experiments were tested for dose-related trends.
No evidence of mutagenic activity was obtained with Alkenes, C11-12, hydroformylation products, distn. residues in either the absence or the presence of S9 mix when the exposure period was 4 h. All such assays satisfied the criteria required to demonstrate that results had been obtained at a sufficiently toxic concentration of test item.
Of the 3 assays conducted with an extended exposure period in the absence of S9 mix, only Assay 6 gave a definitive data set fully meeting acceptance criteria and demonstrating that results had been obtained at a sufficiently toxic concentration of test item. Assay 6 gave one statistically significant but biologically irrelevant increase in mutant fraction.
It is therefore concluded that Alkenes, C11-12, hydroformylation products, distn. residues is not mutagenic in mouse lymphoma L5178Y cells, in either the absence or the presence of S9 mix, when tested in acetone at concentrations extending into the toxic range.
Referenceopen allclose all
Table #1: Toxicity test with S. typhimurium strain TA 100
| without metabolic activation | with metabolic activation | |||
| Dose level [µg/plate] | Revertant colony count | Ratio treated/solvent | Revertant colony count | Ration treated/solvent |
| Acetone | 77 | - | 97 | - |
| 17 | 86 | 1.1 | 87 | 0.9 |
| 50 | 81 | 1.1 | 68 | 0.7 |
| 167 | 76 | 1.0 | 60 | 0.6 |
| 500 | 65 | 0.8 | 97 | 1.0 |
| 1667 | 76 P | 1.0 | 83 P | 0.9 |
| 5000 | 48 P ST | 0.6 | 57 P ST | 0.6 |
P = Precipitate / ST= Slightly Thin Lawn
Table #2: First Mutation Assay (Direct Plate Incorporation Method)
| TA 1535 | TA 1537 | TA 98 | ||||||||||
| - S9 mix | + S9 mix | - S9 mix | + S9 mix | - S9 mix | + S9 mix | |||||||
| Dose level[µg/plate] | Mean revertants per plate ± SD | Ratio | Mean revertants per plate ± SD | Ratio | Mean revertants per plate ± SD | Ratio | Mean revertantsper plate± SD | Ratio | Mean revertants per plate ± SD | Ratio | Mean revertants per plate ± SD | Ratio |
| Acetone | 14.0 ± 5.3 | - | 18.7 ± 4.0 | - | 10.0 ± 2.6 | - | 10.0 ± 2.6 | - | 40.0 ± 11.1 | - | 45.0 ± 6.6 | - |
| 17 | 13.0 ± 3.0 | 0.9 | 10.7 ± 1.2 | 0.6 | 5.7 ± 2.9 | 0.7 | 15.0 ± 5.0 | 1.5 | 32.0 ± 19.1 | 0.8 | 31.7 ± 3.2 | 0.7 |
| 50 | 12.7 ± 2.5 | 0.9 | 14.3 ± 3.1 | 0.8 | 7.0 ± 3.0 | 0.7 | 16.3 ± 3.5 | 1.6 | 23.3 ± 4.7 | 0.7 | 38.3 ± 5.5 | 0.9 |
| 167 | 15.3 ± 6.7 | 1.1 | 12.3 ± 4.6 | 0.7 | 11.0 ± 7.0 | 1.1 | 12.7 ± 1.5 | 1.3 | 31.3 ± 2.1 | 0.8 | 36.7 ± 12.9 | 0.8 |
| 500 | 7.0 ± 3.5 | 0.5 | 15.0 ± 0.0 | 0.8 | 8.3 ± 6.0 | 0.8 | 10.3 ± 2.9 | 1.0 | 36.3 ± 18.6 | 0.9 | 33.0 ± 8.2 | 0.7 |
| 1667 | 14.0 ± 4.4 P | 1.0 | 18.0 ± 1.0 P | 1.0 | 8.3 ± 2.1 P ST | 0.8 | 6.7 ± 2.5 P | 0.7 | 19.7 ± 3.2 P | 0.5 | 33.3 ± 5.5 P | 0.7 |
| 5000 | 13.0 ± 4.0 P ST | 0.9 | 16.0 ± 8.2 P | 0.9 | 10.3 ± 2.3 P TL | 1.0 | 7.3 ± 6.7 P ST | 0.9 | 20.0 ± 5.3 P ST | 1.0 | 33.7 ± 4.2 P ST | 0.7 |
| Positive Control | 470.0 ± 31.0 | 33.6 | 592.0 ± 42.5 | 31.7 | 5809.3 ± 170.5 | 581 | 361.7 ± 16.8 | 36.2 | 607.0 ± 21.0 | 15.2 | 822.7 ± 58.2 | 18.3 |
P = Precipitate / ST= Slightly Thin Lawn / TL = Thin Lawn
Table #2 (continued): First Mutation Assay (Direct Plate Incorporation Method)
| TA 100 | WP2uvrA | |||||||
| - S9 mix | + S9 mix | - S9 mix | + S9 mix | |||||
| Dose level [µg/plate] | Mean revertants per plate ± SD | Ratio | Mean revertants per plate ± SD | Ratio | Mean revertants per plate ± SD | Ratio | Mean revertants per plate ± SD | Ratio |
| Acetone | 91.7 ± 11.4 | - | 101.3 ± 6.4 | - | 8.7 ± 1.5 | - | 13.0 ± 2.6 | - |
| 17 | 92.3 ± 7.4 | 1.0 | 88.0 ± 15.0 | 0.9 | 6.0 ± 2.6 | 0.7 | 10.7 ± 2.1 | 0.8 |
| 50 | 89.7 ± 8.5 | 1.0 | 98.3 ± 22.5 | 1.0 | 7.7 ± 1.2 | 0.9 | 9.3 ± 3.1 | 0.7 |
| 167 | 88.3 ± 5.0 | 1.0 | 79.7 ± 2.1 | 0.8 | 7.0 ± 0.0 | 0.8 | 8.0 ± 1.7 | 0.6 |
| 500 | 93.7 ± 8.1 | 1.0 | 88.3 ± 4.0 | 0.9 | 5.7 ± 3.5 | 0.7 | 7.3 ± 1.5 | 0.6 |
| 1667 | 80.0 ± 14.4 P | 0.9 | 86.3 ± 7.4 P | 0.9 | 7.0 ± 3.0 P | 0.8 | 8.7 ± 3.5 P | 0.7 |
| 5000 | 72.0 ± 3.6 P ST | 0.8 | 75.3 ± 3.1 P ST | 0.7 | 6.7 ± 1.2 P ST | 0.8 | 6.7 ± 3.1 P | 0.5 |
| Positive control | 1059.0 ± 60.6 | 11.6 | 1130.0 ± 46.7 | 11.2 | 130.3 ± 24.8 | 15.0 | 469.3 ± 14.3 | 36.1 |
P = Precipitate / ST = Slightly Thin Lawn
Table #3: Second Mutation Assay (Pre-incubation Method)
| TA 1535 | TA 1537 | TA 98 | ||||||||||
| - S9 mix | + S9 mix | - S9 mix | + S9 mix | - S9 mix | + S9 mix | |||||||
| Dose level [µg/plate] | Mean revertants per plate ± SD | Ratio | Mean revertants per plate ± SD | Ratio | Mean revertants per plate ± SD | Ratio | Mean revertantsper plate± SD | Ratio | Mean revertants per plate ± SD | Ratio | Mean revertants per plate ± SD | Ratio |
| Acetone | 12.7 ± 3.5 | - | 17.3 ± 4.5 | - | 9.0 ± 2.6 | - | 19.0 ± 2.6 | - | 27.0 ± 4.6 | - | 35.0 ± 4.4 | - |
| 17 | 14.7 ± 8.5 | 1.2 | 18.3 ± 7.6 | 1.1 | 12.7 ± 2.1 | 1.4 | 20.7 ± 4.6 | 1.1 | 22.7 ± 8.5 | 0.8 | 37.7 ± 7.2 | 1.1 |
| 50 | 10.0 ± 1.0 | 0.8 | 12.7 ± 3.8 | 0.7 | 11.3 ± 2.1 | 1.3 | 20.0 ± 4.0 | 1.1 | 23.0 ± 5.0 | 0.9 | 39.7 ± 6.0 | 1.1 |
| 167 | 14.3 ± 5.1 | 1.1 | 14.3 ± 5.9 | 0.8 | 14.7 ± 4.6 | 1.6 | 16.0 ± 2.6 | 0.8 | 20.7 ± 1.2 | 0.8 | 33.0 ± 2.0 | 0.9 |
| 500 | 15.3 ± 4.9 | 1.2 | 18.0 ± 2.0 | 1.0 | 11.3 ± 2.1 | 1.3 | 12.7 ± 3.1 | 0.7 | 27.3 ± 9.0 | 1.0 | 31.7 ± 4.9 | 0.9 |
| 1667 | 13.7 ± 2.1P ST | 1.1 | 12.0 ± 5.6 P | 0.7 | 8.7 ± 4.0 P TL | 1.0 | 4.3 ± 2.1 P ST | 0.2 | 19.7 ± 3.2 P TL | 0.7 | 27.3 ± 4.0 P | 0.8 |
| 5000 | 10.7 ± 4.0 P TL | 0.8 | 13.3 ± 3.2 P ST | 0.8 | 5.3 ± 0.6 P TL | 0.6 | 9.0 ± 2.6 P TL | 0.5 | 24.5 P TL | 0.9 | 32.3 ± 9.8 P ST | 0.9 |
| Positive Control | 525.0 ± 20.0 | 41.4 | 317.7 ± 13.7 | 18.3 | 4462.7 ± 423.7 | 496 | 179.0 ± 29.5 | 9.4 | 377.3 ± 28.1 | 14.0 | 177.7 ± 15.3 | 5.1 |
P = Precipitate / ST = Slightly Thin Lawn / TL = Thin Lawn
Table #3 (continued): Second Mutation Assay (Pre-incubation Method)
| TA 100 | WP2uvrA | |||||||
| - S9 mix | + S9 mix | - S9 mix | + S9 mix | |||||
| Dose level [µg/plate] | Mean revertants per plate ± SD | Ratio | Mean revertants per plate ± SD | Ratio | Mean revertants per plate ± SD | Ratio | Mean revertants per plate ± SD | Ratio |
| Acetone | 100.7 ± 10.5 | - | 95.7 ± 20.6 | - | 11.0 ± 1.7 | - | 9.7 ± 5.5 | - |
| 17 | 78.7 ± 16.2 | 0.8 | 78.7 ± 5.8 | 0.8 | 8.3 ± 6.1 | 0.8 | 7.3 ± 2.5 | 0.8 |
| 50 | 69.7 ± 4.7 | 0.7 | 94.3 ± 11.8 | 1.0 | 9.0 ± 3.6 | 0.8 | 6.3 ± 4.0 | 0.7 |
| 167 | 74.0 ± 19.1 | 0.7 | 100.3 ± 7.6 | 1.0 | 12.7 ± 3.5 | 1.2 | 3.3 ± 1.5 | 0.3 |
| 500 | 72.7 ± 5.0 | 0.7 | 88.0 ± 7.8 | 0.9 | 5.7 ± 0.6 | 0.5 | 5.7 ± 1.5 | 0.6 |
| 1667 | 73.7 ± 6.1 P VT | 0.7 | 85.3 ± 8.1 P | 0.9 | 2.7 ± 1.2 P TL | 0.2 | 5.3 ± 1.5 P | 0.6 |
| 5000 | 67.0 ± 7.0 P TL | 0.7 | 88.3 ± 4.5 P ST | 0.9 | 2.0 P VT | 0.2 | 8.0 ± 2.6 P | 0.8 |
| Positive control | 1112.0 ± 33.5 | 11.0 | 570.7 ± 61.4 | 6.0 | 186.0 ± 36.5 | 16.9 | 242.3 ± 6.4 | 25.1 |
P = Precipitate / ST = Slightly Thin Lawn / TL = Thin Lawn / VT = Very Thin Lawn
Table 1a. Aberration Data: Experiment 1 |
||||||||||
| Exposure duration / Harvest Time | S9 mix | Concentration (µg/ml) | Aberration frequency | Aberrant Cell Frequency (%) | ||||||
| (Lesions/ Cell) | Including Gaps | Excluding Gaps | ||||||||
| 6 h / 24 h | + | 0 (Ethanol 1%) | 0.01 | 1 | 0 | |||||
| 0 (Ethanol 1%) | 0.00 | 0 | 0 | |||||||
| 20 | 0.01 | 1 | 0 | |||||||
| 20 | 0.01 | 1 | 0 | |||||||
| 78 | 0.01 | 1 | 0 | |||||||
| 78 | 0.01 | 1 | 0 | |||||||
| 156 | 0.01 | 1 | 0 | |||||||
| 156 | 0.02 | 2 | 0 | |||||||
| 30 µg/ml CP | 0.13 | 8 * | 7 * | |||||||
| 40 µg/ml CP | 0.11 | 8 * | 8 * | |||||||
| 6 h / 24 h | - | 0 (Ethanol 1%) | 0.01 | 1 | 0 | |||||
| 0 (Ethanol 1%) | 0.00 | 0 | 0 | |||||||
| 39 | 0.00 | 0 | 0 | |||||||
| 39 | 0.02 | 0 | 0 | |||||||
| 78 | 0.00 | 0 | 0 | |||||||
| 78 | 0.01 | 1 | 0 | |||||||
| 156 | 0.01 | 1 | 0 | |||||||
| 156 | 0.00 | 0 | 0 | |||||||
| 30 µg/ml MMC | 0.06 ** | 4 | 4 * | |||||||
| 40 µg/ml MMC | 0.31 | 9 * | 8 * | |||||||
| * positive response ** inconclusive response | ||||||||||
| Table 1b. Aberration Data: Experiment 2 | |||||
| Exposure duriation / Harvest Time | S9 mix | Concentration (µg/ml) | Aberration frequency | Aberrant Cell Frequency (%) | |
| (Lesions/ Cell) | Including Gaps | Excluding Gaps | |||
| 6 h / 24 h | + | 0 (Ethanol) | 0.00 | 0 | 0 |
| 0 (Ethanol) | 0.00 | 0 | 0 | ||
| 25 | 0.00 | 0 | 0 | ||
| 25 | 0.00 | 0 | 0 | ||
| 150 | 0.01 | 1 | 1 | ||
| 150 | 0.02 | 2 | 0 | ||
| 200 | 0.04 | 4 | 1 | ||
| 200 | 0.02 | 1 | 1 | ||
| 250 | 0.01 | 1 | 1 | ||
| 250 | 0.01 | 1 | 0 | ||
| 20 µg/ml CP | 0.02 | 2 | 2 | ||
| 40 µg/ml CP | 0.10 | 7* | 7* | ||
| 22 h / 24 h | - | 0 (Ethanol) | 0.00 | 0 | 0 |
| 0 (Ethanol) | 0.00 | 0 | 0 | ||
| 12.5 | 0.00 | 0 | 0 | ||
| 12.5 | 0.00 | 0 | 0 | ||
| 25 | 0.00 | 0 | 0 | ||
| 25 | 0.01 | 1 | 0 | ||
| 50 | 0.00 | 0 | 0 | ||
| 200 | 0.00 | 0 | 0 | ||
| 20 µg/ml MMS | 0.07** | 6** | 5* | ||
| 30 µg/ml MMS | 0.23* | 12* | 10* | ||
| 22 h / 48 h | - | 0 (Ethanol) | 0.01 | 1 | 0 |
| 0 (Ethanol) | 0.01 | 1 | 0 | ||
| 12.5 | 0.01 | 1 | 0 | ||
| 12.5 | 0.00 | 0 | 0 | ||
| 25 | 0.01 | 1 | 1 | ||
| 25 | 0.01 | 1 | 0 | ||
| 50 | 0.00 | 0 | 0 | ||
| 50 | 0.00 | 0 | 0 | ||
| 20 µg/ml MMS | 0.07** | 6** | 4* | ||
| 30 µg/ml MMS | 0.23* | 10* | 8* | ||
| * positive response ** inconclusive response | |||||
| Table 2: Polyploid data | |||||
| Concentration (µg/ml) | No. Of Diploid cells | No. of Polyploid cells | Frequency of Polyploid cells | ||
| Normal | Endoploid | ||||
| 0 (Ethanol) | 300 | 1 | 0 | 0.33 | |
| 0 (Ethanol) | 300 | 0 | 0 | 0.00 | |
| 12.5 | 300 | 0 | 1 | 0.33 | |
| 12.5 | 300 | 1 | 0 | 0.33 | |
| 25 | 300 | 0 | 0 | 0.00 | |
| 50 | 300 | 2 | 0 | 0.66 | |
| 200 | 300 | 1 | 1 | 0.66 | |
| 200 | 300 | 1 | 0 | 0.33 | |
Additional information
In Vitro
In Vitro Bacterial Reverse Mutation Assay: Alkenes, C11 -12 hydroformylation products, distn. residues was tested for mutagenic activity in Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA100 and in Escherichia coli WP2uvrA according to OECD guideline 471and the European Commission Annex V Test Method B13 and B14.
Two independent tests were conducted in triplicate in the absence and presence of a metabolic activator (S9 mix). The first test was conducted by the direct plate incorporation method, while the second test was conducted by the pre-incubation method. The test item was dosed at concentrations ranging from 17 to 5000 µg/plate in both assays. No evidence of mutagenic activity was obtained with any strain in either test.
It was concluded that Alkenes, C11 -12, hydroformylation products, distn. residues was not mutagenic in strains of Salmonella typhimurium and Escherichia coli when tested in acetone in the absence and presence of metabolic activation. The test item was tested to the predetermined maximum of 5000 µg per plate, at which concentration toxicity was encountered. In addition, the test item was tested up to and beyond its limits of solubility in the test system.
In Vitro Mammalian Chromosome Aberration Test: Alkenes, C11 -12 hydroformylation products, distn. residues was assessed for clastogenic potential in an in vitro mammalian chromosome aberration test in Chinese hamster ovary cells. This reliable (Klimisch 1) and GLP compliant study was conducted according to OECD 473 guidelines. All the cultures treated with the test item had levels of structural aberrations within the 95% confidence limits for a negative response. An extra assessment of polyploidy was carried out on the cultures treated in the absence of S9 mix and harvested at 48 h. All the cultures treated with alkenes, C11-12, hydroformylation products, distn. residues had levels of polyploidy within the 95% confidence limits for a negative response. Consequently it can be concluded that alkenes, C11-12, hydroformylation products, distn. residues was not clastogenic when tested with Chinese hamster ovary cells in vitro.
Mouse Lymphoma Mutation Study: Alkenes, C11-12, hydroformylation products, distn. residues (CAS No. 90622-27-8) were assayed for mutagenic potential in the mouse lymphoma L5178Y cell line. Tests were conducted both in the absence and in the presence of a metabolic activator (S9 mix). The study was designed to be consistent with ICH Guidelines, OECD Guideline No. 476 and EC Directive 2000/32/EC B.17. No evidence of mutagenic activity was obtained with alkenes, C11-12, hydroformylation products, distn. residues in either the absence or the presence of S9 mix when the exposure period was 4 h. All such assays satisfied the criteria required to demonstrate that results had been obtained at a sufficiently toxic concentration of test item. It is therefore concluded that alkenes, C11-12, hydroformylation products, distn. residues is not mutagenic in mouse lymphoma L5178Y cells, in either the absence or the presence of S9 mix, when tested in acetone at concentrations extending into the toxic range.
No mutagenic potential was reported for Alkenes, C11-12, hydroformylation products, distn. residues in a range of in vitro genotoxicity studies conducted according to REACH annex VII or VIII requirements.
In Vivo
In accordance with REACH regulation Annex IX 8.4 column 2; 'Appropriate in vivo mutagenicity studies shall be considered in case of a positive result in any of the genotoxicity studies in Annex VII or VIII.' No positive findings have been reported across the range of REACH Annex VII or VIII in vitro genotoxicity studies for alkenes, C11-12, hydroformylation products, distn residues. Consequently there is no mandatory requirement any in vivo genotoxicity studies to be presented in this dossier.
On the basis of available in vitro data no genotoxic potential has been identified for alkenes, C11-12, hydroformylation products, distn. residues.
Short description of key information:
In vitro: 3 in vitro genotoxicity studies have been conducted with
alkenes, C11-12, hydroformylation products, distn residues. In a
reliable (Klimisch 1) GLP compliant bacterial reverse mutation assay
conducted according to OECD 471 guidelines, alkenes, C11-12,
hydroformylation products, distn residues were reported to be negative
for mutagenic activity
A reliable (Klimisch 1) GLP compliant in vitro mammalian chromosome
aberration test (Klimisch 1) conducted according to OECD 473 guidelines
reported that the test item, alkenes, C11-12, hydroformylation products,
distn residues was not clastogenic.
Furthermore in a reliable (Klimisch 1) GLP compliant mouse lymphoma
mutation study alkenes, C11-12, hydroformylation products, distn
residues were reported to be negative (with and without metabolic
activation) for mutagenic activity.
In Vivo: In accordance with REACH regulation Annex IX 8.4 column 2;
'Appropriate in vivo mutagenicity studies shall be considered in case of
a positive result in any of the genotoxicity studies in Annex VII or
VIII.'
No positive findings have been reported across the range of REACH Annex
VII or VIII in vitro genotoxicity studies for alkenes, C11-12,
hydroformylation products, distn residues. Consequently there is no
mandatory requirement any in vivo genotoxicity studies to be presented
in this dossier.
Endpoint Conclusion: No adverse effect observed (negative)
Justification for classification or non-classification
The negative results reported in in vitro genotoxicity assays do not warrant the classification of Alkenes, C11-12, hydroformylation products, distn. residues as a substance with genotoxic potential. Consequently, Alkenes, C11-12, hydroformylation products, distn. residues is not classified as a genotoxin under the new Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
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.
