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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 225-207-5 | CAS number: 4717-96-8
- 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
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2009-03-27 to 2009-04-09
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 009
- Report date:
- 2009
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 1997
- Deviations:
- no
- Principles of method if other than guideline:
- n/a
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- Tetrahydro-4-methyl-2H-pyran
- EC Number:
- 225-207-5
- EC Name:
- Tetrahydro-4-methyl-2H-pyran
- Cas Number:
- 4717-96-8
- Molecular formula:
- C6H12O
- IUPAC Name:
- 4-methyltetrahydro-2H-pyran
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Chemical name: 4-methyltetrahydropyran (MTHP)
- CAS no.: 4717-96-8
- EC-no.: not assigned
- Source and lot/batch No.of test material: Kuraray / MTHP204347
- Expiration date of the lot/batch: not stated
- Molecular weight: 100.16 g/mol
- Purity: 99.98%
Method
- Target gene:
- see below
Species / strain
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Additional strain / cell type characteristics:
- not applicable
- Cytokinesis block (if used):
- n/a
- Metabolic activation:
- with and without
- Metabolic activation system:
- phenobarbital / 5,6-benzoflavone
- Test concentrations with justification for top dose:
- Dose range finder: -/+S9: 0, 1.22, 4.88, 19.5, 78.1, 313, 1250, 5000 ug/plate
Main study:
-S9:
TA100; WP2uvrA; TA98: 0, 156, 313, 625, 1250, 2500, 5000 ug/plate
TA1535; TA1537: 0, 39.1, 78.1, 156, 313, 625, 1250 ug/plate
+S9:
TA100; TA1535; TA1537: 0, 39.1, 78.1, 156, 313, 625, 1250 ug/plate
WP2uvrA; TA98: 0, 156, 313, 625, 1250, 2500, 5000 ug/plate - Vehicle / solvent:
- DMSO
Controlsopen allclose all
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- +S9: TA1535, WP2uvrA
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- Remarks:
- +S9: TA100, TA98, TA1537
- Positive controls:
- yes
- Positive control substance:
- furylfuramide
- Remarks:
- -S9: TA100, TA98, WP2uvrA
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- -S9: TA1535
- Positive controls:
- yes
- Positive control substance:
- other: ICR-191 (6-Chloro-9-[3-(2-chloroethylamino)propylamino]-2-methoxyacridine dihydrochloride)
- Remarks:
- -S9: TA1537
- Details on test system and experimental conditions:
- The pre-incubation methodology was used for the dose range finder and a main test. Duplicate plates were used for the dose range finder and main tests.
Test tubes containing 0.1 mL of vehicle, positive control or test article formulation were mixed with 0.5 mL S9 mix (or PBS in the absence of metabolic activation). 0.1 mL fresh bacterial culture was added and the mixture was incubated while shaking at 37°C for 20 minutes.
After pre-incubation, 2 mL of top agar (kept at 45°C) was added to each tube and this mixture was shaken and overlaid onto Vogel-Bonner agar plates (minimal glucose agar plates). E.coli containing tubes were poured onto minimal agar plates.
Agar plates were incubated at 37°C for 48 h in the dark for the bacterial colonies (his+ or typ+ revertants) counted.
The background lawns of the plates were examined for signs of toxicity. Other toxicity indicators that may have been noted included a marked reduction in revertants compared to the concurrent vehicle controls and/or a reduction in mutagenic response. - Evaluation criteria:
- The test chemical was considered positive in this assay if the following criteria were met:
- dose-related and reproducible increase in the number of revertant colonies (i.e. doubling of the spontaneous mutation rate in at least one tester strain either –S9 or +S9)
A test substance was generally considered non-mutagenic in this test if:
- The number of revertants for all tester strains were within the historical negative control range under all experimental conditions in two experiments carried out independently of each other. - Statistics:
- Statistics not warranted
Results and discussion
Test resultsopen allclose all
- 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 applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
Any other information on results incl. tables
A. Dose range finder:
No precipitation was observed at any dose level, - or + S9. Growth inhibition (evaluation by bacterial background lawn) was observed at 1250 ug/plate and above for strains TA100 (+S9), TA1535 (+/-S9); TA1537 (+/-S9) and at 5000ug/plate for strains TA100 (-S9), WP2uvrA (+/-S9), TA98 (+/-S9). MTHP was deemed not mutagenic in the dose range finder experiment following a pre-incubation methodology. For the main mutation test, as growth inhibition was the limiting factor the maximum dose level was set at 1250 ug/plate for strains TA98 (+S9), TA1535 (+/-S9) and TA1537 (+/-S9).for all other strains +/-S9 the maximum dose level was 5000 ug/plate.
Table 7.6.1/01-1: Bacterial (reverse) gene mutation pre-incubation data – Dose range finder
Conc. (ug/plate) | TA100 | TA1535 | WP2uvrA | TA98 | TA1537 | ||||||
-S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | ||
0 | 92 | 137 | 13 | 10 | 27 | 27 | 32 | 57 | 7 | 11 | |
1.22 | 96 | 109 | 12 | 9 | 29 | 28 | 26 | 47 | 4 | 6 | |
4.88 | 98 | 114 | 9 | 6 | 21 | 25 | 29 | 42 | 7 | 5 | |
19.5 | 103 | 96 | 14 | 11 | 28 | 26 | 32 | 39 | 7 | 7 | |
78.1 | 108 | 117 | 12 | 10 | 26 | 21 | 42 | 54 | 2 | 7 | |
313 | 97 | 118 | 12 | 13 | 23 | 28 | 35 | 43 | 4 | 8 | |
1250 | 115 | 111B | 8B | 8B | 28 | 34 | 36 | 42 | 5B | 8B | |
5000 | 0A,B | 77B | 0A,B | 4B | 19B | 21B | 0A,B | 18B | 0A,B | 5B | |
+ve | 545 | 964 | 226 | 220 | 85 | 1122 | 478 | 432 | 1318 | 127 | |
A: total growth inhibition B: reduced background lawn +ve controls: -S9 (absence of metabolic activation): TA100, WP2uvrA, TA98: furylfuramide TA1535: sodium azide TA1537: ICR-191 | +S9 (presence of metabolic activation): TA100, TA98, TA1537: Benzo[a]pyrene TA1537, WP2urvA: 2-aminoanthracene | ||||||||||
B. Main mutation tests
No precipitation was observed at any dose level. For main mutation test, growth inhibition (evaluation by bacterial background lawn) was observed at 1250 ug/plate, the maximum dose tested for strains TA100 (+S9), TA1535 (+/-S9) and TA1537 (+/-S9); at 2500ug/plate and above for strains TA100 (+S9); TA98 (+S9), WP2uvrA (+/-S9), TA98 (+/-S9) and at 5000 ug/plate for strains Wp2uvrA (+/-S9)
The positive controls induced an acceptable increase in revertant colony numbers, thereby demonstrating the sensitivity and specificity of the test system.
Following MTHP treatments of all the test strains in the absence and presence of S-9, no increases in revertant numbers were observed that were equal to or greater than 2-fold above the concurrent vehicle control in two independent experiments. This study was therefore considered to have provided no evidence of any mutagenic activity in this assay system (refer to Table 7.6.1/01-2,).
Table 7.6.1/01-2: Bacterial (reverse) gene mutation pre-incubation data – Main mutation experiment
Conc. (ug/plate) | TA100 | TA1535 | WP2uvrA | TA98 | TA1537 | ||||||
-S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | ||
0 | 106 | 122 | 11 | 14 | 30 | 22 | 22 | 41 | 7 | 10 | |
39.1 | NT | 123 | 13 | 13 | NT | NT | NT | NT | 9 | 11 | |
78.1 | NT | 119 | 12 | 14 | NT | NT | NT | NT | 4 | 13 | |
156 | 100 | 119 | 12 | 14 | 28 | 31 | 24 | 29 | 9 | 12 | |
313 | 110 | 123 | 10 | 12 | 29 | 22 | 30 | 38 | 6 | 7 | |
625 | 107 | 135 | 13 | 16 | 23 | 23 | 29 | 44 | 5 | 14 | |
1250 | 117 | 123B | 12B | 17B | 20 | 29 | 32 | 41 | 8B | 9B | |
2500 | 114B | NT | NT | NT | 23 | 18 | 29 | 33B | NT | NT | |
5000 | 29B | NT | NT | NT | 12B | 8B | 0B | 13B | NT | NT | |
+ve | 595 | 1112 | 317 | 308 | 72 | 1103 | 583 | 441 | 1333 | 140 | |
B: reduced background lawn NT: not treated +ve controls: -S9 (absence of metabolic activation): TA100, WP2uvrA, TA98: furylfuramide TA1535: sodium azide TA1537: ICR-191 | +S9 (presence of metabolic activation): TA100, TA98, TA1537: Benzo[a]pyrene TA1537, WP2urvA: 2-aminoanthracene | ||||||||||
Table 7.6.1/01-3: Bacterial (reverse) gene mutation data – Historical vehicle and positive control data
Conc. (ug/plate) | TA100 | TA1535 | WP2uvrA | TA98 | TA1537 | ||||||
-S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | -S9 | +S9 | ||
Vehicle control | |||||||||||
Mean ±SD | 123 | 136 | 10 | 10 | 21 | 23 | 20 | 35 | 11 | 14 | |
Lower limit | 86 | 95 | 4 | 4 | 9 | 11 | 8 | 17 | 4 | 6 | |
Upper limit | 159 | 176 | 16 | 16 | 34 | 34 | 32 | 52 | 18 | 22 | |
Positive control | |||||||||||
Mean ±SD | 592 | 1061 | 317 | 284 | 78 | 945 | 468 | 383 | 1383 | 127 | |
Lower limit | 473 | 849 | 222 | 199 | 54 | 756 | 375 | 307 | 691 | 89 | |
Upper limit | 710 | 1274 | 412 | 369 | 101 | 1134 | 562 | 460 | 2074 | 165 | |
Lower limit: ± 2 S.D Upper limt: ± 2 S.D
-S9 (absence of metabolic activation): TA100, WP2uvrA, TA98: furylfuramide TA1535: sodium azide TA1537: ICR-191 | +S9 (presence of metabolic activation): TA100, TA98, TA1537: Benzo[a]pyrene TA1537, WP2urvA: 2-aminoanthracene | ||||||||||
C. Deficiencies:
Under the requirements of OECD 471 triplicate plates should be used for each dose level, although the use of duplicate plating is acceptable when scientifically justified.
This study was conducted in compliance with GLP and under the Japanese regulations, with the reproducibility was confirmed in two independent experiments. For this reason the use of duplicate plates was considered acceptable.
Applicant's summary and conclusion
- Conclusions:
- It was concluded that MTHP did not induce mutation in four histidine-requiring strains (TA98, TA100, TA1535 and TA1537) of Salmonella typhimurium, and one tryptophan-requiring strain (WP2uvrA) of Escherichia coli when tested under the conditions of this study. These conditions included treatments at concentrations up to 5000 µg/mL (the maximum recommended concentration in accordance with current regulatory requirements), in the absence and presence of a rat liver metabolic activation system (S9) using pre-incubation methodology.
- Executive summary:
In a reverse gene mutation assay in bacteria, S. typhimurium strains TA98, TA100, TA1535 and TA1537 and E. coli strain WP2uvrA were exposed to MTHP formulated in dimethyl sulphoxide (DMSO). The pre-incubation methodology was used. Following a dose range-finder experiment, a main mutation experiment was conducted using concentrations which spanned the range of 39.1 – 5000 ug/plate. Growth inhibition was observed in all strains, at differing concentrations.
For main mutation test, growth inhibition (evaluation by bacterial background lawn) was observed at 1250 ug/plate, the maximum concentration tested for strains TA100 (+S9), TA1535 (+/-S9) and TA1537 (+/-S9); at 2500 ug/plate and above for strains TA100 (+S9); TA98 (+S9), WP2uvrA (+/-S9), TA98 (+/-S9) and at 5000 ug/plate for strains Wp2uvrA (+/-S9). No precipitation was observed at any concentration.
The positive controls induced an acceptable increase in revertant colony numbers, thereby demonstrating the sensitivity and specificity of the test system.
Following MTHP treatments of all the test strains in the absence and presence of S-9, no increases in revertant numbers were observed that were equal to or greater than 2-fold above the concurrent vehicle control. This study was therefore considered to have provided no evidence of any mutagenic activity in this assay system.
It was concluded that MTHP did not induce mutation in four histidine-requiring strains (TA98, TA100, TA1535 and TA1537) of Salmonella typhimurium, and one tryptophan-requiring strain (WP2uvrA) of Escherichia coli when tested under the conditions of this study. These conditions included treatments at concentrations up to 5000 µg/mL (the maximum recommended concentration in accordance with current regulatory requirements), in the absence and presence of a rat liver metabolic activation system (S9) using pre-incubation methodology.
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.