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EC number: 222-824-1 | CAS number: 3623-51-6
- 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
No data is available for (±)-neomenthol. Reliable data are available from L-menthol and menthol.
In most available information about the testing of methanol's genotoxic potential, no activity over background was found. In those chromosome aberration tests in which menthols were due to cytotoxic doses weak positive tested the chromosomal aberration is interpreted as false positive result, being generated by secondary effects of toxicity.
L-menthol and menthol and thus (±)-neomenthol is not genotoxic in vitro as found from a weight of evidence approach.
Link to relevant study records
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- Please refer to IUCLID section 13 for a detailed justification of the category approach.
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- not specified
- Genotoxicity:
- ambiguous
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at 1.5 mM of menthol the number of cells in culture was only 45% of control
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- ambiguous
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 33% of controls surviving cells
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- human lymphoblastoid cells (TK6)
- Metabolic activation:
- without
- Genotoxicity:
- positive
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- 20% of control surviving cells
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Species / strain:
- other: Chinese Hamster Lung Fibroblast (CHL)
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Remarks:
- at the highest non cytotoxic dose
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- valid
- Positive controls validity:
- not specified
- Species / strain:
- lymphocytes: human
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Species / strain:
- other: human embryonic lung cells (WI-38)
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: results from study from 1998a
- Conclusions:
- In four of six cytogencity tests menthol did not show chromosome aberration potential. In two studies postive or ambigous results were observed at cytotoxic concentrations therefore these were interpreted as false positive results, being generated by secondary effects of toxicity.
In conclusion no cytogenicity is considered for menthol. - Executive summary:
Cytogenicity tests are available from structural analogue menthol (CAS 89-78-1). It is concluded that (±)-neomenthol does not induce cytogenicity in mammalian cells. As explained in the justification for type of information, the differences in molecular structure between the target and the source are unlikely to lead to differences in genetic toxicity.
- Endpoint:
- in vitro DNA damage and/or repair study
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- Please refer to IUCLID section 13 for a detailed justification of the category approach.
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Species / strain:
- lymphocytes: human
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Remarks on result:
- other: results from study from 1996
- Conclusions:
- Methanol did not show DNA damaging potential in 3 different tests.
- Executive summary:
DNA damaging tests are available from structural analogue menthol (CAS 89-78-1). It is concluded that (±)-neomenthol does not induce DNA damage in mammalian cells. As explained in the justification for type of information, the differences in molecular structure between the target and the source are unlikely to lead to differences in genetic toxicity.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- Please refer to IUCLID section 13 for a detailed justification of the category approach.
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Evaluation criteria:
- no data
- Species / strain:
- S. typhimurium, other: TA98, 100, 97a, 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at highest concentration with and without S9 mix for TA97a and 102
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100, TA 1538
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100, TA 92, TA 94
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Remarks:
- at the highest non-cytotoxic dose
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- at the highest concentration with and without S9 mix
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100, TA 97
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- not specified
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- not specified
- Species / strain:
- S. typhimurium, other: FU 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- other: LD50 without S9 >16 µg/mL; LD50 with S9 >9 µg/mL
- Vehicle controls validity:
- not specified
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Remarks on result:
- other: reults from Ames 1998 (L-menthol)
- Conclusions:
- Based on 5 gene mutation studies in bacteria menthol showed no genotoxic potential in these in vitro tests. One Ames test performed with L-menthol showed also negative results.
- Executive summary:
Ames tests are available from structural analogue L-menthol (CAS 2216-51-5) and menthol (CAS 89-78-1). It is concluded that (±)-neomenthol does not induce gene mutation in bacteria. As explained in the justification for type of information, the differences in molecular structure between the target and the source are unlikely to lead to differences in genetic toxicity.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- Please refer to IUCLID section 13 for a detailed justification of the category approach.
- Reason / purpose for cross-reference:
- read-across source
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- DL Menthol was usually lethal at concentration of 200 µg/ml in the absence or presence of S9 mix, and 150 µg /ml caused average RTG values that ranged from 24% to 27% without S9 and 52% to 94% with S9 respectively.
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not specified
- Positive controls validity:
- valid
- Additional information on results:
- No evidence for mutagenicity was obtained. In nonactivation experiment Trial 2, a highly toxic (10% RTG) treatment of one culture with 200 pg/mL caused no change in the mutant frequency (MF).
- Conclusions:
- Under the conditions tested, menthol showed in C5178Y Mouse Lymphoma Cells no gene mutation effects.
- Executive summary:
A mouse lymphoma test is available from structural analogue menthol (CAS 89 -78 -1). It is concluded that (±)-neomenthol does not induce gene mutation in mammalian cells. As explained in the justification for type of information, the differences in molecular structure between the target and the source are unlikely to lead to differences in genetic toxicity.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
No data is available for (±)-neomenthol. Reliable data are available from menthol.
All in vivo tests showed no genotoxic potential.
Menthol and thus (±)-neomenthol is not genotoxic in vivo as found from a weight of evidence approach.
Link to relevant study records
- Endpoint:
- genetic toxicity in vivo, other
- Remarks:
- micronucleus, dominant lethal assay, bone marrow chromosome aberration, host mediated assay
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- Please refer to IUCLID section 13 for a detailed justification of the category approach.
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Control animals:
- yes, concurrent vehicle
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- only for the highest dose (1000 mg/kg)
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Remarks on result:
- other: results from mouse micronucleus assay (1993)
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Remarks on result:
- other: results from dominant lethal assay (1975)
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Remarks on result:
- other: results from bone marrow chromosome aberration test (1975)
- Sex:
- male
- Genotoxicity:
- ambiguous
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not examined
- Positive controls validity:
- valid
- Remarks on result:
- other: results from host mediated assay (1975)
- Conclusions:
- Menthol did not show genetic toxicity in mouse micronucleus test, dominant lethal test or bone marrow chromosme aberreation test. In a host mediated assay ambigous results were found. Since this is an outdated assay and all other assays were negative it can be concluded that menthol does not possess a genotoxic potential.
- Executive summary:
Four different in vivo genotoxicity tests are available from structural analogue menthol (CAS 89-78-1 and CAS 15356-70-4). It is concluded that (±)-neomenthol does not possess genotoxic potential in vivo. As explained in the justification for type of information, the differences in molecular structure between the target and the source are unlikely to lead to differences in genetic toxicity.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Testing data on genetic toxicity of ±-neomenthol is not available. The evaluation of ±-neomenthol is based on read across data and/or published data. All available information were used for a weight of evidence approach to assess the genetic toxicity of ±-neomenthol.
Read Across Justification:
Based on the identical profiles of the different menthols and supported by the Read-Across Justification for menthols (IUCLID chapter 13) all studies on stereoisomers of (±)-neomenthol are used for read across. These isomers are L-menthol (CAS 2216-51-5), (+)-menthol (CAS 15356-60-2), D/L-menthol (CAS 1490 -04 -6) and menthol (CAS 89-78-1).Moreover, a comparative physico-chemical profile of these isomers reinforces this similarity. As structural isomers, the members of the menthol category share the same molecular weight. Of particular importance to environmental effects and human effects are the values for partition coefficient (log Pow between 3.12 and 3.45 at 25°C), vapour pressure (from 3.6 to 21 Pa at 25°C) and water solubility (moderately soluble from 231 to 456 mg/L at 25°C). The read across is consistent based on these physico-chemical parameters.
Detail on the genetic toxicity study endpoint:
Despite the absence of experimental data on ±-neomenthol we conclude by read across from the genetic toxicity information of the other isomers and on the basis of a weight of evidence approach that this endpoint is sufficiently covered.
Bacteria reverse test:
Menthol (DL-menthols and the isomeric mixture) was not mutagenic in Ames tests using the tested strains S. typhimurium TA92, TA 97a, TA 98, TA 100, TA 102, TA 1535, TA 1537, FU 100, and TA 1538 with and without metabolic activation (1992, 1984 (1), 1984, 2005, 1988, 1998).
It is concluded that the menthols and thus (±)-neomenthol is not mutagenic to the Salmonella typhimurium strains mentioned above.
In vitro mammaliam cells tests:
· Chromosomal aberration tests performed with menthol showed mainly negative results.
· Tests conducted with CHO cells in concentrations of 100, 150 and 200 µg/mL without metabolic activation and in concentrations of 50, 124 and 200 µg/mL with metabolic activation (1989) were negative.
· A cytogenetic assay with CHL cells performed by (1984) showed a negative result without metabolic activation. The concentrations tested were 100, 150 and 200µg/mL.
· A study of (1998 (1)) showed ambiguous results. Weak but statistically significant increases in chromosomal aberrations were observed in CHO cells and TK6 human lymphocytes after treatment with DL-menthol in concentrations of 250 to 281 µg/mL (cell viability 47-33% of controls) and 128 to 187 µg/mL (cell viability at 187 µg/mL 20% of controls), respectively, without metabolic activation. Due to the cytotoxic doses tested the observed weak chromosomal aberration is interpreted as false positive result, being generated by secondary effects of toxicity.
· A further chromosome aberration test with CHO cells was positive, showing maximal 7% aberrant metaphases (1998). Again menthol was tested at cytotoxic concentrations. The authors conclude that “the data, however, support the concept that when there is good evidence that a compound and its metabolites do not react with DNA (or topoisomerases), aberrations at toxic doses that inhibit DNA synthesis may be induced indirectly, and may not constitute a risk of mutagenicity at low exposure levels associated with a good safety margin".
· Experimental data from the testing of 31 chemicals (including DL-menthol) for mutagenicity at the TK locus in L5178Y mouse lymphoma cells are presented and evaluated. If mutagenic activity was not obtained for the chemical added to suspension cultures for 4 hours, then the testing was repeated in the presence of hepatic S9 mix prepared from Aroclor 1254 induced male Fischer 344 rats. Multiple trials were performed for each chemical, and mutagenic treatments were analyzed for the induction of small and large mutant colony populations. A negative result was obtained for DL-menthol with and without metabolic activation (1991). The concentration range tested was 12.5 to 200 µg/mL; the lethal dose was 200 µg/mL.
· The genotoxic potential of menthol was investigated by analyzing the frequencies of sister chromatid exchange (SCE) and chromosomal aberrations in cultured human lymphocytes exposed to menthol. Phytohaemagglutinin-stimulated human lymphocyte cultures grown in the presence of menthol at final concentrations of 0.1, 1 or 10mM, with or without S-9, had polyploid cell and structural chromosomal aberration frequencies similar to those seen in the solvent controls. Furthermore, menthol, either in the presence or absence of S-9, did not alter the SCE frequency in the tested human chromosomes. The results suggest that menthol does not have a chromosomal-damaging effect in human lymphocytes (1991).
· An alkaline elution assay to detect DNA damage in primary rat hepatocytes – testing concentrations of 0.1, 0.3, 0.7, 1.0, 1.3 mM up to cytotoxic concentrations - was negative (1996).
· A sister chromatid exchange test with chinese hamster ovary cells was concluded negative with and without metabolic activation (1989)
· The chromatids damage induced by the menthol was investigated by in vitro method to human embryonic lung cells, at concentrations of 0.1, 1.0 and 10.0mg/mL in 0.85% saline. Cells were incubated at 37°C and examined twice daily. Cells were harvested by shaking when sufficient mitoses were observed, usually 24-48 hours after planting, and fixed in absolute methanol: glacial acetic acid (3:1) for 30 minutes. Microscopic inspection was conducted to count aberrations (bridges pseudochiasmata, multipolar cells, acentric fragments, etc.) in treated- and control groups. Outcome was that the test substance produced no significant aberration in the anaphase of human tissue culture chromosomes under test conditions (1975).
Test results in detail are given in following table.
Test system |
Protocol |
Concentrations |
Results |
Reference |
||
|
|
Exp. [µg/mL] |
Cytotox.[µg/ml](% cell viability) |
+ MA |
- MA |
|
CHO |
Exposure time: 8 hrs(-); 2 hrs(+) Harvest time: 10.50 (-),12.50 (+) hrs |
100, 150, 200 (- MA), 50, 124, 250 (+ MA) |
200 |
- |
- |
1989 |
CHL |
Exposure time: 24, 48 hrs |
100, 150, 200 |
200 = 50% cell- |
n.d. |
- |
1984 |
CHO |
Exposure time: 3 hrs |
203, 219, 234 |
234 (45 %) |
+ |
1998 |
|
CHO |
Exposure time: 3 hrs |
46-297 |
(47%), |
+ |
+ |
1998 (1) |
TK6 human lymphocytes |
Exposure time: 3 hrs |
128-187 |
187 (20%) |
n.d. |
+ |
1998 (1) |
L5178Y mouse lymphoma cells | Exposure time: 4 hrs |
15 - 200 | Lethal at 200µg/ml in the absence or presence of S9 mix, and 150µg/ml caused average RTG values that ranged from 24% to 27% without S9 and 52% to 94% with S9. | - | - | 1991 |
Human lymphocytes chromosome aberration assay | no data | 0.1, 1, and 10 nM | At concentrations higher than 10 mM, it significantly affected the growth of human lymphocytes in phytohaemagglutinin-stimulated cultures | - | - | 1991 |
Human lymphocytes SCE assay |
no data | no data | At concentrations higher than 10 mM, it significantly affected the growth of human lymphocytes in phytohaemagglutinin-stimulated cultures | - | - | 1991 |
alkaline elution assay | Exposure time: 3 hr |
0.1, 0.3, 0.7, 1.0, 1.3 mM |
negative | n.d. | n.d. | 1996 |
Human embryonic lung culture (WI-38) | 24 -48hours | 0.1, 1.0 and 10.0 mg/mL | negative without metabolic activation | n.d | - | 1975 |
Genotoxicity in vivo:
· In a micronucleus assay in bone marrow cells of B6C3F1 mice, the test organisms received daily intraperitoneal injections of 0, 250, 500 or 1000 mg/kg bw/day menthol (CAS No. 15356-70-4) for 3 days (1993). No increase in micronuclei in bone marrow polychromatic erythrocytes was observed. The data indicated that cytotoxic effects on bone marrow cells could not be expected under the test conditions.
· In a host mediated assay in mice effects of oral administered menthol on genmutation and recombination was investigated in Salmonella typhimurium (his G-46 and TA-1530) and saccharomyces cerevisiae (the diploid strain D-3) injected into the mice peritoneum. Menthol caused no significant increases in mutant or recombinant frequencies when tested against Salmonella G-46 at all dose levels, Salmonella TA-1530 subacute dose levels and Saccharomyces D3 acute dose levels, respectively. Test against TA-1530 acute levels showed increasing mutant frequencies with increasing dose levels with the high dose being weakly positive but significant reaction. The subacute levels with Saccheromyces D3 showed increased recombinant frequencies with no dose response (1975).
· In the further study of same report (1975), the in vivo chromosomal aberration test in bone marrow cells of rat was conducted for menthol. Test substance was suspended in 0.85% saline and administered to male rats by intubation. The dose levels used were 145 mg/kg, 14.5 mg/kg and 1.45 mg/kg in the first test both by acute method (single dose/ after 6, 24 and 48 hours animals were killed) and subacute method (one dose per day for 5 days, animals were killed 6 hours after last administration.). In test II the used concentrations were 500 and 3000 mg/kg for the acute treatment, and 1150 mg/kg for the subacute treatment. After exposure the bone marrow from one femur was isolated. Polychromatic erythrocytes were stained by Giemsa. Polychromatic erythrocytes were microscopically inspected to count the chromosomal aberrations. The results showed that under test conditions the substance does not induce chromosomal aberration in rat bone marrow polychromatic erythrocytes.
· Additionally, the in vivo Rodent Dominant Lethal Test in rat was conducted with menthol. Test substance was suspended in 0.85% saline and administered to male rats by intubation. The dose levels used were 145 mg/kg, 14.5 mg/kg and 1.45 mg/kg in the first test both by acute method (single dose) and subacute method (one dose per day for 5 days). In test II the 500 and 3000 mg/kg were used for the acute test, and 1150 mg/kg for the subacute test. Treated males were sequentially mated to 2 females per week for 8 weeks and 7 weeks for acute and subacute test repectively. Two virgin female rats were housed with male for 5 days (Monday to Friday). These two females were removed and housed in a cage until killed. The males were rested on Saturday and Sunday and two new females introduced to cages on Monday. Females were killed using CO2 at day 14 after separating from males, and at necropsy the uterus was examined for total number of implantations, total number of corpora lutea, pre-implantation losses, and dead implants. The results showed that under test conditions the substance does not induce a dominant lethal event after exposure to the test substance, which indicates that the substance has not affected the germinal tissue of rat (1975).
Overall
it can be conclude that menthol and its isomers do not possess a
genotoxic potential.
Justification for classification or non-classification
(±)-neomenthol does not meet the criteria for classification and labelling for genetic toxicity as set out in Regulation (EC) No 1272/2008.
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.