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EC number: 905-013-3 | CAS number: -
- 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
Effects on fertility
Link to relevant study records
- Endpoint:
- toxicity to reproduction
- Data waiving:
- other justification
- Justification for data waiving:
- other:
- Reproductive effects observed:
- not specified
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- no study available
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Screening for reproductive/developmental study:
Screening for reproductive/developmental study could be waived since according to REACH (Regulation (EC) No 1907/2006, Annex VIII, column 2, paragraph 8.7.1), this study does not need to be conducted if a pre-natal developmental toxicity study is available.
Two-generation reproductive toxicity:
There is no reproductive toxicity data on Reaction mass of isomenthone and trans-menthone.
Justification for read across: Menthol is the major metabolite of Reaction mass of isomenthone and trans-menthone in experimental animals. It is anticipated that Menthol is rapidly formed from the Reaction mass of isomenthone and trans-menthone during and after uptake through the gastrointestinal tract. It is therefore possible to use experimental data on Menthol for read across as described in the Read-Across Justification (see section 13). Reaction mass of isomenthone and trans-menthone will be reduced to menthol. Investigations on toxicokinetics show that L-, D-, D/L- and the unspecified menthol are well absorbed via the oral route. For all the isomers, elimination is rapid and mainly occurs as glucuronic acid conjugates via urine. Minor amounts are excreted via faeces (RIFM, 2008). Significant differences in toxicokinetic properties of menthol isomers were not reported. The available toxicity data indicate very similar toxicity profiles for the unspecified menthol isomer mixture. In mammalian species the low toxicity is manifested in LD50 values generally near or greater than 2000 mg/kg bw in acute studies, limited toxicity in repeated dose studies, and no effects in teratology evaluations. Irritation to skin and eyes was slight to moderate (RIFM, 2008). D/L-menthol is a racemic mixture of the D- and L- isomers and contains both isomers in equal proportions. Data gaps for Reaction mass of isomenthone and trans-menthone can therefore be filled by using the respective results of studies conducted with the racemic mixture or the L- or D-menthol isomers.
Due to above discussion, to this endpoint, reproductive properties of Reaction mass of isomenthone and trans-menthone can be thought equivalent to the tested substance DL-Menthol (The NOAEL in chronic study on rats was determined > 375 mg/kg bw/d).
Two-generation reproductive toxicity study could be waived since histopathological examinations of the reproduction organs of rats and mice did not show any changes in repeated dose toxicity studies of D/L-menthol and also in carcinogenicity studies of D/L- menthol, we can anticipate the same conclusion for Reaction mass of isomenthone and trans menthone.
Short description of key information:
According to REACH (Regulation (EC) No 1907/2006, Annex VIII, column 2, paragraph 8.7.1), the screening for reproductive/developmental toxicity does not need to be conducted if a pre-natal developmental toxicity study is available.
No changes were observed during the histopathological examinations of the reproductive organs of rats and mice in repeated dose toxicity studies and in carcinogenicity studies following the exposure to the different menthol isomers: D/L menthol. Therefore, no study on toxicity to reproduction needs to be conducted.
Effects on developmental toxicity
Description of key information
NOEL (maternal/teratogenicity/fetotoxicity) = 215 mg/kg bw/day Reaction mass of isomenthone and trans-menthone (data derived from L-menthone study with maternal, teratogenicity and fetotoxicity NOEL = 218 mg/kg bw/day, a maximal given dose)
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 1973
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study well documented Restriction: no full macroscopic examination; no data on statistical evaluation
- Qualifier:
- according to guideline
- Guideline:
- other: unspecified
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- VEHICLE
- Amount of vehicle (if gavage): 10 ml/kg bw - Details on mating procedure:
- Virgin adult were mated with young adult males (observation of the vaginal sperm plug was considered Day 0 of gestation)
- Duration of treatment / exposure:
- gestation days 6-15
- Frequency of treatment:
- daily
- Duration of test:
- 10 consecutive days
- Remarks:
- Doses / Concentrations:
2.18 mg/kg bw/d
Basis:
no data - Remarks:
- Doses / Concentrations:
10.15 mg/kg bw/d
Basis:
no data - Remarks:
- Doses / Concentrations:
47.05 mg/kg bw/d
Basis:
no data - Remarks:
- Doses / Concentrations:
218.0 mg/kg bw/d
Basis:
no data - No. of animals per sex per dose:
- 25 females per dose
No of pregnant animals (2.18, 10.15, 47.05, 218 mg/kg bw): 22, 23, 23, 22 - Control animals:
- yes, sham-exposed
- other: NEGATIVE CONTROL: 25 pregnant... (see attached file)
- Maternal examinations:
- CAGE SIDE OBSERVATIONS:No data
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: day 0, 6, 11, 15, 20
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day #20
- Organs examined: urogenital tract - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes / No / No data
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: No data
- Number of implantations: Yes
- Number of resorptions: Yes - Fetal examinations:
- - External examinations: Yes: 1/3 per litter
- Soft tissue examinations: Yes: 1/3 per litter
- Skeletal examinations: Yes: 2/3 per litter
- Head examinations: No data
Other :
- Fetus weight : Yes: all per litter
- Abnormalities/malfunctions : Yes: all per litter - Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
No clinical signs of maternal toxicity - Dose descriptor:
- NOEL
- Effect level:
- 218 mg/kg bw/day
- Based on:
- other: L-menthol
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOEL
- Effect level:
- 215 mg/kg bw/day
- Based on:
- other: isomenthone and transmenthone
- Basis for effect level:
- other: maternal toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
No clinical signs of fetotoxicity - Dose descriptor:
- NOEL
- Effect level:
- 218 mg/kg bw/day
- Based on:
- other: L-menthol
- Basis for effect level:
- other: teratogenicity
- Dose descriptor:
- NOEL
- Effect level:
- 218 mg/kg bw/day
- Based on:
- other: L-menthol
- Basis for effect level:
- other: fetotoxicity
- Dose descriptor:
- NOEL
- Effect level:
- 215 mg/kg bw/day
- Based on:
- other: isomenthone and transmenthone
- Basis for effect level:
- other: teratogenicity
- Dose descriptor:
- NOEL
- Effect level:
- 215 mg/kg bw/day
- Based on:
- other: isomenthone and transmenthone
- Basis for effect level:
- other: fetotoxicity
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- L-Menthol was not embryo- or fetotoxic and had no teratogenic properties in well performed gavage studies in rat at non-maternally toxic doses (218 mg/kg bw).
Reference
Maternal toxicity:
- Survival of dams: no deaths
- Body weight of dams: no compound-related changes compared to control (only positive control treated mice showed decreased body weight gain)
Fetotoxicity :
- Death : no dead fetuses in dosage groups (3 deaths in positive control)
- Average fetus weight: no change in treated groups compared to controls
- Abnormalities/malfunctions (no. of fetuses affected/no. of litters affected) (sham control, pos. control, 1.85, 8.59, 39.9, 185.5 mg/kg bw)
- Skeletal findings:
sternebrae (incomplete oss.): 80/22, 94/18, 92/20, 93/22, 101/19, 92/19
sternebrae (missing): 14/6, 11/19, 11/8, 17/5, 11/4, 0/22
skull (incomplete closure): 41/16, 114/19, 46/15, 63/16, 67/20, 49/17
- Soft tissue abnormalities:
pos. control: 7 pups with meningoencephalocele and spina bifida
10.15 mg/kg: 1 pup: petechiae, 1 pup: anophthalmia
47.05 mg/kg: 2 pups anophthalmia, 2 pups: gastroschisis,1 pup hydrocephalus
All other findings were completely in the range of spontaneous abnormalities found in negative controls.
ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC):
- Organ weights P and F1: no
- Histopathology P and F1:
P: urogenital tract, number of implantation and resorption sites
F1: All fetuses were examined grossly, one-third of fetuses of each litter underwent detailed visceral examinations employing 10x magnification, two-third were examined for skeletal defects
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- All developmental toxicity / teratogenicity studies (in mouse, rat, rabbit and hamster) are reliable with restrictions.
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
There is no developmental toxicity data on Reaction mass of isomenthone and trans-menthone.
- Read across from L-menthol:
Teratogenicity studies with L-menthol were conducted in rats, mice, hamsters and rabbits (Morgareidge1973). In all four developmental toxicity studies, maternally toxic dose levels were not used. For Wistar rats the doses of 2.18, 10.15, 47.05 and 218.0 mg/kg bw/d were administered by gavage from gestation day 6 to 15. There was no maternal toxicity and foetotoxicity. Therefore the NOEL derived for maternal and foetal toxicity and teratogenicity in rats can be determined as 218.0 mg/kg bw/d. For CD-1 Mice the doses of 1.85, 8.59, 39.9 and 185.0 mg/kg bw/d were administered from gestation day 6 to 15. There was no maternal toxicity and foetotoxicity. The NOEL derived for maternal and foetal toxicity and teratogenicity was 185.0 mg/kg bw/d. For Rabbits the doses of 4.25, 19.75, 91.7 and 425.0 mg/kg bw/d were administered to from gestation day 6 to 18. Few of the rabbits died or aborted before day 29 ( at 4.25 mg/kg bw/d 2 animals died on day 13 , at 19.75 mg/kg bw/d 3 animals died on day 13, at 91.7 mg/kg bw/d 1 animals died on day 11, at 425.0 mg/kg bw/d 4 animals died on day 14), however, these effects were not dose related and are not considered to be a consequence of test substance toxicity, but due to administration errors. There was no maternal toxicity and foetotoxicity. The NOEL derived for maternal and foetal toxicity and teratogenicity was therefore 425.0 mg/kg bw/d. For Syrian hamsters the doses of 4.05, 21.15, 98.2 and 405.0 mg/kg bw/d were administered during gestation days 6 to 10. There was no maternal toxicity and foetotoxicity. The NOEL for maternal and foetal toxicity and teratogenicity was therefore 405.0 mg/kg bw/d. Since only a NOEL for these 4 species could be derived and no developmental or foetotoxic effects were observed we can consider that L-Menthol has inconclusive developmental toxicity and teratogenic properties.
Justification for classification or non-classification
No changes were observed during the histopathological examinations of the reproductive organs of rats and mice in the combined repeated dose and 2 years carcinogenicity toxicity studies following exposure to the different menthol isomers: D/L menthol. Therefore, no toxicity to reproduction study needs to be conducted. Based on the above stated read-across assessment from L-menthol on the reproduction toxicity potential, Reaction mass of isomenthone and trans-menthone is deemed not to be toxic to the reproduction and accordingly do not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.
The L-Menthol has no developmental toxicity and no teratogenicty properties in well performed gavage studies in various species (rat, mouse, rabbit, hamster) at the highest dose of 185 (for mice) to 425 (for rabbits) mg/kg bw. Since we could only derive a NOEL for these 4 species we can not consider that the L-menthol has inconclusive developmental or teratogenicity hazard. Based on the above stated read-across assessment from L-Menthol of the developmental toxicity/teratogenicity potential, Reaction mass of isomenthone and trans-menthone could not be classified for developmental toxicity/teratogenicity according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.
Additional information
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.
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