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EC number: 612-179-8 | CAS number: 61597-98-6
- 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
Developmental toxicity / teratogenicity
Administrative data
- 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
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 973
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: unspecified
- GLP compliance:
- no
Test material
- Reference substance name:
- L-menthol
- EC Number:
- 218-690-9
- EC Name:
- L-menthol
- Cas Number:
- 2216-51-5
- Molecular formula:
- C10H20O
- IUPAC Name:
- (1R,2S,5R)-2-isopropyl-5-methyl-cyclohexanol
- Details on test material:
- Name : Menthol natural brazilian, FDA 71-57
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
Administration / exposure
- 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
Doses / concentrationsopen allclose all
- 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)
Examinations
- 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
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
No clinical signs of maternal toxicity
Effect levels (maternal animals)
open allclose all
- 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:
- 323 mg/kg bw/day
- Based on:
- other: Menthyl lactate
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
No clinical signs of fetotoxicity
Effect levels (fetuses)
open allclose all
- 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:
- 323 mg/kg bw/day
- Based on:
- other: Menthyl lactate
- Basis for effect level:
- other: teratogenicity
- Dose descriptor:
- NOEL
- Effect level:
- 323 mg/kg bw/day
- Based on:
- other: Menthyl lactate
- Basis for effect level:
- other: fetotoxicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
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
Applicant's summary and conclusion
- 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).
- Executive summary:
Teratologic evaluation of FDA 71-57 (menthol natural, Brazilian) was performed according to unspecified guideline. Twenty five female Wistar rats per group were assigned to five dosage groups. Virgin adult females were mated with young adult males. Observation of the vaginal sperm plug was considered Day 0 of gestation. Suspensions of the test substance or the vehicle, corn oil, were administered orally via gavage to 0, 2.18, 10.15, 47.05 and 218.0 mg/kg bw/day at a volume of 10 mL/kg on days 6 through 15 of gestation. Detailed clinical observations were performed daily. Body weight was examined on days 0, 6, 11, 15 and 20. The animals were scarified on gestation day 20 and urogenital tract, number of implantations and resorptions were examined. Foetus was weighted per litter. In addition external, soft tissue and skeletal examinations were performed. There was no cleary discernible effect on nidation or on maternal or fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occuring spontaneously in the sham-treated controls. Therefore the NOEL for maternal toxicity and teratogenicity/fetotoxicity is considered to be at 218 mg/kg bw/day of L-Menthol, i.e. the highest applied dose. The NOEL for maternal toxicity and teratogenicity/fetotoxicity extrapolated to Mentyl lactate is considered to be at 323 mg/kg bw/day.
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