Mentha arvensis, ext.

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

supporting 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:

1973

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: unspecified

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

L-menthol

EC Number:

218-690-9

EC Name:

L-menthol

Cas Number:

2216-51-5

Molecular formula:

C10H20O

IUPAC Name:

2-isopropyl-5-methylcyclohexanol

Details on test material:

Name : Menthol natural brazilian, FDA 71-57

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 / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
2.18 mg/kg bw/d
Basis:
no data

Doses / concentrations 2

Remarks:

Doses / Concentrations:
10.15 mg/kg bw/d
Basis:
no data

Doses / concentrations 3

Remarks:

Doses / Concentrations:
47.05 mg/kg bw/d
Basis:
no data

Doses / concentrations 4

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)

Dose descriptor:

NOEL

Effect level:

218 mg/kg bw/day

Based on:

no data

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)

1

Dose descriptor:

NOEL

Effect level:

218 mg/kg bw/day

Based on:

no data

Basis for effect level:

other: teratogenicity

2

Dose descriptor:

NOEL

Effect level:

218 mg/kg bw/day

Based on:

no data

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).