DL-menthol

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented and scientifically acceptable

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1973

Materials and methods

Principles of method if other than guideline:

Virgin adult femate albino rats (Wistar derived stock) were individually housed in mesh bottom cages intemperature and humidity-controlled
quarters with free access to food and fresh tap water.
They were mated with young adult males, and observation of the vaginal sperm plug was considered Day 0 of gestation. Beginning on Day 6
and continuing daily through Day 15 of gestation, the females were dosed with the indicated dosage s by oral intubations. The controls
were sham treated with the vehicle at a level equivalent to the group receiving the highest test dose.
Body weights were recorded on Days 0, 6, 11, 15, and 20 of gestation. All animals were observcd daily for appearance and behavior
with particular attention to food consumption and weight, in order to rule out any abnormalities which may havc occurred as a
result of anoraxic effects in the pregnant female animal.
On Day 20 all dams were subjectcd to Cacsarean section under surgical anesthesia. and the numbers of implantation sites, resorption
sites, and live and dead fetuses were recorded. The body weights of the live pups were also recorded.The urogenital tract of each dam
was examined in detail for anatomical normality.
All fetuses were examined grossly for the presence of external congenital abnormalities. One-third of the fetuses of each litter
underwent detailed visceral examinations employing l0 x magnification. The remaining two-thirds were cleared in potassium hydroxide (KOH) ,
stained with alizarin red S dye and examined for skeletal defects.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

DL-menthol

EC Number:

216-074-4

EC Name:

DL-menthol

Cas Number:

1490-04-6

Molecular formula:

C10H20O

IUPAC Name:

2-isopropyl-5-methylcyclohexanol

Details on test material:

Test substance: menthol natural, brazilian (l-menthol)

Test animals

Species:

rat

Strain:

Wistar

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on mating procedure:

They were mated with young adult males, and observation of the vaginal sperm plug was considered Day 0 of gestation

Duration of treatment / exposure:

Beginning on Day 6 and continuing daily through Day 15 of gestation, the females were dosed with the indicated dosage s by oral intubations. The controls were sham treated with the vehicle at a level equivalent to the group receiving the highest test dose.
On Day 20 all dams were subjectcd to Cacsarean section under surgical anesthesia

Frequency of treatment:

daily

Duration of test:

20 days

Doses / concentrations

Remarks:

Doses / Concentrations:
2.18, 10.15, 47.05 or 218.0 mg/kg bw/d
Basis:

No. of animals per sex per dose:

22-23 animals/dose

Control animals:

other: sham treated with corn oil

Details on study design:

Sex: female

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:

NOEL

Effect level:

218 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

all dose groups: no clearly discernible effect on nidation
or on maternal or fetal survival; the number of
abnormalities seen in either soft or skeletal tissues not
differing from the number occurring spontaneously in the
controls

Applicant's summary and conclusion

Executive summary:

The administration of up to 218 mg/kg (body weight) of the test material to pregnant rats for 10 consccutive days had no clearly descernible 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 occurring spontaneously in the sham-treated controls.