3-Cyclohexene-1-methanol, α,4-dimethyl-α-(4-methyl-3-penten-1-yl)-

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Remarks:

Test substance represents a main component (stereoisomer) of the registered substance

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, limited documentation

Data source

Reference

Reference Type:

publication

Title:

Pharmakologische Untersuchungen von Kamillen-Inhaltsstoffen

Author:

Habersang S., Leuschner F., Isaac O., Thiemer K.

Year:

1979

Bibliographic source:

Planta medica, 37(2):115-123.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

no data

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Levomenol

EC Number:

245-423-3

EC Name:

Levomenol

Cas Number:

23089-26-1

Molecular formula:

C15H26O

IUPAC Name:

(2S)-6-methyl-2-[(1S)-4-methylcyclohex-3-en-1-yl]hept-5-en-2-ol

Test material form:

other: oily liquid

Details on test material:

- Name of test material: (-)-alpha-Bisabolol, 6-methyl-2-(4-methylcyclohex-3-en-1-yl)hept-5-en-2-ol

Test animals

Species:

rat

Strain:

other: Sprague Dawley and/or Wistar Br 46-11 (not further specified))

Details on test animals or test system and environmental conditions:

- Source: Sprague Dawley (S. Ivanovas; Kißlegg, Germany) Wistar Br 46-11 (Brünger, Bokel, Germany)
- Weight at study initiation: 200 - 262 g

Administration / exposure

Route of administration:

oral: gavage

Details on exposure:

no data

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

Sexual maturity, female rats were assembled for 15 hours (5 pm - 8 am) with males of the same breeding strain (male/female ratio of 1/1). In case of unsuccessful pairing, the experiment was repeated.
- Proof of pregnancy: sperm positive, d0 pc.

Duration of treatment / exposure:

pregnant rats were dosed daily via gavage on days 6 through 15 of gestation with the test substance

Frequency of treatment:

daily

Duration of test:

20 days

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.25 other: ml/kg bw/d

Remarks:

approx. 230 mg/kg bw/d

Doses / concentrations 2

Dose / conc.:

0.5 other: ml/kg bw/d

Remarks:

approx. 470 mg/kg bw/d

Doses / concentrations 3

Dose / conc.:

1 other: ml/kg bw/d

Remarks:

approx. 930 mg/kg bw/d

Doses / concentrations 4

Dose / conc.:

3 other: ml/kg bw/d

Remarks:

approx. 2790 mg/kg bw/d

No. of animals per sex per dose:

no data

Control animals:

yes

Details on study design:

Sex: female
Duration of test: until day 20 of gestation

Examinations

Maternal examinations:

no data

Ovaries and uterine content:

no data

Fetal examinations:

The fetuses were dissected and thoracic and abdominal organs examined for abnormalities. This was followed by staining of the skeleton with alizarin for the examination of the skeletal system (2/3rd of animals). The study of body sections according to Wilson for abnormalities and malformations was carried out (1/3rd of animals).

Statistics:

no data

Indices:

no data

Historical control data:

no data

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

1 other: ml/kg bw/d

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

1 other: ml/kg bw/d

Sex:

not specified

Basis for effect level:

other: developmental toxicity

Overall developmental toxicity

Developmental effects observed:

yes

Lowest effective dose / conc.:

3 other: ml/kg bw/d

Treatment related:

yes

Relation to maternal toxicity:

developmental effects as a secondary non-specific consequence of maternal toxicity effects

Dose response relationship:

yes

Relevant for humans:

no

Any other information on results incl. tables

1) Teratology study (0.25; 0.5; 1 ml/kg bw/d): There was no adverse effect on the prenatal development and no maternal toxicity after dosing with the test substance at up to 1 mL/kg bw/d.

2) determination of the maternally toxic dose level (3 ml/ kg bw/d = 2790 mg/kg bw/d):

Slight sedation, ataxia, reduced food consumption and significant depression of body weight gain was observed in dams.

The number of fetuses was significant decreased and the number of resorptions was significantly increased. There were no dead or malformed fetuses.

According to the authors, these results suggested that the lowest toxic dose level was less than 3 mL/kg bw/d and greater than 1 mL/kg bw/d, and was within the same range for dams and fetuses.