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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted according to OECD 414 Guideline without deviations.
Cross-reference
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2021

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.31 (Prenatal Developmental Toxicity Study)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
(-)-pin-2(3)-ene
EC Number:
232-077-3
EC Name:
(-)-pin-2(3)-ene
Cas Number:
7785-26-4
Molecular formula:
C10H16
IUPAC Name:
2,6,6-trimethylbicyclo[3.1.1]hept-2-ene
impurity 1
Chemical structure
Reference substance name:
(+)-pin-2(3)-ene
EC Number:
232-087-8
EC Name:
(+)-pin-2(3)-ene
Cas Number:
7785-70-8
Molecular formula:
C10H16
IUPAC Name:
(1R,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-2-ene
impurity 2
Chemical structure
Reference substance name:
(1S)-2,2-dimethyl-3-methylenebicyclo[2.2.1]heptane
EC Number:
227-337-8
EC Name:
(1S)-2,2-dimethyl-3-methylenebicyclo[2.2.1]heptane
Cas Number:
5794-04-7
Molecular formula:
C10H16
IUPAC Name:
(1S,4R)-2,2-dimethyl-3-methylenebicyclo[2.2.1]heptane
impurity 3
Chemical structure
Reference substance name:
(1R)-2,2-dimethyl-3-methylenebicyclo[2.2.1]heptane
EC Number:
227-336-2
EC Name:
(1R)-2,2-dimethyl-3-methylenebicyclo[2.2.1]heptane
Cas Number:
5794-03-6
Molecular formula:
C10H16
IUPAC Name:
(1R,4S)-2,2-dimethyl-3-methylenebicyclo[2.2.1]heptane
impurity 4
Chemical structure
Reference substance name:
(-)-pin-2(10)-ene
EC Number:
242-060-2
EC Name:
(-)-pin-2(10)-ene
Cas Number:
18172-67-3
Molecular formula:
C10H16
IUPAC Name:
(1S,5S)-6,6-dimethyl-2-methylenebicyclo[3.1.1]heptane
impurity 5
Chemical structure
Reference substance name:
1,7,7-trimethyltricyclo[2.2.1.02,6]heptane
EC Number:
208-083-7
EC Name:
1,7,7-trimethyltricyclo[2.2.1.02,6]heptane
Cas Number:
508-32-7
Molecular formula:
C10H16
IUPAC Name:
1,7,7-trimethyltricyclo[2.2.1.0~2,6~]heptane
impurity 6
Chemical structure
Reference substance name:
(1R,5R)-6,6-dimethyl-2-methylenebicyclo[3.1.1]heptane
Cas Number:
19902-08-0
Molecular formula:
C10H16
IUPAC Name:
(1R,5R)-6,6-dimethyl-2-methylenebicyclo[3.1.1]heptane
Test material form:
liquid
Details on test material:
Batch No. : 1000107238
Purity : 89%
Name of test material (as cited in study report): (-)-alpha-pinene
Physical state: colourless liquid
Storage Conditions: +2°C to +8°C, under nitrogen and protected from light
Expiry Date: 30 November 2021
Specific details on test material used for the study:
Alpha-pinene multiconstituent or (-)-alpha-pinene, depending on the results of the on-going preliminary study on (-)-alpha-pinene, designed to check if both substances have similar toxicity.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl:CD(SD)

Administration / exposure

Route of administration:
oral: gavage
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
Females were treated from Day 6 to Day 19 (inclusive) after mating
Frequency of treatment:
Once daily at approximately the same time each day
No. of animals per sex per dose:
20 mated females/dose
Control animals:
yes, concurrent vehicle

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Animals were inspected visually at least twice daily for evidence of ill-health or reaction to treatment. Cages were inspected daily for evidence of animal ill-health amongst the occupant(s).
During the acclimatization period, observations of the animals and their cages were recorded at least once per day.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Detailed observations were recorded daily at the following times in relation to dose administration: At the end of dosing each group; One to two hours after completion of dosing all groups; As late as possible in the working day
A detailed physical examination was performed on each animal on Days 0, 5, 12, 18 and 20 after mating to monitor general health.

BODY WEIGHT: Yes
- Time schedule for examinations: The weight of each adult was recorded on Days 0, 3 and daily from Day 6 after mating.

FOOD CONSUMPTION: Yes
- The weight of food supplied to each adult, that remaining and an estimate of any spilled was recorded for the periods Days 0-2, 3-5, 6-9, 10 -13, 14-17 and 18-19 after mating inclusive.

POST-MORTEM EXAMINATIONS: Yes
- Animals were killed on Day 20 after mating by Carbon dioxide asphyxiation
- Necropsy: All adult animals were subject to a detailed necropsy. After a review of the history of each animal, a full macroscopic examination of the tissues was performed. All external features and orifices were examined visually. Any abnormality in the appearance or size of any organ and tissue (external and cut surface) was recorded and the required tissue samples preserved in appropriate fixative.
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight (including cervix and ovaries): Yes
- Number of corpora lutea: Yes
- Number of implantation sites: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Number of Fetuses (live and dead): Yes
Fetal examinations:
Method of kill for fetuses: Chilling on a cool plate (approximately 0 °C)
Examination of all viable fetuses and placentae: Dissected from the uterus, individually weighed and identified within the litter using a coding system based on their position in the uterus. Examined externally with abnormalities recorded. The sex of each fetus was recorded.
Examination of nominally 50% of fetuses in each litter: Sexed internally and eviscerated.
Fixation: Fetuses eviscerated were fixed in Industrial Methylated Spirit (IMS). Remaining fetuses were fixed whole in Bouin’s fluid.
Processing: Bouin’s fixed fetuses were subject to free-hand serial sectioning.
IMS fixed fetuses were processed and stained with Alizarin Red.

Fetal Pathology Examination
Bouin’s fixed fetuses: Serial sections were examined for visceral abnormalities.
Alizarin Red stained fetuses: Assessed for skeletal development and abnormalities.
Statistics:
See " Any other information on materials and methods incl. tables"
Indices:
Pre-implantation loss (%) = [(Number of corpora lutea – Number of implantations) / Number of corpora lutea] x 100
Post-implantation loss (%)= [(Number of implantations – Number of live fetuses) / Number of implantations] x 100

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Description (incidence and severity):
To be completed
Description (incidence):
To be completed
Description (incidence and severity):
To be completed
Description (incidence and severity):
To be completed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Description (incidence and severity):
To be completed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Other effects:
not examined

Maternal developmental toxicity

Number of abortions:
no effects observed
Pre- and post-implantation loss:
no effects observed
Total litter losses by resorption:
no effects observed
Early or late resorptions:
no effects observed
Dead fetuses:
no effects observed
Changes in pregnancy duration:
no effects observed
Other effects:
no effects observed

Effect levels (maternal animals)

Based on:
test mat.
Remarks on result:
other: On-going study

Maternal abnormalities

Description (incidence and severity):
On-going study

Results (fetuses)

Description (incidence and severity):
On-going
Description (incidence and severity):
On-going
Description (incidence and severity):
On-going
Description (incidence and severity):
On-going
Changes in postnatal survival:
not examined
Description (incidence and severity):
On-going
Description (incidence and severity):
On-going
Description (incidence and severity):
On-going

Effect levels (fetuses)

Remarks on result:
other: On-going

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
On-going study
Executive summary:

On-going study