Registration Dossier

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

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:
other: Study according to OECD test guideline 422 under GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1-Octadecanol
- Molecular formula (if other than submission substance): C18H38O
- Analytical purity: 99% (Sigma L 5751)

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Mollegard breeding center, Denmark
- Age at study initiation: females: 7 weeks; males: 8 weeks
- Housing: The rats were kept in steel wire cages type 3 until day 20 in
pregnancy where the pregnant female were placed in macroIon cages type 3.
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C.
- Humidity (%): 55 ± 10%.
- Photoperiod (hrs dark / hrs light): Fluorescent light was on from 20 pm. to 8 am.








Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: IT CHOW 101
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Rate of preparation of diet (frequency): once
- Mixing appropriate amounts with (Type of food):
BARLEY 6,060 KG
MINERALMIXTURE 0,660 KG
VITAMINS B-K 0,240 KG
1-0CTADECANOL 0,600 KG
SKIM MILK POWDER 6,540 KG
OATS 5,400 KG
SOIA BEAN OIL,cc A.D.E. VIT. 0,500 KG


VEHICLE
- Justification for use and choice of vehicle (if other than water): feed, as the substance is well digestable
- Concentration in vehicle: 3%
Analytical verification of doses or concentrations:
no
Details on mating procedure:
After a 14 days dosing period the females were placed together with the males, 1 to
1. Check for mating included inspection for plugs during the morning, at lunch time and
dUring the afternoon. The day on which a plug was recorded at lunch time or during
the afternoon was defined day O. The day on which a plug was recorded during the
morning was defined day 1 in pregnancy. Females, in which no mating was recorded,
were kept together with the same male for a 14 days period. If no plug and no
indication on pregnancy was found after a 14 days period, the female rat was placed
together with an other male for an 8 days period.
Duration of treatment / exposure:
females: 14 days
males: 45 days
Frequency of treatment:
daily by diet
Duration of test:
females: 14 treatment before mating; mating for up to 22 days; termination 5 days after birth
males: 45 day
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
100 mg/kg bw
Basis:
actual ingested
calculated from food consumption
Remarks:
Doses / Concentrations:
500 mg/kg bw
Basis:
actual ingested
calculated from food consumption
Remarks:
Doses / Concentrations:
2000 mg/kg bw
Basis:
other: calculated from food consumption
No. of animals per sex per dose:
12
Control animals:
yes, plain diet
Details on study design:
2000 mg/kg bw

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: No

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: No
- Skeletal examinations: No
- Head examinations: Yes
- Malformations of internal organs

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
In a study according to OECD test guideline 422, the NOAEL of 1-Octadecanol for reproductive/developmental toxicity was determined to be 2000 mg/kg bw.
Executive summary:

The reproductive/developmental toxicity of 1-octadecanol was determined in a study according to OECD test guideline 422 under GLP.

The substance was administered to rats in doses of 0, 100, 500, and 2000 mg/kg bw/day via the diet over 14 days.

Developmental parameters examined were external and head examinations, as well as organ formations.

No indication for effects of the test substance on any of these parameters were found. Consequently, the NOAEL of 1-Octadecanol for reproductive/developmental toxicity was determined to be 2000 mg/kg bw.