Alcohols, C6-24, distn. residues

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

based on test type (migrated information)

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

Guideline:

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

Test material information

Constituent 1

Reference substance name:

112-95-5

IUPAC Name:

112-95-5

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

Sex:

male/female

Details on test animals or test system 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%

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 day period.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

14 days

Frequency of treatment:

daily by diet

Details on study schedule:

females: 14 treatment before mating; mating for up to 22 days; termination 5 days after birth
males: 45 day

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
100 mg/kg bw
Basis:
actual ingested
calculated from food consumption

Doses / concentrations 2

Remarks:

Doses / Concentrations:
500 mg/kg bw
Basis:
actual ingested
calculated from food consumption

Doses / concentrations 3

Remarks:

Doses / Concentrations:
2000 mg/kg bw
Basis:
actual ingested
calculated from food consumption

No. of animals per sex per dose:

12

Control animals:

yes, plain diet

Details on study design:

1-0ctadecanol was mixed in the diet. In a preliminary test, 1-octadecanol was placed on the skin and mixed in the diet. The skin application was without success as the compound remained on the skin or failed off in cakes so the mixing in the diet procedure was chosen. Doses too were chosen from results of the preliminary test.
The intake as calculated from the food consumption and the concentrations in the diet.

Examinations

Parental animals: Observations and 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

Litter observations:

number of pups per litter, weight, sex distribution and dead foetuses from day 1-5

Postmortem examinations (parental animals):

Females
Macroscopic examinations
Total gross pathological examinations were performed on each animal. Corpora lutea and implantations were counted. Organ weight was determined for the liver, kidneys and thymus. The following organs were fixed in formalin: Liver, kidneys, adrenals, brain, heart, spleen, ovaries, thymus, and other organs with observed pathological changes.

Histopathological examinations
All fixed organs, except thymus, in the control and highest dose group were prepared for histopathological examinations.



Males
Macroscopic examinations
Total macroscopic examinations were performed on each animal.
Organ weight was determined for the following organs: Liver, kidneys, thymus, testis, epididymides. The following organs were fixed in formalin: Liver, kidneys, adrenals, brain, heart, spleen, thymus and organs with pathological changes per indication. Testis and epididymides were fixed in Bouin's solution.

Histopathological examinations
All fixed organs, except thymus, in the control and highest dose group were prepared for histopathological examinations.

Postmortem examinations (offspring):

Macroscopic examinations
Pups killed on day 5 were weighed and examined for external malformations including the head (especially eyes and cleft palate) and then opened to the abdomen and thoracic cave for study of sex and malformations of the internal organs.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

not examined

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

2 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Results: F1 generation

General toxicity (F1)

Clinical signs:

not specified

Mortality / viability:

not specified

Body weight and weight changes:

no effects observed

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings:

no effects observed

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

2 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Overall reproductive toxicity

Reproductive 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.

Reproductive parameters examined were pregancy rate, length of gestation period, findings of corporea luteae, implantations, resorptions and number of fetuses at birth, number of pups per litter, weight, sex distribution, dead foetuses from day 1-5 and macroscopy.

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.