Isotridecan-1-ol

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

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)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dodecan-1-ol

EC Number:

203-982-0

EC Name:

Dodecan-1-ol

Cas Number:

112-53-8

Molecular formula:

C12H26O

IUPAC Name:

dodecan-1-ol

Details on test material:

- Name of test material (as cited in study report): 1-dodecanol (from Sigma (# L 5375))
- Analytical purity: 99%

Specific details on test material used for the study:

Purity of the product used: 99% (Sigma L 5375).

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
- Age at study initiation: 8 weeks
- Weight at study initiation: Males: x-x g; Females: x-x g
- Housing: singly in steel wire cages
- Diet (e.g. ad libitum): IT chow 101 ad lib.
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 10%
- Photoperiod (hrs dark / hrs light): 12h/12h (light was provided from 8 p.m. to 8 a.m.)

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Rate of preparation of diet (frequency):
- Mixing appropriate amounts with (Type of food):
- Storage temperature of food:

Details on mating procedure:

no data

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

14 days (Duration of test: 5 weeks)

Frequency of treatment:

permanent by diet

Details on study schedule:

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 aftemoon. The day on which a plug was recorded at lunch time or during the afternoon was defined day 0. 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 maie for an 8 days period.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

1 500 ppm

Remarks:

equiv. to 100 mg/kg b.w.

Doses / concentrations 2

Dose / conc.:

7 500 ppm

Remarks:

equiv. to 500 mg/kg b.w.

Doses / concentrations 3

Dose / conc.:

30 000 ppm

Remarks:

equiv. to 2000 mg/kg b.w.

No. of animals per sex per dose:

12

Control animals:

yes, concurrent no treatment

Details on study design:

- Dose selection rationale: based on range finding study

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes / No / No data
- Time schedule:

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes

Blood was taken on day 37 fromall males
CLINICAL CHEMISTRY
The following parameters were measured: Protein, alkaline phosphatase, alanine aminotransferase, glucose, urea, creatinine, total and free cholesterol, and triglyceride

Hematology
The following parameters were measured: Hematocrit, hemoblogin, total erythrocyte, total leucocytes, differential leucocyte counts

Postmortem examinations (parental animals):

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, testis, epididymides. The following organs were fixed in formalin: Liver, kidneys, adrenals, brain, heart, spleen, ovaries, thymus, and other organs with observed pathological changes. Testis and epididymides were fixed in Bouin's solution.

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

Postmortem examinations (offspring):

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.

Reproductive indices:

Pregnancy rate, lenght of gestation, number of implantations sites, corpora lutea, and resorptions

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

no effects observed

Haematological findings:

effects observed, non-treatment-related

Description (incidence and severity):

A significant (p< 0.05) reduction in plasma freecholestorol was observed in group 3. A significant reduction of plasma triglyceride was observed in group 4. Ail other parameters were at the same level as the control group.

Organ weight findings including organ / body weight ratios:

no effects observed

Reproductive function / performance (P0)

Reproductive performance:

no effects observed

Details on results (P0)

No effects were seen on reproductive or developmental parameters up to doses of 2000 mg/kg bw/day. 1-Dodecanol in the doses administered had no influence on body weight, weight gain, food consumption and food efficiency in the parental generation. Pregnancy rates were not statistically altered and there were no differences in the lengths of the gestation periods. No organ toxicity was observed in the females. Autopsy indicated no effect from 1-Dodecanol under the conditions of this experiment.

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

2 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no effect observed

Results: F1 generation

Details on results (F1)

There was no effect on the number of pups per litter, weight, sex ratio or mortality rate from days 1-5 after birth.

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

2 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no effect observed

Overall reproductive toxicity

Reproductive effects observed:

no