Registration Dossier

Toxicological information

Toxicity to reproduction

Currently viewing:

Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: Repeat dose toxicity study with histopathology of reproductive organs.
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles and provides screening data for reproductive endpoints
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Deviations:
not applicable
Principles of method if other than guideline:
Wistar-SLC rats were fed for 3 months with test substance mixed into theIr food at a level of 0%, 0.2%, 1.0% or 5.0%. Clinical symptoms, body weights, food and water intake, food efficiency, blood analysis, urine analysis and blood enzymes were evaluated along with gross appearance, weight and pathology of tissues from a wide range of organs, including the reproductive organs.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Reference substance name:
75782-87-5
EC Number:
616-261-4
Cas Number:
75782-87-5
IUPAC Name:
75782-87-5
Details on test material:
- Name of test material (as cited in study report): Dobanol-45
- Substance type: technical product
- Physical state: not reported
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data
- Other: Tradename Dobanol 45 C14-16 alcohols Type A

Test animals

Species:
rat
Strain:
other: Wister-SLC
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: 5 weeks
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: "cages" (no further details given)
- Diet (e.g. ad libitum): CE-2, made by Nihon Kurea, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 2 degrees centigrade
- Humidity (%): 60 +/- 5%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): no data
- Mixing appropriate amounts with (Type of food): CE-2 solid food, made by Nihon Kurea
- Storage temperature of food: no data
Details on mating procedure:
Animals were not mated.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Exposure period: 90 days
Frequency of treatment:
continuously
Details on study schedule:
No schedule: animals were not mated.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 0.2, 1.0, and 5.0%
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
0, 169, 702, 3548 mg/kg bw/day (average)
Basis:
actual ingested
No. of animals per sex per dose:
11
Control animals:
yes, concurrent no treatment

Examinations

Postmortem examinations (parental animals):
SACRIFICE
- at 90 days

HISTOPATHOLOGY / ORGAN WEIGHTS
- thyroid, testes or ovaries
Statistics:
STATISTICAL METHODS: Student  t test.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
On testes and ovaries
Other effects:
effects observed, treatment-related

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
not examined

Details on results (P0)

Absolute testes and ovary weights were not significantly affected at any dose. Microscopic examination of these organs did not reveal any abnormalities.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
5 other: %
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: At the highest dose level of 5% in the diet, absolute weights of testes and ovaries were not affected; the microscopic appearance of these organs was normal.

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

The effects below refer to relative organ weights, but it is usual to evaluate absolute organ weights for the reproductive organs.

There were increases in both testes and ovary weights (p<0.1) at the top dose level of 5% (ca 3500 mg/kg/day). Testes weight was also increased at  the 1% dose level (p<0.05).

The NOAEL determined below is derived from the relative weight of the reproductive organs, whereas there were no effects on absolute weight of reproductive organs at the highest dose tested:

The NOAEL for systemic toxicity and  effects on the reproductive organs is 0.2% in the diet (ca 200 mg/kg/day)  

(males 171 mg/kg/day; Females 167 mg/kg/day).

Applicant's summary and conclusion

Conclusions:
In a reliable study, conducted using a protocol similar to OECD guideline 408, male and female rats were fed diets containing 0, 0.2%, 1% or 5% Dobanol-45 for 90 dyas. An NOAEL of 5% (equivalent to a dose of 3605 mg/kg bw/day in males and 3491 mg/kg bw/day in females) was identified since there were no effects on absolute weights of the testes or ovaries, or on the microscopic appearance of these organs, even at the highest dose level.