Reaction mass of Fatty acids, montan-wax and Fatty acids, montan-wax, calcium salts and Montan wax

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

2004

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication which meets basic scientific principles, for justification of read-across see Chapter 1 of CSR

Data source

Reference

Reference Type:

publication

Title:

Evaluation of the reproductive and developmental toxicity of the D-003, a mixture of long-chain fatty acids, in rats and rabbits

Author:

Rodríguez MD, González JE, Alemán C, Rodeiro I, Arango E, Gámez R., Valdés S, García H, Coicochea E, Acosta CP

Year:

2004

Bibliographic source:

Food and Chemical Toxicology 42: 1977-1985

Report date:

2004

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

Remarks:

two dose groups only

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

312700-63-3

Cas Number:

312700-63-3

IUPAC Name:

312700-63-3

Constituent 2

Reference substance name:

D-003

IUPAC Name:

D-003

Details on test material:

- Name of test material (as cited in study report): D-003
- Substance type: Mixture of long-chain fatty acids isolated and purified from sugar cane wax
- Analytical purity: Purity checked by gas chromatography
- Other: obtained from Chemistry Department of the Centre of Natural Products, La Habana, Cuba

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CEN-PALAB, La Habana, Cuba
- Weight at study initiation: 2.5 - 3.5 kg
- Housing: individually
- Diet (e.g. ad libitum): CENPALAB-certified Rabbit Lab chow
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 2
- Humidity (%): approx. 50
- Photoperiod (hrs dark / hrs light): 12 h light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1% Acacia Gum in distilled water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: test item mixed with Acacia Gum in distilled water. Suspensions were prepared freshly each week and refrigerated. Stability of test item under these conditions was verified.

VEHICLE
- Amount of vehicle (if gavage): 5 ml/kg bw

Analytical verification of doses or concentrations:

no

Details on mating procedure:

Female rabbits were mated with males of the same breed until copulation was observed. Day of mating = day 0

Duration of treatment / exposure:

On gestation days 6-18 to pregnant females

Frequency of treatment:

daily

Duration of test:

until gestational day 29

No. of animals per sex per dose:

27 mated females per dose group

Control animals:

yes, concurrent vehicle

Details on study design:

Random assigment of animals to groups. On gestational day 29 females were euthanised by ether overdosing, followed by Caesarion section.

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: No detailed data

DETAILED CLINICAL OBSERVATIONS: daily observations

BODY WEIGHT: Yes

FOOD CONSUMPTION: Yes

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 29
- Organs examined: Corpora lutea

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes

Fetal examinations:

- External examinations: Yes
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: No data
- sex ratio
- body weight of fetuses

Statistics:

Litter was taken as experimental unit. Body weights were analysed by parametric analysis of variance acording to Tukey's multple comparison test. Other parameters were analised by the Kruskal-Wallis test followed by Mann-Whitney U-test. Comparison of malformation incidences between groups was performed by Chi square and Fischer's exact probability test for fetuses and litters, respectively. Trend analysis was performed by ANOVA (continuous data), Jonckheere's test (discrete data) and Cochran-Armitage test (proportional data). Tests for statistical significance were made at the p<0.05 level.

Indices:

Preimplantation loss ((Corp lut minus implantation sites)/Corp lut) x 100
Postimplantation loss ((Implantation sites minus viable fetuses)/Implant sites) x 100
sex ratio m/f

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
No unusual behaviour or clinical signs of toxicity, no effect on food consumption or body weigths

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No evidence of developmental toxicity based on postimplantation survival, fetal weight, and external, visceral or skeletal examination

Effect levels (fetuses)

Remarks on result:

other: not specified

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

No signs of developmental toxicity or teratogenicity was observed in rabbits in a study similar to OECD 414.

Executive summary:

In a prenatal developmental toxicity study (similar to OECD 414, RL 2) groups of rabbits (27 females per dose group) were mated and exposed by gavage to 0, 500 or 1000 mg/kg bw D-003 during gd 6 - 18. After C-section on gd 29 maternal and fetal observations were recorded. No substance-related change in maternal body weights, food consumption or clinical signs of toxicity was observed. Examination of pre- and postimplantation loss, fetus survival, fetal weights, external, visceral o r skeletal examinations and other parameters did not reveal any sign of developmental toxicity or teratogenicity.

The NOAEL for developmental toxicity derived from this study is 1000 mg D-003/kg bw/day.