Fatty acids, C9-13-neo-

Toxicity to reproduction

Administrative data

Endpoint:

three-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report which meets basic scientific principles: pre-GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1968

Report date:

1968

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)

Deviations:

yes

Remarks:

3 generations used, dietary administration

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Neodecanoic acid

EC Number:

248-093-9

EC Name:

Neodecanoic acid

Cas Number:

26896-20-8

Molecular formula:

C10H20O2

IUPAC Name:

neodecanoic acid

Details on test material:

TS-Freetext:
CAS No. 26896-20-8; Neodecanoic acid (2,2-dimethyloctanoic acid)
- Name of test material (as cited in study report): MRD-67-21
- Physical state: clear liquid with a faint odor
- Analytical purity: assumed 100%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Age at study initiation: (P) young
- Weight at study initiation: (P) Males: 108-164 g; Females: 101-144 g;
- Diet (e.g. ad libitum): prepared, ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:

oral: feed

Details on exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): Fresh diets were prepared every 2 weeks or weekly as needed.
- Mixing appropriate amounts with (Type of food): Purina Laboratory Chow
- Storage temperature of food: Room temperature

Details on mating procedure:

- M/F ratio per cage: 1/2
- Length of cohabitation: week
- After successful mating each pregnant female was caged (how): individually

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

Premating exposure period (males): P1: 9 weeks
Premating exposure period (females): P1: 9 weeks
Duration of test: 3 generations

Frequency of treatment:

Continuous

Details on study schedule:

P1 GENERATION
Prior to initiation of the first and second breeding phases, the parental generation animals were maintained in individual cages and fed the appropriate diets until they reached maturity, 9 weeks. At the end of the ninth week, two females and one male within each group were mated. Males were rotated for 3 weeks.

F1A GENERATION
Twenty-four hours after birth, the F1A litters were arbitrarily reduced to a maximum of eight pups for nursing. After 21 days, representative pups from each litter were sacrificed and gross necropsies were performed. All other weanlings were discarded.

F1B GENERATION
One week after weaning the last F1A litter, the P1 parents were re-mated are previously described to produced the F1B generation. After a 21-day nursing period, 20 female and 10 male weanlings were designated as the P2 generation. One third of the remaining weanlings were gross necropsied, the remaining were discarded.

P2 GENERATION
The P2 animals were individually hosed until they reached 100 days of age. Mating occurred as described previously.

F2A GENERATION
As described previously – F1A

F2B GENERATION
As described previously – F1B

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 100, 500, 1500 ppm in diet
Basis:
nominal in diet
approximately 5, 25 and 75 mg/kg/day, respectively

No. of animals per sex per dose:

20 Females, 10 Males

Control animals:

yes

Examinations

Parental animals: Observations and examinations:

Observations were made at 5 and 9 weeks

Oestrous cyclicity (parental animals):

No data

Sperm parameters (parental animals):

No data

Litter observations:

Immediately after birth

Postmortem examinations (parental animals):

All parent animals

Postmortem examinations (offspring):

All offspring

Statistics:

N/A

Reproductive indices:

Fertility, gestation, live birth, lactation.

Offspring viability indices:

Fertility, gestation, live birth, lactation.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

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:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

Details on results (P0)

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
One control P1 female was found dead following the second F1B mating period. The right adrenal was enlarged and dark red in color, and the lungs were dark red in color. Two intermediate level P2 males were found dead following the first F2A mating period. The gastrointestinal tract of both animals was filled with gas, the lungs of one were dark gray in color, and the lungs of the other were distended and dark red with grayish areas.

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
No effects noted

TEST SUBSTANCE INTAKE (PARENTAL ANIMALS)
No effects noted

REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS)
No effects noted

REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS)
No effects noted

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
No effects noted

ORGAN WEIGHTS (PARENTAL ANIMALS)
No effects noted

GROSS PATHOLOGY (PARENTAL ANIMALS)
No effects noted

HISTOPATHOLOGY (PARENTAL ANIMALS)
No effects noted

OTHER FINDINGS (PARENTAL ANIMALS)
No effects noted

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

1 500 ppm

Sex:

male/female

Basis for effect level:

clinical signs

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings:

no effects observed

Details on results (F1)

F1A and F1B – The various indices, litter size, pup body weights, appearance, and behavior of the newborn and of the pups during lactation were comparable among the control and test groups for both cycles. The pups from one high level F1A litter were noted to be cold to the touch at birth. During delivery of this litter, a bloody-appearing vaginal discharge was observed in the dam. Pups noted to be thin and/or small in size at birth or during lactation were found in all of the groups. Sings of nasal discharge and wheezing were observed in a few pups. Spasmodic breathing was noted in one intermediate level F1A pup which was gray in color. In the F1B litters, a few control and test pups were found with eyes squinted and eyelids red in color. One low level F1B pup had enlarged eyes. No adverse effects were noted during necropsy.

F2A and F2B – The various indices, litter size, pup body weights, appearance, and behavior of the newborn and of the pups during lactation were comparable among the control and test groups for both cycles. At birth, two pups from one high level F2A litter were found cold to the touch. Minor incidental findings were also noted.

Effect levels (F1)

1

Dose descriptor:

NOAEL

Generation:

F1a

Effect level:

1 500 ppm

Sex:

male/female

Basis for effect level:

clinical signs

2

Dose descriptor:

NOAEL

Generation:

F1b

Effect level:

1 500 ppm

Sex:

male/female

Basis for effect level:

clinical signs

Results: F2 generation

Effect levels (F2)

1

Dose descriptor:

NOAEL

Generation:

F2a

Effect level:

1 500 ppm

Sex:

male/female

Basis for effect level:

clinical signs

2

Dose descriptor:

NOAEL

Generation:

F2b

Effect level:

1 500 ppm

Sex:

male/female

Basis for effect level:

clinical signs

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

No adverse effects on reproduction or development were noted.

Executive summary:

This study was conducted to evaluate the effects of long-term ingestion of neodecanoic acid on reproduction in albino rats.  Neodecanoic acid was administered in the diet at levels of 100, 500, and 1500 ppm fed to the rats through two parental and to two-litter filial generations.  Following nine weeks of dietary administration to the F2B weanlings designated as the third parental generation, the study was terminated.  There was no evidence at any test level of an adverse effect on the survival, appearance, behavior, body weight gain, and food consumption of the parental generations; on the reproductive performance of the parents reflected by the various indices; or on the growth, appearance, and behavior of the offspring.  Gross and macroscopic pathological findings revealed no evidence of a compound-related effect at any of the dietary levels.