Registration Dossier

Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2015

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: inhouse breeding
- Housing: individually after confirmation of pregnancy
- Age at study initiation: adult, 110 days
- Diet: standard purified control diet (CD), standard purified control diet with c9,t11-CLA (CLA), high fat diet (HF), HF with c9,t11-CLA (HFCLA)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
P0 females: 160 days
F1: 150 days
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Dose / conc.:
0 other: %
Remarks:
control diet (CD)
Dose / conc.:
0 other: %
Remarks:
high fat diet (HF)
Dose / conc.:
1 other: %
Remarks:
control diet with c9,t11-CLA (CLA)
Dose / conc.:
1 other: %
Remarks:
HF with c9,t11-CLA (HFCLA)
No. of animals per sex per dose:
7 dams
8 pups/litter
Control animals:
yes, plain diet
Details on study design:
Female rats were fed for 10 days prior to time mated. Mating point was determined using a estrous cycle monitor (EC-40; Fine Science Tools).
Statistics:
Statistical analysis was performed using SigmaPlot 12.0 (Systat Software Inc.). All data were analyzed by two-way factorial ANOVA, with maternal HF and maternal CLA intake as factors. Holm-Sidak post hoc tests were performed where indicated to detect further differences between groups.

Results and discussion

Effect levels

Key result
Sex:
male/female
Remarks on result:
other: no treatment related adverse effects were observed.

Observed effects

The age of pubertal onset was significantly reduced in high fat diet (HF) compared to control diet (CD), control diet with conjugated linoleic acid (CLA), and high fat diet with conjugated linoleic acid (HFCLA) offspring. The weight at puberty was significantly increased in HF offsprings.
HF offspring had significantly increased plasma leptin concentrations compared to CD, CLA, and HFCLA offspring. Triglyceride as well as cholesterol concentrations were significantly increased in HF compared to CD, CLA, and HFCLA fed animals. An significant increase in hepatic IGF-1 expression in HF-offsprings at P24 was observed compared to all other groups, but no significant differences were observed at P150. IL-1b and IL-6 expression was increased in HF-offsprings compared to all other groups. However, there was no difference between groups in TNFa or IL-10 expression. CD36, DGAT1, and FASN were significantly upregulated in offspring of HF mothers compared with CD, CLA, and HFCLA offspring. ApoE was significantly increased in HF and HFCLA compared to CD and CLA groups. Female HF-offsprings showed prolonged or irregular estrous cycles compared to CD, CLA, and HFCLA groups.

Applicant's summary and conclusion