Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 March 2004 to 04 November 2004
Reliability:
1 (reliable without restriction)
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar

Administration / exposure

Route of administration:
oral: feed
Vehicle:
acetone
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The test item fortified food was sampled for active ingredient analysis at the start of the treatment(contentration determinated from samples collected for the homogenetly test) and once in 3 month intervals thereafter
No. of animals per sex per dose:
30 male and 30 female/dose
Details on study design:
Control animals: 30 male and 30 female

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
A significant decrese in the terminal body weight and food intake was observed in high dose males and females.
A reduced number of corpora lutea and implantations in the dams was observed

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
One female had extra ribs

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
>= 138 - <= 154 mg/kg bw/day (nominal)
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

The incidence of rudimentary extra ribs # 14 was significantly increased in dosed group 50.5% compared to 0.66% in control group.

It is apparent that pups with extra ribs have markedly lower body weights than the ones without.

It has been demonstrated that extra ribs in rats and mice teratology studies are associated with a foetal retardation and are indicative of maternal/foetal toxicity and not a developmental malformation

The foetal retardation can also be seen in delayed ossification of other skeletal elements and the presence of dumbball shaped vertebrae.

Applicant's summary and conclusion