5-(Acetyl-(3-(acetyl-(3,5-bis(2,3-dihydroxypropylcarbamoyl)-2,4,6-triiodophenyl)amino)-2- hydroxypropyl)amino)-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodobenzene-1,3-dicarboxamide; 5,5'-((2-Hydroxytrimethylene)bis(acetylimino))bis(N,N'-bis(2,3-dihydroxypropyl)-2,4,6- triiodoisophthalamide);

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

19.05.1989-11.07.1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study meets the requirements of the Principles of Good Laboratory Practice

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

This study describes the preliminary experiment performed to assess the effect of intravenous administration on pregnancy of the rabbit and in utero development of the offspring in order to select the highest dose level for subsequent teratology study in rabbit. A preliminary teratology study was conducted in Chbb:HM rabbits (16). Five groups of three mated female rabbits were administered 0 (saline control), 0.3, 1.0, 2.0 or 3.0 gI/kg/day iodixanol by daily intravenous injections from day 6 up to and including day 18 of gestation. Day 0 was defined as the day of mating. Maternal clinical signs, body weight and food consumption were recorded. On day 29 of pregnancy the rabbits were sacrificed and the uterus and ovaries examined for the following: number of implantation sites; number of early and late resorption sites; distribution and number of live and dead foetuses and resorptions in the uterine horns; number of corpora lutea; sex and weight of each foetus, weight of placenta, weight of uterus. External abnormalities of each foetus were also recorded. The mean values of all maternal and foetal parameters in the dosed groups were comparable to those of the control group.Control animals received sterile saline (0.9% NaCl solution).

GLP compliance:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test animals

Species:

rabbit

Strain:

Himalayan

Administration / exposure

Route of administration:

intravenous

Details on mating procedure:

Fifteen pregnant rabbits weighing between 1.7 and 2.7 kg and approximately 4 months of age (SPF albino female rabbits of the Chbb:HM, C.H.Boehringer/Biberach:Himalaya strain) were delivered on the day of mating.Mating took place in the facilities of the breeder with males of proven fertility.Mated females were allocated to dose group and cage in the rack in the order of mating, i.e. females mated each day were evenly distributed between dose groups.

Duration of treatment / exposure:

Daily intravenous injections on days 6 up to and including day 18 of gestation

Frequency of treatment:

Daily

No. of animals per sex per dose:

Five groups of three mated female rabbits were administered 0 (saline control), 0.3, 1.0, 2.0 or 3.0 gI/kg/day iodixanol.

Control animals:

yes

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Basis for effect level:

other: maternal toxicity

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:

NOAEL

Basis for effect level:

other: fetotoxicity

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

It was concluded that iodixanol did not cause maternal or foetal toxicity in the rabbit at intravenous dosages up to 3.0 gI/kg/day

Executive summary:

A preliminary teratology study was conducted in Chbb:HM rabbits (16). Five groups of three mated female rabbits were administered 0 (saline control), 0.3, 1.0, 2.0 or 3.0 gI/kg/day iodixanol by daily intravenous injections from day 6 up to and including day 18 of gestation. Day 0 was defined as the day of mating. Maternal clinical signs, body weight and food consumption were recorded. On day 29 of pregnancy the rabbits were sacrificed and the uterus and ovaries examined for the following: number of implantation sites; number of early and late resorption sites; distribution and number of live and dead foetuses and resorptions in the uterine horns; number of corpora lutea; sex and weight of each foetus, weight of placenta, weight of uterus. External abnormalities of each foetus were also recorded. The mean values of all maternal and foetal parameters in the dosed groups were comparable to those of the control group. It was therefore concluded that iodixanol did not cause maternal or foetal toxicity in the rabbit at intravenous dosages up to 3.0 gI/kg/day.