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);

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02.06.1989-05.01.1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study meets the requirements of the OECD Principles of Good Laboratory Practice, Paris, 1992

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

The effects of iodixanol on peri- and post-natal development was studied in the rat. Daily dosages of 0 (saline control), 0.3, 1.0 and 2.0 gI/kg/day were administered via the lateral tail vein to groups of 25 time-mated female rats from day 17 of pregnancy to day 21 postpartum, inclusive. The females were allowed to litter and rear their young to weaning, when selected offspring were retained and assessed for behavioural and reproductive performance. Twenty Fl females originating from each group were paired with 20 F1 males originating from the same group and allowed to litter and rear their young (F2 generation) to weaning. Kidney weights were recorded for F0 and F1 adults.

GLP compliance:

yes

Type of method:

in vivo

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

female

Administration / exposure

Route of administration:

intravenous

Duration of treatment / exposure:

Daily dosages of 0 (saline control), 0.3, 1.0 and 2.0 gI/kg/day were administered via the lateral tail vein to groups of 25 time-mated female rats from day 17 of pregnancy to day 21 postpartum, inclusive.

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:0 (saline control), 0.3, 1.0 and 2.0 gI/kg/day Basis:

No. of animals per sex per dose:

F0: Female: 25F1: Male 20 and Female 20

Control animals:

yes

Results and discussion

Effect levels

Dose descriptor:

NOAEL

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Observed effects

Dosages op to and including 2.0 grI/kg/day, did not adversely affect the ability of the F0 and F1 dams to satisfactorily rear their respective litters to weaning

Applicant's summary and conclusion

Conclusions:

Treatment of F0 females did not adversely affect the performance of untreated F1 offspring in specific behaviour tests, mating performance, pregnancy rate, duration of pregnancy or overall ability to rear F2 offspring to weaning.

Executive summary:

The effects of iodixanol on peri- and post-natal development was studied in the rat. Daily dosages of 0 (saline control), 0.3, 1.0 and 2.0 gI/kg/day were administered via the lateral tail vein to groups of 25 time-mated female rats from day 17 of pregnancy to day 21 postpartum, inclusive. The females were allowed to litter and rear their young to weaning, when selected offspring were retained and assessed for behavioural and reproductive performance. Twenty Fl females originating from each group were paired with 20 F1 males originating from the same group and allowed to litter and rear their young (F2 generation) to weaning. Kidney weights were recorded for F0 and F1 adults.

Treatment of parental F0 females with 2.0 gI/kg/day iodixanol was associated with increased kidney weights, transient reddening of the pinnae post dosing, slightly reduced food consumption during lactation, and slight, but not statistically significant reduction in litter and pup mean weights through weaning. Increased kidney weight was also apparent in the 1.0 gI/kg/day dosage group. Treatment with 0.3 or 1.0 gI/kg/day iodixanol resulted in no other toxicologically important effects.

Mean weekly body weights for male and female F1 adults derived from dams treated with 2.0 gI/kg/day, and for F1 males from dams treated at 1.0 gI/kg/day, were slightly lower than controls. Mean pup weights on days 12 and 21 were marginally reduced for animals derived from the 0.3 and 1.0 gI/kg/day dosage groups, which was probably related to the slightly larger litter sizes. None of these differences from control values were statistically significant.

In summary, treatment of F0 females did not adversely affect the performance of untreated F1 offspring in specific behaviour tests, mating performance, pregnancy rate, duration of pregnancy or overall ability to rear F2 offspring to weaning.