Iohexol

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06.09.1980-01.12.1980

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was conducted scientifically and in accordance with Good Laboratory Practices.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Sixty male and 120 sexually mature female rats were used in this study of fertility and general reproduction performance with Iohexol. These rats were approximately 12 weeks of age and had been acclimated in this laboratory for 26 days prior to study initiation. Each rat was assigned a unique number and ear-tagged for identification when placed on study. Prior to mating, all rats were housed individually in suspended wire-mesh cages in a temperature, humidity and light controlled room. All rats were randomly assign according to body weights by a computer-generated program to one control and three treatment groups consisting of 15 males and 30 females each.All females were smeared daily to establish estrous cycles 10 days prior to test article administration and until evidence of copulation was obatined or until the mating period terminated. Following initial treatment of the female rats (every other day for 14 days), one untreated male was housed with two females of the same strain and source in a platic case with gound corn corb bedding for a mating period of 10 days. The occurence of copulation was determined by a vaginal smear for sperm or by daily inspection for a copulatory plug. The day evidence of mating was detected was designated day 0 of gestation and the female was returned to an individual plastic cage. If evidence of copulation was not found during the initial 10 day period, the female was placed with another male from the same treatment group for an additional five days or until evidence of mating was detected. At the end of the second mating period, all animals were separated, at this time the males were returned to individual suspended wire-mesh cages and the females were housed in individual plastic cages with corn cob bedding.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Iohexol

EC Number:

266-164-2

EC Name:

Iohexol

Cas Number:

66108-95-0

Molecular formula:

C19H26I3N3O9

IUPAC Name:

5-[acetyl(2,3-dihydroxypropyl)amino]-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

intravenous

Duration of treatment / exposure:

Dosages of 0, 1 , 2, 4 gr I/kg were administered intravenously to the female as a single dose every other day beginning 14 days prior to mating, daily on gestation days 0 through 6 andon alternate days thereafter, until weaning of the pups at lactation day 21.

Frequency of treatment:

Dosages of 0, 1 , 2, 4 gr I/kg were administered intravenously to the female as a single dose every other day beginning 14 days prior to mating, daily on gestation days 0 through 6 andon alternate days thereafter, until weaning of the pups at lactation day 21.

Doses / concentrations

Remarks:

Doses / Concentrations:0, 1 , 2, 4 gr I/kgBasis:

No. of animals per sex per dose:

Groups of 15 males and 30 females were used. Dosages of 0, 1 , 2, 4 gr I/kg were administered intravenously to the female as a single dose every other day beginning 14 days prior to mating, daily on gestation days 0 through 6 andon alternate days thereafter, until weaning of the pups at lactation day 21.

Control animals:

yes

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:

dose level: 4

Remarks:

gI/kg

Effect level:

ca. 10.8 other: mL/kg

Sex:

male/female

Basis for effect level:

other: No NOAEC or NOAEL identified

Remarks on result:

not measured/tested

Remarks:

Effect level not specifiedGeneration not specified (migrated information)

Results: F1 generation

Effect levels (F1)

Dose descriptor:

other: 0

Remarks:

No record

Generation:

F1

Effect level:

0 other: No record

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: No record

Remarks on result:

not measured/tested

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

The fertility index in this study was extremely low, although there was no evidence to suggest that the reduced fertility was treatment-related. There was no evidence of maternal toxicity in the F0 generation and the mean uterine examination values, pup survival indices and mean pup body weights in all treated groups were comparable to the controls. There was no effect on F0 female estrus cycle, fertility, parturition or mean gestation length. Treatment of the F0 female rats did not effect the appearance, behavious, litter size, number of stillborn pups, bodyweight at birth or survival of the F1 generation.

Applicant's summary and conclusion

Conclusions:

No treatment related findings were observed on F0 females or pups.

Executive summary:

This study was conducted in Spraque-Dawley rats. Groups of 15 males and 30 females were used. Dosages of 0, 1 , 2, 4 gr I/kg were administered intravenously to the female as a single dose every other day beginning 14 days prior to mating, daily on gestation days 0 through 6 andon alternate days thereafter, until weaning of the pups at lactation day 21. The concentration of iodine adminiestered was 370 mg I/ml. The control group received physiological saline. The males were not treated. 10 females per group were killed on day 13 and the remaining females allowed to deliver. The fertility index in this study was extremely low, although there was no evidence to suggest that the reduced fertility was treatment-related. There was no evidence of maternal toxicity in the F0 generation and the mean uterine examination values, pup survival indices and mean pup body weights in all treated groups were comparable to the controls. There was no effect on F0 female estrus cycle, fertility, parturition or mean gestation length. Treatment of the F0 female rats did not effect the appearance, behavious, litter size, number of stillborn pups, bodyweight at birth or survival of the F1 generation.