Iohexol

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06.03.1980-07.10.1980

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

Report date:

1981

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Sexually mature proven breeder males (age of 4-5 months and body weight > 350 grams) and mature virgin females (age of 2.5 months and body weight range of 193-292 grams at Day 0) Charles River CD albino rats were used. Male stock breeders were house three per cage except during mating. Females were housed up to three per cage during acclimatization and then housed individually following insemination. Each male was house nightly with up to three females until mating was completed. Vaginal washings were made on the morning after each exposure to a male and the days of positive identification of spermatozoa in the washing was designed as Day 0 of pregnancy. Iohexol was administered intravenously into the tail veins as a bolus injection at 1.0; 2.0 and 4.0 gr I/kg to the three groups of 25 rats each. An additional group of 25 rats similarly received 10.8 ml/kg of sterile saline (0.9 % NaCl). The dams were medicated once daily from the sixth through the fifteenth day of pregnancy for a total of ten medications.The dams were observed daily for changes in appearance and behaviour and for any drug-related effects upon the course of pregnancy. They were weighed on Day 0, 6, 8, 0, 12, 15 and 20 of pregnancy. On the twentieth day of pregnancy, all surviving dams were sacrificed by cervical dislocation. The abdominal wall was opened and the ovaries and uterine horns were excised. The ovaries were examined and corpora lutea were counted. The uterine horns were opened longitudinally and fetuses displaced to one side to facilitate gross examination of the horns for resorption sites. The number of viable and non-viable fetuses, resorption, and implantation sites were determined. The remaining organs, thoracic, and abdominal were examined and any gross changes were noted. Fetuses of one-third of the litters were examined with the aid of a steroscope for abnormalities of the abdominal and thoracic viscera and of the cranial cravity and then discarded. Fetuses in the remaining two-thirds of the litters were individually identified and fixed in 70 % ethanol. These fetuses were later eviscerated and processed for skeletal examination using modification of the rapid clearing technique, KOH Alizarin Red-S method for fetal bone. Examination was made of the skull bones and sutura, vertebrae, ribs, pelvis, sternebrae, clavicle, scapule and appendages.

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

Administration / exposure

Route of administration:

intravenous

Frequency of treatment:

The rats were dosed daily from the sixth through the fifteenth day of pregnancy for å total 10 injections.

Duration of test:

15 days

Doses / concentrations

Dose / conc.:

4 mg/kg bw/day (nominal)

No. of animals per sex per dose:

4

Control animals:

yes

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Effect levels (maternal animals)

Effect level:

>= 1 - <= 4 mg/kg bw/day (nominal)

Remarks on result:

not determinable due to adverse toxic effects at highest dose / concentration tested

Results (fetuses)

Effect levels (fetuses)

1

Dose descriptor:

NOAEL

Basis for effect level:

other: embryotoxicity

Remarks on result:

not determinable

Remarks:

no NOAEL identified

2

Dose descriptor:

NOAEL

Basis for effect level:

other: teratogenicity

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:

The compound was neither embryotoxic, nor teratogenic at the dosages tested.

Executive summary:

In this study, a pregnant Sprague-Dawley rats received intravenous injections of 1, 2 and 4 g I/kg. A fourth group of rats was dosed with saline and acted as controls. The dosages had been decided from a preliminary study. The rats were dosed daily from the 6th trough the 15th day of pregnancy (total of 10 injections). On day 20 the dams were killed and the foetuses removed and evaluated. Iohexol had no effect on the behaviour of the dams, body weight, pregnancy rate, corpora lutea, number of implantations, litter size, number of resorptions, foetal weight and viability, sex ratio or pre and post implantation losses at any dossage level. There were no drug related effects in the foetuses derived from these dams. The compound was neither embryotoxic, nor teratogenic at the dosages tested.