Iohexol

Repeated dose toxicity: other routes

Administrative data

Endpoint:

chronic toxicity: other route

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28.05.1980

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:

1980

Materials and methods

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:

monkey

Strain:

Macaca fascicularis

Sex:

male/female

Administration / exposure

Route of administration:

intravenous

Duration of treatment / exposure:

28 consecutive days

Frequency of treatment:

Once a day

Doses / concentrations

Remarks:

Doses / Concentrations:0.33 g I/kg/day; 1.0 g I/kg/day; 3.0 g I/kg/day

No. of animals per sex per dose:

3 male and 3 female

Control animals:

yes

Results and discussion

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

There were no overt clinical signs of toxicity; body weight and food consumption were unaffected. No effects on the heart rate, respiratory rate and body temperature were recorded and the ECG studies showed no abnormalities. There were no significant ophtalmoscopic findings. Haematological parameteres were within the normal range and the only significant biochemical finding was a slight elevation of serum leucine arylamide values, indicating some minor liver disturbance at high dose level ( 3 g I/kg/day). Postmorten examination showed some bruising at the injection site. There was an increase in kidney weights at the high dose level. Histopathological examination showed minor vacuolation of the hepatocytes at 3 g I/kg and the vacuolation of the tubular epithelial cells in some animals receiving 1 and 3 g I/kg/day. 0.33 g I/kg/day was shown to be a no effect dose.

Executive summary:

In this study iohexol was administered to groups of 3 male and female cynomolgus monkeys at dosage levels equivalent to 0.33, 1 and 3 g I/kg/day. Control animals were dosed with the appropriate volume of physiological saline. The preparation of iohexol administered contained 370 mg I/ml and was given for 28 consecutive days. There were no overt clinical signs of toxicity; body weight and food consumption were unaffected. No effects on the heart rate, respiratory rate and body temperature were recorded and the ECG studies showed no abnormalities. There were no significant ophtalmoscopic findings. Haematological parameteres were within the normal range and the only significant biochemical finding was a slight elevation of serum leucine arylamide values, indicating some minor liver disturbance at high dose level ( 3 g I/kg/day). Postmorten examination showed some bruising at the injection site. There was an increase in kidney weights at the high dose level. Histopathological examination showed minor vacuolation of the hepatocytes at 3 g I/kg and the vacuolation of the tubular epithelial cells in some animals receiving 1 and 3 g I/kg/day. 0.33 g I/kg/day was shown to be a no effect dose.