Iron trinitrate

Repeated dose toxicity: other routes

Administrative data

Endpoint:

short-term repeated dose toxicity: other route

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

No data

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: 4e The study did not meet current guideline requirements for repeated dose toxicity. It does, however, add weight of evidence for subacute toxicity.

Data source

Reference

Reference Type:

publication

Title:

Comparative toxicology of iron compounds.

Author:

Weaver L C, Gardier R W, Robinson V B, Bunde C A

Year:

1961

Bibliographic source:

American Journal of Medical Sciences, 241(3): 296-302

Materials and methods

Test guideline

Qualifier:

no guideline available

Deviations:

yes

Remarks:

Documentation is insufficient for assessment, no individual animal data or statistical analysis reported, no control group. Single dose level only for ferrous sulphate.

Principles of method if other than guideline:

This subacute study is part of a series of investigations carried out to investigate the comparative toxicity of a series of iron compounds which include ferrous sulphate. The emetic dose for dogs was also determined.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Iron sulphate

EC Number:

231-753-5

EC Name:

Iron sulphate

Cas Number:

7720-78-7

IUPAC Name:

iron(2+) sulfate

Details on test material:

- Name of test material (as cited in study report): Ferrous sulfate

Test animals

Species:

dog

Strain:

other: mongrel

Sex:

not specified

Administration / exposure

Route of administration:

other: oral

Vehicle:

other: gelatin capsule

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

Approximately one month

Frequency of treatment:

Twice daily

Doses / concentrations

Remarks:

Doses / Concentrations:
Total daily dose of 0.5 g

No. of animals per sex per dose:

Five in total (sex not recorded)

Control animals:

no

Details on study design:

Post-exposure period: none

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Details on results:

Average bodyweights of dogs given ferrous sulphate and the iron carbohydrate complex at the two higher doses levels were reduced during the first 
week of dosing, after this bodyweights remained constant or increased. Changes ranged from 0.6 to 0.8 kg for the 3 affected groups. There were no 
other clinical signs of toxicity. Emesis was not reported. There were no gross or histopathological changes indicative of iron toxicity in any of the test 
groups. The authors state that no significant differences were observed in iron staining in the liver, spleen or bone marrow in any test group. Total red
blood cell count and haemoglobin were within the normal range for each dog.

Effect levels

Dose descriptor:

other: emesis induction level

Effect level:

62 mg/kg bw (total dose)

Based on:

other: capsule administration

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Average bodyweights of dogs given ferrous sulphate and the iron carbohydrate complex at the two higher doses levels were reduced during the first 

week of dosing, after this bodyweights remained constant or increased. Changes ranged from 0.6 to 0.8 kg for the 3 affected groups. There were no 

other clinical signs of toxicity. Emesis was not reported. There were no gross or histopathological changes indicative of iron toxicity in any of the test 

groups. The authors state that no significant differences were observed in iron staining in the liver, spleen or bone marrow in any test group. Total red

blood cell count and haemoglobin were within the normal range for each dog.

Applicant's summary and conclusion

Conclusions:

In a limited subacute toxicity study (reliability score 4) conducted prior to the adoption of OECD test guidelines and GLP, it appears that a dose of 0.5 g/day ferrous sulphate (salt) was tolerated by dogs the principle effect being a reduction in bodyweight, the limited toxicological assessment does not suggest overt iron toxicity.

Executive summary:

In a limited subacute toxicity study (reliability score 4) conducted prior to the adoption of OECD test guidelines and GLP, it appears that a dose of 0.5 g/day ferrous sulphate (salt) was tolerated by dogs the principle effect being a reduction in bodyweight, the limited toxicological assessment does not suggest overt iron toxicity.