Registration Dossier

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

Reference
Name:
Unnamed
Type:
Constituent
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.