Diiron tris(sulphate)

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Publication, reasonably documented, acceptable for assessment.

Data source

Reference

Reference Type:

secondary source

Title:

Safe upper levels for vitamins and minerals. Report of the Expert Group on Vitamins and Minerals.

Author:

EVM Expert Group on Vitamins and Minerals

Year:

2003

Bibliographic source:

ISBN 1-904026-11-7 Self-published in May by the Food Standards Agency, U.K. 360 p. (Iron on p 274-85) http://cot.food.gov.uk/pdfs/vitmin2003.pdf

Materials and methods

Study type:

other: Literature survey

Endpoint addressed:

acute toxicity: oral

repeated dose toxicity: oral

Test material

Test material information

Constituent 1

Reference substance name:

Iron

EC Number:

231-096-4

EC Name:

Iron

Cas Number:

7439-89-6

IUPAC Name:

iron(2+)

Results and discussion

Clinical signs:

Supplementary doses of 100-200 mg iron/day and above have been associated with nausea, vomiting and epigastric pain. Other studies have reported a range of gastrointestinal effects, including diarrhoea, nausea, vomiting, constipation and epigastric pain, following supplementary doses of between 50 and 220 mg/day. However, such effects were variable and appeared to vary depending on the formulation of the iron supplement given, with fewer adverse effects reported by subjects given supplementary iron as chelated iron or haem iron than by subjects given ferrous sulphate.

Results of examinations:

A review of the safety of vitamin and mineral supplements in food looked at: exposure to iron; the biological function of iron; iron deficiency; interactions with other metals; absorption and bioavailability; distribution, metabolism and excretion; toxicity. Guidance levels were established. The review reported average daily losses of 1.0 mg/day in healthy adult male humans and 1.3 mg/day in pre-menopausal women. The acute doses were considered to be: 20 mg/kg for infants (under the age of six) by gastrointestinal irritation, with systemic effects not occurring below 60 mg/kg bw; 200-300 mg/kg for children; 1400 mg/kg bw for adults. It was considered that there is not enough evidence to reach conclusions on specific links between iron and development of cancers.

Outcome of incidence:

Outcome of incidence: One study found an association between supplementation with ferrous sulphate (equivalent to 60 mg elemental iron/day) during pregnancy and reduced birth weight in women who were aspartate carriers for the sickle cell anaemia genotype.
Individuals with pre-existing gastrointestinal tract disease or chronic hepatitis have been shown to be vulnerable to the toxic effects of iron.
Several inherited diseases, for example, hereditary haemochromatosis (HHC), are associated with increased iron absorption. Hereditary anaemias, such as thalassemia or sideroblastic anaemia, frequently require treatment by repeated blood transfusions, which may result in iron overload and toxicity.

Applicant's summary and conclusion

Conclusions:

In humans acute iron poisoning is associated with severe gastrointestinal damage which may include haemorragic gastroenteritis. Blood and other fluid loss may lead to shock and coma. In some cases, apparent recovery may take place, possibly due to a latency period during which the iron is distributed throughout the body. Systemic iron toxicity is characterised by multi-system damage, principally in the liver, metabolic acidosis, aoagulopathies and cardiovascular collapse. Acute poisoning is relatively unusual in adults, the lethal dose being approximately 100 g, but is more common in children.
Iron overload as a result of dietary intake is unusual in the normal population and only ahandful of case reports exist describing this phenomenon. This may be due to the reduction in iron absorption that occurs as exposure increases.
Individuals with conditions such as heriditary haemochromatosis (HHC) are particularly vulnerable to iron overload, which occurs as a result of enhanced uptake. In subjects heterozygous for the condition, a small increase in iron storage may occur. It has been suggested thet heterozygous subjects (up to 1 % of the population) may have an increased risk of cardiovascular disease but this remains controversial. Similarly, the suggestion that high iron status may be associated with other chronic conditions remains unresolved.