Iron orthophosphate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No studies are provided for the endpoint 'reproductive toxicity'. The standard testing requirement for chemicals manufactured or imported into the EU in quantities of >1,000 have been adapted on the basis that there is sufficient data to permit a robust conclusion on reproductive and developmental toxicity.

Link to relevant study records

Reference

Endpoint:

extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reproductive effects observed:

not specified

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

The justification for not conducting in vivo studies to investigate the reproductive and developmental toxicity of iron orthophosphate is as follows:

During pregnancy, accompanying physiological changes reduce the concentration of haemoglobin, leading to apparent anaemia in spite of an increase in red blood cell mass.

It is estimated that approximately >700 mg of iron is needed during pregnancy to allow for increased erythropoiesis and the transfer of iron to the placenta and foetus. This additional iron must come from iron stores and from increased absorption from dietary sources of iron and from supplements. As the absorption of iron from any source is relatively low (approximately 10% of dietary iron is absorbed) it is proposed that pregnant women require approximately 30 mg Fe/day (1).           

As with cases of traditional iron-deficiency anaemia, ferrous sulphate is often given to pregnant women as a therapeutic supplement on a routine basis. Ferrous sulphate has therefore been rigorously evaluated under the relevant pharmaceutical legislation and is not considered to be a reproductive or developmental toxicant). Ferrous sulphate is considerably more soluble than iron orthophosphate and a number of investigations have been performed that suggest that the bioavailability or iron from iron orthophosphate as compared to ferrous sulphate is considerably lower (values ranging from 11%-50%) and can subsequently be considered to pose less of a risk to pregnant animals or humans.

 

Furthermore, other forms of inorganic phosphate have been assessed for reproductive and developmental toxicity and no effects have been noted with regards to maternal toxicity, reproductive functions or offspring development at dose levels well in excess of normal human exposure. This suggests that inorganic orthophosphates are not a significant risk to the reproductive process in females or males and not a significant risk to the developing foetus.

 

On the basis of the above discussion it does not seem scientifically or ethically justified to perform further in vivo studies to assess the risk of reproductive or developmental toxicity of iron orthophosphate as any studies performed would not be expected to indicate a risk of reproductive or developmental toxicity.

 

(1)       Opinion of the Scientific Panel on Dietetic Products, Nutrition and Allergies on a Request from the Commission related to the Tolerable Upper Intake Level of Iron. The EFSA Journal, 2004, 125: 1-34

Effects on developmental toxicity

Description of key information

No studies are provided for the endpoint 'developmental toxicity'. The standard testing requirement for chemicals manufactured or imported into the EU in quantities of >1,000 have been adapted on the basis that there is sufficient data to permit a robust conclusion on reproductive and developmental toxicity.

Link to relevant study records

Reference

Reference 1

Endpoint:

developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Species:

rat

Reference 2

Endpoint:

developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Species:

rabbit

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

See discussion provided under the endpoint 'effects on fertility'.

Justification for classification or non-classification

There are no data to suggest that exposure to iron orthophosphate will result in reproductive toxicity and therefore in accordance with Regulation (EC) No 1272/2008 no classification for toxicity to reproductiion is proposed.