Registration Dossier

Administrative data

Description of key information

LD50, Oral, Rats > 2000 mg/kg bodyweight.
LD50 (4 hours), Inhaled, Rats > 5.75 mg/L.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

An acute oral toxicity study in rats was conducted (Huntingdon Life Sciences, 2010) to determine the acute LD50 of Fe3P when administered orally. The study was conducted according to EC test guideline B1, OECD guideline 423, and US EPA and Japanese test guidelines, and in compliance with GLP.

Two groups of three fasted female rats received a single oral gavage dose at 300 mg/kg bodyweight; as the results at this level indicated that the LD50 was greater than 300 mg/kg bodyweight, a further two groups of three fasted females received a single oral gavage dose of 2000 mg/kg bodyweight.

There were no deaths during the study. The only clinical sign of a reaction to treatment noted during the observation period was abnormally coloured faeces (black) seen in all animals dosed at 300 mg/kg, and three females dosed at 2000 mg/kg; these signs had resolved by day 2 of observation. A low bodyweight gain was observed late in the observation period for two animals at 300 mg/kg and three animals dosed at 2000 mg/kg. No abnormalities were noted in any animal during the macroscopic examination at study termination.

The acute median lethal oral dose to rate was demonstrated to be greater than 2000 mg/kg bodyweight.

An acute inhalation toxicity study in rats was conducted (Huntingdon Life Sciences, 2011) to determine the acute LD50 of Fe3P by inhalation exposure. The study was conducted according to EC test guideline B2, OECD test guideline 403, and US EPA and Japanese test guidelines, and was performed in compliance with GLP.

1 control group and 1 test group each consisting of 5 male and 5 female Sprague Dawley rats were administered a single 4 -hour snout-only exposure, then observed over 14 days prior to sacrifice and macropathological examination. The time-weighted average aerosol concentration of Fe3P in the treated group was 5.75 mg/L, which was close to the target concentration of 5 mg/L. Individual and mean calculated Mass median aerodynamic diameter (MMAD) values were above the optimal range of 1 - 4 µm; the average MMAD was 8 µm.

There were no unscheduled deaths during the study. Clinical signs were limited to grey staining of the head in all animals of the treated group, and the forepaws in the majority of animals in the treatment group. This was no longer evident at the first check during the observation period. There were no treatment related effects on bodyweight. Macroscopic pathological examination following sacrifice revealed a dark brown colour in the lungs of treated animals, a higher relative weight of lungs in the treated group by comparison to the control group, and enlarged tracheobronchial lymph nodes seen in treated animals.

The LC50 (4 hour) in rats of Fe3P was found to be greater than 5.75 mg/L under the conditions applied during this test.

Justification for classification or non-classification

The oral LD50 in rats of Fe3P was determined to be greater than 2000 mg/kg bodyweight. According to both the Classification Labelling and Packaging Regulation (CLP, EC number 1272/2008) and the Dangerous Substances Directive (DSD, Directive 67/548/EEC), classification for acute oral toxicity only applies where the oral LD50in rats is equal to or less than 2000 mg/kg bodyweight; on this basis Fe3P does not require classification for acute oral toxicity.

The inhaled LC50in rats of Fe3P was determined to be greater than 5 mg/L. According to both the CLP Regulation and the DSD as above, classification for acute oral toxicity only applies where the inhaled LC50in rats is equal to or less than 5 mg/L; on this basis Fe3P does not require classification for acute inhaled toxicity.

Although the studies noted above were designed to determine the lethal dose / concentration of Fe3P, and signs of sublethal toxicity were not observed in detail, the macroscopic pathology in each case did not indicate Specific Target Organ Toxicity (STOT, single exposure) by either administration route. The differences between the lungs of the treated group animals and the control group animals seen in the acute inhalation study (Huntingdon Life Sciences, 2011) were expected, and relate to the presence of test material in the lungs of the treated animals (increased lung weights and dark brown colour in the lungs) and the elimination response (enlarged tracheobronchial lymph nodes); these observations are not indicators of substance-specific toxicity.

On this basis, Fe3P does not require classification for STOT following single exposure by either the oral or inhaled exposure routes. Despite that no data are available for dermal exposure, classification of Fe3P for single-exposure STOT via this route is also not anticipated in view of its chemical inertness and its poor water solubility.