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Description of key information

There are no data for the ammonium salts of DTPMP. Therefore data have been read across from sodium salt of DTPMP and ammonia (& salts)
In a good quality 90-day feeding study (CTL, 1998) conducted to OECD 408 and GLP, groups of 12 male and 12 female Wistar-derived rats were fed diets containing 0 (control), 100, 1000 or 10000 ppm (equivalent to 8.2, 82.5 and 841.9 mg/kg bw/day in males and 9.2, 92.3 and 902.6 mg/kg for females) Dequest 2066A (sodium salt of DTPMP) for 90 consecutive days. There were no deaths and the majority of parameters were unaffected by the treatment. Minor changes in certain haematological parameters (red blood cell count was significantly increased, mean cell volume and mean cell haemoglobin concentration were significantly decreased) were noted at the highest dose. There was also a decreased incidence in Perls' staining of the spleen. Bone density was significantly increased in both sexes in the highest dose group, and the incidence of microlithiasis in the kidney was reduced at all dose levels. These changes are indicative of the influence of Dequest 2066A on calcium homeostasis, however, without causing any changes in calcium plasma levels. Therefore, the changes were not considered to be of toxicological significance, and the NOAEL was 10000 ppm (equivalent to to 841.9 and 902.6 mg/kg bw/day of the salt in males and female, respectively).
However, it is the opinion of the author of this study summary that anaemia in humans is of concern, and therefore the NOAEL is reduced to 1000 ppm (equivalent to 82.5 and 92.3 mg/kg bw/day for males and females, respectively).

Key value for chemical safety assessment

Additional information

The key study was the most reliable study available for the sodium salt of DTPMP. (CTL 1988 rel.2)

There are no data on the ammonium salt of DTPMP. However, administration of this salt can be assumed to lead to the systemic effects observed following the independent administration of DTPMP and ammonia (and salts). Therefore the repeated dose toxicity of ammonia is of relevance. The following discussion is taken from the SIAR for ammonia.

In a 13 week repeated-dose feeding study in rats given ammonium sulfate up to 1,975 mg/kg bw/day, no effects were observed on body weight, food consumption or hematological and clinical parameters. However, increased kidney weights (in males and females) and increased liver weights (females) were observed at the highest dose without histopathological changes. The NOAEL was 1,975 mg/kg bw/day for females and 886 mg/kg bw/day for males (diarrhea). In a combined repeated-dose/reproduction/developmental oral gavage screening study in rats exposed to 0. 250, 750 and 1,500 mg/kg bw diammonium phosphate for 35 days, a NOAEL of 250 mg/kg bw was derived based on increased alkaline phosphatase and decreased total protein in blood.

Justification for classification or non-classification

The data suggest that there is no need to classify for adverse effects following repeated exposures. Although the NOAEL for effects on haematological parameters was within the classifiable range, the effects are not sufficiently severe to trigger classification.

DTPMP ammonium salt is not classified for human health. Aqueous ammonia is subject to formal specific concentration limits for hazard classification according to the CLP regulations. However in DTPMP salt preparations the pH falls into a neutral pH range and the proportion of free ammonia in salt products is very small, being dominated by the highly soluble form NH4+which is of low bioavailability. As explained in the ammonia category SIAR, “As pH decreases, the concentration of ammonium ion increases with respect to decreases of unionized ammonia concentrations. However, the toxicity of the unionized ammonia is considered several orders of magnitude greater than the more abundant ammonium ion”. Some relevant toxicity data are available for relevant ammonia salts which would under normal conditions have pH in the neutral range; the pH of the tested substances is not reported but is assumed to be the same.

The NOAEL from oral repeated dose studies with ammonium salts (assumed to have pH in the neutral range) is 250 mg/kg bw/d (based on increased alkaline phosphatase and decreased total protein in blood). There are no effects on reproduction or foetal development. There is an existing inhalatory OEL for ammonia of 14 mg/m3.