Manganese bis(dihydrogen phosphate)

Endpoint summary

Additional information

Read-across in accordance with Annex XI, Section 1.5 of Regulation (EC) No. 1907/2006 (REACH) is justified on the following basis:

Manganese phosphates such as manganese hydrogen phosphate and manganese bis(dihydrogen phosphate) are soluble manganese-containing inorganic compounds. The toxicology of these materials is considered to be related to the presence of the Mn2+ ion (as phosphate itself is not considered to be toxic). As such it is scientifically justified to read-across to other manganese phosphates. When considering a testing strategy for manganese phosphates, tests have been performed on manganese hydrogen phosphate as that contributes the greater amount of Mn2+ on a %w/w basis (36.4% as compared to 22% in manganese bis(dihydrogen phosphate. These results will be directly read across to manganese bis(dihydrogen phosphate) as they are representative of a worst-case for manganese phosphates.

In vitro gene mutation

In bacteria (AMES):

The vehicle (dimethyl sulphoxide) control plates gave counts of revertant colonies within the normal range. All of the positive controls used in the test induced marked increases in the frequency of revertant colonies, both with or without metabolic activation. Thus, the sensitivity of the assay and the efficacy of the S9-mix were validated.

The test item caused no visible reduction in the growth of the bacterial background lawn at any dose level and was, therefore, tested up to the maximum recommended dose level of 5000 μg/plate. A test item precipitate (fine and particulate in appearance) was noted at 5000 μg/plate, this observation did not prevent the scoring of revertant colonies.

No significant increases in the frequency of revertant colonies were recorded for any of the bacterial strains, with any dose of the test item, either with or without metabolic activation or exposure method.

In mammalian cells (mouse lymphoma assay):

The GEF value was not exceeded at any individual dose level in either Experiment 1or 2.

The test item induced weak but statistically significant and reproducible increases in the mutant frequency at the TK +/- locus in L5178Y cells in both 4 hour exposure groups in the presence of metabolic activation.

The responses seen, although statistically significant, were relatively small and were less than or bordering on the upper limit of the historical range for the vehicle control of the relevant exposure group and therefore cannot conclusively be considered to be part of a true genotoxic effect. The test item contains Manganese which is essential to mammals and is involved in metalloenzyme systems substituting for magnesium. Work by Umeda and Nishimura (1979) demonstrated that substances containing manganese induced chromosome breaks fragments and exchanges in cultured mammalian cells. It is therefore most likely that the effects observed in this study that only occur at cytotoxic dose levels are due to the action of manganese and are not due to a true genotoxic mechanism.

In vitro cytogenicity (chromosome aberration test):

All vehicle (dimethyl sulphoxide) controls had frequencies of cells with aberrations within the range expected for normal human lymphocytes. All the positive control items induced statistically significant increases in the frequency of cells with aberrations indicating that the sensitivity of the assay and the efficacy of the S9-mix were validated.

The test item was moderately toxicity at the maximum concentration tested in Experiment 1 and tested to the toxic limit in Experiment 2. The test item did not induce any toxicologically significant increases in the frequency of cells with aberrations in the exposure groups dosed in the presence or absence of S9, which included a dose level that was just outside 50% mitotic inhibition (particularly in Experiment 2).

The test item, IP 35: Manganese hydrogen phosphate, was considered not to induce any toxicologically significant increases in the frequency of cells with aberrations and, therefore was considered to be non-clastogenic.

Justification for selection of genetic toxicity endpoint
No study was selected, since all data suggest that manganese hydrogen phosphate is not genotoxic.

Short description of key information:
Key studies are submitted for the following REACH endpoints:
- in vitro gene mutation in bacteria (REACH Endpoint 8.4.1)
- in vitro cytogenicity study in mammalian cells (REACH Endpoint 8.4.2)
- in vitro gene mutation in mammalian cells (REACH Endpoint 8.4.3)


These studies are conducted to the appropriate modern OECD guideline and under the conditions of GLP. Studies are performed on an analogous substance.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

No classification for in vitro genetic toxicity is proposed for manganese bis(dihydrogen phosphate). As the data has been generated according to the recommended guidelines and under the conditions of GLP, this data is considered to be adequate for the purposes of classification and labelling in accordance with Regulation (EC) No.1272/2008 (EU CLP) and no further in vivo investigation is considered necessary.