Morpholinium toluene-4-sulphonate

Endpoint summary

Additional information

In vitro

An Ames test was conducted with morpholinium toluene-4-sulphonate according to OCED 471 (BASF SE, 2013). Negative results were found in all tested strains (TA 1535, TA 1537, TA 98, TA 100, and E.coli WP2) for the applied concentrations of 0, 33, 100, 333, 1000, 3500, and 7000 µg/plate with and without metabolic activation.

In addition, several studies are available for morpholine and p-toluenesulphonic acid.

Morpholine was evaluated for its mutagenic potential in a mouse lymphoma forward mutation assay equivalent to OECD 476 (Huntsman, 1979). Here, L5178Y TK +/- cells were used and concentrations up to 1.25 µL/mL in the presence and absence of metabolic activation (S9 mix) were tested. The assay was repeated; in a third assay concentrations ranging from 1.2 to 2 µL/mL were also tested. The positive controls induced the appropriate responses. The test material induced small increases in the mutation frequency over the applied concentration range of 0.625 to 1.25 µL/mL without metabolic activation. These treatments were highly toxic and the mutant frequency increases (approximately 2.5 -fold) were at the limit of detectability for this assay with microsomal activation; concentrations up to 1.0 - 1.25 µL/mL were not very toxic and not detectably mutagenic. Concentrations from 1.2 - 1.5 µl/mL were excessively lethal. Under the conditions of this study, Morpholine was considered to be very weakly mutagenic in the assay without metabolic activation.

In a sister chromatid exchange assay performed similar to OECD 479, Chinese hamster ovary cells (CHO cells) were treated with morpholine at concentrations of 3.13, 6.25, 12.50, 25.00, 50.00 or 100.00 nL/mL in the presence and absence of mammalian metabolic activation (S9 mix) (Huntsman, 1980). Positive control items induced the appropriate responses. The maximum increases in sister chromatid exchange noted were only 25 % and 22 % with and without S9 mix, respectively. Morpholine did not cause a meaningful increase in sister chromatid exchange under the conditions of this assay.

Furthermore, a mammalian chromosome aberration test forp-toluenesulphonic acid is available, performed according to OECD 473 under GLP. Here, Chinese hamster lung fibroblasts (V79) were treated with and without metabolic activation with concentrations up to 1902 µg/mL(Habrinol, 1988).No significant reproducible enhancement of the chromosome aberration rate compared to the solvent control was found with any of the concentrations used, neither with, nor without metabolic activation by S9-mix.

In vivo

No studies are available for morpholinium toluene-4-sulphonate.

In atransplacental mutagenesis study, sodium nitrite combined with Morpholine or Morpholine alone (500 mg/kg bw) were administered by single oral gavage to pregnant Syrian golden hamsters on day 11 or 12 of pregnancy (Inui et al., 1979). Twenty-four hours after treatment, the hamster embryos were excised and examined for chromosomal aberrations, micronucleus formation, morphological or malignant transformation and drug resistance mutation. Cells exposed in utero to Morpholine showed no increases in the numbers of chromosomal aberrations, micronuclei, 8 -azaguanine- or ouabain-resistant mutants, or transformation rates. The number of resistant colonies was markedly increased after administration of sodium nitrite together with Morpholine only, showing that Morpholine alone has no mutagenic effect in vivo under the conditions of this study. In this in vivo study there was no evidence for mutagenic effects of Morpholine over background.

Endpoint Conclusion:

Justification for classification or non-classification

Based on the results of reliable studies obtained in vitro and in vivo for the source chemicals morpholinium toluene-4 -sulphonate, morpholine, and p-toluenesulphonic acid, the target chemical morpholinium toluene-4 -sulphonate is not considered to be subject to classification for genetic toxicity according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (GHS/CLP).