Tetrakis(hydroxymethyl)phosphonium chloride

Endpoint summary

Additional information

The available data set contains in vitro(Table 1) and in vivo (Table 2) genotoxicity studies. Basically in vitro studies showed no mutagenic effects in Ames tests and in UDS test (read-across with THPS) but clastogenic effects in Mouse Lymphoma, Sister Chromatide Exchange and chromosome aberration assay. These effects on nucleus material (clastogenic only) were observed in in vitro systems and were not confirmed by in vivo assays. In addition, no carcinogenic effects were detected in two 2-year studies in rats and mice (NTP, 1987). Therefore, it is concluded that any potential for mutagenicity is not expressed in vivo, and THPC is not considered a genotoxic substance.

 

Note: Information from THPS is judged relevant because as an ionic salt, THPC is completely dissociated into THP+ and Cl- in aqueous solutions and the equivalent is true for most of the THP+ salts, including sulphate salt. As a consequence hazard properties evaluated in aqueous solution could reasonably be predicted using data from the equivalent sulphate salt. Therefore a read-across approach could be done for certain hazard properties between THPC (chloride salt) and THPS (sulphate salt).

 

Table 1: In vitrogenotoxicity

Test system	Reference	Result	Reliability
Ames test	NTP (1987), Zeigeret al. (1987)	Negative	2
Ames test	MacGregoret al.(1980)	Negative	3
Ames test	Kawachi et al.(1980)	Negative	4
Ames test	Ishidae et al.(1981)	Negative	4
Ames test like (Bacillus subtilis)	Kawachi et al.(1980)	Positive	4
Mouse Lymphoma Assay	NTP (1987), Myhr et al.(1990)	Positive	2
Sister Chromatide Exchange	NTP (1987), Loveday et al.(1989)	Positive	2
Chromosome Aberration	NTP (1987), Loveday et al.(1989)	Positive	2
Chromosome Aberration	Ishidae et al. (1981)	Positive	4
Chromatide breaks	Sasaki et al. (1980)	Positive	3
Unscheduled DNA Synthesis (read across with THPS)	Downey et al. (1990)	Negative	2

 

 

Table 2:In vivogenotoxicity

Test system	Reference	Result	Reliability
Micronucleus	NTP (1995)	Negative	2
Micronucleus	Kawachi et al.(1980)	Ambigous	4

 

 

Short description of key information:
THPC effects on nucleus material (clastogenic only) were observed in in vitro systems and were not confirmed neither in in vivo assays nor in two carcinogenicity sutides in rats and mice (2-year oral administration). Therefore THPC is not considered a genotoxic substance.

Endpoint Conclusion:

Justification for classification or non-classification

According to in vivo data and carcinogenicity studies THPC should not be classified for germ cell mutagenicity properties.