Tetrakis(hydroxymethyl)phosphonium chloride, oligomeric reaction products with urea

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The read-across approach is based on the assumption, that Tetrakis(hydroxymethyl)phosphonium chloride (THPC, CAS 124-64-1), as part of the technical product 'Tetrakis(hydroxymethyl)phosphonium chloride, oligomeric reaction products with urea' (THPC-urea, CAS 27104-30-9), is the relevant, most hazardous compound. The (local) mode of action based on direct chemical reactivity is the same in both compounds. Additionally the read-across approach is based on the worst-case assumption that the reaction mixture THPC-urea is as reactive as THPC. In the confirmatory information it becomes obvious, that THPC is at least 6 times more hazardous than THPC, oligomeric reaction products with urea. For the detailed justification of the read-across hypothesis see “overall remarks, attachments”. When considering both the read-across hypotheses, the direct read-across from data obtained with technical THPC (80%) onto technical THPC-urea (65-68%) do not lead to an underestimation of the hazard. Reliability: Published test report from National Toxicology Program (US). Evaluated data from a reliable secondary source (US-CPSC).

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1987

Report date:

1987

Reference 2

Reference Type:

secondary source

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

not specified

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.5265 (The Salmonella typhimurium Bacterial Reverse Mutation Test)

Deviations:

not specified

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Tetrakis(hydroxymethyl)phosphonium chloride

EC Number:

204-707-7

EC Name:

Tetrakis(hydroxymethyl)phosphonium chloride

Cas Number:

124-64-1

Molecular formula:

C4H12O4P.Cl

IUPAC Name:

tetrakis(hydroxymethyl)phosphonium chloride

Constituent 2

Reference substance name:

Tertrakis(hydroxymethyl)phosphonium chloride

IUPAC Name:

Tertrakis(hydroxymethyl)phosphonium chloride

Details on test material:

Name: Tetrakis(hydroxymethyl)phosphonium chloride (THPC)
Molecular formula: C4H12O4P.Cl
Structure: [Cl-].OC[P+](CO)(CO)CO
Molecular weight: 190.56
Substance type: ionic substance
Physical state: solid
Further details (analytical purity etc) not reported

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Details on mammalian cell type (if applicable):

not applicable

Additional strain / cell type characteristics:

not specified

Remarks:

no growth without histidin or mutagenic treatment

Metabolic activation:

with and without

Metabolic activation system:

S9 of Aroclor 1254-induced male Sprague-Dawley rat and male Syrian hamster liver

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

see attached bachground material

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

see attached bachground material

Vehicle controls validity:

valid

Untreated negative controls validity:

not valid

Positive controls validity:

valid

Additional information on results:

NTP short-term test data reveal no mutagenic effect of THPC in bacteria. The chemical was not mutagenic in the Salmonella/microsome assay with the preincubation protocol in strains TA98, TA100, TA1535, or TA1537 with or without metabolic activation from S9 of Aroclor 1254-induced male Sprague-Dawley rat and male Syrian hamster liver (Appendix J , Table J1)

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'. Remarks: in separate

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

THPC is not mutagenic in the Salmonella reverse mutation assay w/wo metabolic activation.