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Toxicological information

Genetic toxicity: in vitro

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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

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1987
Report Date:
1987
Reference Type:
secondary source
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
not specified
Qualifier:
equivalent or similar to
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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Details on mammalian cell lines (if applicable):
not applicable
Additional strain 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:
no
Remarks:
see attached bachground material
Vehicle controls valid:
yes
Negative controls valid:
no
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'. Remarks: in separate
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)

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.