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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
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: Experimental data published in peer reviewed journal (J Env Path Tox, 1980) Evaluated data from a reliable secondary source (US-National Toxicology Program). Evaluated data from a reliable secondary source (US-CPSC).

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1980
Report Date:
1979
Reference Type:
publication
Title:
Unnamed
Year:
1987
Report Date:
1987
Reference Type:
secondary source
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Principles of method if other than guideline:
Bone marrow from THPS-treated mice was analysed for micronucleated polychromatic erythrocytes (MN-PCEs) and for metaphase cells showing chromosomal aberrations. The animals were administered the THPS orally or dermally or treated fabric were incorporated into the animals feed.
GLP compliance:
no
Type of assay:
other: mouse bowne marrow CA and MN-PCEs (in vivo)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Tetrakis (hydroxymethyl) phosphonium sulfate - 75% (THPS, 25% water)

Test animals

Species:
mouse
Strain:
ICR
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
saline

Results and discussion

Additional information on results:
The in vivo mutagenicity of oral (gavage) doses of THPS was inverstigated in Swiss (ICR) mice. Oral doses of 2, 10 or 50 mg/kg bw /day for 14 days were used. Bone marrow from THPS-treated mice was analysed for micronucleated polychromatic erythrocytes (MN-PCEs) and for metaphase cells showing chromosomal aberrations. There was no effect on the number of MN-PCEs nor on the number of chromosomal aberrations (report table 5 and 8).

Any other information on results incl. tables

NTP-summary: Results of in vivo tests for mutagenic effects of THPS in rodents were presented by Connor et al. (1980). THPS was administered to mice by gavage or dermal application or by mixing treated cloth with the animals’ feed. The urine of these dosed mice was analyzed for mutagenicity in the Salmonelldmicrosome assay, and frequencies of micronuclei and chromosomal aberrations were evaluated in bone marrow cells. None of these investigations demonstrated mutagenic activity for THPS.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative