Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
cytotoxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1987

Materials and methods

GLP compliance:
no
Type of method:
in vitro

Test material

Constituent 1
Chemical structure
Reference substance name:
Dodecanedioic acid
EC Number:
211-746-3
EC Name:
Dodecanedioic acid
Cas Number:
693-23-2
Molecular formula:
C12H22O4
IUPAC Name:
dodecanedioic acid

Test animals

Species:
other: in vitro human and mouse melanoma cells

Administration / exposure

Details on exposure:
Human (B008) and murine (Harding-Passey B16 and Cloudman S 91) melanoma  cells were exposed to concentrations 
ranging from 0.001 M to 0.1 M of C6,  C9 and C12-dicarboxylic acids (sodium salts, pH 7.2 - 7.4) for 1 or 6  hours in tissue culture, 
and the effects on shape and surface topography  were examined by scanning electron microscopy.

Results and discussion

Details on results:
Human (B008) and murine (Harding-Passey B16 and Cloudman S 91) melanoma  cells were exposed to concentrations  ranging from 0.001 M to 0.1 M of C6,  C9 and C12-dicarboxylic acids (sodium salts, pH 7.2 - 7.4) for 1 or 6  hours in tissue culture,  and the effects on shape and surface topography  were examined by scanning electron microscopy.
Effects, i.e., rounding up, concentration of microvilli, blebbing, and prominence of retraction fibrils were time and dose dependent, and for the same concentrations and exposure times, C12 had a greater effect than C9, and both a significantly greater effect than C6. These differential reactions to the three diacids parallel previously reported effects on cell kinetics and viability. The changes could be due to a prime effect on the cell membrane, or they might reflect phases of the cell cycle directed by action of the diacids on the nucleus; this latter seems unlikely. An effect on the cytoskeleton is possibly involved.

Applicant's summary and conclusion

Executive summary:

Human (B008) and murine (Harding-Passey B16 and Cloudman S 91) melanoma  cells were exposed to concentrations  ranging from 0.001 M to 0.1 M of C6,  C9 and C12-dicarboxylic acids (sodium salts, pH 7.2 - 7.4) for 1 or 6  hours in tissue culture,  and the effects on shape and surface topography  were examined by scanning electron microscopy.

Effects, i.e., rounding up, concentration of microvilli, blebbing, and prominence of retraction fibrils were time and dose dependent, and for the same concentrations and exposure times, C12 had a greater effect than C9, and both a significantly greater effect than C6. These differential reactions to the three diacids parallel previously reported effects on cell kinetics and viability. The changes could be due to a prime effect on the cell membrane, or they might reflect phases of the cell cycle directed by action of the diacids on the nucleus; this latter seems unlikely. An effect on the cytoskeleton is possibly involved.