Registration Dossier

Toxicological information

Specific investigations: other studies

Currently viewing:

Administrative data

Endpoint:
cytotoxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Publication, main features reported, non-standard method

Data source

Reference
Reference Type:
publication
Title:
Differential effects of raising and lowering intracellular GSH levels on the cytotoxicity of allyl isothiocyanate, tert.-butylhydroperoxide and chlorodinitrobenzene
Author:
Bruggemann, I. M.; et al
Year:
1988
Bibliographic source:
Toxic. in vitro 2: 31-35 (1988)

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
cloning efficiency of Chang cells was assessed in presence of increased or reduced intracellular glutathione levels
GLP compliance:
not specified
Type of method:
in vitro

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
commercial sample of DNCB

Test animals

Species:
human
Strain:
other: epithelial like human liver cells (chang cells)
Sex:
not specified

Administration / exposure

Route of administration:
other: in vitro
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
no data
Frequency of treatment:
single, 2 h
Post exposure period:
10 days
No. of animals per sex per dose:
no applicable
Details on study design:
cells were pretreated with glutathione ethyl ester to increase intracellular glutathione (GSH) or with diethyl maleate to reduce intracellular GSH. Afterwards cells were treated with DNCB and the cloning effinciency was determined.

Examinations

Examinations:
Cloning efficiency after 2 h treatment and subsequent 10 days incubation at 37 C.

Results and discussion

Details on results:
Increased GSH-levels gave rise to increased cytotxicity (reduced cloning effficiency, while reduced GSH reduced the toxci effects of DNCB in these cells.

Applicant's summary and conclusion

Conclusions:
The toxic mechanism of DNCB in a human liver cell line seems to envolve GSH in activation of DNCB. Cytotoxicity was found inversely proportional to GSH concentration in vitro.