4-nitrophenol

Genetic toxicity: in vitro

Administrative data

Endpoint:

genetic toxicity in vitro

Remarks:

Type of genotoxicity: other: Procaryotic organisms: gene mutation, DNA damage/repair, Mammalian cells: DNA repair, forward mutation, inhibition of DNA synthesis

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Toxicological profile prepared after examination and interpretation of available toxicological data in accordance with guidelines developed by ATSDR and EPA using peer-reviewed key literature.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

review article or handbook

Title:

Toxicological Profile for Nitrophenols: 4-nitrophenol

Year:

1992

Bibliographic source:

Agency for Toxic Substances and Disease Registry (ATSDR) US Public Health Service

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: not applicable; the guidelines according to which the cited studies were performed are not stated in the toxicological profile

Deviations:

not applicable

Principles of method if other than guideline:

Not applicable

GLP compliance:

not specified

Type of assay:

other: Procaryotic organisms: plate incorporation, spot test, disc assay; Mammalian cells: not further specified

Test material

Test material information

Constituent 1

Reference substance name:

4-nitrophenol

EC Number:

202-811-7

EC Name:

4-nitrophenol

Cas Number:

100-02-7

Molecular formula:

C6H5NO3

IUPAC Name:

4-nitrophenol

Details on test material:

- Name of test material (as cited in study report): 4-nitrophenol

Method

Target gene:

Not applicable; No detailed information on the methods used are provided in the toxicological profile; The test organisms (and test methods) are cited as follows:
Procaryotic organisms - S. typhimurium (plate incorporation / disc assay), E. coli (plate incorporation / spot test / disc assay), P. mirabilis (plate incorporation), B. subtilis (plate incorporation);
Mamalian cells - Rat hepatocyte culture, mouse lymphoma cells, chinese hamster ovary cell culture

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium, other: not applicable; the strain is not further specified

Species / strain 2

Species / strain / cell type:

E. coli, other: not applicable; the strain is not further specified

Species / strain 3

Species / strain / cell type:

bacteria, other: Proteus mirabilis

Species / strain 4

Species / strain / cell type:

bacteria, other: Bacillus subtilis

Species / strain 5

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Species / strain 6

Species / strain / cell type:

mouse lymphoma L5178Y cells

Species / strain 7

Species / strain / cell type:

other: rat hepatocytes, culture

Metabolic activation:

with and without

Test concentrations with justification for top dose:

Not applicable; No information on the test substance concentration is provided in the report (toxicological profile)

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Remarks:

No information provided in the report on the controls used for the assays.

Evaluation criteria:

Not applicable

Statistics:

Not applicable

Results and discussion

Additional information on results:

One positive result is cited from a plate incorporation assay where DNA damage was induced when tested in Bacillus subtilis without metabolic activation. However, according to the authors of this study, this assay appears to be more sensitive for nitro compounds in general than the standard AMES test.Two further tests showed a weakly positive result, one plate incorporation assay in Proteus mirabilis and one DNA synthesis inhibition test in chinese hamster ovary cells, both of which were conducted in the absence of metabolic activation only, and, therefore, provide only limited information on the genotoxic potential of 4-nitrophenol in vivo. All other tests cited in the report (toxicological profile) were negative, including 7 gene mutation assays (in procaryotes), 3 DNA repair tests (one in rat hepatocytes, 2 in procaryotes) and two forward mutation assays (in mouse lymphoma cells). Thus, the overall evidence indicates that 4-nitrophenol is not mutagenic in the presence or absence of metabolic activation both in procaryotic test systems and in mammalian cells.

Any other information on results incl. tables

 Results of genotoxicity tests on 4-nitrophenol:

Species (Test System)	Endpoint	Result
		With metabolic activation	Without metabolic activation
Procaryotic organisms:
S. typhimurium (plate incorporation)	Gene mutation	negative	negative
S. typhimurium (plate incorporation)	Gene mutation	negative	negative
S. typhimurium (plate incorporation)	Gene mutation	negative	negative
S. typhimurium (plate incorporation)	Gene mutation	negative	negative
S. typhimurium (plate incorporation; S9 + flavin mononucleotide mixture)	Gene mutation	negative	negative
E. coli (plate incorporation)	Gene mutation	negative	negative
E. coli (spot test)	Gene mutation	negative	negative
E. coli (plate incorporation)	Prophage induction	negative	no data
P. mirabilis (plate incorporation)	DNA damage	no data	weakly positive
E. coli (disc assay)	DNA repair	no data	negative
S. typhimurium (disc assay)	DNA repair	no data	negative
B. subtilis (plate in corporation)	DNA damage	no data	positive
Mammalian cells:
Rat hepatocytes, culture	DNA repair	no data	negative
Mouse lymphoma cells	Forward mutation	negative	negative
Mouse lymphoma cells	Forward mutation	negative	no data
Chinese hamster ovary cells, culture	Inhibition of DNA synthesis	no data	weakly positive

S. = Salmonella

E. = Escherichia

P: = Proteus

B. = Bacillus

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

The overall evidence indicates that 4-nitrophenol is not mutagenic in the presence and in the absence of metabolic activation when tested both in procaryotes and mammalian cells.

Executive summary:

In the toxicological profile on 4 -nitrophenol, toxicological studies are reviewed. Several genotoxicity tests, performed in procaryotes and mammalian cells, are cited. One test in Bacillus subtilis was reported to be positive for DNA damage when tested in the absence of metabolic activation. The authors of this test stated that the assay appears to be more sensitive for nitro compounds than the standard AMES assay. Two further tests are cited which show a weakly positive result in the absence of metabolic activation (AMES test in P. mirabilis and DNA synthesis inhibition test in CHO cells). However, all of these test were performed without metabolic activation and, thererfore, provide only limited evidence on the genotoxic potential of 4 -nitrophenol in vivo. All of the other genotoxicity tests (13 out of 16) on 4 -nitrophenol, including AMES assays, DNA repair tests and forward mutation assays, were negative.

Thus, the overall evidence indicates that 4-nitrophenol is not mutagenic in the presence and in the absence of metabolic activation when tested both in procaryotes and mammalian cells.