2-nitrophenol

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: gene mutation

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Similar to guideline study with accepatble restrictions (males are only 24 h old at study initiation).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 477 (Genetic Toxicology: Sex-linked Recessive Lethal Test in Drosophila melanogaster)

Deviations:

yes

Remarks:

(males are only 24 h old at study initiation)

GLP compliance:

not specified

Type of assay:

Drosophila SLRL assay

Test material

Test material information

Constituent 1

Reference substance name:

2-nitrophenol

EC Number:

201-857-5

EC Name:

2-nitrophenol

Cas Number:

88-75-5

Molecular formula:

C6H5NO3

IUPAC Name:

2-nitrophenol

Details on test material:

- Name of test material (as cited in study report): o-Nitrophenol
No further details are given.

Test animals

Species:

Drosophila melanogaster

Strain:

other: Canton-S wild-type

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: No more than 24 h at the beginning of the treatment.

Administration / exposure

Route of administration:

other: oral (feeding), if no response was obtained the substance was injected in a following experiment

Vehicle:

FEEDING EXPERIMENTS: 5% sucrose solution into which the test chemical was dissolved (solvents included water, ethyl alcohol, or DMSO)
INJECTION EXPERIMENTS: A solution of test chemical dissolved in saline or suspended in peanut oil

Details on exposure:

The test chemical was assayed in the SLRL test by feeding for 3 days to adult Canton-S wild-type males. Toxicity tests were performed to attempt to set concentrations of test chemical at a level that ideally would induce 30% mortality after 72 hours of feeding or 24 hours after injection, while keeping induced sterility at an acceptable level.
Canton-S males were allowed to feed for 72 hours. If no response was obtained, the chemical was retested by injection into adult males. To administer a chemical by injection, a glass Pasteur pipette was drawn out in a flame to a microfine filament and the tip was broken off to allow delivery of the test solution. Injection was performed either manually, by attaching a rubber bulb to the other end of the pipette and forcing through sufficient solution (0.2-0.3 µL) to slightly distend the abdomen of the fly, or by attaching the pipette to a microinjector that automatically delivers a calibrated volume. Flies were anaesthetized with ether and immobilized on a strip of tape. Injection into the thorax, under the wing, is performed with the aid of a dissecting microscope.
Treated males were mated individually to three Basc females for 3 days and given fresh females at 2-day intervals to produce three matings of 3, 2, and 2 days (sperm from successive matings had been treated at successively earlier post-meiotic stages). F1 heterozygous females were mated with their siblings and then placed in individual vials. F1 daughters from the same parental male were kept together to identify clusters. (A cluster occurs when a number of mutants from a given male result from a single spontaneous premeiotic mutation event, and is identified when the number of mutants from that male significantly exceeds the number predicted by a Poisson distribution). If a cluster was identified, all data from the male in question were discarded. Presumptive lethal mutations were identified as vials containing fewer than 5% of the expected number of wild-type males after 17 days; these were retested to confirm the response.

Duration of treatment / exposure:

3 days feeding or single injection, respectively.

Frequency of treatment:

3 days feeding or single injection, respectively.

Post exposure period:

24 hours after injection

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
400 and 500 ppm
Basis:
other: feeding conc., not further specified

Doses / concentrations 2

Remarks:

Doses / Concentrations:
2500 and 5000 ppm
Basis:
other: injection conc., not further specified

No. of animals per sex per dose:

no data

Control animals:

other: yes, but not further specified

Examinations

Tissues and cell types examined:

X-chromosomes

Statistics:

SLRL data were analyzed by simultaneous comparison with the concurrent and historical controls (Mason et al., 1992) using a normal approximation to the binomial test (Margolin et al., 1983). A test result was considered positive if the P value was less than 0.01 and the mutation frequency in the tested group was greater that 0.10 %, or if the P value was less than 0.05 and the frequency in the treatment group was greater than 0.15 %. A test was considered to be inconclusive if (a) the P value was between 0.05 and 0.01 but the frequency in the treatment group was between 0.10% and 0.15 %, or (b) the P value was between 0.10 and 0.05 but the frequency in the treatment group was greater than 0.10 %. A test was considered negative if the P value was greater than 0.10 or if the frequency in the treatment group was less than 0.10 %.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

not examined

Additional information on results:

In some Drosophila SLRL studies, clusters (mutations concluded to result from a single spontaneous pre-meiotic event) in a single male were identified and all the data from that male were excluded from the study analysis. The published reports of these data present the adjusted values. The SLRL data here are uncorrected for the removal of clusters. However, the overall conclusion of the study matches the published conclusion. If one requires access to the corrected data, please refer to the associated journal or contact the NTP for a copy of the printed report.

Any other information on results incl. tables

Tab 1: Drosophila Sex-Linked Recessive Lethal Study Details

Route of	Dose	Percent	Percent	Lethals			Tests			Total Lethals	Total Tests	Percent Lethals	Cluster Removed
Exposure	(ppm)	Mortality	Sterility	Br 1	Br 2	Br 3	Br 1	Br 2	Br 3
Adult Feeding for three days.	500	19	0	0	1	4	838	820	876	5	2534	0.20	N
	0			0	0	2	720	513	695	2	1928	0.10	N
	400	33	6	0	0	0	1175	986	791	0	2952	0.00	N
	0			0	1	1	1108	1007	933	2	3048	0.07	N
										P= 0.426
Adult Injection	5000	9	76	1	0	0	97	66	65	1	228	0.44	N
	0			0	0	0	409	390	326	0	1125	0.00	Y
	2500	5	1	1	0	0	2546	1317	1255	1	5118	0.02	N
	0			1	1	8	1941	1378	945	10	4264	0.23	Y
										P= 0.922

Br = Brood

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative