N-1-naphthylaniline

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1976

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1977

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)

Principles of method if other than guideline:

Study performed before actual guideline was established.

GLP compliance:

not specified

Type of assay:

rodent dominant lethal assay

Test material

Test material information

Constituent 1

Reference substance name:

N-1-naphthylaniline

EC Number:

201-983-0

EC Name:

N-1-naphthylaniline

Cas Number:

90-30-2

Molecular formula:

C16H13N

IUPAC Name:

N-phenylnaphthalen-1-amine

Details on test material:

- Name of test material (as cited in study report): N-Phenyl-Alpha-Naphtylamine
- Substance type: red-brown pellets
- Physical state: solid
- Analytical purity: no data
- Other: Source: United States Air Force

Test animals

Species:

mouse

Strain:

ICR

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Flow
- Age at study initiation: 7 to 8 weeks
- Weight at study initiation: 30 ± 2.5 g
- Housing: 5/cage while treated, then after 2 days rest separately with two females for mating
- Diet (e.g. ad libitum): 4 % fat diet ad libitum
- Water (e.g. ad libitum): acidified according to approved laboratory animal health standards, ad libitum

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: corn oil

Duration of treatment / exposure:

5 days

Frequency of treatment:

daily

Post exposure period:

2 days

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

50 mg/kg bw/day (actual dose received)

Doses / concentrations 2

Dose / conc.:

166 mg/kg bw/day (actual dose received)

Doses / concentrations 3

Dose / conc.:

500 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

10 males

Control animals:

yes, concurrent vehicle

Positive control(s):

triethylenemelamine
- Route of administration: intraperitoneal
- Doses / concentrations: 0.3 mg/kg bw in 0.85 % saline

Examinations

Tissues and cell types examined:

number of dead, living, and total embryos in the uterus

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION:
1/10, 1/30 and 1/100 of LD50; but high dose of 500 mg/kg bw was selected by the contract monitor, other doses were then calculated in relation to this dose.

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields):
Males were treated for 5 consecutive days, after 2 days rest each male was mated with 2 virgin females from Monday through Friday. This sequence was repeated weekly with 2 new females each week for 8 weeks (period of spermatogenesis). Fourteen days from the midweek in which they were caged with the males (mid-pregnancy), females were sacrificed, dissected, and the number of dead, living, and total embryos in the uterus as well as the level of fertility recorded.

Evaluation criteria:

Dominant lethality is indicated by a high percentage of dead implants to total implants.

Statistics:

The number of dead, living, and total embryos in the uteri were statistically analyzed for indications of dominant lethality, and compared with control data for significance.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Any other information on results incl. tables

Dominant lethality was not demonstrated by data from PANA administered to mice. In comparison, the positive control compound TEM demonstrated a clear dominant lethal effect in mice during weeks 1 through 3.

Dead implants / total implants:

Week	Negative control	50 mg/kg	166 mg/kg	500 mg/kg	Positive control
1	0/72 = 0.0	1/45 = 0.02	1/64 = 0.02	0/34 = 0.0	7/16 = 0.44*
2	3/118 = 0.03	3/126 = 0.02	5/77 = 0.06	5/135 = 0.04	39/50 = 0.78**
3	7/117 = 0.06	1/75 = 0.01	0/84 = 0.0	5/97 = 0.05	20/46 = 0.43**
4	4/138 = 0.03	5/81 = 0.05	5/61 = 0.08	1/106 = 0.01	8/160 = 0.05
5	4/50 = 0.07	5/106 = 0.06	1/44 = 0.02	3/60 = 0.05	0/12 = 0.0
6	4/204 = 0.02	3/143 = 0.02	9/148 = 0.06*	4/142 = 0.03	7/183 = 0.04
7	5/139 = 0.04	1/28 = 0.04	6/112 = 0.05	7/116 = 0.06	4/117 = 0.03
8	7/135 = 0.05	8/125 = 0.06	4/74 = 0.05	2/68 = 0.03	1/132 = 0.01

* P<0.05

**P<0.01

Isolated instances of apparent significant dominant lethality did occur among the experimental data. They were not associated with dose-related trends and had dead implant/total input ratios that fell within the range of all negative controls (intermediate dose, week 6).