2-methoxy-5-nitroanilinium chloride

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data from peer reviewed journal

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Chronic Toxicity, Teratologic, and Reproduction Studies with Hair Dyes

Author:

THEODORE WBRNICK,BEN MARR LANMAN AND JEAN LOUIS FIUUX

Year:

1975

Bibliographic source:

TOXICOLOGY AND APPLIED PHARMACOLOGY 32,450-460 (1975)

Reference 2

Reference Type:

publication

Title:

Final Report on the Safety Assessment of Amino Nitrophenols as Used in Hair Dyes

Author:

Burnett CL, Bergfeld WF, Belsito DV, Klaassen CD, Marks JG Jr, Shank RC, Slaga TJ, Snyder PW, Alan Andersen F.

Year:

2009

Bibliographic source:

International Journal of Toxicology 2009;Nov-Dec;28(6 Suppl 2):217S-51S.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Reproductive toxicity study of 2-amino-4-nitrophenol was performed on CFE-S rats

GLP compliance:

not specified

Limit test:

no

Justification for study design:

No data available

Test material

Test material information

Constituent 1

Reference substance name:

2-amino-4-nitrophenol

EC Number:

202-767-9

EC Name:

2-amino-4-nitrophenol

Cas Number:

99-57-0

Molecular formula:

C6H6N2O3

IUPAC Name:

2-amino-4-nitrophenol

Details on test material:

- Name of test material (as cited in study report):2-amino-4-nitrophenol
- Molecular formula : C6H6N2O3
- Molecular weight :154.124 mol/g
- Substance type: organic
- Physical state:No data available

Specific details on test material used for the study:

- Name of test material (as cited in study report):2-amino-4-nitrophenol
- Molecular formula : C6H6N2O3
- Molecular weight :154.124 mol/g
- Substance type: organic
- Physical state:No data available

Test animals

Species:

rat

Strain:

other: CFE-S

Details on species / strain selection:

No data available

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 15 week old

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Details on exposure:

Details on exposure
PREPARATION OF DOSING SOLUTIONS:
Test material mixed with feed .
DIET PREPARATION
- Rate of preparation of diet (frequency):No data available
- Mixing appropriate amounts with (Type of food )
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle: 0,97.5,616 mg/kg bw/day (0,1950,7800 ppm)
- Amount of vehicle (if gavage): No data available

- Lot/batch no. (if required): No data available
- Purity: No data available

Details on mating procedure:

- M/F ratio per cage:1:1
- Length of cohabitation: No data available
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy:The presence of sperm during daily vaginal inspections (day 0 of pregnancy). .
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility.
- Further matings after two unsuccessful attempts: [no / yes (explain)]No data available
- After successful mating each pregnant female was caged (how): individual

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

9 days ( from day 6 through day 15 of gestation )

Frequency of treatment:

Daily

Details on study schedule:

No data available

Doses / concentrations

Remarks:

0, 97.5,616 mg/kg bw/day (0,1950,7800ppm)

No. of animals per sex per dose:

Total:120
0 mg/kg bw/day:20male and 20 female
97.5mg/kg bw/day:20male and 20 female
616mg/kg bw/day:20male and 20 female

Control animals:

yes

Details on study design:

No data available

Positive control:

No data available

Examinations

Parental animals: Observations and examinations:

Parental animals observation and examinations
CAGE SIDE OBSERVATIONS: yes

DETAILED CLINICAL OBSERVATIONS: Yes

Time schedule:


BODY WEIGHT: Yes
Time schedule for examinations: biweekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):

Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data: No data available

Oestrous cyclicity (parental animals):

No data available

Sperm parameters (parental animals):

No data available

Litter observations:

Each fetus was weighed, measured, and examined for gross abnormalities

Postmortem examinations (parental animals):

Postmortem examinations (Parent Animal)
SACRIFICE : All females were killed by chloroform inhalation on the 19th day of pregnancy and the fetuses delivered by Caesarian section.

Male animals: All surviving animals [describe when, e.g. as soon as possible after the last litters in each generation were produced.]: No data
Maternal animals: yes

GROSS NECROPSY: The number and distribution of fetuses, and the number of corpora lutea, live and
stillboin fetuses, and early and late resorptions were recorded
HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.:
macroscopic examination was performed

Postmortem examinations (offspring):

Each fetus was weighed, measured, and examined for gross abnormalities. One-third of each litter was examined for visceral abnormalities by employing the slicing method of Wilson (1965). The remaining two-thirds were cleared and the bone structure stained with alizarin red S in order to define any skeletal abnormalities

Statistics:

Statistical analysis using the 95% confidence level. The methods used included chi square test, analysis of variance and t test, and the Fisher exact probability test (Snedecor, 1962)

Reproductive indices:

No data available

Offspring viability indices:

No data available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

The 616 mg/kg /day dose group excreted blue-brown colored urine

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Description (incidence and severity):

No dose related significant deference were observed in the average number of implantation sites, live pups, or early and late resorptions per litter, or in the number of females with one or more resorption sites.

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

616 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

reproductive performance

Remarks on result:

other: overall no toxic effects on reproductive parameters

Target system / organ toxicity (P0)

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

not specified

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Description (incidence and severity):

No grossly abnormal pups were noted in the 97.5 mg/kg /day dose group (244 pups); there was one in control group (244 pups). One grossly abnormal pup was noted out of the 262 examined in the 616 mg/kg /day dose group.

Histopathological findings:

not specified

Other effects:

not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):

not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:

not specified

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

616 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

gross pathology

other: overall no developmental toxic effects observed

Remarks on result:

other: overall no developmental toxic effects observed

Target system / organ toxicity (F1)

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Overall reproductive toxicity

Reproductive effects observed:

not specified

Treatment related:

not specified

Relation to other toxic effects:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

No Observed Adverse Effect Level (NOAEL) for reproductive and developmental toxicity was considered to be 616 mg/kg/day (7800ppm. When male and female CFE-S rats were treated with 2-amino-4-nitrophenol (99-57-0) orally.

Executive summary:

Reproductive and developmental toxicity study of 2-amino-4-nitrophenol(99-57-0) was performed on male and female CFE-Srats .20 male and 20 female rats /dose group were used.One male was mated with one female until copulation was confirmed by the presence of sperm during daily vaginal inspections (day 0 of pregnancy).The females then were weighed, transferred into individual cages.The test materialmixed with feed were administers in dose concentration 0, 97.5,616 mg/kg bw/day (0, 1950,7800 ppm)from day from day 6 through day 15. Pregnancy was further confirmed by biweekly weighing of the females. All females were killed by chloroform inhalation on the 19th day of pregnancy and the fetuses delivered by Caesarian section. The number and distribution of fetuses, and the number of corpora lutea, live and stillboin fetuses, and early and late resorptions were recorded. Each fetus was weighed, measured, and examined for gross abnormalities. One-third of each litter was examined for visceral abnormalities by employing the slicing method of Wilson (1965). The remaining two-thirds were cleared and the bone structure stained with alizarin red S in order to define any skeletal abnormalities (Murphy, 1965

 

No dose-related significant differences were observed in the parameters examined. The 616mg/kg /day (7800 ppm) dose group excreted blue-brown colour urine.No grossly abnormal pups were noted in the 97.5 mg/kg /day dose group (244 pups); there was one in control group (244 pups). One grossly abnormal pup was noted out of the 262 examined in the 616 mg/kg /day dose group.however, the average numbers of implantation sites, live pups, and early or late resorptions were not significantly different among the groups. HenceNo Observed Adverse Effect Level (NOAEL) for reproductive and developmental toxicity was considered to be 616 mg/kg/day (7800ppm.When male and femaleCFE-Srats were treated with2-amino-4-nitrophenol(99-57-0)orally.