Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28.02.2008 - 20.03.2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD ) and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2011

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): N-methyl-4-nitroaniline
- Physical state: yellow to orange cyristalline powder
- Analytical purity: 99.3 %
- Purity test date: CoA dated 06-Feb-2008
- Lot/batch No.: 304269
- Expiration date of the lot/batch: 30-Nov-2008
- Storage condition of test material: at room temperature, protected from light

Test animals

Species:
rat
Strain:
other: Crl:WI(Han), SPF quality
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sulzfeld, Germany
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: Males 188 g to 199 g, females 161 g to 181 g
- Fasting period before study: over night
- Housing: groups of up to three animals and one gender per cage (Noryl, type V).
- Diet (e.g. ad libitum): pelleted dry food ad libitum
- Water (e.g. ad libitum): municipal water ad libitum
- Acclimation period: 28.02.2008: arrival of animals, 04.03.2008: start of administration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C ± 2 °C
- Humidity (%): 45 % - 75 %
- Air changes (per hr): approximately of 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12 hours

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5 % aqueous hydroxyethylcellulose
Details on oral exposure:
VEHICLE

- Amount of vehicle (if gavage): 20 mL/kg

Doses:
300 mg/kg body weight
2000 mg/kg body weight
No. of animals per sex per dose:
300 mg/kg: 3 females
2000 mg/kg: 3 females and 3 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
clinical observation: at least twice daily, on non-working days once
Body weight: Day before administration, Day 2, Day 8 and Day 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,PATHOLOGY

Results and discussion

Preliminary study:
In animals at 300 mg/kg, no mortality, no clinical signs or influence on body weight
development were noted during the course of the study. No macroscopic changes were
observed at necropsy.
Effect levels
Sex:
male/female
Dose descriptor:
other: ALD
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was noted during the study.
Clinical signs:
300 mg/kg (females)
No clinical signs were noted during the study.

2000 mg/kg (males and females)
In all animals, rough coat, decreased locomotor activity, hunched posture, narrow palpebral
fissure and intensively yellow colored urine were noted on Day 1. These signs were absent by
Day 2 at the latest. Additionally, in females, stilted gait was observed 1 h post administration
on Day 1.
From Day 7/8 (males/females) until the end of the observation period, yellowish stained coat
and tail was noted
Body weight:
No effects on body weight and body weight development were noted in males and females
during the study.
Gross pathology:
No macroscopic changes were noted at necropsy in male and female rats.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the present study, a single oral administration of
N-methyl-4-nitroaniline at doses of 300 (females) and 2000 mg/kg (males and females) was
associated with no deaths but distinct signs of toxicity at 2000 mg/kg on the day of dosing.
The approximate lethal dose (ALD) is considered to be above 2000 mg/kg in rats.