4,4'-Methylene-bis-(3-chloro-2,6-diethylaniline)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

402-130-7

EC Name:

-

Cas Number:

106246-33-7

Molecular formula:

C21 H28 Cl2 N2

IUPAC Name:

4-[(4-amino-2-chloro-3,5-diethylphenyl)methyl]-3-chloro-2,6-diethylaniline

Details on test material:

- Substance code: P5367
- Batch No.: Muster 3/85
- Appearance: Off-white to yellowish powder
- Storage: At ambient temperature in the dark

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under storage conditions: stable
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/dispersant/vehicle/test medium: stable

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate
- Weight at study initiation: Males 256 - 289 g; females 204 - 231 g.
- Fasting period before study: overnight fast prior to dosing
- Housing: groups of 5 by sex in grid floor stainless steel cages
- Diet: SQC Rat and Mouse Maintenance Diet No. 1, Expanded; Specia1 Diets Services Ltd., Witham
- Water: Mains water was provided at all times and dispensed from glass water bottles
- Acclimation period: 3 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 25°C
- Humidity: 40 - 70%
- Air changes: 10 changes /hour; single air-conditioned room
- Photoperiod: 12 hours darkness; 12 hours fluorescent lightning

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1% aqueous methyl cellulose

Details on oral exposure:

The test article preparations were administered once only by oral gavage using a metal stomach tube attached to a disposable plastic syringe.

Doses:

PRETEST (SCREENING):
- Dose levels of 250, 500, 1000, 2000 and 5000 mg/kg; 2 fasted rats (1 male and 1 female) per dose group

MAIN STUDY (LIMIT TEST):
- Single dose level of 5000 mg/kg; 10 fasted rats (5 males, 5 females}

No. of animals per sex per dose:

PRETEST (SCREENING):
- Five groups of 1 male & 1 female per dose level (250, 500, 1000, 2000 and 5000 mg/kg)

MAIN STUDY (LIMIT TEST):
- Group of 5 males & 5 females at a dose level of 5000 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Frequency of observations and weighing:
All animals were observed for overt signs of toxicity or behavioural changes at 15 min, 1, 2 and 4 hours after -treatment and subsequently once daily for 14 days. All observations were recorded. Individual body weights were recorded on the day before treatment (day-1), on the day of treatment, on days 7 and 14 or at death.

Results and discussion

Preliminary study:

The male animal receiving 5000 mg/kg died during this study. The oral LD50 was considered to be in excess of 5000 mg/kg.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

MALES:
- 5000 mg/kg bw: One male out of five was found dead on day 8. No other deaths were noted.


FEMALES:
- 5000 mg/kg bw: No mortality observed in females.

Clinical signs:

other: All animals appeared normal on the day of dosing and up to 5 days after treatment. On days 6 and 7, one male appeared emaciated with hunched posture and staining to the body. This animal was found dead on day 8. All other animals continued to appear norma

Gross pathology:

The male which died during the study was emaciated and at necropsy showed dark lungs and enlarged liver which also appeared pale w ith dark and yellow patches. All animals necropsied at termination were unremarkable.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 on Wistar rats (males and females) was found to be > 5000 mg/kg.

Executive summary:

The study was performed 1988 as GLP-test following EU-testing method B.1. A pretest (screening) with five groups of 1 male & 1 female per dose level (250, 500, 1000, 2000 and 5000 mg/kg) was performed as DRF-study.

The used species were Wistar rats. In the main study, 5 males and 5 females were treated with a single dose of 5000 mg/kg. The test item was dissolved in 1% aqueous methyl cellulose. One male died on day 8 after showing clinical symptoms. Necropsy examination of this animal showed effects in several organs. The remaining animals shower neither clinical signs nor effects on organs.

In conclusion, the acute oral LD50 on both sexes was determined to be > 5000 mg/kg.