2,6-diisopropylaniline

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: study performed under GLP and in accordance with the corresponding OECD-/EU-testing guidelines

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

P 5175

IUPAC Name:

P 5175

Constituent 2

Reference substance name:

2,6-diisopropylaniline

EC Number:

246-305-4

EC Name:

2,6-diisopropylaniline

Cas Number:

24544-04-5

Molecular formula:

C12H19N

IUPAC Name:

2,6-bis(propan-2-yl)aniline

Details on test material:

- Name of test material (as cited in study report): P5175
- Appearance and physical state: dark brown liquid
- Stability under test conditions: stable
- Storage condition of test material: at room temperature in the dark

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., Manston Road, Margate, Kent
- Age at study initiation: between 6 and 10 weeks
- Weight at study initiation: males 129 to 151 g, females 125 to 148 g
- Housing: gang-housing in groups of 5 by sex
- Diet (e.g. ad libitum): SQC Rat and Mouse Maintenance Diet No.1, Expanded, Special Diets Services Ltd., Stepfield, Witham, Essex
- Water (e.g. ad libitum): Tap water, free of contaminants
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C, single air-conditioned room
- Humidity (%): 52-70%
- Photoperiod: Fluorescent lighting, automatically controlled to give a cycle of 12 hours light (06.00 to 18.00 hr) and 12 hours darkness

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

see table under subsection "any other information on materials and methods incl. tables"

Doses:

1770, 2500, 3530 and 5000 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: at 15 minutes, 1, 2 and 4 hours after treatment and subsequently once daily for 14 days
- Frequency of weighing: on the day before treatment (day -1), on the day of treatment, 7 and 14 days after treatment and at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: yes

Statistics:

The acute oral median lethal dose (LDso) for combined male and female groups were calculated using a probit analysis (Finney, D.J. (1964), Statistical Method for Biological Assay, 2nd Edition, London, Charles Griffin). Separate LDso values were calculated for male and female animals. The mortalities did not allow the calculation of 95% fiducial limits for male animals.

Results and discussion

Preliminary study:

Four groups, each of 2 fasted rats (1 male, 1 female), were treated with dose levels of 50, 250, 1250 and 5000 mg/kg.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 077 mg/kg bw

Based on:

test mat.

95% CL:

3 331 - 6 052

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

5 107 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no CL determined

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

3 710 mg/kg bw

Based on:

test mat.

95% CL:

2 816 - 5 272

Mortality:

A total of 12 (5 male, 7 female) of the 40 animals died during the study period. All deaths were noted 24 or 48 hours after treatment.

Clinical signs:

other: 1770 mg/kg: All animals treated with 1770 mg/kg appeared normal 2 hours after dosing. The antmals appeared prostrate and/or lethargic 4 hours after dosing but recovered and all animals appeared normal on day one and throughout the study period. 2500 mg/k

Gross pathology:

Major pathological findings in animals dying during the study were associated with the stomach and gastrointestinal tract. These organs appeared distended or filled with gas.The lungs occasionally showed red patches on all lobes.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral toxicity LD50 on Wistar rats was determined to be 4077 mg/kg combined for both sexes, 5107 mg/kg for male and 3710 mg/kg for female rats.

Executive summary:

The study was performed 1983, in accordance with OECD 401 and under GLP. Following a screening study, 4 groups, each of 10 fasted rats (5 male, 5 female) were treated with a single oral dose of P5175 at dose levels of 1770, 2500, 3530 and 5000 mg/kg. The vehicle used was corn oil.

1. Clinical observations:

Clinical signs were observed throughout all dose groups and included prostration, lethargy, tremor, ataxia and piloerection. Surviving animals appeared normal within 1-2 days after treatment.

2. Mortality:

5 males and 7 females died during the study period. All deaths occured 24 or 48 hours after treatment.

Based on the test results, the test item has no classification/labelling requirements.