2,6-diethyl-p-toluidine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-compliant guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,6-diethyl-p-toluidine

EC Number:

246-307-5

EC Name:

2,6-diethyl-p-toluidine

Cas Number:

24544-08-9

Molecular formula:

C11H17N

IUPAC Name:

2,6-diethyl-4-methylaniline

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): p-Ditolin
- Physical state: liquid
- Expiration date of the lot/batch: 07-October-1989
- Stability under test conditions: stable
- Storage condition of test material: room temperature, at a dry place

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen (Germany)
- Strain: Bor: WISW (SPF Cpb)
- Age at study initiation: Males 8 weeks and females 10 weeks
- Weight at study initiation: mean males 190 g and females 171 g
- Fasting period before study: 16 hours before treatment
- Housing: gang housing à 5 animals per cage and sex
- Diet (e.g. ad libitum): Altromin® 1324 Pellets (manufacturer: Altromin GmbH und Co KG, Lage, Germany)
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 50 +/- 10%
- Air changes (per hr): 10 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours (6 hours artificial light)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

peanut oil

Doses:

200, 312, 630, 1000 and 2000 mng/kg

No. of animals per sex per dose:

5 animals per sex and dose

Control animals:

no

Results and discussion

Preliminary study:

no pretest

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

443 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

630 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

male

Dose descriptor:

LD50

Effect level:

312 mg/kg bw

Based on:

test mat.

Mortality:

200 mg/kg:
No mortality was observed in both sexes.

312 mg/kg:
No mortality was noted in males, whereas one female was found dead five days after treatment.

630 mg/kg:
Four out of five male animals were found dead between days 1 to 4 after dosing. All females died within two to three days after treatment.

1000 mg/kg and 2000 mg/kg:
All males and females died within 2 days after dosing.

Clinical signs:

other: 200 mg/kg: Salivation and ruffled fur was noted in some animals. 312 mg/kg up to 2000 mg/kg: In addition to salivation and ruffled fur, males and females aat these dose levels showed also sedation, gasping, chromodacryorrhoe, tremor, unsteady gait and ov

Gross pathology:

200 mg/kg:
One surviving male showed pale discolored kidneys.

312 mg/kg:
No treatment-related findings observed.

630 mg/kg up to 2000 mg/kg:
Aerogastria, red or black discoloured mucuous mebranes of the stomach and small intestines were noted in both sexes. Females died at 630 mg/kg also showed pale discolored livers. There were some further findings in one died male and in one surviving male.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 on Wistar rats was found to be 443 mg/kg.

Executive summary:

The acute oral LD50 study was conducted as GLP-study according to OECD no. 401. The test was performed as full test on male and female Wistar rats with doses of 200, 312, 630, 1000 and 2000 mg/kg. Mortality occured at concentrations of 312 mg/kg and above, slight to moderate clinical symptoms were noted in almost all dose groups, body weight gain was slightly reduced in surviving males at 312 mg/kg and above. At necrospy, a number of treatment-related effects were noted, such as salivation, ruffled fur, discolored kidneys and liver etc. in all dose groups.

Therefore, based on the oral LD50 of 443 mg/kg, the test item has to be classified as harmful.