6-ethyl-2-toluidine

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: in compliance with the guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Principles of method if other than guideline:

Method: other: acute inhalation toxicity study (5 rats/sex/conc., 4 hrs, aerosol exposure, whole-body inhalation, 14-day observation period with subsequent necropsy)

GLP compliance:

yes

Test type:

other: Acute inhalation toxicity study

Test material

Test material information

Constituent 1

Reference substance name:

6-ethyl-2-toluidine

EC Number:

246-309-6

EC Name:

6-ethyl-2-toluidine

Cas Number:

24549-06-2

Molecular formula:

C9H13N1

IUPAC Name:

2-ethyl-6-methylaniline

Details on test material:

IUCLID4 Test substance: other TS: 2-methyl-6-ethylanilin, purity: 99.45 %

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratory, Portage, MI
- Age at study initiation: ca 9- 10 weeks
- Weight at study initiation: males: ca. 323 g, females ca. 203 g
- Housing : individual suspended stainless steel mesh cages, over paper bedding
- Diet: ad libitum, except during exposure
- Water: ad libitum, except during exposure
- Acclimation period: 10 d

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 64 to 79 °F
- Humidity (%): 40 to 70%
- Photoperiod (hrs dark / hrs light): 12 h

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: a 300 liter New York University-style stainless steel chamber with a pyramidal top and bottom
- Exposure chamber volume: 300 liter New York University-style
- Method of holding animals in test chamber: individual stainless steel wire mesh cages, positioned in two tiers in the chamber
- Method of particle size determination: analysis performed with an Anders cascade inpactor

Analytical verification of test atmosphere concentrations:

yes

Remarks:

4 per exposure at approx. one-hour intervals

Duration of exposure:

4 h

Concentrations:

2.1, 2.5, 3.2 mg/l in air

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: during exposure observations: approx. hourly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

LC50 males: calculated by Binomial method, LC 50 females and combined LC50: calculated by Probit method

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

ca. 2.6 mg/L air

Exp. duration:

4 h

Mortality:

group 2.1 mg/l: males 0/5, females 2/5; group 2.5 mg/l: males: 0/5, females 4/5; group 3.2 mg/l: males 3/5, females 5/5

Clinical signs:

other: Signs of intoxication: --during exposure: hypoactivity and clear nasal discharge --immediately after exposure: nonresponsive, disuse of limbs, labored respiration, clear nasal discharge, salivation --post-exposure day 1-4: nonresponsive, prostrate, d

Body weight:

weight loss in all animals by post-exposure day 2, by post-exposure day 14 all animals were gained weight and exceeded their pre-exposure weights

Gross pathology:

Gross necropsy findings noted in unscheduled deaths were corneal opacity, abnormal discharge/encrustation about eyes, abnormal liver color, fecal stained skin, abnormal color of testis, and abnormal contents (green fluid) of urinary bladder. The only necropsy findings noted at the scheduled sacrifices were corneal opacity and hydronephrosis. Hydronephrosis, however is relatively common in animals of this strain and age and was not considered test-related.

Any other information on results incl. tables

RS-Freetext:
LC50 (male):  3.1 mg/l
LC50 (female): 2.2 mg/l
LC50 (combined 2.6 mg/l

Mortality 
occurred from the first day post exposure:
2.1 mg/l-gr.: 0/5 males, 2/5 females
2.5 mg/l-gr.: 0/5 males, 4/5 females
3.2 mg/l-gr.: 3/5 males, 5/5 females

Signs of intoxication:
--during exposure: hypoactivity and clear nasal discharge
--immediately after exposure: 
nonresponsive, disuse of lims, labored respiration, clear nasal  discharge, salivation
--post-exposure day 1-4:
nonresponsive, prostrate, disuse of limbs, labored respiration, slow  respiration, rattling sounds, red/brown perinasal encrustation, purulent  ocular discharge, lacrimation, ocular opacity, periocular encrustation
--post-exposure day 5-14:
ocular opacity

mean Particle size(Mass Median Aerodynamic Diameter):
2.1 mg/l: 3.9 micrometer
2.5 mg/l: 3.9 micrometer
3.2 mg/l: 3.6 micrometer

Applicant's summary and conclusion

Executive summary:

In an acute inhalation study (Bechtel 1989) three groups of 5 male and 5 female Sprague-Dawley rats were each exposed for 4 hours to an atmosphere of aerosolized 2-methyl-6-ethylaniline at mean analytical concentrations of 2.1, 2.5, or 3.2 mg per liter in air (whole body exposure). Exposure was followed by a 14-day observation period and subsequent necropsy. At the highest exposure concentration eight rats died, at the 2.5 mg/l level four animals dies and at the 2.1 mg/l level two animals died. The calculated LC50 values for both sexes were 2.6 mg/l, for females 2.2 mg/l. and for the males 3.1 mg/l. The observations during exposure showed a visible hypo-activity of the animals and clear nasal discharge. The clinical signs noted immediately after exposure were non-responsiveness, disuse of limbs, labored respiration, clear nasal discharge, and salivation. The observations made during post-exposure day one and four showed non-responsiveness, prostrate, disuse of limbs, respiration difficulties, and ocular opacity. From post-exposure days 5 to 14 the only clinical sign noted was ocular opacity. There was weight loss in all animals by post-exposure day 2. By post-exposure day 14 all animals were gained weight and exceeded their pre-exposure weights. Gross necropsy findings noted in unscheduled deaths were corneal opacity, abnormal discharge/encrustation about eyes, abnormal liver color, fecal stained skin, abnormal color of testis, abnormal contents of urinary bladder. The only necropsy findings noted at the scheduled sacrifices were corneal opacity and hydronephrosis, which is relative common in animals of this strain and age and was not considered test-related. The LC50 for both sexes for 2-methyl-6-ethylaniline as administered in this study is 2.6 mg/l in air.

The LC50 for 2-methyl-6-ethylaniline as administered in this study is 2.6 mg/l/ 4 h in air. According to the findings of this study MEA should be classified as harmful by inhalation.