6-ethyl-2-toluidine

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: basic data given, comparable to standards but with limitations concerning dosage and observation parameters compared to the guideline study

Data source

Reference

Reference Type:

publication

Title:

Subacute Toxicity of Several Ring-Substituted Dialkyanilines in the Rat.

Author:

Short, C.,R; King, C.; Sistrunk, P.; Kriklyn, M.,K

Year:

1983

Bibliographic source:

Fund Appl Toxicol 3: 285-292

Materials and methods

Principles of method if other than guideline:

Method: other subacute toxicity study

GLP compliance:

not specified

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-ethylaniline, purity: 98.7%

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

Source: Charles River Breeding Laboratories, Wilminton, MA; animals were held for a 10-day acclimatization period after random assignment to test groups; the rats were housed two per cage in stainless steel cages in a room with 12-hour light cycle and 72°F (+/-2°F) temperature; purina rat chow and tap water were provided ad libitum.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test material was administered orally via gavage needle without vehicle at 25% of the estimated oral LD50.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Duration of treatment / exposure:

5, 10 or 20 d

Frequency of treatment:

once daily

Doses / concentrations

Remarks:

Doses / Concentrations:
221 mg/kg bw/d
Basis:

No. of animals per sex per dose:

30 rats per dose group; 10 rats were sacrificed at 5 days (after five consecutive doses), 10 rats were sacrificed at 10 days, and the final ten at twenty days, following continual daily dosing

Control animals:

yes

Details on study design:

Post-exposure period: no

Positive control:

Aniline and o-toluidine were included in the study as positive controls for the production of splenic and bone marrow effects

Examinations

Observations and examinations performed and frequency:

Body and organ weights (liver, kidney, spleen) were measured at each sacrifice period, i. e., at 5, 10 and 20 days of treatment or sham gavage (controls); clinical signs and mortality: daily

Sacrifice and pathology:

Histopathological evaluation of: spleen, bone marrow, liver, esophagus, trachea, thyroid, para-thyroid, urinary bladder and kidney,
histopathological evaluations were conducted using a scoring system which graded the severity of lesions from 0 (no effect) to 4 (severe).

Statistics:

Analysis of body and organ weight changes (compared to matched concurrent controls) was conducted by analysis of variance and Dunnett's procedure, with differences in means accepted at the p<0.05 level, mean scores for lesions and exposure-related mortality were examined for significant difference from controls using the Fischers Exact Test

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Details on results:

The study was designed to evaluate the subacute toxicity of several industrially important disubstituted anilines on selected tissues: liver, kidney, spleen, bone marrow. o-toluidine was included as positive control for the production of splenic and bone marrow effects.

Effect levels

Dose descriptor:

LOAEL

Effect level:

221 mg/kg bw/day (nominal)

Sex:

male

Basis for effect level:

other: hypercellularity in the bone marrow

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

    
    

MORTALITY
- number of death: 0/30

TOXIC RESPONSE/EFFECTS BY DOSE LEVEL:
---Clinical signs: none
---Body weight: not significant different to concurrent control rats  (dose group versus controls): 
-after  5 days: 193.3g versus 214.0g             
-after 10 days: 221.4g versus 225.4g
-after 20 days: 211.1g versus 232.9g  
---Organ weights: 
liver, kidney and spleen: not significant different to the concurrent  control rats 
 
HISTOPATHOLOGY
---liver, esophagus, trachea, thyroid, para-thyroid, unrinary bladder and spleen: no histopathological lesions  
---bone marrow - hypercellularity: 
mean scores (TS versus Controls: d5, d10, d10):
0.56, 1.30(sign.*), 0.33 versus 0.0, 0.0, 0.0




  
  

*significantly different from matched control value by Fishers Exact Test, <=0.05

Applicant's summary and conclusion

Executive summary:

In a subacute toxicity study male Fischer 344 rats were treated orally via gavage needle with 2-methyl-6-ethylaniline (221 mg/kg and day). The rats were treated for 5, 10 or 20 days. No clinical signs and mortality were seen in the 2-methyl-6-ethylaniline (MEA) treated rats. The body weight of the treated rats was not significant different to the concurrent control rats. No significant differences in organ weights of liver, kidney and spleen were found in the treated rats compared to the control group. In addition no histopathological lesions were found in the liver, esophagus, trachea, thyroid, para-thyroid, urinary bladder, and spleen after MEA treatment, whereas a hypercellularity in the bone marrow was seen after MEA treatment. The effect was significant different from control on day 10, but not on day 20 (Short 1983).