6-methoxy-m-toluidine

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Insufficient description of study parameters and study results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

no guideline available

Guideline:

other: guideline not specified

Deviations:

not applicable

Principles of method if other than guideline:

dose range finding study for carcinogenicity study

GLP compliance:

no

Remarks:

prior to GLP implementation

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

6-methoxy-m-toluidine

EC Number:

204-419-1

EC Name:

6-methoxy-m-toluidine

Cas Number:

120-71-8

Molecular formula:

C8H11NO

IUPAC Name:

2-methoxy-5-methylaniline

Details on test material:

- Name of test material (as cited in study report): p-Cresidine
- Analytical purity: 98.9 +- 0.1 %

Test animals

Species:

other: rats (F344) and mice (B6C3F1), 5/sex/group

Strain:

other: Fischer F 344(rats) and B6C3F1 (mice)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Upon arrival a sample of animals was examined for parasites and other signs of disease. Animals to be used in the chronic study were quarantined by species for 2 weeks prior to initiation of test. All animals were housed by species in rooms having a temperature range of 23 °C to 34°C. Incoming air was filtered through Tri-Dek 15/40 denier Dacron filters providing six changes of room air per hour. Fluorescent light was provided on a 12 hour daily cycle. Food and water were available ad libitum.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: acetone / diet

Details on oral exposure:

the p-cresidine was dissolved with an appropriate amount of acetone (0.016 Vol-% of the final mix) with the help of mortar and pestle. This liquid mixture was hand-blended in an aluminium bowl with an aliquaot of the ground feed until all liquid was adsorbed and visual homogeneity was attained. This premix was then placed into a 6 kg capacity Patterson-Kelley standard model twin-shell stainless steel V-blender along with the remainder of the diet. The blender was sealed and operated for 20 minutes. The mixture was then emptied into stainless steel trays and allowed to sit under the exhaust hood for 2.5 hours while being stirred with a glass rod every 0.5 hour, allowing evaporation of a large protion of the acetone. Prrpared diets wre placed in double clear plastic bags and stored in the dark at 4°C. Diets were prepared weekly and any unused protions were discarded after 2 weeks

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

8 weeks

Frequency of treatment:

via the diet, available ad libitum

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 1.0, 3.0 % in diet
Basis:
nominal in diet

No. of animals per sex per dose:

5

Control animals:

yes, plain diet

Details on study design:

In order to establish the maximum tolerated concentrations of p-cresidine for administration to dosed animals in the chronic studies, subchronic tests were conducted with both rats and mice. Animals of each species were distributed amomg 3 groups, each consiting of 5 males and 5 females. p-Cresidine was administered to two of the three groups of each species at dietary concentrations of 1.0 and 3.0 % for 8 weeks. The third group of each species served as control group, receiviung only the basal laboratory diet.

Examinations

Observations and examinations performed and frequency:

As deaths occurred among all groups except male rats receiving 3.0 % p-cresidine in the feed, the high concentration chosen for the chronic study was 1.0 % p-cresidine for both rats and mice

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

mortality

Mortality:

mortality observed, treatment-related

Description (incidence):

mortality

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Details on results:

Deaths occurred among all groups except male rats receiving 3.0 % p-cresidine in the feed

Effect levels

1

Dose descriptor:

conc. level: 30000 mg/kg diet

Effect level:

30 000 mg/kg diet

Based on:

test mat.

Sex:

female

Basis for effect level:

other: mortality

2

Dose descriptor:

conc. level: 30000 mg/kg diet

Effect level:

30 000 mg/kg diet

Based on:

test mat.

Sex:

male

Basis for effect level:

other: no mortality

3

Dose descriptor:

conc. level: 10000 mg/kg diet

Effect level:

10 000 mg/kg diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: mortality

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Mortality occurred among all groups except male rats receiving 3.0 percent p-cresidine in the feed.

Executive summary:

Mortality occurred among all groups except male rats receiving 3.0 percent p-cresidine in the feed.