1,4-dimethoxybenzene

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Not enough details of experimental procedure for an evaluation of the study.

Data source

Reference

Reference Type:

publication

Title:

Short-term toxicity tests on the mono and di methyl ethers of hydroquinone

Author:

Hodge HC, Sterner JH, Maynard EA, Thomas J.

Year:

1949

Bibliographic source:

J. Ind. Hyg. Toxicol. 31, 79-92.

Materials and methods

Principles of method if other than guideline:

Subacute toxicity by oral feed

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,4-dimethoxybenzene

EC Number:

205-771-9

EC Name:

1,4-dimethoxybenzene

Cas Number:

150-78-7

Molecular formula:

C8H10O2

IUPAC Name:

1,4-dimethoxybenzene

Details on test material:

no data

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

no data

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
- Rate of preparation of diet: no data
- Type of food: fox chow
- Storage of food : no data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Duration of treatment / exposure:

5 weeks

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0; 0.5; 2 and 10%
Basis:
nominal in diet

No. of animals per sex per dose:

10 males and 10 females per group were used

Control animals:

yes, concurrent no treatment

Details on study design:

no data

Positive control:

no data

Examinations

Observations and examinations performed and frequency:

BODY WEIGHT: Yes
- Time schedule for examinations: 1 time a week, so 6 times during study (week 0 to 4).
ORGAN WEIGHT: yes (Heart, lungs, spleen, liver, kidneys, brain, stomach, testes)
MORTALITY: Yes
- Time schedule for examinations: no data
FOOD CONSUMPTION: No data
WATER CONSUMPTION: No data
CLINICAL SIGNS: Yes
- Time schedule for examinations: no data
FUNCTIONAL OBSERVATIONS: No data
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
Time schedule for collection of blood: on 2 to 3 selected rats: 2 days prior the start of experiment, days 15-16 after beginning of experiment and days 29-30 after beginning of experiment.
Anaesthetic used for blood collection: No data
Animals fasted: No data
How many animals: 2 or 3
Parameters: haemoglobin, red blood cell counts, white blood cell counts, differential counts, description of the red cell characteristics.
CLINICAL CHEMISTRY: No data

Sacrifice and pathology:

GROSS PATHOLOGY: No data
HISTOPATHOLOGY: yes
AUTOPSY: tissues sections of organs weighted and also small and large intestine were taken and observed.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

no effects observed

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

not specified

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

effects observed, treatment-related

Details on results:

0.5% of PDMB produced no depression in growth in both male and female rats, but a stimulation to growth which amounted to about 10 g for males.
2% of paradimethoxybenzene caused a small but apparent diminution of growth; this amounted to 18 g in the male rats and 8 g in the female. The inclusion of 10% of paradimethoxybenzene was followed by almost complete inhibition of growth.
The animals lost weight somewhat during the early period, but had approximately regained their initial weight at the end of the experiment. Male and female weighed less than the control group (94 g for males, 51 g for females).
There was no mortality in any of the groups.
The hemoglobin values ranged between 12.2 and 18.7 g; most of the values fell around 14 to 16. Red blood cell counts ranged from 5.2 to 6.7 millions, which are normal values. The white blood cell counts were mostly 6 to 12 thousand, although an occasional value of 15-20 thousand was encountered. Scattered high counts like this are not uncommon. The differential counts appear to be normal; in most cases there were 70-80% lymphocytes.
No organ weight changes which could not adequately be explained on the basis of depression of general body growth.

At necropsy:
- one rat fed at 0.5% PDMB had congestion in the lung.
- one rat fed at 2% PDMB had hemorragic testes.
- in the rat fed at 10%, the organs appeared smaller than normal. In 2 rats, kidneys were smaller and darkened and in 2 others brownishgray streaks were observed on liver capsule. One rat had a reddened gastric mucosa and another a hemorragic lung.
Microscopically, the lungs exhibited round cells collected about the blood vessels in some rats in all groups.
The absence of signs of irritation in the gastrointestinal tract, and especially the absence of toxic changes in the liver and kidneys, are noteworthy.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

2 other: %

Sex:

male/female

2

Dose descriptor:

NOEL

Effect level:

0.5 other: %

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

It is quite possible that there is sufficient odor and flavor connected  with large percentage addition of this ether to the diets to decrease the  palatability 

of the ration and possibly reduce the total food intake.
Hematological studies in general gave normal values. Urine analyses were  normal. Organ weights studies did not reveal evidence of specific toxic 

effects. There were no significant histological changes which could be  attributed to the inclusion of paradimethoxybenzene.