3,5-xylenol

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3,5-xylenol

EC Number:

203-606-5

EC Name:

3,5-xylenol

Cas Number:

108-68-9

Molecular formula:

C8H10O

IUPAC Name:

3,5-dimethylphenol

Constituent 2

Reference substance name:

3,5 xylenol

IUPAC Name:

3,5 xylenol

Details on test material:

- Name of test material (as cited in study report): 3,5-dimethylphenol
- Physical state: Solid (yellow crystalline)
- Analytical purity: 99.7%
- Impurities (identity and concentrations): Not stated
- Lot/batch No.: MA 2087L
- Expiration date of the lot/batch:
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions: Confirmed for the dosing phase of the study
- Storage condition of test material: Room temperature in the dark

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

28 consecutive days

Frequency of treatment:

Once daily

Doses / concentrations

Remarks:

Doses / Concentrations:
30, 100, 300 mg/kg/day
Basis:

No. of animals per sex per dose:

5 animals/sex/group

Control animals:

yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:

NOEL

Effect level:

<= 30 mg/kg bw/day (actual dose received)

Sex:

male/female

Basis for effect level:

other: overall effects clinical signs; increased salivation, slightly lower bodyweight gain and food consumption were obnserved in male and female rats dosed at 100 and 300 mg/kg/day

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Clinical signs:

At 300 mg/kg/day a persisent increase in post dosing salivation was recorded for both sexes from Day 4 to termnation. This observation was also observed in aniamsl dosed at 100 mg/kg/day, however this wa sporadic in incidence. Such a finding is common in rats dosed orally, and is considered to rise as a result of teh unpalatability of the test substance. Therefore such a finding was considered to be of no toxicological importance.

At 30 mg/kg/day post dosing salivation was comparable to that of the vehicle control group.

Bodyweight:

Slightly lower (than control) bodyweight gains were noted for male rats receiving 100 or 300 mg/kg/day, these differences were however not statistically significant.

Food consumption:

Slightly lower (than control) food consumption values were seen throughout the study for male rats receiving 100 or 300 mg/kg/day, which was also consistent with the lower bodyweight gains noted for these groups. For females the weekly consumption was slightly higher than the control, but as no changes in bodyweight gains were observed these changes were considered coincidental.

Organ weights:

No changes in organ weights (that were considered to be of toxicological importance) were observed, however one male rat had a slightly lower combined testis/epididymides weight. This resulted in a significantly (p<0.05) decreased group weight compared to the controls. Furthermore, the adrenal weight for 1 female (30 mg/kg/day) fell below the historical control range.

Macroscopic pathology:

No changes attributed to the test substance.

Microscopic pathology:

Testis: moderate, unilateral tubular atrophy in a single male at 300 mg/kg/day

Adrenals: moderate cortical hypertrophy in a single rats at 300 mg/k/g/day

Applicant's summary and conclusion

Conclusions:

Based on the results of this study it can be concluded that 30 mg/kg/day represents the NOEL in the rat for 3,5 dimethylphenol.

Executive summary:

In a 28 day oral toxicity study groups of fasted, young adult Sprague-Dawley male and female rats were administered 3,5 xylenol (via gavage)in olive oill at doses of 30, 100 and 300 mg/kg/day. All animals survivied to the scheduled necropsy. A gross necropsy and histological examinations were performed on all animals at the time of death.

  

Clinical signs of toxicity during the study included increased salivation in animals dosed at 100 and 300 mg/kg/day. Slightly lower bodyweight gain and food consumption was noted for males dosed at 100 and 300 mg/kg/day. No effects attributed to treatment on organ weight, haematology or clinical chemistry were observed.

Based on the results of the study it can be concluded that a dose of 30 mg/kg/day represented the NOEL.