4-amino-6-chlorotoluene-3-sulphonic acid

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OECD guideline used. A reliability of 2 is assigned for read-across.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

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:

4-aminotoluene-3-sulphonic acid

EC Number:

201-831-3

EC Name:

4-aminotoluene-3-sulphonic acid

Cas Number:

88-44-8

Molecular formula:

C7H9NO3S

IUPAC Name:

2-amino-5-methylbenzenesulfonic acid

Details on test material:

Mitsuboshi Chemical Co., Ltd.: purity >99%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS
age: 5 weeks
weight at initiation: 168-183 g for males, 138-162 g for females
pellet food and water: free take

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Sesame oil

Details on oral exposure:

Application volume: 5ml/kg bw

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

28 days exposure, 14 days recovery period

Frequency of treatment:

once a day

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 100, 300 and 1000 mg/kg/day
Basis:
actual ingested

No. of animals per sex per dose:

6

Control animals:

yes, concurrent vehicle

Details on study design:

Post-exposure period: 14 days for 0 mg/kg and 1000 mg/kg group

Examinations

Observations and examinations performed and frequency:

clinical signs and mortality: every day
body weight: twice a week, total 9 times during the 28 days, and additional 4 times during the 14 days recovery period
food consumption: once a week (24hr consumption)
water consumption: not checked
Hematology: checked
Clinical Chemistry: checked
Organ weights: checked

Results and discussion

Results of examinations

Details on results:

PRELIMINARY EXAMINATION
Four males and four females were used for the 14-day preliminary examination. No toxicological effects in the clinical signs, body weight, food consumption, urinary findings, hematological findings, blood chemical findings and weight of organs were seen up to 2000 mg/kg bw/day. At necropsy enlargement of cecum was observed in all animals at 2000 mg/kg bw/day group.
MORTALITY AND CLINICAL SIGNS
Neither mortality nor changes in behaviour were observed in any groups.
BODY WEIGHT AND FOOD CONSUMPTION
No toxic effects on body weight and food consumption were observed in any groups.
URINALYSIS
Increase in specific gravity and decrease in pH were observed in males treated with 1000 mg/kg bw/day. However no related change was observed in other findings.
HEMATOLOGY AND CLINICAL CHEMISTRY
Slight decreases in white blood cell count (due lymphopenia) were reported for the males of the 1000 mg/kg bw/day group.However, no pathological changes were observed in the lymphatic tissues (e.g. thymus, lymph node and spleen).
Slight increases in GPT in females, slight decreases in total cholesterol in males and slight decreases in glucose in females were observed in the 1000 mg/kg bw/day group. However, no pathological changes could be noticed in any of the related organs including the liver. According to the author, the changes were within normal range, based on other study data.
NECROPSY
Slight enlargement of cecum was seen in one male and one female of the 1000 mg/kg bw/day group. However neither diarrhea nor growth abnormalities had been reported.
Referring to organ weights, decreases in thymus weight at 100 mg/kg bw/day and increases in spleen weight at all dose levels in females were observed. However these changes showed no dose level-relationship.
REVERSIBILITY
All of the changes reported above returned to normal during the 14 days recovery period.

Effect levels

1

Dose descriptor:

NOEL

Effect level:

300 mg/kg bw/day (actual dose received)

Sex:

male/female

Basis for effect level:

other: Reversible and slight effects in hematology, clinical chemistry and gross necropsy

2

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (actual dose received)

Sex:

male/female

Basis for effect level:

other: No adverse effects observed

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Toxicological effects included decreases in white blood cell count, total cholesterol and urine pH, and enlargement of cecum in male at 1000 mg/kg bw/day; increases in GPT, decreases in glucose and enlargement of cecum in female at 1000 mg/kg bw/day. Since all findings were reversible within 14 days, the NOEL can be set at 300 mg/kg bw/day for both sexes.