4-aminotoluene-3-sulphonic acid

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline used

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD TG421

GLP compliance:

yes

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-methylbenzene-1-sulfonic acid

Details on test material:

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

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Sesame oil

Details on exposure:

VEHICLE
- Amount of vehicle (if gavage): 5 ml/kg bw

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

According to the random sampling, actual dose received was between -
12.5 to -0.4 % of each dose level

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1:1

Duration of treatment / exposure:

male: 48 days, female: 41-48 days

Frequency of treatment:

once a day by oral gavage

Duration of test:

male: 48 days, female: 41-48 days

No. of animals per sex per dose:

12 per sex per dose

Control animals:

yes, concurrent vehicle

Details on study design:

ADMINISTRATION
- male: before mating 14 days, during mating 14 days, after mating 20 days; total 48 days
- pregnant female: before mating 14 days, during mating (max.) 14 days, during gestation (about 21 days), after pregnant 3 days; total 41-46 days; not pregnant female: till 25 days after gestation; total 41-43 days; not copulated female: till 20 days after mating period; total 48 days
- According to the random sampling, actual dose received was between 12.5 to -0.4 % of each dose level.

Examinations

Maternal examinations:

CLINICAL OBSERVATION AND FREQUENCY
- clinical signs and mortality: daily
- male body weight: once a week, total 8 times in the 49 days
- female body weight: 1st, 8th, l5th day before mating; 0th, 7th, 14th, 21st day after copulated; 0th, 4th day after pregnance
- food consumption: in conformity with those body weight, except during mating for female
- water consumption: not checked

Fetal examinations:

- Pups number, sex, weight by sex in each litter, appearance were observed on 0th and 4th day. Dead pups were checked separately.

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

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

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

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

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

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

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

STATISTICAL RESULTS

There were no significant differences in number of offspring or live offspring, sex ratio, the live birth index, the viability index and the body weight. No abnormal findings related to the test substance were noted for external features, clinical signs, or on necropsy finding for the offspring. No pups with malformation were found in any group. No change in clinical signs and necropsy finding were observed in offspring.

FINDINGS OF DELIVERY IN DAMS AND OBSERVATIONS ON THEIR PUPS (F1)

Dose (mg/kg)	0	100	300	1000
No.of dams observed	11	10	12	12
No. of dams delivered live pups	11	10	12	12
Duration of gestation (mean±sd)	22.7±0.6	22.4±0.5	22.3±0.5	22.8±0.4
No. of total corpora lutea	216	170	218	222
Mean ± sd	19.6±4.5	17.0±2.1	18.2±3.7	18.5±3.2
No. of total implants	188	161	186	175
Mean ± sd	17.1±1.6	16.1±2.0	15.5±3.0	14.6±3.0
No. of total pups born	172	150	178	160
Mean±sd(=litter size)	15.6±1.6	15.0±1.8	14.8±2.6	13.3±3.3
Live Male	81	69	91	79
Mean±sd	7.4±1.9	6.9±2.3	7.6±2.4	6.6±1.8
Live Female	87	81	87	81
mean±sd	7.9±1.9	8.1±1.7	7.3±1.9	6.8±2.7
Sex ratio (male/female, mean±sd)	1.00±0.41	0.93±0.51	1.13±0.43	1.21±0.81
No. of total live pups an day 4; Male	66	66	85	78
Mean ± sd	6.0±3.2	6.6±2.2	7.1±2.5	6.5±1.7
Female	66	77	80	79
Mean ± sd	6.0±3.3	7.7±1.4	6.7±1.6	6.6±2.6
No. of total dead pups born	4*	0	0	0
Mean±sd	0.4±1.2	0.0±0.0	0.0±0.0	0.0±0.0
Gestation index(%)	100.0	100.0	100.0	100.0
Implanation index (%, mean ± sd)	89.5±12.3	94.7±2.0	86.6±15.8	80.2±18.2
Delivery index (%, mean ± sd)	91.6±5.6	93.5±7.7	96.2±4.8	90.9±8.6
Livebirth index (%, mean ± sd)	97.4±8.6	100.0±0	100.0±0	100.0±0
Viability index on day 4(%, mean ± sd); Male	77.8±39.1	96.0±8.4	93.1±9.7	99.1±3.2
Female	77.0±39.1	95.7±5.6	94.4±15.8	98.0±4.8

Gestation index = (No. of females with live pups/No. of pregnant females) x 100

Implanation index = (No. of implant/ No. of corpora Iutea) x 100

Delivery index = (No. of pups born/No. of implants) x 100

Livebirth index = (No. of live pups born/No. of pups born) x 100

Viability index an day 4 = (No. of live pups an day 4 after birth/No. of live pups born) x 100

*The reason of 4 dead pups born at 0 mg/kg bw was cannibalism.

Applicant's summary and conclusion

Conclusions:

NOAEL for Developmental Toxicity and Teratogenicity is considered to be 1000 mg/kg/day.
Of low toxicity to offspring

Executive summary:

There were no significant differences in number of offspring or live offspring, sex ratio, the live birth index, the viability index and the body weight. No abnormal findings related to the test substance were noted for external features, clinical signs, or on necropsy finding for the offspring. No pups with malformation were found in any group. No change in clinical signs and necropsy finding were observed in offspring.