4-aminotoluene-3-sulphonic acid

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

based on test type (migrated information)

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:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

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-methylbenzene-1-sulfonic acid

Details on test material:

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

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS
- age: 10 weeks
- weight at initiation: 375-414 g for males, 239-266 g for females
- pellet food and water: free take

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:

yes

Duration of treatment / exposure:

Exposure period: male 48 days; female 41-48 days
Premating exposure period (males): 14 days
Premating exposure period (females): 14 days
Duration of test: male: 48 days, female: 41-48 days

Frequency of treatment:

once a day, every day

Details on study schedule:

male 48 days; female 41-48 days

Doses / concentrations

Remarks:

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

No. of animals per sex per dose:

12

Control animals:

yes, concurrent vehicle

Examinations

Parental animals: Observations and 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

Litter observations:

- 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: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

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

Sex:

male/female

Basis for effect level:

other: no effects observed

Results: F1 generation

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

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

Sex:

male/female

Basis for effect level:

other: no effects observed

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

STATISTICAL RESULTS

No effects were observed in the copulation index, fertility index, gestation Iength, number of corpora Iutea or implantations, implantation index, gestation index, parturition or maternal behaviour. 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.

 

SUMMARY OF REPRODUCTIVE PRFORMANCE

Dose (mg/kg bw)	0	100	300	1000
No. of pairs mated	12	12	12	12
No. of pairs coupled	12	11	12	12
No. of pregnant females	11	10	12	12
Copulation index(%)	100.0	91.7	100.0	100.0
Fertility index(%)	91.7	90.9	100.0	100.0
Estrus cycle (days, mean±sd)	4.5±0.7	4.2±0.5	4.2±0.4	4.5±0.5

Copulation Index = (No. of animais with successful couplation/No, of animais mated) x 100

Fertility index = (No. of pregnant animals/No, of animais with successful couplation> x 100

 

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 on 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 lutea) 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 on day 4 = (No. of live pups on 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 both reproductive and developmental toxicity are
considered to be 1000mg/kg/day for both parental animals and
offspring.