Registration Dossier

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

Constituent 1
Chemical structure
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.