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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
one-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from J-check

Data source

Referenceopen allclose all

Reference Type:
other: Authorized database
Title:
"Preliminary Reproduction Toxicity Screening Test of 2-Amino- 5-methylbenzenesulfonic acid by Oral Administration in Rats".
Author:
J-check Ministry of Health & Welfare, Japan
Year:
1999
Bibliographic source:
Toxicity Testing Reports of Environmental Chemicals, vol.7 p163-171,
Reference Type:
secondary source
Title:
Assessment Report for 4-AMINOTOLUENE-3-SULFONIC ACID CAS N°: 88-44-8
Author:
OECD SIDS
Year:
2003
Bibliographic source:
SIDS Initial Assessment Report For SIAM 16 Paris, 27-30 May 2003

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
Principles of method if other than guideline:
Reproduction Toxicity Screening Test of 2-Amino-5-methylbenzenesulfonic acid by Oral Administration in Rats
GLP compliance:
not specified
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 sulfonic acid
Details on test material:
- Name of test material (IUPAC name): 2-Amino-5-Methylbenzenesulfonic Acid
- Common name: p-Toluidine-m-sulfonic acid
- Molecular formula: C7H9NO3S
- Molecular weight: 187.2181 g/mol
- Smiles notation: Cc1ccc(c(c1)S(=O)(=O)O)N
- InChl: 1S/C7H9NO3S/c1-5-2-3-6(8)7(4-5)12(9,10)11/h2-4H,8H2,1H3,(H,9,10,11)
- Substance type: Organic
- Physical state: Solid
Specific details on test material used for the study:
- Name of test material (as cited in study report): 4-aminotoluene-3-sulphonic acid
- Substance type: Organic
- Physical state: Solid

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 10 weeks
- Weight at study initiation: 375-414 g for males, 239-266 g for females
- Diet (e.g. ad libitum): NMF solid feed (radiation sterilized feed) and was taken free during the breeding period, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
other: sesame oil, 0.5mL/100g body weight
Details on exposure:
vehicle: sesame oil, 0.5mL/100g body weight
schedule: once a day by oral gavage
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 couplated female: till 20 days after mating period; total 48 days
Details on mating procedure:
- M/F ratio per cage: 1:1
- Length of cohabitation: max. 14 days
- Further matings after two unsuccessful attempts: No data
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
male 48 days; female 41-48 days.
Premating exposure period
Male :14 days
Female :14 days
Frequency of treatment:
once a day, every day
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
100 mg/kg bw/day
Dose / conc.:
300 mg/kg bw/day
Dose / conc.:
1 000 mg/kg bw/day
No. of animals per sex per dose:
12 per sex per dose
Control animals:
yes, concurrent vehicle
Details on study design:
Duration of test : male: 48 days, female: 41-48 days.

Examinations

Parental animals: Observations and examinations:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: every day to all animals.
BODY WEIGHT: Yes
- Time schedule for examinations:
Male body weight: once a week, total 8 times in the 49 days
Female body weight: 1st, 8th, 15th day before mating; 0th, 7th, 14th, 21st day after copulated; 0th, 4th day after pregnant
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): in conformity with those body weights, except during mating for female.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): not checked
Oestrous cyclicity (parental animals):
Sexual cycle was observation
Sperm parameters (parental animals):
Spermatogenesis of the epididymis was observed.
Litter observations:
Pups number, sex, weight by sex in each litter, appearance were observed on 0th and 4th day. Dead pups were checked separately
Postmortem examinations (parental animals):
Organ weight, gross pathology and histopathology were examined.
Postmortem examinations (offspring):
Gross pathology were examined.
Statistics:
Weight, food consumption, number of corpus luteums, number of implantation traces, number of births, number of stillbirths, sex ratio, average sex, pregnancy period, implantation rate, delivery rate, birth rate, abnormal incidence of abnormal outer table, newborn 4th Multiple comparison test 2-4) was performed on the survival rate, organ weight and relative weight of the subjects.
For the birth rate, mating rate and conception rate, χ ^ 2 tests 5, 6) were used. The incidence of findings of pathological examination was tested using Fisher's direct probability test method 6). In addition, as for the results on newborns during the nursing period, the average per mother was taken as one sample. The level of significance was set at two levels of *: P <0.05 and **: P <0.01.
Reproductive indices:
copulation index, fertility index, gestation length, number of corpora lutea or implanations, implanation index, gestation index, parturition or maternal behavior.
Offspring viability indices:
sex ratio, the live birth index, the viability index

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Description (incidence and severity):
Ocular secretion in 100 mh/kg bw, hair loss in 300 and 1000 mg/kg bw were observed in male rats and hair removal was observed in the 100 mg / kg group through pregnancy
and nursing periods, and in the control group of female rats. No change due to administration of the test substance was observed
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
No mortality were observed in treated rats as compared to control.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No test substance related change in body weight were observed in treated rats as compared to control.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
When treated wtih 1000 mg/kg bw, statistically significant increase in food consumption from 1 to 15 days of administration in male rats
no effect on female rats were observed.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
Seminiferous tubular atrophy of the teste, testicular and epididymal atrophy, stromal cell proliferation, spermatogenesis of the epididymis were observed at 300 mg/kg bw and cell infiltration of the epididymis at 1000 mg / kg However, since it is low frequency expression, it was not considered to be influence of the test substance.
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Description (incidence and severity):
No effect on estrous cycle were observed in treated female rats as compared to control.
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Description (incidence and severity):
No effect on copulation index, fertility index, gestation length, number of corpora lutea or implantations, implantation index, gestation index, delivery index, purturition or maternal behavior in treated rats.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical signs
mortality
body weight and weight gain
food consumption and compound intake
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic
reproductive function (oestrous cycle)
reproductive performance
Remarks on result:
other: No effects were observed

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Description (incidence and severity):
No clinical signs were observed in treated male and female pups as compared to control.
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Description (incidence and severity):
No effect on survival of treated pups were observed as compared to control.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effect on offspring body weight were observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Description (incidence and severity):
No external changes were observed in offspring
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
viability
clinical signs
mortality
body weight and weight gain
gross pathology
Remarks on result:
other: No effect observed

Target system / organ toxicity (F1)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 1000 mg/kg bw when Crj: CD (SD) male and female rats were treated with 2-Amino-5-methylbenzenesulfonic acid orally by gavage for 48 days.
Executive summary:

In a Preliminary Reproduction Toxicity Screening Test, Crj: CD(SD) male and female rats were treated with 2-Amino-5-methylbenzenesulfonic acid in the concentration of 0 (vehicle), 100, 300, 1000 mg/kg/day orally by gavage in Sesame oil. Ocular secretion in 100 mh/kg bw, hair loss in 300 and 1000 mg/kg bw were observed in male rats and hair removal was observed in the 100 mg / kg group through pregnancy and nursing periods, and in the control group of female rats. No change due to administration of the test substance was observed. No mortality and change in body weight were observed as compared to control. Statistically significant increase in food consumption from 1 to 15 days of administration in male rats at 1000 mg/kg bw and no effect on female rats were observed. In addition, statistically significant decrease in epididymis weight was observed at 300 mg/kg bw but there was no difference in the relative weight, and a similar change was observed in the 1000 mg / kg group There was not. There was no difference between the control group and each test substance administered group as testicular weight. No gross pathological change was observed in treated rats. Seminiferous tubular atrophy of the teste, testicular and epididymal atrophy, stromal cell proliferation, spermatogenesis of the epididymis were observed at 300 mg/kg bw and cell infiltration of the epididymis at 1000 mg / kg However, since it is low frequency expression, it was not considered to be influence of the test substance. Similarly, No effect on estrous cycle, copulation index, fertility index, gestation length, number of corpora lutea or implantations, implantation index, gestation index, delivery index, purturition or maternal behavior in treated rats. No clinical signs, mortality and change in body weight were observed as compared to control. Therefore, NOAEL was considered to be 1000 mg/kg bw when Crj: CD (SD) male and female rats were treated with 2-Amino-5-methylbenzenesulfonic acid orally by gavage for 48 days.