m-(4,5-dihydro-5-imino-3-methyl-1H-pyrazol-1-yl)benzenesulphonic acid

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data from secondary source

Data source

Reference

Reference Type:

secondary source

Title:

Hazard Characterization - Sulfanilic Acids Category

Author:

U. S. Environmental Protection Agency (EPA) Office of Pollution Prevention and Toxic Substances (OPPTS)

Year:

2015

Bibliographic source:

U. S. Environmental Protection Agency, Hazard Characterization Document, March, 2015

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Reproduction toxicity screening test of sulfanilic acid by oral administration in rats

GLP compliance:

not specified

Limit test:

no

Justification for study design:

No data available

Test material

Test material information

Constituent 1

Reference substance name:

Sulphanilic acid

EC Number:

204-482-5

EC Name:

Sulphanilic acid

Cas Number:

121-57-3

Molecular formula:

C6H7NO3S

IUPAC Name:

4-aminobenzenesulfonic acid

Test material form:

solid

Details on test material:

- Name of test material: Sulphanilic acid
- Molecular formula: C6H7NO3S
- Molecular weight: 173.191 g/mol
- Substance type: Organic
- Physical state: solid
- Purity: No data
- Impurities (identity and concentrations): No data

Specific details on test material used for the study:

- Name of test material: Sulphanilic acid
- Molecular formula: C6H7NO3S
- Molecular weight: 173.191 g/mol
- Substance type: Organic
- Physical state: No data
- Purity: No data
- Impurities (identity and concentrations): No data

Test animals

Species:

rat

Strain:

Wistar

Details on species / strain selection:

No data available

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
Test material diluted with water.
DIET PREPARATION
- Rate of preparation of diet (frequency):Not specified
- Mixing appropriate amounts with (Type of food): Not specified
- Storage temperature of food:Not specified

VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle: 0 (water), 62.5 (50), 250 and 1000 mg/kg-bw
- Amount of vehicle (if gavage): Not specified
- Lot/batch no. (if required): Not specified
- Purity:Not specified

Details on mating procedure:

- M/F ratio per cage:Not specified
- Length of cohabitation: Not specified
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancyNot specified
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility.
- Further matings after two unsuccessful attempts: [no / yes (explain)]Not specified
- After successful mating each pregnant female was caged (how): Not specified
- Any other deviations from standard protocol:Females showing no evidence of copulation were re-grouped with proven sires for a second mating phase

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Males were dosed daily for a minimum of four weeks, including a minimum of two weeks prior to mating and continued throughout the mating period until the study was terminated. Females were dosed two weeks prior to mating, until conception, throughout pregnancy and at least four days after delivery

Frequency of treatment:

Daily

Details on study schedule:

No data available

Doses / concentrations

Remarks:

0 (water), 62.5 (50), 250 and 1000 mg/kg-bw

No. of animals per sex per dose:

Total: 96
0 mg/kg/day: 12 male, 12 female
62.5 mg/kg/day: 12 male, 12 female
250 mg/kg/day: 12 male, 12 female
1000 mg/kg/day: 12 male, 12 female

Control animals:

yes

Details on study design:

No data available

Positive control:

No data available

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data available

BODY WEIGHT: Yes
- Time schedule for examinations:

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations:No data available

OTHER:

Oestrous cyclicity (parental animals):

No data available

Sperm parameters (parental animals):

No data available

Litter observations:

No data available

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: All surviving animals [describe when, e.g. as soon as possible after the last litters in each generation were produced.]
- Maternal animals: All surviving animals [describe when, e.g. after the last litter of each generation was weaned.]

GROSS NECROPSY: yes gross necropsy was performed, with organ mass recorded, tissues and organs preserved and processed histologically.


HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively. A histopathological examination was conducted on samples from the 1000 mg/kg /day dose groups and the vehicle groups.

Postmortem examinations (offspring):

No data available

Statistics:

No data available

Reproductive indices:

No data available

Offspring viability indices:

No data available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Description (incidence and severity):

Rats at the 1000mg/kg /day dose showed oronasal bleeding during the first week and occasionally throughout the study.

Dermal irritation (if dermal study):

not specified

Mortality:

no mortality observed

Description (incidence):

No mortality were observed in treated male and femlae rats as compared to control.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

No effects on body weight were observed in treated male and femlae rats as compared to control.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

No effects on food consumption were observed in treated male and femlae rats as compared to control.

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:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Description (incidence and severity):

No changes in organ weights of reproductive organs

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

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

Remarks on result:

other: No effects on reproductive organ weight

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:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

not specified

Body weight and weight changes:

not specified

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:

not specified

Histopathological findings:

not specified

Other effects:

effects observed, treatment-related

Description (incidence and severity):

Noteworthy were the statistically insignificant, mild effects on litter mass of the high dose group and on pre-implantation loss of the 250mg/kg-bw/day and 1000mg/kg-bw/day dose group. Similarly there was a mild tendency of relatively low total numbers of pups born with increasing test item dosage and a low mean number of live pups per dam at day 4 post-partum.

Developmental neurotoxicity (F1)

Behaviour (functional findings):

not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:

not specified

Effect levels (F1)

Dose descriptor:

LOAEL

Generation:

F1

Effect level:

250 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

viability

other: overall developmental effects

Remarks on result:

other: decreased numbers of live pups

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:

In reproductive toxicity study NOAEL was considered to be 1000 mg/kg/day for P generation and LOAEL was considered to be 250 mg/kg bw /day for F1 generation ,when male and female wistar rats treated with Sulfanilic acid (121-57-3)orally by gavage.

Executive summary:

In a Reproduction Toxicity Screening Test, wistar male and female rat were treated with Sulfanilic acid (121-57-3)in the dose concentration of0 (water), 62.5 (50), 250 and 1000 mg/kg-bw orally by gavage in water .12 males and 12 females were placed in each dose group. Males were dosed daily for a minimum of four weeks, including a minimum of two weeks prior to mating and continued throughout the mating period until the study was terminated. Females were dosed two weeks prior to mating, until conception, throughout pregnancy and at least four days after delivery. Females showing no evidence of copulation were re-grouped with proven sires for a second mating phase. All the animals were observed for Survival, general condition, body weights, food and water consumption. At the end of the in-life phase, gross necropsy was performed, with organ mass recorded, tissues and organs preserved and processed histologically. A histopathological examination was conducted on samples from the 1000mg/kg-bw/day dose groups and the vehicle groups.

No mortality was observed in treated male and female rats as compared to control. Rats at the1000mg/kg-bw/day dose showed oronasal bleeding during the first week and occasionally throughout the study. No effects were seen on body mass as well as food and water consumption was noted. at gross necropsy, No changes in organ weights of reproductive organs were noted. Noteworthy were the statistically insignificant, mild effects on litter mass of the high dose group and on pre-implantation loss of the 250mg/kg-bw/day and 1000 mg/kg-bw/day dose group. Similarly there was a mild tendency of relatively low total numbers of pups born with increasing test item dosage and a low mean number of live pups per dam at day 4 post-partum. Hence NOAEL was considered to be 1000 mg/kg/day for P generation and LOAEL was considered to be 250 mg/kg bw /day for F1 generation, when male and female wistar rats treated with Sulfanilic acid (121-57-3) orally by gavage .