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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental 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 from peer reviewed journal

Data source

Reference
Reference Type:
publication
Title:
Chronic Toxicity, Teratologic, and Reproduction Studies with Hair Dyes
Author:
THEODORE WBRNICK, BEN MARR LANMAN AND JEAN LOUIS FIUUX
Year:
1975
Bibliographic source:
TOXICOLOGY AND APPLIED PHARMACOLOGY 32,450-460 (1975)

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Reproductive toxicity study of Sodium m-nitrobenzenesulfonate was performed on Sprague Dawley rats.
GLP compliance:
not specified
Limit test:
no
Justification for study design:
No data available

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: pearls
Details on test material:
- Name of test material (as cited in study report): Sodium 3-nitrobenzenesulphonate
- Molecular formula (if other than submission substance): C6H5NO5S.Na
- Molecular weight (if other than submission substance): 226.16
- Substance type: Organic
- Physical state: Solid
- Lot/batch No.: 2542
Specific details on test material used for the study:
Name of test material (as cited in study report): Sodium 3-nitrobenzenesulphonate
- Molecular formula (if other than submission substance): C6H5NO5S.Na
- Molecular weight (if other than submission substance): 226.16
- Substance type: Organic
- Physical state: Solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on species / strain selection:
No data available
Sex:
male/female
Details on test animals and environmental conditions:
Details on test animals and env. conditions
TEST ANIMALS
- Source: No data available
- Age at study initiation: No data available
- Weight at study initiation: male rats: 240 to 280 g and Females: 180 to 220 g.
- Fasting period before study: No data available
- Housing: No data available
- Use of restrainers for preventing ingestion (if dermal): yes/no
- Diet (e.g. ad libitum): Purina laboratory chow, ad libitum except Food was withheld during period of mating.
- Water (e.g. ad libitum): ad libitum
Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available
IN-LIFE DATES: From: To: No data available

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
The test material mixed with into basal diet
DIET PREPARATION
- Rate of preparation of diet (frequency):twice weekly
- Mixing appropriate amounts with (Type of food ): the basal diet of Purina laboratory chow
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle: 0, 1950, and 7800 ppm(0, 86 and 351 mg/kg bw )
- Amount of vehicle (if gavage): No data available

- Lot/batch no. (if required): No data available
- Purity: No data available
Details on mating procedure:
- M/F ratio per cage:1:2
- Length of cohabitation: From 4 PM to 8 AM the following day.
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy:The appearance of sperm in a vaginal smears (day 0 of pregnancy).
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility.
- Further matings after two unsuccessful attempts: [no / yes (explain)]No data available
- After successful mating each pregnant female was caged (how): Pregnant females then were placed in individual cages
- Any other deviations from standard protocol:No data available
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
In Part I, the females received the basal diet from 8 week prior to mating through the weaning of their litters. The males siring these litters were fed the test diets for 8 week prior to mating and during the mating period. In Part II, males received the basal diet for 8 week prior to and during mating, while the females received the test diets 8 week prior to mating and during gestation and 21 days of lactation.
Frequency of treatment:
daily
Details on study schedule:
No data available
Doses / concentrations
Remarks:
0, 1950, and 7800 ppm(0, 86 and 351mg/kg bw )
No. of animals per sex per dose:
Total:180
Part I
0ppm:10 male and 20 female
1950 ppm :10 male and 20 female
7800ppm:10 male and 20 female
Part II
0ppm: 10 male and 20 female
1950 ppm : 10 male and 20 female
7800ppm: 10 male and 20 female

Control animals:
yes
Details on study design:
No data available
Positive control:
No data available

Examinations

Parental animals: Observations and examinations:
Parental animals observation and examinations
CAGE SIDE OBSERVATIONS: yes

DETAILED CLINICAL OBSERVATIONS: Yes

Time schedule: daily


BODY WEIGHT: Yes
Time schedule for examinations: daily
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
Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data: No data available


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

Oestrous cyclicity (parental animals):
No data available
Sperm parameters (parental animals):
No data available
Litter observations:
The litters’ were examined for numbers of live and stillborn pups and gross abnormalities. The pups were weighed at birth, and at 4 and 21 days
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: One female pregnant by each male was killed by chloroform inhalation on day 13 of her pregnancy to obtain information regarding the early stages of gestation.
GROSS NECROPSY
The uterus was examined for the number and distribution of embryos, the presence of empty implantation sites, and the number of embryos undergoing resorption. Each embryo was examined under a dissecting microscope. The remaining dams were allowed to deliver normally. A necropsy was performed on all females that did not deliver a litter to determine whether pregnancy had occurred.

HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.
Postmortem examinations (offspring):
SACRIFICE
- The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at [#?] days of age.
- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows:

GROSS NECROPSY
- the litters’ were examined for numbers of live and stillborn pups and gross abnormalities

HISTOPATHOLOGY / ORGAN WEIGTHS
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.
Statistics:
The data were subjected to statistical analysis, using the 95% confidence level. The methods used included chi square test, analysis of variance and t test, and the Fisher exact probability test (Snedecor, 1962).
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):
No treatment-related clinical signs were observed
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
Description (incidence and severity):
At the dietary concentration fed, there were no effects on body weight gains of either males or females
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
At the dietary concentration fed, there were no effects on food consumption of either males or females
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:
not specified
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):
There were no dose-related significant differences in any of the parameters examined which included male and female fertility, length of gestation, numbers of females with resorption sites, live pups per litter, pup body weights, and pup survival. The female fertility index in the high dosage group in Part I and the average pup weight in the high dosage group in Part II were lower than the control values, but the differences were not statistically significant at the 95% confidence level.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
351 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
food consumption and compound intake
reproductive performance
Remarks on result:
other: No effects on reproductive performance was observed

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: 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:
no effects observed
Description (incidence and severity):
No abnormal pups were seen upon dissection of embryos after 13 days of gestation or upon gross examination at weaning after 21 days.

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:
351 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: overall developmental effects
Remarks on result:
other: No abnormal pups were observed upon gross examination at weaning after 21 days.

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, the NOAEL was considered to be 7800ppm (351mg/kg)as no dose related effects on reproductive parameters were observed. When male and female Sprague Dawley rats were treated with Sodium m-nitrobenzenesulfonate (127-68-4) orally
Executive summary:

The reproductive toxicity study ofSodium m-nitrobenzenesulfonate (127-68-4) was performed on male and femaleSprague Dawley rats. The 180 animals divide into six groups; each group consists of 10 males and 20 females.The body weights of the male rats ranged from 240 to 280 g while those of the females ranged from 180 to 220 g.All the animals provided with water and foodbasal diet of Purina laboratory chowad libitum exceptFood was withheld during period of mating. The test material mixed with feed in dose concentration 0, 1950, and 7800 ppm (0, 86 and 351mg/kg bw ). The study divide into two parts, In Part I, and the females received the basal diet from 8 weeks prior to mating through the weaning of their litters. The males siring these litters were fed the test diets for 8 weeks prior to mating and during the mating period. In Part II, males received the basal diet for 8 weeks prior to and during mating, while the females received the test diets 8 week prior to mating and during gestation and 21 days of lactation. One male was placed in a cage with two females from 4 PM to 8 AM the following day. This procedure was continued until copulation was confirmed by the appearance of sperm in a vaginal smear (day 0 of pregnancy). Males were rotated within their dietary groups at I0-day intervals until conception was confirmed or until each female had been mated with a maximum of two males. If one of the two females caged with the male became pregnant, the male was considered fertile. A female was considered infertile if she failed to become pregnant after mating with two different males for 10 days each. Pregnant females then were placed in individual cages. One female pregnant by each male was killed by chloroform inhalation on day 13 of her pregnancy to obtain information regarding the early stages of gestation. The uterus was examined for the number and distribution of embryos, the presence of empty implantation sites, and the number of embryos undergoing resorption. Each embryo was examined under a dissecting microscope. The remaining dams were allowed to deliver normally. A necropsy was performed on all females that did not deliver a litter to determine whether pregnancy had occurred. The duration of gestation was noted and the litters’ were examined for numbers of live and stillborn pups and gross abnormalities. The pups were weighed at birth, and at 4 and 21 days. At 21 days all surviving pups were killed by chloroform inhalation and examined grossly for abnormalities.

 

At the dietary concentration fed, there were no effects on food consumption and body weight gains of either males or females.There were no dose-related significant differences in any of the parameters examined which included male and female fertility, length of gestation, numbers of females with resorption sites, live pups per litter, pup body weights, and pup survival. The female fertility index in the high dosage group in Part I and the average pup weight in the high dosage group in Part II were lower than the control values, but the differences were not statistically significant at the 95% confidence level.No abnormal pups were seen upon dissection of embryos after 13 days of gestation or upon gross examination at weaning after 21 days.Hence, the NOAEL was considered to be 7800ppm (351mg/kg) as no dose related effects on reproductive parameters were observed. When male and femaleSprague Dawley rats were treated withSodium m-nitrobenzenesulfonate (127-68-4) orally.