Sodium 4-chloro-3-nitrobenzenesulphonate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for Sodium 4-chloro-3-nitrobenzenesulphonate (17691-19-9).Male and female reproductive parameters were unaffected by test material administration. Hence, NOAEL was estimated to be 368.75 mg/kg bw when male and femaleCrj: CD(SD)rats were exposed with Sodium 4-chloro-3-nitrobenzenesulphonate (17691-19-9) orally.

Link to relevant study records

Reference

Endpoint:

toxicity to reproduction

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is from OECD QSAR toolbox v3.3 and the QMRF report has been attached.

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3, 2017

GLP compliance:

not specified

Limit test:

no

Justification for study design:

No data available

Specific details on test material used for the study:

- Name of the test material: Sodium 4-chloro-3-nitrobenzenesulphonate
- IUPAC Name : sodium 4-chloro-3-nitrobenzene-1-sulfonate
- Molecular formula: C6H4ClNO5SNa
- Molecular weight: 259.601 g/mol
- Smiles: S(=O)(=O)([O-])c1cc([N+]([O-])=O)c(Cl)cc1.[Na+]
- InChI: 1S/C6H4ClNO5S.Na/c7-5-2-1-4(14(11,12)13)3-6(5)8(9)10;/h1-3H,(H,11,12,13);/q;+1/p-1
- Substance type: Organic
- Physical state: Solid powder (Off white to pale yellow)

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data available

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

No data available

Details on mating procedure:

No data available

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

43 days

Frequency of treatment:

Daily

Details on study schedule:

No data available

Dose / conc.:

368.75 mg/kg bw/day (nominal)

No. of animals per sex per dose:

13

Control animals:

yes, concurrent vehicle

Details on study design:

No data available

Positive control:

No data available

Parental animals: Observations and examinations:

No data available

Oestrous cyclicity (parental animals):

No data available

Sperm parameters (parental animals):

No data available

Litter observations:

No data available

Postmortem examinations (parental animals):

No data available

Postmortem examinations (offspring):

No data available

Statistics:

No data available

Reproductive indices:

No data available

Offspring viability indices:

No data available

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects 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:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Dose descriptor:

NOAEL

Effect level:

368.75 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

histopathology: non-neoplastic

reproductive performance

Remarks on result:

other: No effects on reproductive parameters.

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

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:

not specified

Behaviour (functional findings):

not specified

Developmental immunotoxicity:

not specified

Dose descriptor:

other: not specified

Generation:

other: not specified

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

not measured/tested

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

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

The prediction was based on dataset comprised from the following descriptors: NOAEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((("a" or "b" )  and "c" )  and ("d" and "e" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups AND SN1 AND SN1 >> Nucleophilic attack after diazonium or carbenium ion formation AND SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups AND SN1 >> Nucleophilic attack after reduction and nitrenium ion formation AND SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitroarenes with Other Active Groups AND SN2 AND SN2 >> SN2 attack on activated carbon Csp3 or Csp2 AND SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.3

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Aromatic nitro by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "d"

Parametric boundary:The target chemical should have a value of log Kow which is >= -3.14

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3

Conclusions:

In reproductive toxicity study, NOAEL was estimated to be 368.75 mg/kg bw when male and female Crj: CD(SD) rats were exposed with Sodium 4-chloro-3-nitrobenzenesulphonate (17691-19-9) orally.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for Sodium 4-chloro-3-nitrobenzenesulphonate (17691-19-9).Male and female reproductive parameters were unaffected by test material administration. Hence, NOAEL was estimated to be 368.75 mg/kg bw when male and femaleCrj: CD(SD)rats were exposed with Sodium 4-chloro-3-nitrobenzenesulphonate (17691-19-9) orally.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

368.75 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2017)

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

In different studies, Sodium 4-chloro-3-nitrobenzenesulphonate (17691-19-9) has been investigated for reproductive toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for Sodium 4-chloro-3-nitrobenzenesulphonate (17691-19-9).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for Sodium 4-chloro-3-nitrobenzenesulphonate (17691-19-9).Male and female reproductive parameters were unaffected by test material administration. Hence, NOAEL was estimated to be 368.75 mg/kg bw when male and female Crj: CD(SD)rats were exposed with Sodium 4-chloro-3-nitrobenzenesulphonate (17691-19-9) orally.

It is further supported by experimental study conducted by THEODORE WBRNICK, BEN MARR LANMAN AND JEAN LOUIS FIUUX (TOXICOLOGY AND APPLIED PHARMACOLOGY 32,450-460 (1975))on structurally similar read across substance m-nitrobenzenesulfonate (127-68-4) .The reproductive toxicity study of Sodium m-nitrobenzenesulfonate (127-68-4) was performed on male and female Sprague 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 food basal diet of Purina laboratory chow ad libitum except Food 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 female Sprague Dawley rats were treated with Sodium m-nitrobenzenesulfonate (127-68-4) orally.

It is further supported by experimental study conducted by California Environmental Protection Agency (Cal/EPA) Department of Pesticide Registration (DPR) (DPR MEDICAL TOXICOLOGY D53157>T120306, 6 march 2012)on structurally similar read across substance Mesotrione(104206-82-8).The multi– generation reproductive toxicity study of Mesotrione(104206-82-8) was performed on 26 male and 26 female. The test material mixed with fed in dose concentration0, 10,50, 350, 1500 or 7000ppm(0,1,5,35,150 or 700 mg/kg ) and administered for 8 weeks before mating and rearing the F1A litters to weaning. Selected F1A pups went through the same breeding program to produce F2A pups after at least 8 weeks of pre-mating period. All the animals were observed for body weight, food consumption, clinical sings and toxicity. Decreased food consumption during lactation period for both F0 and F1 adults were observed in the 7000 ppm groups. Body weight decrease was observed in 7000 ppm and 1500 ppm treated F0 adult during lactation period, in F1 male and female pups and adults during pre-mating period, gestation period and lactation period, and in F2 male and female pups. Decreased body weight was seen also in >10 ppm treated F1 male and female pups on days 22 and 29. Increased eye opaqueness or cloudiness was seen in 7000 treated F0 adult males, F1 adult males and females and F2A litter males at termination. Microscopic findings at termination showed increased eye unilateral or bilateral cataractous change in F0 adult male, F1 adult males and females and F2 litter males. Increased plasma tyrosine concentrations were seen in all treated groups in a dose dependent manner from F1 male and female adults and F2A male and female pups. Increased age of preputial separation was observed in >10 ppm treated F1 adults and in >350 ppm treated F2 adults. The slight delay in preputial separation did not result in any functional deficit in terms of reproductive performance. Increased incidence of eye opaqueness was seen in 7000 ppm treated F2A litter, increased incidence of eye(s) shut was seen in 10ppm and 7000 ppm treated F2A litter. Hence Reproductive No Observed Adverse Effect Level (NOAEL) was considered to be >7000ppm (700mg/kg) due to no effects on reproductive.

Thus, based on the above studies and predictions on Sodium 4-chloro-3-nitrobenzenesulphonate (17691-19-9) and its read across substances it was considered that no adverse effects on reproductive parameter were observed. Thus, comparing this value with the criteria of CLP regulation Sodium 4-chloro-3-nitrobenzenesulphonate (17691-19-9) cannot be classified as reproductive toxicant.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus, comparing this value with the criteria of CLP regulation Sodium 4-chloro-3-nitrobenzenesulphonate (17691-19-9) cannot be classified as reproductive toxicant.