Sodium hydrogen m-sulphonatobenzoate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study planned

Justification for type of information:

TESTING PROPOSAL ON VERTEBRATE ANIMALS

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out:
sodium hydrogen m-sulphonatobenzoate (EC n. 241-602-5; CAS n. 17625-03-5)
- Name of the substance for which the testing proposal will be used:
sodium hydrogen m-sulphonatobenzoate (EC n. 241-602-5; CAS n. 17625-03-5)

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION [please address all points below]:
- Available GLP studies
no GLP study is available to address developmental toxicity for sodium hydrogen m-sulphonatobenzoate.
- Available non-GLP studies
no experimental (non-GLP) study is available to address developmental toxicity for sodium hydrogen m-sulphonatobenzoate.
- Historical human/control data
no case-control study nor cohort study is available to address developmental toxicity for sodium hydrogen m-sulphonatobenzoate.
- (Q)SAR
no robust (Q)SAR models are available to reliably predict the developmental toxicity of sodium hydrogen m-sulphonatobenzoate.
- In vitro methods
no validated in vitro methods are available to investigate the developmental toxicity of sodium hydrogen m-sulphonatobenzoate.
- Weight of evidence
although sodium hydrogen m-sulphonatobenzoate did not exert significant toxicity in a screening test, weight of evidence is not sufficient to fully exclude developmental toxicity.
- Grouping and read-across
no structural analogue was found to be used as "source chemical" for assessing the developmental toxicity of sodium hydrogen m-sulphonatobenzoate.
- Substance-tailored exposure driven testing:
not applicable.
- Approaches in addition to above:
none.
- Other reasons:
none.

CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
According to Annex IX of RECH Reg. (EU) 1907/2006, the developmental toxicity study (OECD TG 414) should be submitted as adaptations are not applicable and no significant information is available in literature nor a read-across approach can be performed due to the absence of structural analogues. Moreover, robust (Q)SAR models and validated in vitro methods are not available for investigating developmental toxicity. Therefore, a testing proposal for a developmental toxicity study (OECD TG 414) in rats is provided in accordance with Annex IX.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
none.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

no

Remarks:

not foreseen at testing proposal level.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sodium hydrogen m-sulphonatobenzoate

EC Number:

241-602-5

EC Name:

Sodium hydrogen m-sulphonatobenzoate

Cas Number:

17625-03-5

Molecular formula:

C7H6O5S.Na

IUPAC Name:

sodium 3-sulfobenzoate

Test material form:

solid: particulate/powder

Details on test material:

White crystalline powder.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

Total No. of Rats = 170 (120 Females + 50 males)
Note: Males will be used only for cohabitation.
Age of receipt: 10 to 12 weeks

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

2 times during treatment period.

Duration of treatment / exposure:

16 days per animal

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (actual dose received)

Remarks:

Control group

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw/day (actual dose received)

Remarks:

Low dose group

Doses / concentrations 3

Dose / conc.:

300 mg/kg bw/day (actual dose received)

Remarks:

Intermediate dose group

Doses / concentrations 4

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

Remarks:

High dose group

No. of animals per sex per dose:

25 presumed pregnant females per group

Control animals:

yes

Examinations

Maternal examinations:

In life:
General clinical signs observations:
- at least once daily throughout the experimental period until sacrifice;
- more frequently, when signs of toxicity observed.
▪ Mortality and morbidity:
- twice daily throughout the experimental period until sacrifice.
▪ Body weight:
- on gestation day (GD) 0, 3, 5, 8, 11, 14, 17, 20 and 21 (on the day of caesarean section).
▪ Feed consumption:
- gestation day (GD) 0 to 3, 3 to 5, 5 to 8, 8 to 11, 11 to 14, 14 to 17, 17 to 21 coinciding with body weights.

Post- mortem observations:
▪ Gravid uterus weight and corrected body weight for maternal increase on the day of caesarean section.
▪ Examination of ovaries for number of corpora lutea.
▪ Examination of uterine contents for number of implantations, number and percent of live and dead fetuses, and resorptions.
▪ Determination of pre- and post-implantation losses per dam.
▪ Necropsy and gross pathological examination including gross examination of placenta.
▪ Serum T3, T4 and TSH estimations for all animals.
▪ Thyroid along with parathyroid weights.
▪ Histopathology of thyroid along with parathyroid from all the animals.

Fetal examinations:

Examinations of Fetuses on the day of caesarean section:
The following observations will be recorded per litter on the day of
caesarean section:
- Number of live fetuses, dead fetuses (if any), early resorptions (if any) and late resorptions (if any) and sex ratio (m/f) per litter.
- Fetal weights.
- Fetal Anogenital distance measurement.
- Fetal crown rump length.

Fetal External Examination:
All fetuses from each litter will be observed externally for development and alterations will be categorized as malformations or variations litter wise.

Fetal Visceral/Soft Tissue Examination:
Approximately one-half of fetuses from each litter will be subjected for visceral examinations (both soft tissue and head sections) and anomalies will be categorized as malformations or variations litter wise.

Fetal Skeletal Examination:
Approximately one-half of fetuses from each litter will be subjected to Alizarin Red S staining (single staining) for bone development and observed for skeletal anomalies. Anomalies will be categorized as malformations or variations litter wise.