Sodium p-cumenesulphonate

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Description of key information

The HYDROTOPES Category comprises the following 6 substances:
STS - Sodium toluene 4-sulphonate (CAS 657-84-1, EC 211-522-5)
SXS - Sodium (xylenes and 4-ethylbenzene) sulfonates (EC 701-037-1)
NH4XS - Ammonium (xylenes and 4-ethylbenzene) sulfonates (EC 943-024-5)
SCS - Sodium p-cumenesulphonate (CAS 15763-76-5, EC 239-854-6)
KCS - Potassium p-cumenesulphonate (CAS 164524-02-1, EC 629-764-9)
NH4CS - Ammonium p-cumenesulphonate (CAS 680972-33-2, EC 811-484-5) 
In addition CaXS (Calcium Xylenesulphonate, CAS 28088-63-3, EC 248-829-9) was evaluated for complete the assessment despite it is not registered under REACH.

In a reproductive and developmental toxicity screening study (OECD 421) Sodium p-toluene sulphonate was administered to male and female Sprague-Dawley rats by oral gavage at dose levels of 0, 100, 300 or 1000 mg/kg bw/day on a total of 46 days before the start of mating, during the mating period and after the end of mating to male rats and before the start of mating, during the mating and gestation periods up to day 3 of lactation to female rats. Males and females in the 1000 mg/kg bw/day group showed diarrhoea or soft faeces, and males showed mild inflammatory cell infiltration of the lamina propria and squamous cell hyperplasia in the limiting ridge of the stomach. There were no effects from administration of the substance on the reproductive function or development and growth of the next generation in any dose group. Therefore, it was considered that the NOAEL for parental toxicity was 300 mg/kg bw/day and the NOAEL for reproductive and developmental toxicity was 1000 mg/kg bw/day.

The 90-day oral rat and oral mouse studies and the 2-year chronic dermal rat and mouse studies (OECD 453) on Sodium (xylenes and 4-ethylbenzene) sulfonates included examination of sex organs of both sexes. No treatment related effects on reproductive organs were reported at doses.

No treatment related effects on reproductive organs were reported in any study. A new OECD 443 was performed on Sodium (xylenes and 4-ethylbenzene) sulfonates which is the most representative member of the hydrotropes category since it contains a significant proportion of both mono-alkyl (ethyl) and di-alkyl (dimethyl) chemical species and thus best represents the substances within the category.

The available results on reproductive and developmental toxicity are:
STS, OECD 421 (2004): NOAEL = 1000 mg a.i./kg bw               
SXS, OECD 443 (2022): NOAEL for SYSTEMIC TOXICITY = 1000 mg/kg/day for P and F1 male/female
                                    NOAEL for REPRODUCTION and DEVELOPMENT = 1000 mg/kg/day

The NOAEL value used for the risk assessment for toxicity to reproduction is 1000 mg/kg bw from the new OECD 443 performed on SXS. 

 

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Sufficient to meet requirements.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Effects on developmental toxicity

Description of key information

The HYDROTOPES Category comprises the following 6 substances:
STS - Sodium toluene 4-sulphonate (CAS 657-84-1, EC 211-522-5)
SXS - Sodium (xylenes and 4-ethylbenzene) sulfonates (EC 701-037-1)
NH4XS - Ammonium (xylenes and 4-ethylbenzene) sulfonates (EC 943-024-5)
SCS - Sodium p-cumenesulphonate (CAS 15763-76-5, EC 239-854-6)
KCS - Potassium p-cumenesulphonate (CAS 164524-02-1, EC 629-764-9)
NH4CS - Ammonium p-cumenesulphonate (CAS 680972-33-2, EC 811-484-5) 
In addition CaXS (Calcium Xylenesulphonate, CAS 28088-63-3, EC 248-829-9) was evaluated for complete the assessment despite it is not registered under REACH.

The study with Calcium Xylenesulphonate performed under similar condition of OECD 414 guideline showed no adverse effects. In this developmental toxicity study on Calcium Xylenesulphonate, thirty (30) female rats received 0, 150, 1500 or 3000 mg test substance/kg bw/day by oral gavage on days 6 to 15 of gestation. Clinical symptoms were noted daily through day 20. Body weight and food consumption were recorded every three days through day 20. All females were macroscopically examined on day 20. The uteri were removed, weighed and examined for number of corpora lutea, implant sites, and number, and location of foetuses and resorptions. Foetuses were inspected on total number, sex, weight and external, visceral (one-half) and skeletal (one-half) defects. One death occurred at the 1500 mg/kg bw/day dose but it was considered a gavage injury. There were no abnormal clinical observations or necropsy findings. There were no effects on body weight or body weight gain. There was a siginifcant increase in food consumption for the 3000 mg/kg bw/day dose during gestation interval (day) 12 -16, but this was considered normal biological variation and not a direct effect of the substance. All indices were comparable to the corresponding controls. The NOAEL based on active ingredient of the test substance is 936 mg/kg bw/day. The NOAEL for both maternal and foetal toxicity was the highest dose tested and the conclusion of the study was no indications of developmental toxicity including teratogenesis.

The OECD 414 performed on Sodium p-cumenesulphonate confirms the absence of effects on developmental toxicity.

OECD 414 was performed on a second species (rabbits) according OECD Guideline 414 to assess the influence of Sodium (xylenes and 4-ethylbenzene) sulfonates on on embryo-fetal survival and development when administered during the organogenesis and fetal growth phases of pregnancy in the New Zealand White Rabbit. Three groups of 22 females received Sodium Xylene Sulphonate at doses of 100, 300 or1000 mg/kg/day by oral gavage administration at a volume-dose of 5 mL/kg body weight from Day 6 to Day 28 after mating, inclusive. A similarly constituted Control group received the vehicle, purified water, at the same dose volume and for the same duration as those receiving the test item. Based on the results obtained in this study of embryo-fetal development, it was concluded that the dose level of 1000 mg/kg/day represented the No Observed Adverse Effect Level (NOAEL) for maternal toxicity and for embryo-fetal survival, growth and development.

A new OECD 443 was performed on Sodium (xylenes and 4-ethylbenzene) sulfonates which is the most representative member of the hydrotropes category since it contains a significant proportion of both mono-alkyl (ethyl) and di-alkyl (dimethyl) chemical species and thus represents both the mono-alkyl and di-alkyl substances contained within the category.

The available results on developmental toxicity are:    

SCS, OECD 414 (2020): NOAEL = 1000 mg a.i./kg bw
SXS, OECD 414 (rabbits, 2017): NOAEL = 1000 mg a.i./kg bw
CaXS, similar to OECD 414 (1994): NOAEL = 936 mg a.i./kg bw
SXS, OECD 443 (2022):NOAEL = 1000 mg a.i./kg/bw

The NOAEL value used for the risk assessment for developmental toxicity is 936 mg a.i./kg bw from the OECD 414 performed on CaXS.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

936 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The available developmental study was fully documented and conducted in accordance with GLP. A study in a second species (New Zealand white rabbit) confirms this result with a NOAEL of 1000 mg/kg bw/day

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

From the available studies of hydrotropes, there is no concerns for reprodution and developmenatl toxicity.