Registration Dossier

Administrative data

Description of key information

There are six oral and four dermal repeat dose studies, all conducted on sodium xylene sulphonate. This includes two dermal chronic/carcinogenicity studies.  The studies were conducted in both the rat and mouse. The key oral study is the 90-day sub-chronic study, conducted in 1968,  which is generally comparable to the OECD 408 guideline study.  The NOAEL was 763 mg a.i./kg/day based on loss of relative weight of the spleen. The key dermal study is the two year chronic/carcinogenticity study in the rat.  The NOAEL for females is 60 mg a.i./kg/day based on epidermal hyperplasia. No systemic toxicity was observed in this or any of the other repeat dose dermal studies.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
763 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Sufficient to meet requirements

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
The two important routes of exposure have been addressed. Hence no need for inhalation repeated dose.

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The database of available repeat dose dermal studies includes two sub-chronic 90 day studies as well as two chronic/carcinogenicity studies, conducted in both rats and mice. These studies were limited in design such that not all important endpoints were investigated. These studies found only local effects and no systemic toxicity. So for the purpose of calculating a DNEL value for systemic effects, the oral NOAEL has been used together w ith information on relative absorption by the oral and dermal routes.

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
0.48 mg/cm²
Study duration:
chronic
Species:
rat
Quality of whole database:
Exceeds requirements

Additional information

There are a total of 6 oral and 4 dermal repeated dose toxicity studies on the hydrotrope category substances. All of these studies were conducted on a single category member, sodium xylene sulphonate.

The key oral study is the 90 day sub-chronic study, conducted in 1968, which is generally comparable to the OECD 408 guideline study. In that study, the highest dose for female rats - 4092 mg active ingredient (a.i.) per kilogram body weight - resulted in a loss in relative weight of the spleen. The 2nd highest dose for females - 763 mg a.i. per kilogram body weight - had no measureable adverse effects and therefore establishes the repeat dose oral NOAEL for the substance. The highest oral dose for male rats - 3534 mg a.i. per kilogram body weight - had no measurable adverse effects. No adverse effects were reported in the 90 day sub-chronic mouse study.

The key dermal study is the two year chronic/carcinogenicity study in the rat, which was generally comparable to the OECD 453 guideline study. There were no treatment related incidences of mononuclear cell leukaemia, neoplasms, or non-neoplastic lesions of the skin and other organs. In that study the NOAEL for females is 60 mg a.i./kg/day based on epidermal hyperplasia. This value was then used for the NOAEL for local dermal effects. No systemic toxicity was observed in this or any of the other repeat dose dermal studies.

There is no need for repeat dose data by the inhalation route since the two important routes of exposure have been addressed.


Justification for selection of repeated dose toxicity dermal - local effects endpoint:
The study with the lowest NOAEL for local effects (hyperplasia of the epidermis) is the 2 year dermal carcinogenicity study in the rat, where the NOAEL for females was 60 mg/kg. Taking a mean body weight figure for the female rats in the 60 mg/kg dose group of 0.2kg (stated range = 0.107 to 0.288 kg) and assuming a surface area of dosing of 25 cm2, gives a NOAEL of 0.48 mg/cm2.

Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: spleen

Justification for classification or non-classification

Based on the reported findings from a variety of repeat dose studies by both the oral and dermal routes, there is no justification for hazard classification.