Reaction product of Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs. and Benzenesulfonic acid, 4-methyl- and sodium hydroxide

Endpoint summary

Description of key information

There are no repeated dose studies with the substance to register (Marlon ARL). There are however oral repeat dose studies for both of the substances that comprise Marlon and dermal repeat dose studies for one of the substances that comprise Marlon ARL.  These constituent substances (i.e., sodium 4-undecylbenzenesulfonate CAS No. 68411-30-3, and sodium toluene sulfonate CAS No. 12068-03-0 (represented by data from another hydrotrope, sodium xylene sulphonate CAS No. 1300-72-2) provide applicable read across data. The lowest NOAEL from among the key studies is used as asurrogatre for the chemical safety assessment for the substance to register Marlon ARL. 
 
The key repeat dose oral study is a 9-month drinking water study in rats with a NOAEL of 85 mg/kg bw/day of LAS based on decreases in glutamate-oxalate transaminases and lactate dehydrogenase in males and a decrease in renal Na, K-ATPase in males and females.  The key repeat dose dermal studyis a 90-day dermal study of the hydrotrope in mice with a NOAEL for females of 540 mg a.i./kg bw and the NOAEL for males is 440 mg a.i. per kilogram body weight based on epidermal hyperplasia. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

85 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

440 mg/kg bw/day

Study duration:

subchronic

Species:

mouse

Additional information

All 3 studies of the sodium alkylbenzenesulfonate substances were published in the 1970s. The first oral study is a 28-day rat oral gavage study with a NOAEL of 125 mg a.i./kg bw/day based on serum biochemical differences. The second oral study is a 6 month rat study with a NOAEL of 40 mg a.i./kg bw/day based on increased weight of the cecum and slight degeneration of the renal tubes. The 3rd study was a 9-month drinking water study in rats with a NOAEL of 85 mg/kg bw/day based on decreases in glutamate-oxalate transaminases and lactate dehydrogenase in males and a decrease in renal Na, K-ATPase in males and females.

Many of the hydrotrope studies were conducted as range finding studies (14-day oral and 17-day dermal) for 90-day repeat dose rat and mouse studies. No adverse effects are reported for the shorter term studies by either exposure route in either species. There are also 90-day oral and dermal studies for both species conducted mainly to establish doses for 2-year chronic studies. The oral studies were not guideline studies and included the following observations: clinical signs, survival, body weight, feed consumption, gross pathology and non-neoplastic histopathology. The key 90-day rat oral study, conducted in 1968, is generally comparable to the OECD 408 guideline study. The NOAEL was 763 mg a.i. per kilogram body weight based on loss of relative weight of the spleen. The dermal studies were guideline studies (OECD 411) published by the US National Institutes of Health. The key 90-day dermal study is a mouse study. The NOAEL for females is 540 mg a.i./kg bw and the NOAEL for males is 440 mg a.i. per kilogram body weight based on epidermal hyperplasia.

The key 90 -day oral study, conducted in 1968, 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 test 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 mouse study. The dermal studies were guideline studies (OECD 411) published by the US National Institutes of Health. The key 90-day dermal study is a mouse study where the highest doses for males (1300 mg active ingredient per kilogram body weight) and the highest dose for females (1620 mg AI/kg bw) resulted in epidermal hyperplasia. No other adverse effects were observed. The NOAEL for females is 540 mg AI/kg bw and the NOAEL for males is 440 mg a.i. per kilogram body weight which is therefore the repeat dose dermal NOAEL for the test substance. No adverse effects were reported in the 90 day mouse study.

The 6 oral and 4 dermal studies for sodium xylene sulphonate (CAS No. 1300-72-7) are the only repeat dose studies among the closely related compounds known as hydrotropes. The close similarity of the structures and behaviors of all the hydrotrope substances support read-across of the 1300-72-7 data to the other compounds in the category.

The two important routes of exposure have been addressed. Hence no need for inhalation repeated dose.

Repeated dose toxicity: via oral route - systemic effects (target organ) urogenital: other

Repeated dose toxicity: dermal - systemic effects (target organ) other: skin

Justification for classification or non-classification

No classification as a repeated dose toxin is indicated according to the general classification and labeling requirements for dangerous substances and preparations (Directive 67-548-EEC) or the classification, labeling and packaging (CLP) regulation (EC) No 1272/2008.

Value used for CSA (route: oral):

NOAEL: 85 mg/kg bw/day

Target organs: kidneys

Value used for CSA (route: dermal):

NOAEL: 440 mg/kg bw/day

Target organs: other: skin