Benzenesulfonic acid, mono-C11-13-branched alkyl derivs., sodium salts

Endpoint summary

Description of key information

The key study (nine-month drinking water study in rats) reports the NOAEL value of 85 mg/kg bw/day based on activities of glutamate-oxalate transaminase and lactate dehydrogenase and renal Na,K-ATPase.  The NOAEL value of 85 mg/kg bw/day represents the highest NOAEL below the lowest LOAEL in all of the studies and is therefore the appropriate NOAEL for use in the assessment.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study is assigned a reliability score of 2 because the original report was not available for review. However, the study was evaluated by IPCS prior to inclusion in their criteria document.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Male and female rats were exposed to Na-LAS in drinking water daily for 9 months.

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: drinking water

Vehicle:

not specified

Details on oral exposure:

LAS was provided daily in drinking water.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

nine months

Frequency of treatment:

daily in drinking water

Remarks:

Doses / Concentrations:
85, 145, 430 mg/kg bw d. (0.07, 0.2, 0.6%)
Basis:
nominal in water

No. of animals per sex per dose:

Information as cited in IPCS document. 8-9 animals of each sex per dose group.

Control animals:

yes, concurrent no treatment

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food efficiency:

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Details on results:

Body weight gain was suppressed in the male 0.6% group. Hematological examination revealed no significant change in any of the experimental groups, but a dose-related decrease in cholesterol level was seen in males. Significant decreases in the activities of glutamate-oxalate transaminase and lactate dehydrogenase were seen in males at 0.2% and a dose-related increase in the activity of gluatamate-oxalate transaminase in females. A significant decrease in renal Na,K-ATPase was seen in the group given 0.2%. No organ weight changes were observed. The intake of LAS was 50 mg/kg bw/day in the male 0.07% group and 120 mg/kg bw/day in the female group. The values for the 0.2% group were 120 and 170 mg/kg bw/day for males and females, respectively.

Dose descriptor:

NOAEL

Effect level:

85 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: activities of glutamate-oxalate transaminase and lactate dehydrogenase and renal Na,K-ATPase

Dose descriptor:

LOAEL

Effect level:

145 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Significant decreases in the activities of glutamate-oxalate transaminase and lactate dehydrogenase in males. A significant decrease in renal Na,K-ATPase in males and females.

Critical effects observed:

not specified

Conclusions:

NOAEL = 85 mg/kg bw/day; LOAEL = 145 mg/kg bw/day

Executive summary:

Male and female rats were exposed to LAS in drinking water daily for 9 months. Body weight was suppressed in the highest dose group only. Significant decreases in transaminase activity and renal Na,K-ATPase was seen in the 0.2% group. The resultant LOAEL and NOAEL values were 145 and 85 mg/kg bw/day, respectively. The NOAEL represents the highest NOAEL below the lowest LOAEL in all the studies.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

85 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

The reliability rating of each the four studies performed on the analogue substance Na-LAS was 2.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There is one oral repeated does study available with BABS Na salt. Note that the endpoint records reflect data from BABS Na salt and the analogue substance, linear alkylbenzene sulfonate, sodium salt (commonly known as LAS or Na-LAS). LAS is the sodium salt of linear alkylbenzene sulfonic acid with alkyl chain lengths ranging from C10 to C13 and averaging 11.6. The primary structure is a C10 to C13 linear alkyl chain with a para-substituted benzene sulfonic acid sodium salt group attached at any of the secondary alkyl carbon positions. BABS Na salt is the sodium salt of branched alkylbenzene sulfonic aicd with alkyl chain lengths ranging from C11 to C13. The primary difference between LAS and BABS Na salt is the alkyl chain, branched vs. linear. Given their structural and functional similarities, LAS is a good analgoue for read-across for instances where data are available on it but not on BABS Na salt.

In a repeated dose study, groups of 15 male and female rats were fed doses of 0, 50, or 250 mg/kg/day of BABS Na salt or LAS in the diet. Exposure lasted 28 days. Animals were observed daily for clinical signs. Body weights were taken weekly. Blood and urine analyses were done at week 6 and 12 of exposure. At the end of the exposure period, all animals were sacrificed and gross pathology and histopathology exams performed. Rats of both sexes in the high dose BABS Na salt groups showed increased liver weights. Female rats in the high dose LAS group also showed increased liver weights. Males in the high dose LAS group showed increased cecal weights. Based on these endpoints, the 28-day NOAEL for both BABS Na salt and LAS was 50 mg/kg/day. The 28-day LOAEL for both BABS Na salt and LAS was 250 mg/kg/day. The results of this study support the use of LAS as an analogue for read-across to BABS Na salt for repeated dose studies.

Three repeated dose studies used LAS for read-across. In the first study, male and female rats were exposed to LAS in drinking water daily for 9 months. Body weight was suppressed in the highest dose group only. Significant decreases in transaminase activity and renal Na, K-ATP-ase was seen in teh 0.2% group. The resultant LOAEL and NOAEL values were 145 and 85 mg/kg bw/day, respectively. The NOAEL represents the highest NOAEL below the lowest LOAEL in all the studies. In the second stury, male and female rats were exposed to AS in the diet daily for 6 months. Diarrhea, suppressed growth, increased cecal weight, and degeneration of renal tubes characterized the highest dose group. Similar but less severe signs were seen in other doses with the exception of the lowest dose of 0.07%, which showed no adverse effects related to exposure to LAS. The resultant LOAEL and NOAEL values were 115 and 40 mg/kg bw/day, respectively. The represents the lowest LOAEL of any study.

In the third study, male and female rats were exposed to LAS via gavage for 28 days. Body weight gain was suppressed, some serum biochemical measures were different from the controls, and some organ weights were either decreased (spleen, heart, thymus) or increased (liver) in either the male or female high dose groups. No mortalities or histopathological abnormalities were observed. The resultant LOAEL and NOAEL values were 250 and 125 mg/kg bw/day, respectively.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

The resultant LOAEL and NOAEL values were 145 and 85 mg/kg bw/day, respectively. The NOAEL represents the highest NOAEL below the lowest LOAEL of all the studies.

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

Justification for classification or non-classification

Based on the results of the oral repeated dose studies, the appropriate LOAEL and NOAEL values for use in the assessmenet are 115 and 85 mg/kg bw/day, respectively. These values do not meet the criteria for classification under the DSD or CLP and therefore the substance is not classified.