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Description of key information

In the key repeated dose oral toxicity study (Yoneyama et al. 1976), male and female rats were exposed to LAS (read across) in drinking water daily for 9 months. Test doses were 85, 145 and 430 mg/kg bw/d plus the control. Eight to nine animals of each sex were exposed per group. Body weight was suppressed in the highest dose group only. Significant decreases in transaminase activity and renal Na,K-ATPase were seen in the 145 mg/kg bw/d group. No significant haematological or organ weight changes were noted. Based on enzyme activity, the resultant LOAEL and NOAEL values were 145 and 85 mg/kg bw/day, respectively.

In the key repeated dose dermal toxicity study (Ito et al. 1978), male and female rats were transdermally exposed to C10-13 magnesium linear alkylbenzene sulphonate (LAS-Mg, read across) in 3% polyethylene glycol (PEG, MW: 200) for 26 weeks. Test doses were 0 (water), 3% PEG, 0.5, 1.0 and 5.0% of test substance dissolved in 3% PEG. No toxicologically relevant changes were observed at any dose level. The no observed adverse effect level (NOAEL) is 5.0%, the highest dose tested.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
85 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Key study, read-across, experimental results reliable with restrictions.

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 adverse effect observed
Dose descriptor:
NOAEL
Study duration:
subchronic
Species:
rat
Quality of whole database:
NOAEL dose: 5%
Key study, read-across, experimental results are reliable with restrictions.

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral Administration

Six studies are available to document the potential effects from repeated oral exposures to LAB-Sulfonic Acid.

In the key study (Yoneyama et al. 1976), male and female rats were exposed to LAS in drinking water daily for 9 months. Test doses were 85, 145 and 430 mg/kg bw/d plus the control. Eight to nine animals of each sex were exposed per group. Body weight was suppressed in the highest dose group only. Significant decreases in transaminase activity and renal Na,K-ATPase were seen in the 145 mg/kg bw/d group. No significant haematological or organ weight changes were noted. Based on enzyme activity, the resultant LOAEL and NOAEL values were 145 and 85 mg/kg bw/day, respectively.

In a supporting study (Yoneyama et al. 1972), male and female rats were exposed to LAS in the diet daily for 6 months. The doses were 40, 115, 340 and 1030 mg/kg bw/d plus the control group. Significant diarrhea, suppressed growth, increased cecal weight, and degeneration of renal tubes were observed in the highest dose group. Similar but less severe signs were seen in other doses with the exception of the lowest dose of 40 mg/kg bw/d, 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.

In another supporting study (Ito et al. 1978), male and female rats were exposed to LAS via gavage daily for 28 days at three dose levels plus the control (0, 125, 250 and 500 mg/kg bw/d). 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, based on serum-biochemical differences from the controls.

The same authors (Ito et al. 1978) also conducted a study using Mg LAS at doses of 0, 75, 150 and 300 mg/kg bw/d and following the same protocol. The resultant LOAEL and NOAEL values were 300 and 150 mg/kg bw/day, respectively, based on body weight gain, hematology, serum-biochemical and organ weight differences from the controls.

The same authors (Ito et al. 1978) also conducted a 26-weeks repeated dose toxicity study (oral) using male and female CRJ-SD rats to evaluate the chronic effects of C10-13 magnesium linear alkylbenzene sulphonate (LAS-Mg; purity: 96.9%). The test substance was administered daily at 4 dose levels of i.e. 0, 75, 150 and 300 mg/kg bw/day using a metallic gastric sonde to CRJ-SD rats with 20 animals/sex/dose group. One male animal in 300 mg/kg bw/day dose group died (in week 21) from weakness due to significant weight loss involving diarrhea and loss of appetite. There were wetting in the area surrounding animals’ mouths after dosing, and a few animals had abnormal airway sounds. Soft stools were seen in animals after one month, then recovered in few days. There was slight body weight suppression in the male animals of 300 mg/kg bw/day dose group. No toxicologically significant changes were observed in food efficiency of treated animals when compared to controls. At end of dosing period, haematological findings revealed significant reduction in hematocrit levels for female animals in 300 mg/kg bw/day dose group. There was significant reduction in bilirubin, protein, albumin and calcium levels in male animals and significant reduction in s-GPT, glucose, calcium and magnesium levels in female animals of 300 mg/kg bw/day dose group. There was also significant reduction in s-GOT, s-GPT, alkaline phosphatase, protein, albumin, sodium and calcium levels in male animals and significant reduction in chloride levels in female animals of 150 mg/kg bw/day dose groups. Changes were also observed in protein levels in urine in treated male animals as compare to control groups. Necropsy revealed atrophy and bloating of the liver and spleen, respectively. Significant increased relative liver weights (males), thymus weights (males) and pituitary (males) weights were observed in 150 mg/kg bw/day dose group animals as compare to control. Reduction in relative heart weights (females), kidneys weights (males) and adrenal gland weights (females) were also observed in highest dose treated group. Significant increased relative thymus weights were observed in male animals as compare to control and decreased relative heart weights in females and relative kidneys weights in males of 150 mg/kg bw/day dose group. Significant dip in relative adrenal glands weights of females was seen in low dose group. Histopathological examinations revealed Kupffer cell migration (at 150 mg/kg bw/day dose group), focal necrosis (at 75 mg/kg bw/day dose group) and sinusoid bleeding in the liver. In the kidneys, renal tubular epithelial cell swelling, hyaline casts and interstitial small round cell infiltration were observed (at 300 mg/kg bw/day dose group). Fibrosis of islets of Langerhans (at 75 mg/kg bw/day dose group) was also observed. However, histopathological effects seen in liver and pancreas were not dose dependent. Oral administration of C10-13 magnesium linear alkylbenzene sulphonate (LAS-Mg; purity: 96.9%) to CRJ-SD rats at dose levels of 0, 75, 150 and 300 kg/kg bw/day for 26 weeks revealed no observed adverse effect level (NOAEL) of 150 mg/kg bw/day, based on weight suppression, mortality, fluctuations in hematological and serum biochemistry, altered organ weights and histopathological alterations in kidney at 300 mg/kg bw/day.

In the final study (Yoneyama et al. 1976), a 9 month sub-chronic oral toxicity study of LAS was performed in SLC-ICR mice, focusing on the liver and kidneys. 4 week old male and female SLC-ICR mice were administered LAS daily at following dose levels for 9 months: 1) Mixed in diet: 0 and 0.6% (equivalent to 0 and 780 mg/kg bw/day); 9 males in 0.6% fed group and 8 males in control group; 8 females in control as well as 0.6% fed group or 2) Dissolved in drinking water: 0, 0.07, 0.2 and 0.6 (equivalent to 0,133, 380 and 1140 mg/kg bw/day); 9 animals each in test substance treatment groups and 8 animals in control group. Mice in 1.8% dose group of both feeding and drinking water study exhibited severe weight loss so LAS administration was stopped after 2 weeks. No mortality was observed throughout the study. There was significant inhibition of weight increase in both males and females of 0.6% dose group consuming LAS water compared to controls, while there was a significant increase in body weight compared to controls in males of 0.6% dose group fed with LAS in diet and 0.07% dose group consuming LAS water. Individual daily food consumption was higher in all treatment groups compared to controls. Water consumption was reduced in males of 0.6% dose group (drinking water study) and in females of 0.6% dose group (dietary study) and 0.2% dose group (drinking water study) and increased in males of 0.6% dose group (dietary study), 0.07 and 0.2% dose groups (drinking water study) and female of 0.07% dose groups (drinking water study). In males of 0.6% dose group (dietary study) and 0.07% dose group (drinking water study), the absolute liver weight was significantly increased, in males of 0.6% dose group (dietary study), 0.2 and 0.6 dose groups (drinking water study), the relative liver weight was significantly increased, and in 0.07% (drinking water) males the relative liver weight was increased. Relative lung, heart and kidney weights were also increased in male mice consuming 0.07% LAS water. In females, the relative liver weight was significantly increased in all treatment groups. Relative spleen, heart and kidney weights were also increased in female mice consuming 0.6% LAS water. There were reductions in LDH activity in male mice of 0.6% group fed with LAS diet and GOT activity in male mice of 0.6% group consuming LAS water were significant. GOT activity in female mice of 0.2% group (drinking water study) was also significantly reduced. G6Pase was significantly reduced in males and female mice of 0.6% group consuming LAS water compared to controls, and also reduced in other treatment groups. No NOAEL can be identified for dietary study in mice, as only one dose level for LAS was fed to animals throughout the study. Administration of LAS to SLC-ICR mice by either test diets (0 and 0.6) or drinking water (0, 0.07, 0.2 and 0.6) for 9 months (focusing on the liver and kidneys) revealed an NOAEL of 0.07% (133 mg/kg bw/day in drinking water), based on observed adverse effects on organ weight and liver and kidney enzymes. Repeated administration of LAS impair renal and liver function.

 
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Highest NOAEL below lowest LOAEL from three long term studies = 85 mg/kg bw

Dermal Administration

The key dermal study evaluates the potential effects from repeated exposures to LAS-Mg, the magnesium salt analogue of LAS (read across). Repeated dose oral studies demonstrate that LAS-Mg has comparable repeated dose toxicity to LAS. The study covers transdermal administration of LAS-Mg in 3% polyethylene glycol for 26 weeks. No adverse effects were observed. The resultant NOAEL value is 5% LAS-Mg.

Justification for classification or non-classification

Effects in long-term repeated dose studies conducted on LAS and lasting up to 9 months (subchronic studies) are related to enzymatic, body and organ weight reductions but not mortality.