Benzenesulfonic acid, 4-C15-16-sec-alkyl derivs.

Endpoint summary

Description of key information

Three studies are available that evaluate the potential effects from repeated oral exposures to LAS, which is a read-across source substance. The three studies cover oral doses by gavage, in the diet, and in drinking water for 28 day, 6 months and 9 months, respectively. No mortalities were observed and effects were related to serum biochemical measures, either decreases or increases in some organ weights, suppressed growth, and enzyme activity. The resultant NOAEL values were 125 mg/kg bw/day, 40 mg/kg bw/d, and 85 mg/kg bw/d for the 28 day (gavage), 6 month (diet) and 9 month (drinking water) studies, respectively.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Reference 1

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

see read-across document

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Vehicle:

not specified

Clinical signs:

not specified

Mortality:

not specified

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:

not specified

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Details on results:

Diarrhea was observed in the 500 mg/kg group and soft stools were observed in the other 2 groups. Body weight gain was suppressed in all the male groups and in the female 500 mg/kg group. Haematological examinations revealed no abnormalities. Serum-biochemical examinations revealed several differences among the mid and high dose group compared to the control group. The weight of the spleen and the heart significantly decreased in the male high dose group. In the female high dose group, the weight of the liver increased while the weight of the heart and thymus decreased. Histological findings of the liver revealed no abnormalities.

Key result

Dose descriptor:

NOAEL

Effect level:

125 other: mg/kg bw d

Sex:

male/female

Basis for effect level:

other: Serum-biochemical differences

Key result

Dose descriptor:

LOAEL

Effect level:

250 other: mg/kg bw d

Sex:

male/female

Basis for effect level:

other: Serum-biochemical differences

Key result

Critical effects observed:

not specified

Conclusions:

NOAEL = 125 mg/kg bw/day; LOAEL = 250 mg/kg bw/day

Executive summary:

Male and female rats were exposed to Na-LAS via gavage daily 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.

Reference 2

Endpoint:

sub-chronic toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Justification for type of information:

see read-across document

Reason / purpose for cross-reference:

read-across source

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:

no effects observed

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not specified

Details on results:

The 1.8% group showed diarrhea, markedly suppressed growth, increased weight of the cecum, and remarkable degeneration of the renal tubes. the 0.6% group showed slightly suppressed growth, increased weight of the cecum, increased activity of serum alkaline phosphatase (ALP), a decrease in serum protein and degeneration of the renal tubes. The 0.2% group showed increased weight of the cecum and slight degeneration of the renal tubes. The 0.07% group showed no adverse effects related to the administration of LAS. The intake of LAS in the 0.07% group was about 40 mg/kg bw/d.

Key result

Dose descriptor:

NOAEL

Effect level:

40 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: increased weight of the cecum and slight degeneration of the renal tubes

Key result

Dose descriptor:

LOAEL

Effect level:

115 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: increased weight of the cecum and slight degeneration of the renal tubes

Key result

Critical effects observed:

not specified

Conclusions:

NOAEL = 40 mg/kg bw/day; LOAEL = 115 mg/kg bw/day

Executive summary:

Male and female rats were exposed to Na-LAS 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. This represents the lowest LOAEL of any study.

Reference 3

Endpoint:

sub-chronic toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

see read-across document

Reason / purpose for cross-reference:

read-across source

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.

Key result

Dose descriptor:

NOAEL

Effect level:

85 mg/kg bw/day (nominal)

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.

Key result

Dose descriptor:

LOAEL

Effect level:

145 mg/kg bw/day (nominal)

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.

Key result

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 Na-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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

85 mg/kg bw/day

Study duration:

subchronic

Species:

rat

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

Three studies are available that evaluate the potential effects from repeated oral exposures to LAS, which is used as surrogate for the read-across source substance LAB Sulfonic Acids that are intermediates in the manufacture of LAS. The three studies cover oral doses by gavage, in the diet, and in drinking water for 28 day, 6 months and 9 months, respectively. No mortalities were observed and effects were related to serum biochemical measures, either decreases or increases in some organ weights, suppressed growth, and enzyme activity. The resultant NOAEL values were 125 mg/kg bw/day, 40 mg/kg bw/d, and 85 mg/kg bw/d for the 28 day (gavage), 6 month (diet) and 9 month (drinking water) studies, respectively.

In the first key study (Ito et al. 1978), male and female rats were exposed to the read-across substance 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.

In the second key study (Yoneyama et al. 1972), male and female rats were exposed to the read-across substance 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 the read-across source substance. The resultant LOAEL and NOAEL values were 115 and 40 mg/kg bw/day, respectively.

In the third key study (Yoneyama et al. 1976), male and female rats were exposed to the read-across substance 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.