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Repeated dose toxicity: oral

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Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1976
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.
Justification for type of information:
Read Across from the analogous substance, Linear alkylbenzene sulfonate, sodium salt.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1976
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.
Justification for type of information:
Read Across from the analogous substance, Linear alkylbenzene sulfonate, sodium salt.
Reason / purpose for cross-reference:
reference to same study
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.

Reason / purpose for cross-reference:
read-across: supporting information
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
1978
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.
Justification for type of information:
Read Across from the analogous substance, Linear alkylbenzene sulfonate, sodium salt.
Reason / purpose for cross-reference:
reference to other study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Male and female rats were exposed to Na-LAS via gavage daily for 28 days.
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
one month
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
125, 250, 500 mg/kg bw d.
Basis:
no data
No. of animals per sex per dose:
Information as cited in IPCS document. 12 animals 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:
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:
no effects observed
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.
Dose descriptor:
NOAEL
Effect level:
125 other: mg/kg bw d
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Serum-biochemical differences
Dose descriptor:
LOAEL
Effect level:
250 other: mg/kg bw d
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Serum-biochemical differences
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 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.

Reason / purpose for cross-reference:
read-across: supporting information
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
1972
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.
Justification for type of information:
Read Across from the analogous substance, Linear alkylbenzene sulfonate, sodium salt.
Reason / purpose for cross-reference:
reference to other study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Male and female rats were exposed to Na-LAS in the diet daily for 6 months.
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: feed
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
six months
Frequency of treatment:
daily in feed
Remarks:
Doses / Concentrations:
40, 115, 340, 1030 mg/kg bw d. (0.07, 0.2, 0.6, 1.8%)
Basis:
nominal in diet
No. of animals per sex per dose:
Information as cited in IPCS document. 12 animals 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:
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.
Dose descriptor:
NOAEL
Effect level:
40 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: increased weight of the cecum and slight degeneration of the renal tubes
Dose descriptor:
LOAEL
Effect level:
115 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: increased weight of the cecum and slight degeneration of the renal tubes
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.

Reason / purpose for cross-reference:
read-across: supporting information
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
1965
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well-documented journal publication.
Justification for type of information:
Read Across from peer reviewed acute toxicity study reported in scientific literature conducted on branched alkyl benzene sulfonate with nominal chain length of 12 carbon atoms (range C10 - C14) and Linear Alkyl Benzene sulfonate with a nominal chain length of 12 carbon atoms (range C9 - C15).
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
other: Fitzhugh, OG, and Schouboe, PJ. (1959). Subacute toxicity. In: Appraisal of the Safety of Chemicals in Foods, Drugs, and Cosmetics. pp. 26-35. Assoc. of Food and Drug Officials of the US, Bureau of Food and Drugs, Texas State Dept. Of Health, Austi
GLP compliance:
no
Remarks:
Study was done in 1965 prior to implementation of GLP.
Limit test:
no
Species:
rat
Strain:
other: albino FDRL
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: weanling
- Housing: individually in wire-mesh cages
- Diet (e.g. ad libitum): ad libitum, Purina Laboratory Chow
- Water (e.g. ad libitum): ad libitum, tap water

Route of administration:
oral: feed
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
12 weeks
Frequency of treatment:
Daily
Remarks:
Doses / Concentrations:
0.05, 0.25 g/kg/day
Basis:
nominal in diet
No. of animals per sex per dose:
15 of each sex
Control animals:
yes, concurrent no treatment
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
- Cage side observations: appearance, behaviour, and overt signs of toxicity

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, half of animals of each sex
- Time schedule for examinations: weekly

HAEMATOLOGY: Yes, half of animals of each sex
- Time schedule for collection of blood: weeks 6 and 12
- Parameters checked: hemoglobin, hematocrit, total and differential leucocyte count, blood glucose, and urea nitrogen

URINALYSIS: Yes, half of animals of each sex
- Time schedule for collection of urine: weeks 6 and 12
- Parameters checked: albumin, pH, glucose, microscopic examination of sediment
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, all animals
liver, kidneys, spleen, heart, adrenals, pituitary, and cecum were weighed

HISTOPATHOLOGY: Yes, 5 rats of each sex in control and high dose groups, all animals of the low dose group though only the liver spleen, stomach, kidneys, and cedum of this group was examined.
liver, spleen, stomach, small intestine, large intestine, pancreas, kidney, bladder, adrenal, gonads, thyroid, pituitary, thymus, salivary gland, lymph node, heart, lung, femoral marrow, aorta, muscle, spinal cord, brain
Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
CLINICAL SIGNS AND MORTALITY
Occasional signs of wetting in the ventral regions of females in the high dose BABS Na salt and high dose LAS groups.

BODY WEIGHT AND WEIGHT GAIN
Body weight gain was normal in all groups.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Normal in all groups.

FOOD EFFICIENCY
Normal in all groups.

HAEMATOLOGY
Normal in all groups.

CLINICAL CHEMISTRY
Normal in all groups.

URINALYSIS
Normal in all groups.

ORGAN WEIGHTS
Increased liver weights were noted in females in the high dose LAS group, and in both sexes in the high dose BABS Na salt group. Increased cecal weights were noted in the high dose male BABS Na salt group.

GROSS PATHOLOGY
No treatment related changes noted.

HISTOPATHOLOGY: NON-NEOPLASTIC
No dose related changes noted.


Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: BABS Na salt: increased liver weight in both sexes LAS: increased liver weights in females, and increased cecal weights in males
Dose descriptor:
LOAEL
Effect level:
250 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: BABS Na salt: increased liver weight in both sexes LAS: increased liver weights in females, and increased cecal weights in males
Critical effects observed:
not specified

Body Weight Gain and Organ Weights

 

Control

0.05 g/kg BABS Na salt

0.25 g/kg BABS Na salt

0.05 g/kg LAS

0.25 g/kg LAS

Body Weight Gain

 

 

 

 

 

Females (g)

169

168

152

164

163

Males (g)

313

298

315

315

314

Liver Weight

 

 

 

 

 

Females (%)

3.86

3.98

4.67

3.77

4.34

Males (%)

3.58

3.76

4.02

3.81

3.79

Cecal Weights

 

 

 

 

 

Females (%)

0.58

0.64

0.65

0.57

0.58

Males (%)

0.47

0.45

0.57

0.49

0.50
Conclusions:
The 12-week NOAEL for both BABS Na salt and LAS was 50 mg/kg/day. The 12-week LOAEL for both BABS Na salt and LAS was 250 mg/kg/day.
Executive summary:

Groups of 15 male and 15 female rats were fed doses of 0, 50, or 250 mg/kg/day of BABS Na salt or LAS in the diet. Exposure lasted 12 weeks. 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 ABS 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 12-week NOAEL for both BABS Na salt and LAS was 50 mg/kg/day. The12-week LOAEL for both BABS Na salt and LAS was 250 mg/kg/day.

Data source

Referenceopen allclose all

Reference Type:
secondary source
Title:
Benzenesulfonic acid, C10-13-alkyl derivs., sodium salts.
Author:
European Commission
Year:
2000
Bibliographic source:
Year 2000 CD-ROM edition.
Reference Type:
publication
Title:
Subacute toxicity of linear alkylbenzene sulfonate. cited in IPCS. 1996. Environmental Health Criteria 169: Linear Alkylbenzene Sulfonates and Related Compounds. World Health Organization, Geneva, Switzerland.
Author:
Yoneyama, M, Mabuchi, Y., Ikawa, M., Kobayashi, H., and Ichikawa, H.
Year:
1976
Bibliographic source:
Ann. Rep. Tokyo Metrop. Res. Lab. Public Health 27:105-112 (in Japanese)

Materials and methods

Test guideline
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

Test material

Constituent 1
Reference substance name:
Benzenesulfonic acid, C10-14-alkyl derivs., sodium salts
EC Number:
274-070-8
EC Name:
Benzenesulfonic acid, C10-14-alkyl derivs., sodium salts
Cas Number:
69669-44-9
IUPAC Name:
sodium 4-dodecylbenzenesulfonate
Details on test material:
C10-14 LAS, sodium salt (CAS #69669-44-9); average alkyl chain length = C11.7

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

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
Doses / concentrations
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

Results and discussion

Results of examinations

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.

Effect levels

open allclose all
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.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

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.