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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 30th 1972 - November 27th 1972
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable study, followed scientific principles/standards, pre-dates GLP
Remarks:
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.

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:
Studies on the toxicity of synthetic detergents. (II) Subacute toxicity...cited in IPCS. 1996. Environmental Health Criteria 169: Linear Alkylbenzene Sulfonates and Related Compounds. World Health Organization, Geneva, Switzerland.
Author:
Yoneyama, M, Fujii, T., Ikawa, M., Shiba, H., Sakamoto, Y., Yano, N., Kobayashi, H., Ichikawa, H., and Hiraga, K.
Year:
1972
Bibliographic source:
Ann. Rep. Tokyo Metrop. Res. Lab. Public Health 24:409-440 (in Japanese)

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The purpose of this study is to determine the sub chronic toxicity of C10 - C14 linear alkylbenzenesulfonic acid sodium salt (LAS) in Wistar SLC rats. Male and female rats were maintained on diets of 0, 0.07, 0.2, 0.6 and 1.8% LAS (equivalent to 0, 40, 115, 340, 1030 mg/kg bw/day) for 26 weeks. Clinical observations, water consumption, food consumption and body weights were recorded weekly. At the end of study, blood was collected for estimation of haematological and clinical chemistry parameters. Urinalysis was also performed 2 weeks before necropsy. All the surviving animals were humanely euthanized and gross necropsy, organs weights and histopathology was performed.
GLP compliance:
no
Remarks:
Pre-dates GLP
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
-Name of test material:
- Linear alkylbenzene sulfonic acid sodium salt (LAS); NeoPlex F-60
- Average molecular weight: 345.8 g

No further details on test substance are provided in the study report.

Test animals

Species:
rat
Strain:
Wistar
Remarks:
SLC
Sex:
male/female
Details on test animals and environmental conditions:
Source: Male and female were obtained from Shizuoka Agricultural Cooperative Association for Laboratory Animals
- Age at study initiation: Approximately 4 weeks
- Weight at study initiation: 80 - 90 g (male rats), 65 - 80 g (female rats)
- Fasting period before study: No
- Housing: 5 animals were housed per stainless steel cage.
- Diet: FII food (from Funabashi Farm); ad libitum
- Water: Tap water; ad libitum
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature: 25 ± 1°C
- Humidity: 55 - 65%
- Air changes: Not reported
- Photoperiod: 12 hours dark /12 hours light

Administration / exposure

Route of administration:
oral: feed
Details on route of administration:
C10 - C14 LAS was administered to animals by mixing 0.07, 0.2, 0.6 and 1.8% with pulverized FII feed, the powders were shaped into solid form before being freely provided for feeding along with tap water. As control, solid FII feed was provided to the animals.
Vehicle:
unchanged (no vehicle)
Remarks:
C10 - C14 LAS was administered in diet
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
26 weeks
Frequency of treatment:
Continuous in diet (ad libitum)
Doses / concentrationsopen allclose all
Dose / conc.:
40 mg/kg bw/day (nominal)
Remarks:
In diet (corresponding to 0.07% dose level)
Dose / conc.:
115 mg/kg bw/day (nominal)
Remarks:
In diet (corresponding to 0.2% dose level)
Dose / conc.:
340 mg/kg bw/day (nominal)
Remarks:
In diet (corresponding to 0.6% dose level)
Dose / conc.:
1 030 mg/kg bw/day (nominal)
Remarks:
In diet (corresponding to 1.8% dose level)
No. of animals per sex per dose:
10 animals/sex/dose group
Control animals:
yes, plain diet
Positive control:
No.

Examinations

Observations and examinations performed and frequency:
CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Time schedule for examinations: Weekly

WATER CONSUMPTION AND COMPOUND INTAKE: Yes
- Time schedule for examinations: Weekly

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: After 26 weeks, blood was collected from each animal prior to autopsy (for hemoglobin, hematocrit, red blood cells, white blood fractions and platelets) and during e
uthanasia (erythrocyte membrane resistance)
- Anesthetic used for blood collection: No
- Animals fasted: No
- How many animals: All surviving animals
- Parameters: Hemoglobin, hematocrit, red blood cells, white blood fractions and platelets, erythrocyte membrane resistance and blood coagulation time

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: After 26 weeks, blood was collected from each animal after euthanasia.
- Animals fasted: No
- How many animals: All surviving animals
- Parameters: Total proteins, GOT activity, ALP activity, LAP activity, urea nitrogen, A/G ratio and bilirubin

URINALYSIS: Yes
- Time schedule: 2 weeks prior to autopsy, urine isolated and collected from waste was analyzed.
- Metabolism cages used for collection of urine: No
- Animals fasted: No
- How many animals: All surviving animals
- Parameters: Proteins, glucose, ketone bodies, occult blood, bilirubin and urobilinogen

NEUROBEHAVIOURAL EXAMINATION: No

IMMUNOLOGY: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
Gross findings were obtained after euthanizing animals and macroscopic findings were observed.

ORGAN WEIGHTS: Brain, pituitary, thyroid, thymus, heart, lungs, liver, kidneys, spleen, adrenal gland, prostate, testes, uterus, ovaries and appendix

HISTOPATHOLOGY: Yes
Collected tissues (all tissues weighed and also stomach, large and small intestines, pancreas, epidiymis, skin and bones) were examined and subjected to microscopy through H.E., PAS and silver staining.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Severe diarrhea was observed in the high concentration group (1.8%).
Mortality:
mortality observed, treatment-related
Description (incidence):
In 24th week, 1 male animal from the 1.8% dose group died.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
There was significant inhibition of weight gain in both males and females of 1.8% dose group (Table 1).
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Food consumption was low in the 1.8% dose group relative to the control (Table 1).
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Description (incidence and severity):
Water consumption was slightly low in animals of 1.8% dose group (Table 1).
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
In females of 1.8% dose group, a significant decrease in hematocrit and hemoglobin and significant increase in the erythrocyte membrane resistance was observed.
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
There was dose dependent significant increase in ALP levels (at mid and high dose) and significant decrease in total protein (at high dose).
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Organ weight findings are presented in Table 2.

1.8% dose group: Significant increase in relative weights of liver, suprarenal gland, testis, brain and caecum were observed in males and relative weights of heart, thyroid, liver, uterus, brain and caecum of females.

0.6% dose group: Significant increase in caecum relative weights in males and hypophysis in females.

0.2% dose group: Caecum relative weights were significantly increased in males and kidney relative weights were significantly decreased in females.
Gross pathological findings:
no effects observed
Description (incidence and severity):
No significant changes were observed in the animals.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
The main findings were concerned with kidneys, liver and intestinal tract. Kidney damage was seen at and above 0.2% dose groups. Mild hepatocyte changes were observed in animals of 1.8% dose group and microscopic changes in intestinal tract were observed in female rats of the 1.8 and 0.6% dose groups.
Histopathological findings: neoplastic:
not examined
Other effects:
not examined
Details on results:
CLINICAL SIGNS:
- Severe diarrhea was observed in animals in the high concentration groups (1.8%) immediately after starting the study, and although the diarrhea gradually became milder after about 1 week, the animals did not recover fully by the end of the study. The animals moved slowly, and there lower abdomen was dirty.

MORTALITY: During week 24, 1 male animal from 1.8% dose group died.

BODY WEIGHT AND WEIGHT CHANGES: There was significant inhibition of weight gain in both males and females of 1.8% dose group, while the 0.6% dose groups showed slight but not significant trends to suppress weight gain.

FOOD CONSUMPTION AND COMPOUND INTAKE: Food consumption was low in the 1.8% dose group relative to the control.

WATER CONSUMPTION AND COMPOUND INTAKE: Water consumption was slightly low in the 1.8% dose group.

HAEMATOLOGY:
- A significant decrease in hematocrit and hemoglobin, a significant increase in the erythrocyte membrane resistance was observed among female animals in the 1.8% dose groups.
- Male and female rats in 1.8% dose group showed increase in white blood cell count, increase in neutrophil fraction out of the white blood cells and a decrease in lymphocytes.
CLINICAL BIOCHEMISTRY: There was dose dependent increase in ALP levels and decrease in total protein.

URINALYSIS: No effects were observed.

ORGAN WEIGHT:
- In highest concentration group (1.8%), significant increase in relative weights of liver, suprarenal gland, testis, brain and caecum were observed in males and relative weights of heart, thyroid, liver, uterus, brain and caecum of females. In 0.6% dose group, there was significant increase in caecum relative weights in males and hypophysis in females. In 0.2% dose group, caecum relative weights were significantly increased in males and kidney relative weights were significantly decreased in females.

GROSS PATHOLOGY
- The color of the liver in 2 males and 5 females from the 1.8% dose group was lighter than normal and seemed to have a yellowish white color mixed to it.
- In addition, lung tumors were seen in one female rat from the 0.2% dose group.
- Autopsy of one male rat from the LAS-1.8% dose group that died during the study had significant swelling of the abdomen. This was due to the swelling of the stomach and small intestines. The contents from the stomach to the first part of the jejunum was a blackish purple liquid. From thereon, the ileum was filled with a semi-transparent, viscous, gelatinous substance.

HISTOPATHOLOGY
The main findings were concerned with kidneys, liver and intestinal tract. The histological findings concerning the kidneys had differences in the extent and frequency of changes between the dosage and between male and female rats.
Kidneys:
- Chronic appearance of glomeruli indicating moderate level of atrophy (male/females of 0.6% treated groups)
- Glomeruli contributed to overall swelling through dilation of vessel lumen and interstitial swelling (significant in in male/female rats of 0.2 and 0.07% dose groups. They were not very significant in the 1.8 and 0.6%)
- The glomerular interstitum had thawn mildly but chronically (significant for male/female rats in 1.8 and 0.6% groups)
- Cloudy swelling/vacuolar degeneration of proximal renal tubular epithelial cells were seen (slightly significant in LAS treated groups).
- Small, yellowish brown blobs the size of nuclei were observed in the proximal renal tubular epithelial cells (significantly in male/females of 1.8% dose group)
- Blue lead color exhibited on the lumen of the Henle loop through H.E. staining, while substances giving a strong positive PAS response were forming layers in circular forms or were present in small pieces
- The renal tubule had collapsed (significantly in male/females of 1.8% dose group)
- Swelling of surrounding connective tissue was observed in the interstitium (significantly in males of LAS-0.2% dose group and both male and female rats of 0.6% dose group)
- Various changes to the kidneys as seen in 0.2% to 0.07% dose groups differ in their extent and frequency of incidence, but these changes were also seen in the control group, so they were not considered changes that lead to permanent damages like collapse of renal tubule or cyst formation.
Liver: Disappearance of basophilic substances in the hepatocytes and eosin thickening of hepatocytes were observed mildly in male and female rats of the 1.8% dose group.
Intestinal tract: Decrease in height of epithelial cells in the colonic mucosa and disappearance of vacuoles from goblet cells were observed mildly in female rats of the 1.8 and 0.6% dose groups.

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
40 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
haematology
clinical biochemistry
organ weights and organ / body weight ratios
gross pathology
histopathology: non-neoplastic
Remarks on result:
other: Suppression of weight gain, increase in appendix weight, alteration in hematological and clin ical biochemistry parameters, and/ or tissue damages to the large intestines, liver and kidneys in dose levels at ≥ 115 mg/kg bw/day (0.2% diet).

Target system / organ toxicity

Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
115 mg/kg bw/day (nominal)
System:
urinary
Organ:
kidney
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
yes

Any other information on results incl. tables

Table 1: body weight gain, food, water intake and feces excreation

 Sex Group (%) No. of animals  Initial BW (g)  Final BW (g)  BW gain (%) Food (g)/animal/day Water (g)/animal/day Feces (g)/animal/day 
 Male  0  10  85.00±0.87  387.00±9.50  452.10±9.8  14.17  16.90  2.31
   0.07  10  80.90±1.92   387.10±5.93   480.74±13.11  14.48  16.91  2.24
   0.2  10  84.50±0.95   383.40±6.71   453.92±7.60  13.70  18.18  2.28
   0.6  10  86.40±1.54  365.80±8.51  426.23±8.89  13.84  16.28  2.23
   1.8  9/10   85.20±0.55   290.00±5.20   341.09±5.13**  9.84  13.29  1.78
 Female  0  10  71.80±0.51  202.50±2.32  282.24±4.42  9.35  17.48  1.53
   0.07  10   76.00±2.68   203.20±7.17  269.35±10.25  9.35  19.56  1.63
   0.2  10   74.30±1.11   201.10±3.33   271.05±5.31  8.90  17.69  1.39
   0.6  10   74.10±0.67  195.80±4.15  264.25±5.2*  9.04  13.99  1.53
   1.8  10   74.30±0.94  158.80±3.41  214.02±5.29**  7.01  12.14  1.23

* p<0.05 ** p<0.01

Table 2: Organ weight observations

 Group (%)  No. of animals  Spleen (mg) / (mg/100g) Thymus  (mg) / (mg/100g)   Liver  (g) / (g/100g)    Lung  (mg) / (mg/100g) Kidney (R) (mg) / (mg/100g)    Kidney (L)  (mg) / (mg/100g) Hypophysis  (mg/100g)   Heart (mg) / (mg/100g)
 0 10 M  614±14 /  158±2  129±5.7 /  33±0.9    12.0±0.38 /  3.1±0.04   1211±44 /  314±13   1105±33 /  285±6    1126±33 /  219±6    10.0±0.73 /  2.6±0.21    930±13 /  241±3
 0.07  10 M   641±12 /  165±2   129±10.8 /  33±2.5   12.0±0.31 /  3.1±0.05    1285±47 /  332±12   1074±25 /  277±5    1083±52 /  279±12    9.3±0.50 /  2.4±0.13   932±16 /  240±2
 0.2  10 M  644±27 /  168±7    130±9.0 /  33±2.1   12.3±0.42 /  3.2±0.12   1253±63 /  326±14    1083±34 /  282±7    1071±28 /  279±4   8.9±0.48 /  2.3±0.13   918±16 /  239±2
 0.6  10 M  572±15 /  153±4    122±8.8 /  32±2.3   12.0±0.31 /  3.2±0.07   1080±21* /  289±6    1045±31 /  280±9    1049±34 /  281±9   9.4±0.30 /  2.5±0.08   878±18* /  235±4
 1.8  9 M  460±11** /  158±2    102±6.3** /  35±1.7   10.3±0.28** /  3.5±0.08**   971±35** /  324±13    836±19** /  288±3    852±22** /  294±5  8.8±0.42 /  3.0±0.15   694±11** /  239±3
                   
 0  10 F   405±5 /  200±4   134±7.7 /  66±3.9   6.5±0.12 /  3.2±0.08   822±19 /  409±11    720±22 /  359±12   738±18 /  395±11   13.9±0.76 /  6.8±0.39   596±10 /  265±6
 0.07  10 F   408±13 /  201±4   132±2.8 /  65±2.3   6.7±0.30 /  3.3±0.05   801±19 /  396±11   717±23 /  355±13     738±33 /  364±13   16.3±0.94 /  8.0±0.40   596±16 /  294±3
 0.2  10 F   405±8 /  201±4   131±4.6 /  65±2.6   6.5±0.18 /  3.2±0.07   802±26 /  398±10   654±20* /  325±7     665±28* /  330±11*   15.0±1.10 /  7.4±0.53   574±13 /  258±5
 0.9  10 F   387±7 /  198±5   125±5.8 /  63±2.2   6.5±0.22 /  3.3±0.10   793±14 /  406±8   664±16 /  340±9     715±32 /  365±14   16.2±0.94 /  8.3±0.46*   559±11* /  286±5
 1.8  10 F   294±10** /  185±6   102±6.8** /  64±4.1   6.3±0.24 /  3.9±0.12**   673±20** /  425±16   546±16** /  345±13     563±24** /  357±21   12.3±1.08 /  7.7±0.63   426±11** /  269±7*

* p<0.05 ** p<0.01

Table 2: Organ weight observations (continued..)

 Group (%)  No. of animals  Thyroid glands (mg) / (mg/100g) Suprarenal gland (R)  (mg) / (mg/100g)    Suprarenal gland (L)  (mg) / (mg/100g)  Testis/Ovary (R)  (mg) / (mg/100g) Testis/Ovary (L)  (mg) / (mg/100g) Prosate/Uterus  (mg) / (mg/100g) Brain (mg) /  (mg/100g) Caecum (mg) /  (mg/100g)
 0 10 M  14.4±0.42 /  3.7±0.16  18.0±0.61 /  5.0±0.17  19.3±0.44 /  4.6±0.18  1592±20 /  412±7  1622±21 /  420±6  252±16 /  65±4.8 1983±12 /  515±11 837±34 /  216±8
 0.07  10 M  13.6±0.54 /  3.5±0.13  18.7±0.44 /  4.8±0.11   12.0±0.31 /  3.1±0.05  1643±14 /  425±6   1676±15 /  434±7  318±21* /  82±6.1  1918±106 /  494±25 938±38 /  242±9
 0.2  10 M  13.3±0.57 /  3.4±0.11  18.6±0.84 /  4.8±0.23   12.3±0.42 /  3.2±0.12  1621±20 /  423±4    1083±34 /  282±7  298±21 /  78±5.9 2020±11 /  528±8 971±35* /  253±7**
 0.6  10 M  13.2±0.69 /  3.5±0.22  18.2±0.69 /  4.8±0.19   12.0±0.31 /  3.2±0.07  1612±36 /  432±11    1045±31 /  280±9  231±21 /  61±5.7  1969±18* /  528±12 939±41 /  251±11*
 1.8  9 M  11.5±0.76** /  3.9±0.24  17.1±0.65* /  5.9±0.27*   10.3±0.28** /  3.5±0.08**  1501±36** /  518±13**    836±19** /  288±3  231±21 /  79±7.0  1960±22 /  677±11** 1484±30** /  512±12**
                   
 0  9 F  11.2±0.32 /  5.5±0.17 21.9±0.99 /  10.8±0.64  23.2±1.24 /  11.4±0.94   23.3±1.0 /  11.5±0.5  24.4±1.1 /  12.0±0.5  638±27 /  315±13  1832±16 /  906±14   681±18 /  337±11
 0.07  10 F  12.9±0.93 /  6.4±0.55 22.6±0.95 /  11.1±0.35   24.1±0.98 /  11.8±0.33  23.0±1.9 /  11.2±0.6  24.6±1.5 /  12.0±0.5  592±18 /  292±8  1827±18 /  908±30   753±25* /  373±13
 0.2  10 F  12.2±0.96 /  6.0±0.46 21.7±1.11 /  10.7±0.49   22.2±0.92 /  11.0±0.43  23.6±1.0 /  11.7±0.4  23.3±1.2 /  11.5±0.5 594±31 /  296±17  1837±18 /  915±13   688±26 /  343±14
 0.9  10 F  13.9±1.30 /  7.1±0.70 22.9±0.56 /  11.7±0.36   24.0±0.61 /  12.3±0.44  22.8±1.2 /  11.7±0.7  24.5±1.0 /  12.6±0.6  618±32 /  315±15  1840±14 /  943±20   697±21 /  356±7
 1.8  10 F  10.9±0.73 /  6.9±0.53*  15.6±0.81** /  9.8±0.52   16.8±0.84** /  10.6±0.55  17.6±1.4** /  11.1±0.9  18.2±1.8** /  11.5±1.1  292±18** /  185±12**  1780±15* /  1126±28**  929±26** /  586±14** 

* p<0.05 ** p<0.01

Applicant's summary and conclusion

Conclusions:
Administration of linear alkylbenzene sulfonic acid sodium salt (LAS) to Wistar SLC rats at dose levels of 0, 0.07, 0.2, 0.6 and 1.8% (equivalent to 0, 40, 115, 340, 1030 mg/kg bw/day) for 26 weeks revealed an NOAEL of 0.07% (40 mg/kg bw/day), based on tissue damage in caecum, kidney and liver, hematological and/or clinical chemistry parameters changes at higher dose levels (115 mg/kg bw/day and above).
Executive summary:

The 26 weeks sub-chronic oral toxicity study of linear alkylbenzene sulfonic acid sodium salt (LAS) was performed in Wistar SLC rats. Approximately 4 weeks old male and femaleWistar SLC rats(obtained from Shizuoka Agricultural Cooperative Association for Laboratory Animals) with body weight range 80 - 90 g (males), 65 - 80 g (females) were used in the study. Five animals were housed in each stainless steelcage and maintained under controlled environmental conditions (temperature: Average of 25 ± 1°C, humidity:55 - 65%, and 12 hours light /12 hours dark). FII food (from Funabashi Farm) and tap water were provided ad libitum. The animals were administered daily with the LAS in diet at dose levels of 0, 0.07, 0.2, 0.6 and 1.8%

(equivalent to 0,40, 115, 340, 1030 mg/kg bw/day) for 26 weeks. 10 animals/sex/dose group was taken in the study.

Clinical observations, water consumption, food consumption and body weights were recorded weekly. At the end of study, haematological, clinical chemistry and urine parameters were analysed. Gross findings were obtained after euthanizing animals and organs were removed for organ weight measurements.Organ weights for brain, pituitary, thyroid, thymus, heart, lungs, liver, kidneys, spleen, adrenal gland, prostate, testes, uterus, ovaries and appendixwere recorded. Liver and kidney enzymes

were also analysed. Collected tissues were then examined and subjected to microscopy through H.E., PAS and silver staining. One male animal from the 1.8% dose group died. In the 1.8% dose groups, increase in relative weight of organs associated with diarrhea and significant suppression of weight gain has been remarked. There was also anemia and an increasing trend of white blood cell count, in addition to increased serum ALP activity, decrease in serum total protein and a very high level of tissue damage in the kidneys. In the 0.6% dose groups, there were mild suppression of weight gain, increased weight of appendix as well as fluctuations in serum ALP / total protein and tissue damage to the kidneys. In the 0.2% dose groups, there were increase in weight of appendix and histological abnormalities in a part of the kidneys. In the 0.2% dose groups, there were increase in weight of appendix and histological abnormalities in a part of the kidneys. Various changes to the kidneys as seen in 0.2 to 0.07% dose groups differ in their extent and frequency of incidence, but these changes were also seen in the control group, so they were not considered changes that lead to permanent damages like collapse of renal tubule or cyst formation. Administration of linear alkylbenzene sulfonic acid sodium salt (LAS) to Wistar SLC ratsat dose levels of 0, 0.07, 0.2, 0.6 and 1.8% (equivalent to 0,40, 115, 340, 1030 mg/kg bw/day) for 26 weeks identified a NOAEL of 0.07% (40 mg/kg bw/day), based on tissue damage in caecum, kidney and liver, hematological as well as clinical chemistry parameters changes at higher dose levels (115 mg/kg bw/day and above).