Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 946-448-9 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1976
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable study, followed scientific principles/standards, pre-dates GLP
- Remarks:
- Published studies
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 976
Materials and methods
- Principles of method if other than guideline:
- The purpose of this study is to determine the sub chronic toxicity of LAS in Wistar JCL rats, focusing on the liver and kidneys. Male and female rats were maintained on either test diets (0, 0.6 and 1.8%) or drinking water (0, 0.07 and 0.2%) for 9 months. 0.6 and 1.8% rats in drinking water study exhibited severe weight loss so LAS administration was stopped after 2 weeks. Mortality, clinical observations and body weights were recorded during the study. All the surviving animals were humanely euthanized at end of 9 months and gross necropsy, hematological, serum biochemical tests, enzyme tests on the liver and kidneys were performed and organs weights were measured. No histopathology was performed.
- GLP compliance:
- no
- Remarks:
- (pre-dates GLP)
- Limit test:
- no
Test material
- Reference substance name:
- Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.
- EC Number:
- 287-494-3
- EC Name:
- Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.
- Cas Number:
- 85536-14-7
- Molecular formula:
- None available - not a single isomer - see remarks
- IUPAC Name:
- Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.
- Test material form:
- not specified
- Details on test material:
- Name of test material: LAS (Linear alkylbenzene sulfonate); NeoPlex P-60
No further details on test substance are provided in study report.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Wistar JCL
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Male and female rats were obtained from Shizuoka Agricultural Cooperative Association for
Laboratory Animals
- Age at study initiation: 4-weeks old
- Weight at study initiation: 100 - 124 g (male rats), 82 - 100 g (female rats)
- Fasting period before study: No
- Housing: 5 animals were housed per cage.
- Diet: CE-2 food (from CLEA Japan); ad libitum
- Water: ad libitum
- Acclimation period: 1 week before the start of treatment
ENVIRONMENTAL CONDITIONS
- Temperature: 25 ± 1°C
- Humidity: 50 - 60%
- Air changes: Not reported
- Photoperiod: 12 hours dark /12 hours light
IN-LIFE DATES: Not reported
Administration / exposure
- Route of administration:
- other: oral: drinking water and feed
- Details on route of administration:
- LAS was administered to animals by mixing 0.6 and 1.8% in CE-2 food (CLEA Japan) and dissolving to 0.07 and 0.2% in drinking water.
- Vehicle:
- other: Test substance was administered either in diet or drinking water
- Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 9 months
- Frequency of treatment:
- Continuous in diet or drinking water (ad libitum)
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0.6 other: %
- Remarks:
- in diet
- Dose / conc.:
- 1.8 other: %
- Remarks:
- in diet
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Remarks:
- in diet (corresponding to 0.6% dose level)
- Dose / conc.:
- 900 mg/kg bw/day (nominal)
- Remarks:
- in diet (corresponding to 1.8% dose level)
- Dose / conc.:
- 0.07 other: %
- Remarks:
- in drinking water
- Dose / conc.:
- 0.2 other: %
- Remarks:
- in drinking water; 0.6 and 1.8% dose group (equivalent to 857.14 and 2571.43 mg/kg bw/day) were also included, however due to severe weight loss so LAS administration was stopped after 2 weeks.
- No. of animals per sex per dose:
- Feeding study (mixed in diet): 8 animals/sex/dose
Drinking water study: 9 animals/sex/dose - Control animals:
- yes, concurrent vehicle
- yes, plain diet
- Positive control:
- No
Examinations
- Observations and examinations performed and frequency:
- CLINICAL OBSERVATIONS: Yes
- Time schedule: Weekly
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly
FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food consumption: Yes
- Compound intake: Yes
- Time schedule for examinations: Weekly
FOOD EFFICIENCY: No
WATER CONSUMPTION AND COMPOUND INTAKE: Yes
- Time schedule for examinations: Weekly
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: After 9 months, blood was collected from each animal after euthanizing.
- Anesthetic used for blood collection: No
- Animals fasted: Not specified
- How many animals: Not specified
- Parameters: White blood cells (WBC), red blood cells (RBC), Hemoglobin (Hgb), Hematocrit (Hct), mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC)
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: After 9 months, blood was collected from each animal after euthanizing.
- Animals fasted: Not specified
- How many animals: Not specified
- Parameters: Glutamate oxaloacetate transaminase (GOT), glutamate pyruvic transaminase (GPT), glucose content, urea nitrogen, total cholesterol, albumin, alkaline phosphatase (ALP) and cholinesterase
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
IMMUNOLOGY: No
OTHER:
- Liver enzyme tests: Glucose 6-phosphatase (G6Pase), lactase dehydrogenase (LDH) and G6P-DH activity
- Kidney enzyme tests: G6Pase, LDH, GPT, GOT, ALP, acid phosphatase (ACP), Na, K-ATPase, and malate dehydrogenase (MDH) - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (However, no details in study report in mentioned)
Gross findings were obtained after euthanizing animals and organs were removed for organ weight measurements.
ORGAN WEIGHTS: Brain, heart, lungs, liver, spleen, kidneys, adrenal gland, testes, ovary, uterus, and appendix
HISTOPATHOLOGY: No
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Both female and male rats (drinking water study) exhibited a slight redness at the tips of their facial fur, and coarse fur all over their bodies.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- There was significant decrease in body weight gain in males and females of 1.8% dose group fed with diet and in males of 0.2% dose group consuming LAS contained water.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- Increased water consumption was observed in males of 1.8% dose group fed with diet and 0.2% dose group consuming LAS contained water.
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- A significant reduction in WBC was observed in 0.6% (diet) male rats and in MCV and MCH was observed in 1.8% (diet) female rats compared to controls.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- There were significant alteration in cholesterol [decrease; all doses, except female rats of 0.07% dose group (drinking water)], GPT [0.6% dose group (diet) females)], GOT [1.8% dose group (diet) males], albumin [1.8% (diet) males] , ALP levels [male and female rats fed with 1.8% LAS-diet] and cholinesterase levels [in male rats fed with 1.8% LAS-diet].
- Urinalysis findings:
- not examined
- 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):
- In males of 1.8% (diet), the absolute liver and testes weight was significantly decreased and the relative testes and liver weight was significantly increased and both absolute and relative spleen weight were also significantly reduced.
In females of 1.8% (diet), absolute and relative liver and caecum weight was significantly increased.
There was also significant decrease in absolute and relative heart weight in females of 0.6% (diet) and 0.07% (drinking water) dose groups. - Gross pathological findings:
- not specified
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- Liver enzyme tests:
Dietary study: G6Pase activity was reduced in 1.8% dose group males and females, G6P-DH activity was reduced in 0.6 and 1.8% dose group males and females, LDH activity was reduced in 0.6, 1.8% dose group. GOT and GPT activities were clearly reduced in males, while in females GPT activity was reduced only in 1.8% dose group and GOT activity was reduced in 1.8% dose group animals.
Drinking water study: LDH activity was reduced in 0.2% dose group males. GOT and GPT activities were clearly reduced in males and GOT activity was increased in 0.07 and 0.2% dose group animals.
Renal enzyme tests:
Dietary study: A significant difference was also observed in G6Pase activity. In females, G6Pase, Na, K-ATPase, and LDH activity were significantly reduced in 1.8% dose group (diet) animals
Drinking water study: In males, Na, K-ATPase activity was significantly reduced in 0.2% dose group. A significant difference was also observed in G6Pase activity. - Details on results:
- CLINICAL SIGNS: Both female and male rats consuming LAS-containing water exhibited a slight redness at the tips of their facial fur, and coarse fur all over their bodies.
BODY WEIGHT AND WEIGHT CHANGES: There was significant decrease in body weight gain in male and females of 1.8% dose group fed with diet and in males of 0.2% dose group consuming LAS contained water.
WATER CONSUMPTION AND COMPOUND INTAKE: Increased water consumption was observed in males of 1.8% dose group fed with diet and 0.2% dose group consuming LAS contained water.
HAEMATOLOGICAL FINDINGS: A significant reduction in WBC was observed in 0.6% (diet) male rats compared to controls, and a significant reduction in MCV and MCH was observed in 1.8% (diet) female rats compared to controls.
CLINICAL BIOCHEMISTRY: Except female rats of 0.07% dose group (drinking water), a significant reduction or a reduction in cholesterol was observed in male and female rats of all dose groups compared to controls. GPT was significantly reduced in 0.6% dose group (diet) females, and reduced in females of other treatment groups. GOT was significantly reduced in 1.8% dose group (diet) males, and reduced in both females and males of other treatment groups. Albumin was significantly reduced in 1.8% (diet) males and reduced in males of 0.2% dose group (drinking water) and females of 1.8% dose group (diet). There was significant increase in ALP levels in male and female rats fed with 1.8% LAS-diet and cholinesterase levels in male rats fed with 1.8% LAS-diet.
ORGAN WEIGHT: In males of 1.8% (diet), the absolute liver and testes weight was significantly decreased and the relative testes and liver weight was significantly increased and both absolute and relative spleen weight were also significantly reduced. In females of 1.8% (diet), absolute and relative liver and caecum weight was significantly increased. There was also significant decrease in absolute and relative heart weight in females of 0.6% (diet) and 0.07% (drinking water) dose groups.
LIVER ENZYME TESTS: G6Pase activity was reduced in 1.8% dose group (diet) males and females, G6P-DH activity was reduced in 0.6 and 1.8% dose group (diet) males and females, where the percentage reduction was greater in 1.8% dose group (diet) animals. LDH activity was clearly reduced in 0.6, 1.8% dose group (diet), and 0.2% dose group (drinking water) males, but reduced in only 1.8% dose group (diet) females. GOT and GPT activities were clearly reduced in males, while in females GPT activity was reduced only in 1.8% dose group (diet) animals, and GOT activity was increased in 0.07 and 0.2% dose group (drinking water) animals but reduced in 1.8% dose group (diet) animals.
RENAL ENZYME TESTS: In males, Na, K-ATPase activity was significantly reduced in 0.2% dose group (drinking water) animals, and also reduced in other male treatment groups. A significant difference was also observed in G6Pase activity, where the reduction observed was associated with an increase in amount consumed. In females, G6Pase, Na, K-ATPase, and LDH activity were significantly reduced in 1.8% dose group (diet) animals, and G6Pase and LDH activity were also reduced in other treatment groups.
Effect levels
open allclose all
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 300 mg/kg bw/day (nominal)
- Based on:
- act. ingr.
- Remarks:
- (dietery study)
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical biochemistry
- clinical signs
- haematology
- organ weights and organ / body weight ratios
- water consumption and compound intake
- other: Liver and kidney enzyme levels
- Remarks on result:
- other: Adverse effects were observed at all dose levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 85 mg/kg bw/day (nominal)
- Based on:
- act. ingr.
- Remarks:
- (drinking water study)
- Sex:
- male/female
- Basis for effect level:
- clinical biochemistry
- other: Liver and kidney enzyme levels
- Remarks on result:
- other: Based on significant decreases in the activities of glutamate-oxalate transaminase and lactate dehydrogenase in males and significant decrease in renal Na,K-ATPase in males and females at 145 mg/kg bw/day (0.2% drinking water).
Target system / organ toxicity
open allclose all
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 145 mg/kg bw/day (nominal)
- System:
- urinary
- Organ:
- kidney
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- yes
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 145 mg/kg bw/day (nominal)
- System:
- hepatobiliary
- Organ:
- liver
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- yes
Applicant's summary and conclusion
- Conclusions:
- Administration of LAS to Wistar JCL rats by test diets at dose levels of 0, 0.6 and 1.8% for 9 months (focusing on the liver and kidneys) revealed an LOAEL of 0.6% (300 mg/kg bw/day in diet), based on adverse effects at all dose levels.
Administration of LAS to Wistar JCL rats in drinking water at dose levels of 0, 0.07 and 0.2% for 9 months (focusing on the liver and kidneys) revealed an NOAEL of 0.07% (85 mg/kg bw/day in drinking water), based on significant decreases in the activities of glutamate-oxalate transaminase and lactate dehydrogenase in males and significant decrease in renal Na,K-ATPase in males and females at 145 mg/kg bw/day (0.2% drinking water). - Executive summary:
The 9 months sub-chronic oral toxicity study of LAS was performed in Wistar JCL rats, focusing on the liver and kidneys.
4 weeks old male and femaleWistar JCL rats(obtained from Shizuoka Agricultural Cooperative Association for Laboratory Animals) with body weight range100 - 124 g (males), 82 - 100 g (females)were used in the study. 5 animals were housed in each cage and maintained under controlled environmental conditions (temperature: Average of25 ± 1°C, humidity:50 - 60%, and 12 hours light /12 hours dark).CE-2diet (from CLEA Japan) and water were providedad libitum.
The animals were administered daily with the LAS at following dose levels for 9 months:
Mixed in diet: 0, 0.6 and 1.8% (equivalent to 0, 300 and 900 mg/kg bw/day); 8 animals/sex/dose
Dissolved in drinking water: 0, 0.07 and 0.2 % (equivalent to 0,85 and 145mg/kg bw/day); 9 animals/sex/dose
Rats in 0.6 and 1.8% dose group of drinking water study exhibited severe weight loss so LAS administration was stopped after 2 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.Gross findings were observed after euthanizing animals and organs were removed for organ weight measurements. Organ weights for brain, heart, lungs, liver, spleen, kidneys, adrenal gland, testes, uterus, and appendixwere recorded. Liver and kidney enzymes were also analysed. No histopathology was performed.
No mortality was observed throughout the study. Both female and male rats consuming LAS-containing water exhibited a slight redness at the tips of their facial fur, and coarse fur over their bodies. There was significant decrease in body weight gain in male and females of 1.8% dose group fed with diet and in males of 0.2% dose group consuming LAS contained water.Increased water consumption was observed in males of 1.8% dose group fed with diet and 0.2% dose group consuming LAS contained water.
A significant reduction in WBC was observed in 0.6% (diet) male rats compared to controls, and a significant reduction in MCV and MCH was observed in 1.8% (diet) female rats compared to controls. A marked reduction in cholesterol was observed in male and female rats of all dose groups [except female rats of 0.07% dose group (drinking water)] compared to controls. This indicate hepatocyte damage. GPT was significantly reduced in 0.6% dose group (diet) females, and reduced in females of other treatment groups. GOT was significantly reduced in 1.8% dose group (diet) males, and reduced in both females and males of other treatment groups. Albumin was significantly reduced in 1.8% (diet) males and reduced in males of 0.2% dose group (drinking water) and females of 1.8% dose group (diet). There was significant increase in ALP levels in male and female rats fed with 1.8% LAS-diet and cholinesterase levels in male rats fed with 1.8% LAS-diet.
In males of 1.8% (diet), the absolute liver and testes weight was significantly decreased and the relative testes and liver weight was significantly increased and both absolute and relative spleen weight were also significantly reduced. In females of 1.8% (diet), absolute and relative liver and caecum weight was significantly increased. There was also significant decrease in absolute and relative heart weight in females of 0.6% (diet) and 0.07% (drinking water) dose groups.
Liver enzymes were markedly reduced in 1.8% fed rats, due to impaired liver function, indicates reduced enzyme synthesis and direct enzyme inhibition by LAS or its metabolites. Renal G6Pase and Na, K-ATPase activity decreased, indicating kidney impairment.
Administration of LAS to Wistar JCL rats bytest diets at dose levels of 0, 0.6 and 1.8% for 9 months (focusing on the liver and kidneys) revealed an LOAEL of 0.6% (300 mg/kg bw/day in diet), based on adverse effects at all dose levels.
Administration of LAS to Wistar JCL rats in drinking water at dose levels of 0, 0.07 and 0.2% for 9 months (focusing on the liver and kidneys) revealed an NOAEL of 0.07% (85 mg/kg bw/day in drinking water), based onsignificant decreases in the activities of glutamate-oxalate transaminase and lactate dehydrogenase in males and significant decrease in renal Na,K-ATPase in males and females at 145 mg/kg bw/day (0.2% drinking water).
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.