Calcium 1,4-bis(2-ethylhexyl) bis(2-sulphosuccinate)

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1969

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted according to internationally accepted test guidelines and is considered relevant, adequate and reliable. There were some deviations from the study guidelines, however these did not affect the conclusions reached and the validity of the study.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1969

Report date:

1969

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

only one dose per test substance

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sodium Diamylsulfosuccinate

IUPAC Name:

Sodium Diamylsulfosuccinate

Constituent 2

Reference substance name:

Sodium Dicyclohexylsulfosuccinate

IUPAC Name:

Sodium Dicyclohexylsulfosuccinate

Constituent 3

Reference substance name:

Sodium Dihexylsulfosuccinate

IUPAC Name:

Sodium Dihexylsulfosuccinate

Constituent 4

Reference substance name:

Sodium Diisobutylsulfosuccinate

IUPAC Name:

Sodium Diisobutylsulfosuccinate

Constituent 5

Reference substance name:

Sodium Di- (tridecyl) sulfosuccinate

IUPAC Name:

Sodium Di- (tridecyl) sulfosuccinate

Details on test material:

- Name of test material (as cited in study report) + purity, Lot No.
Aerosol A-196: Sodium Dicyclohexylsulfosuccinate (CAS 23386-52-9), 100% active, Lot #90410
Aerosol IB: Sodium Diisobutylsulfosuccinate (CAS 127-39-9), 100% active, S-7919-195, 5/1/69
Aerosol AY: Sodium Diamylsulfosuccinate (CAS 922-80-5), 100% active, Lot #W-90214, SPS#8137
Aerosol MA: Sodium Dihexylsulfosuccinate (CAS 2373-38-8), Lot #W-901090, PS#7997, Notebook #S8484, page 54
Aerosol TR: Sodium Di- (tridecyl) sulfosuccinate (CAS 2673-22-5), 100% , Lot #W-70601, SPS#7623

Test animals

Species:

rat

Strain:

other: Charles River strain albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Charles River Breeding Laboratories, North Wilmington, Mass.
- Weight at study initiation: 101-122 g
- Housing: individually in standard wire-bottomed steel rat cages
- Diet : standard rat ration blended with the appropriate amount of test material in a Hobart Mixer
Fresh diets were prepared each week. Each rat was offered an amount of diet sufficient for one
week ‘ad libitum’ feeding. However, checks were made periodically to ensure that the food jars were
not empty

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: 1.0% in the feed
Taking into account a mean body weight of 250 g and a mean food consumption of 25g/rat/day:
10000 mg/kg diet corresponds with 1000 mg/kg bw/day on average basis:
25 g feed/rat (250g bw)/day = 100 g feed/kg bw/day = 1g active ingredient/kg bw/day = 1000 mg/kg bw/day.

DIET PREPARATION
- Rate of preparation of diet (frequency): Fresh diets were prepared each week
- Mixing appropriate amounts with (Type of food): standard rat ration


VEHICLE: No

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

90 days

Frequency of treatment:

continuously

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
10.000 ppm (1% in the diet)
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
750 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

20 males & 20 females

Control animals:

yes

Positive control:

no

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: no

BODY WEIGHT: Yes
- Time schedule for examinations: biweekly (day 0, 15, 30, 45, 60, 75 and 90).

FOOD CONSUMPTION AND COMPOUND INTAKE: yes
- Food consumption for each animal determined : yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: no

FOOD EFFICIENCY: no

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: yes
- Time schedule for collection of blood: after 84 days
- Anesthetic used for blood collection No data
- Animals fasted:yes (fasted serum glucose concentration)
- How many animals: 5 rats of each sex (=10) and 10 control
- Parameters: Hematocrit, Erythrocyte Count, Hemoglobin Concentration, Total Leukocyte Count, Differential Leukocyte Count

CLINICAL CHEMISTRY: yes
- Time schedule for collection of blood: after 84 days
- Animals fasted: yes
- How many animals: 5 rats of each sex (=10) and 10 control
- Parameters: Blood Urea Nitrogen (BUN), Serum Alkaline Phosphatase (SAP), Serum Glutamic-Pyruvic Transaminase (SGPT), Fasted Serum Glucose Concentration

URINALYSIS: yes
- Time schedule for collection of urine: after 84 days
- Metabolism cages used for collection of urine: No data
- Animals fasted: yes
- Parameters: Glucose Concentration, Albumin Concentration, Microscopic Elements Examination, pH, Specific Gravity

NEUROBEHAVIOURAL EXAMINATION: no

Sacrifice and pathology:

ORGAN WEIGHTS AND ORGAN TO BODY WEIGHT RATIO'S: yes
- organs: liver, kidney

GROSS AND HISTOPATHOLOGY
Following 90 days of feeding, all surviving rats were sacrificed by carbon dioxide asphyxation and autopsied. Animals which died during the study were examined grossly unless examination was precluded by post-mortem autolysis. At the time of gross examination a complete set of organs and other tissues was removed from each rat and preserved in formalin solution. Also at autopsy the weight of the liver and kidneys of ten rats of each sex in every group was determined and recorded.
Microscopic examination of tissues taken from five rats of each sex in every group was conducted. The following tissues, stained with Hematoxylin-Eosin, were included: esophagus, stomach (cardia, fundus and pylorus), small intestine (duodenum, jejunum and ileum), cecum, colon, liver, kidneys, spleen, pancreas, urinary bladder, pituitary gland, adrenal gland, testes, seminal vesicle, ovary, bone marrow, thyroid gland, parathyroid gland, salivary gland, prostate gland, heart, aorta, lung, lymph node (cervical and mesenteric), skeletal muscle, peripheral nerve, bone (femur), spinal cord, uterus, trachea, eye, optic nerve and brain (cerebrum, cerebellum and pons).

Statistics:

Statistical analyses were conducted upon the absolute organ weights and their corresponding ratios to the weight of the body. An Analysis of Variance was conducted first and any significant effects disclosed by that treatment were further studied by “t” –tests.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Description (incidence and severity):

See Table 2

Food consumption and compound intake (if feeding study):

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Effect levels

Dose descriptor:

NOAEL

Effect level:

750 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

clinical signs

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The comparison of final body weights and total weight gains revealed no statistically significant differences between test and control animals.
No outstanding differences in food consumption were noted between test rats and control rats.
No deaths or abnormal behavioral reactions were noted among any of the animals employed in the study.
No outstanding differences between test and control rats were noted with respect to any of the blood parameters studied.
(With the exception of an elevation of both SGPT and SAP values among males fed Aerosol TR,) all data obtained from test rats were not different than those from control animals.
No significant differences between the urine of test rats and control rats were observed.
No outstanding differences between test and control rats were noted at the time of gross pathological examination.
( The only statistically significant difference noted was smaller absolute liver weights among male rats fed 1.0% Aerosol IB.)

Executive summary:

Five groups of 40 albino rats (20 male, 20 female Charles River Strain) plus 1 control group (20 male, 20 female) were fed with 1% test substance mixed into the diet with various category members of Docusate sodium. After 84 days 5 hematological values, 4 blood chemical values, 5 urinalysis values were measured for all animals. 40 tissues have been examined pathologically at the conclusion of the 90-days test period. Organ to body weight and organ to brain weight ratios were calculated. With the exception of an evaluation of both SGPT (serum glutamic pyruvic transaminase) and SAP (serum alkaline phosphatase) values among males fed CAS 2673-22-5 (Aerosol TR) and smaller absolute liver weights among males fed CAS 127-39-9 (Aerosol IB), no significant differences in clinical blood chemistry studies and absolute organ weights have been detected. Body weights organ to body weight ratios, hematologic studies and urinalysis were not different between test and control animals. No deaths or abnormal behavioral reactions occurred; no gross pathological findings were noted.

Administration of category members of Docusate sodium at 1% in the diet (10000 ppm equivalent to 750 mg/kg body weight/day) for 90 days in rats did not result in any relevant changes in the subchronic toxicity study. The NOAEL was therefore considered to be 750 mg/kg bw/day.