Sodium 1,4-dicyclohexyl sulphonatosuccinate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1969

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

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 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:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sodium 1,4-dicyclohexyl sulphonatosuccinate

EC Number:

245-629-3

EC Name:

Sodium 1,4-dicyclohexyl sulphonatosuccinate

Cas Number:

23386-52-9

Molecular formula:

C16H26O7S.Na

IUPAC Name:

sodium 1,4-bis(cyclohexyloxy)-1,4-dioxobutane-2-sulfonate

Test material form:

liquid: viscous

Details on test material:

- Name of test material (as cited in study report): Aerosol A-196, Sodium Dicyclohexylsulfosuccinate (100% active)
- Physical state: The product was dried to remove the liquid phase.
- Purity: 95-97%
- Impurities (identity and concentrations): See confidential details
- Composition of test material, percentage of components: See confidential details
- Purity test date: Not provided
- Lot/batch No.: Lot#90410
- Expiration date of the lot/batch: Not provided
- Stability under test conditions: Not provided
- Storage condition of test material: Not provided

Test animals

Species:

rat

Strain:

other: Charles River albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Charles River Breeding Laboratories, North Wilmington, Mass.
- Age at study initiation: Not provided
- Weight at study initiation: 100g (female rats), 121g (male rats) on average
- 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
- Water: No data provided
- Acclimation period: Not provided

ENVIRONMENTAL CONDITIONS
Not provided

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 20g/rat/day
(Derelanko M.J., 2008, The Toxicologist's Pocket Handbook, Informa).
1% in the diet = 10000 mg/kg diet corresponds with 10 mg/g diet
20 g feed/rat (250g bw)/day = 80 g feed/kg bw/day = 0.8 g active ingredient/kg bw/day = 800 mg/kg bw/day.
A higher feed intake is possible, e.g. 1000 mg/kg at higher body weight and feed intake, but from a conservative viewpoint 750 mg/kg bw is taken


DIET PREPARATION
- Rate of preparation of diet (frequency): Fresh diets were prepared each week
- Mixing appropriate amounts with (Type of food): standard rat ration
- Storage temperature of food: Not provided

VEHICLE: No Vehicle

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

90 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
1.0 %
Basis:
nominal in diet

No. of animals per sex per dose:

For Aerosol A-196: 20 male and 20 female at 1.0 % and 20 male and 20 female as control

Control animals:

yes, plain diet

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily during the investigation

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

FOOD CONSUMPTION : Yes

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 checked in table [No. IV and V] were examined.
Hematocrit Value
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(fasted serum glucose concentration)
- How many animals: 5 rats of each sex (=10) and 10 control
- Parameters checked in table [No.VI and VII] were examined.
Blood Urea Nitrogen (BUN) Concentration
Serum Alkaline Phosphatase (SAP) Activity
Serum Glutamic-Pyruvic Transaminase (SGPT) Activity
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 checked in table [No.VIII] were examined.
Glucose Concentration
Albumin Concentration
Microscopic Elements Examination
pH
Specific Gravity



NEUROBEHAVIOURAL EXAMINATION: No


OTHER: Organ Weight and Organ to Body and Organ to Brain Weight Ratios

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
ORGAN WEIGHTS: Yes

Other examinations:

Organ Weight and Organ to Body and Organ to Brain Weight Ratios (no effects)

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

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

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:

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:

ca. 750 mg/kg bw/day (nominal)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: No effects up to highest concenrtration

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The comparisons 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.
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.
There were no significant differences between the tissues of test and control rats observed upon histopathological examination.

Executive summary:

Six groups of 40 albino rats (20 male, 20 female, Charles River strain) plus 1 control group (20 male + 20 female) were fed with 1% of various test items mixed into the diet. The various test items were category members of the Sulfosuccinates Diester Group including Butanedioic acid, sulfo-, 1,4-dicyclohexyl ester, sodium salt. After 84 days 5 hematological values, 4 blood chemical values and 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. 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. Category members of the test item at 1% in the diet (10000 ppm equivalent to 750 mg/kg bw/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.

The IBT Report, supplemented by the Intox report and the Validation Report of October 15, 1983, may be considered a valid study and the data and conclusions relied upon.