Butanedioic acid, sulfo-, monoesters with lanolin alcs., disodium salts

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

other: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data have been obtained from a publication of a study on a substance with structural similarity considered valid with restriction. Details of the method used are not indicated and the test is pre-GLP.

Data source

Reference

Reference Type:

publication

Title:

Acute mouse and chronic dog toxicity studies of danthron, dioctyl sodium sulfosuccinate, poloxalkol and combinations.

Author:

Case M.T., Smith K., Nelson R.A.

Year:

1977

Bibliographic source:

Drug Chem Toxicol 1(1):89-101, 1977-78.

Materials and methods

Principles of method if other than guideline:

Administration by tablet of Dioctyl Sodium Sulfosuccinate and its combination with Dantron.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dioctyl Sodium Sulfosuccinate (DSS)

IUPAC Name:

Dioctyl Sodium Sulfosuccinate (DSS)

Test material form:

other: tablets

Test animals

Species:

dog

Strain:

Beagle

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Total number of animals: 72
- Age at study initiation: 7-8 months
- Acclimation period: 6 weeks prior the administration

Administration / exposure

Route of administration:

other: tablets

Details on analytical verification of doses or concentrations:

All formulations met appropriate analytical specifications (no details)

Duration of treatment / exposure:

1 year

Frequency of treatment:

once a day
seven days/week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
30 mg/kg DSS
Basis:
other: in tablets

Doses / concentrations 2

Remarks:

Doses / Concentrations:
danthron (5 or 15 mg/kg) + DSS (10 or 30 mg/kg
Basis:
other: in tablets

No. of animals per sex per dose:

8 dogs for each group (4 of each sex)

Control animals:

other: control group received a daily quantity of tables that contained all materials

Examinations

Observations and examinations performed and frequency:

BODY WEIGHT: All dogs were weighed at weekly intervals and doses were adjusted accordingly.

HAEMATOLOGY/CLINICAL CHEMISTRY: Standard haematology parameters and serum chemistries were determined on blood collected from the external jugular vein on days -28, -7, 14, 30, 80, 130,210, 280, and 365.

URINALYSIS: done on urine samples collected pre-dose and at 6 and 12 months.

Other examinations:

Physical examinations were conducted pre-dose and at 3, 6, 9 and 12 months post dose
Fundus photographs were taken pre-dose and just prior to termination;
Various tissues were weighed and examined microscopically at termination.

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):

not examined

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:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

There were no effects of treatment with DSS on organ or body weights, gross and microscopic tissue observations, or haematological, blood chemistry, or urinalysis parameters. No evidence of gastric irritation was noted.

Effect levels

Dose descriptor:

NOAEL

Effect level:

>= 30 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

mortality

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

Dioctyl Sodium Sulfosuccinate (DSS) administered orally for 1 year (once a day, 7days at week) in tablet as dioctyl sodium sulfosuccinate (DSS; 30 mg/kg) and danthron (5 or 15 mg/kg) + DSS(10 or 30 mg/kg) showed NOAEC of 30 mg/Kg.
There were no effects of treatment with DSS on organ or body weights, gross and microscopic tissue observations, or haematological, blood chemistry, or urinalysis parameters. No evidence of gastric irritation was noted.

Executive summary:

72 dogs (7-8 months of age) were conditioned for approximately 6 weeks prior to compound administration and divided into 9 groups of 8 dogs each (4 of each sex).Dioctyl sodium sulfosuccinate (DSS; 30 mg/kg), danthron (5 or 15 mg/kg) + DSS (10 or 30 mg/kg) were orally administered once a day, seven days/week, for one year.

A control group received a daily quantity of tables that contained all materials in tablets except the active substance.

All formulations met appropriate analytical specifications. All dogs were weighed at weekly intervals and doses were adjusted accordingly. Physical examinations were conducted pre-dose and at 3, 6, 9 and 12 months post dose. Urinalyses were done on urine samples collected pre-dose and at 6 and 12 months. Standard haematology parameters and serum chemistries were determined on blood collected from the external jugular vein on days -28, -7, 14, 30, 80, 130, 210, 280, and 365.

Fundus photographs were taken pre-dose and just prior to termination. Various tissues were weighed and examined microscopically at termination.

The NOAEC was defined at 30 mg/Kg.

There were no effects of treatment with DSS on organ or body weights, gross and microscopic tissue observations, or haematological, blood chemistry, or urinalysis parameters. No evidence of gastric irritation was noted.