Docusate sodium

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted equivlent to international guidelines, but predates GLP conditions. The study was conducted in a renomated laboratory and to the standards possible at the time of testing.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to internationally accepted guidelines, but predates GLP conditions. The study was conducted in a renomated laboratory and to the highest standards possible at the time of testing.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

males only

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Route of administration:

oral: unspecified

Doses:

25.2mL/kg, 22.4 mL/kg, 17.8 mL/kg and 14.1 mL/kg ; mixed with water to give a 20% solution

No. of animals per sex per dose:

6 males

Control animals:

no

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 4 200 mg/kg bw

Clinical signs:

other: Animals became prostrate and lethargic.

Gross pathology:

Yellow fluid was observed through the gastrointestinal tract of those found dead.

Table1.Single oral dose in male Sprague-Dawley albino Rats

Conditions: fasted overnight ; mixed with water to give a 20% solution.                                                                

Dosage mL/kg	Onset of (S) Signs, (D) Death, Hours and Days									Died/ Dosed	Mean Wt.		Time of( R) Recovery , Days
	0-6	6-24	2	3	4	5	6	7	8-14		I	T	1	2	3	4	5	6	7-14
25.2		4D	1D							5/5	147	-
22.4		3D								3/5	147	218		2R
17.8		1D								1/5	152	229		4R
14.1										0/5	145	232

 

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

A mortality of 5/5 at 5.0 g/kg bw, 3/5 at 4.5 mg/kg bw and 1/5 at 3.5 g/kg bw (and 0/5 at 2.8 g/kg bw) resulted in an oral LD50 of 4.2 g/kg bw. Animals became prostrate and lethargic; at necropsy, yellow fluid was obsrved through the gastrointestinal tract of those found dead.

Executive summary:

In the current study, 20% dosusate solutions were given of 25.2, 22.4, 17.8 and 14.1 mL/kg bw, corresonding with approximate doses of 5.0, 4.5, 3.5 and 2.8 g/kg bw. A mortality of 5/5 at 5.0 g/kg bw, 3/5 at 4.5 mg/kg bw and 1/5 at 3.5 g/kg bw (and 0/5 at 2.8 g/kg bw) resulted in an oral LD50 of 4.2 g/kg bw. Animals became prostrate and lethargic; at necropsy, yellow fluid was observed through the gastrointestinal tract of those found dead.

Cross-reference 2

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted equivalent to international guidelines, however no reversibility was tested. The study was conducted in a renomated laboratory and to the standards at the time of testing.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: 16 CFR 1500.41

Principles of method if other than guideline:

FHSA procedure: Federal Hazardous Substance Act (6 animals instead of 3)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

other: shaved and abraded

Controls:

no

Amount / concentration applied:

0.5 mL of Aerosol OT-100 under covered patch

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

6

Irritation parameter:

primary dermal irritation index (PDII)

Remarks:

primary irritation score

Basis:

mean

Time point:

other: 24, 72 h

Score:

3.83

Max. score:

4

Reversibility:

no data

Table1. Rabbit skin irritation

Conditions: 0.5mL Aerosol OT-100 under covered patch (FHSA Procedure)

Time, Hours	Reaction	Rabbit Number, Value						Mean Value
		1	2	3	4	5	6
	Erythema
24	Intact	3	3	2	1	3	2	2.33
72	Intact	0	1	1	4	4	0	1.66
24	Abraded	3	3	3	1	3	2	2.50
72	Abraded	0	1	1	4	4	0	1.66
	Edema
24	Intact	3	3	3	2	2	2	2.50
72	Intact	1	0	2	2	1	0	1.0
24	Abraded	3	3	3	2	2	2	2.50
72	Abraded	1	0	2	2	1	1	1.16

 Structure of tissue at the site of contact was not destroyed or changed irreversibly in 24 hours.

The scoring system used herein for skin and eye irritation reactions was that of Draize, J.H., Woodward, G., and Calvery, H.O., J. Pharmacol.Exptl.Therap., 82 :377, 1944. The maximum score value for a skin reaction (excluding necrosis) is 4. The “primary irritation score” was the sum of the mean values divided by 4.

 

Interpretation of results:

Category 2 (irritant)

Remarks:

Criteria used for interpretation of results: other: EU GHS

Conclusions:

Primary Irritation Score of 0.5 ml Aerosol OT-100 is 3.83.

Executive summary:

A volume of 0.5 mL Docusate sodium was applied to intact and abraded skin of 6 male rabbits according to FHSA (Federal Hazard Act Substance) and CFR 1500.41 method for 24 hours under occlusive dressing. The reactions were evaluated after 24 and 72 hours and the substance was strongly irritating as indicated by a mean primary irritation score of 3.83/4.

Cross-reference 3

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted equivalent to international guidelines, however no reversibility was tested. The study was conducted in a renomated laboratory and to the highest standards possible at the time of testing.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: 16 CFR 1500.42

Principles of method if other than guideline:

FHSA procedure: Federal Hazardous Substance Act (6 instead of 3 animals)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.1 g of Aerosol OT-100

Duration of treatment / exposure:

Not provided (evalutation at 24, 48 and 72 hours)

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

14.9

Max. score:

110

Reversibility:

not specified

Irritant / corrosive response data:

See Table 1.

Table1. Rabbit eye irritation

Conditions : 0.1 gm of Aerosol OT-100 (FHSA Procedure)

Time, Hours	Reaction	Rabbit Number, Value						Mean Value
		1	2	3	4	5	6
24	Cornea	5	10	5	40	0	10	11.66
	Iris	0	0	0	5	0	5	1.66
	Conjunctivae	0	4	2	10	0	16	5.33
48	Cornea	0	5	0	30	0	40	12.50
	Iris	0	0	0	5	0	5	1.66
	Conjunctivae	0	4	0	8	2	12	4.33
72	Cornea	0	0	0	10	0	15	4.16
	Iris	0	0	0	5	0	5	1.66
	Conjunctivae	0	0	0	2	0	8	1.66

 Maximum score are: 80 for cornea, 10 for IRIS and 20 for conjunctiva.

 

At any of the readings made at 24, 48 and 72 hours, there was

-no discernible opacity or ulceration of the cornea other than a slight dulling of the normal luster.

-no inflammation of the iris other than slight deepening of the folds, or slight circumcorneal injection.

-no diffuse, deep-crimson red appearance of the conjunctivae, with individual vessels not easily  discernible.

- no obvious swelling of the conjunctivae, excluding cornea and iris, with partial eversion of the lids.

- no destruction or irreversible change of any tissue in 24 hours or less.

Interpretation of results:

moderately irritating

Remarks:

alike Category 2 Criteria used for interpretation of results: other: A procedure: 16 CFR 1500.42 and FHSA

Conclusions:

Not provided, but changes were seen up to 72h.

Executive summary:

A volume of 0.1 mL (0.1g) Docusate sodium was applied in the eyes of 6 rabbits according to CFR and FHSA (Federal Hazard Substance Act). Evaluation after 24, 48 and 72 hours showed that the substance was irritating as indicated by changes of the cornea, iris and conjunctiva up to 72 hour.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

male animals only

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Docusate sodium

EC Number:

209-406-4

EC Name:

Docusate sodium

Cas Number:

577-11-7

Molecular formula:

C20H38O7S.Na

IUPAC Name:

sodium 1,4-bis[(2-ethylhexyl)oxy]-1,4-dioxobutane-2-sulfonate

Details on test material:

- Name of test material (as cited in study report): Aerosol® OT-100, Sodium Dioctyl Sulfosuccinate
- Physical state: white, waxy solid
- Analytical purity: >97%

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Administration / exposure

Type of coverage:

other: covered

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Dermal application to clipped unabraded skin

Duration of exposure:

24 hours

Doses:

10 mL/kg bw; equivalent to 10000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Mortality:

no

Clinical signs:

other: Signs of intoxication: none noted. Skin iritation: fissuring, desquamation, coriaceousness was noted. Rabbits noted pulling fur out.

Gross pathology:

No gross pathology was observed

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

LD50 >10000 mg/kg, dosed as received.

Executive summary:

Docusate sodium dosed dermally in male rabbits at 10000 mg/kg bw did not lead to mortality. Clinical observations included some skin iritation (fissuring, desquamation, coriaceousness, pulling fur out), however no signs of intoxication or gross pathological findings were noted .