Docusate sodium

Endpoint summary

Description of key information

Both for the skin and eye irritation, in vivo key studies according to OECD 404 and 405  were available, demonstrating that the test substance is highly irritating to skin and resulting in irreversible eye damage. The overall  irritation scores  were 7.8 of max. 8 (1- 72 h) in the key study for skin irritation and 47 of max. 110 (1-72 h) in the key study for eye irritation.  This information in combination with supporting studies resulted in skin irritation EU GHS category 2 and eye damage EU GHS category 1.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to internationally accepted test guidelines. As the test material also contains ethanol and methanol, these ingredients may have potential influence on the irritation score.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

other: White Russian, Chbb-SPF

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Fa.Dr. Karl Thomae GmbH, Biberach
- Weight at study initiation: 2,2 - 2,3kg
- Housing: separate in stainless steel cages
- Diet : KZ Alleindiät für Kaninchen, Ssniff Spezialfutter GmbH, 4770 Soest, ad libitum
- Water : public supply, ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20°C +-1°C
- Humidity:60% +-5%
- Air changes (per hr): 15 air replacements/hour
- Photoperiod (hrs dark / hrs light): 12 /12

IN-LIFE DATES: From: 1988-02-23 To: 1988-03-08

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0,5 mL undiluted
- Concentration (if solution): 70% Docusate sodium

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours; 6, 8, 10 and 14 days

Number of animals:

3 male

Details on study design:

TEST SITE
- Area of exposure: 6 cm3
- % coverage:
- Type of wrap if used: polyethylene film (6X6 cm) which was secured in position by means of
an elastic bandage
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Warm water
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to OECD 404: See Table 1

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1h, 24h, 48h, 72h

Score:

7.8

Max. score:

8

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Score = sum of erythema & oedema

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

other: effects still visible at 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

other: effects still visible at 14 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

other: effects still visible at 14 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

other: effects still visible at 14 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

other: effects still visible at 14 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

other: effects still visible at 14 days

Irritant / corrosive response data:

Strongly irritating

Table 1. Dermal irritation scores and observations

Animal No. (Ear No.)	Sex	Response	1 hour	24 hours	48 hours	72 hours	6 days	8 days	10 days	14 days
1 (51227)	M	Erythema	3 x	4 xV	4 xVP	4 xVP	WScp	WScp	WScp	Na
		Oedema	4	4	4	4
2 (51231)	M	Erythema	3 x	4 xV	4 xVP	4 xVP	WScp	WScp	Scp	Scp iA
		Oedema	4	4	4	4
3 (51371)	M	Erythema	3 x	4 xV	4 xVP	4 xVP	WScp	WScp	Scp	Scp abgelöst Na

x= yellow coloration in applicated area (Gelbfärbung im Applikationsbereich)

V= hardening in applicated area(Verhärtung im Applikationsbereich)

W= wavily, can be imprinted (Wellig, last sich eindrücken)

P= perkamen-like (pergamentartig)

Scp=crust (Schorfplatte)

blNa= bloody scars (bluttige Narben)

Na=Scars (Narben)

Ri= Cracked (rissig)

iA= In replacement (in Ablösung)

 

Interpretation of results:

Category 2 (irritant)

Remarks:

Criteria used for interpretation of results: other: EU GHS

Conclusions:

Irriation index = 7.8/8.

Executive summary:

A volume of 0.5 mL Docusate sodium (70% solution in ethanol/methanol and water) was applied according to OECD 404 on 6 cm2 shaved skin of 3 male rabbits by occlusive application. After this period, the skin area was washed with warm water and observed after 1, 24, 48, 72 hours and 6, 8, 10 and 14 days. The results showed that there was an irritation index of 7.8/8 over the 1 -72 hour period and effects were still visible at 14 days.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to internationally accepted test guidelines. As the test material also contains ethanol and methanol, these ingredients may have potential influence on the irritation score.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

other: White Russian, Chbb-SPF

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source:Fa. Dr. Karl Thomae GmbH, Binerach
- Weight at study initiation: 2,2 - 2,6 kg
- Housing: Stainless Steel cages
- Diet (e.g. ad libitum): K4 Alleindiät für Kaninchen, Ssniff Spezialfutter GmbH, 4770 Soest, ad libitum
- Water (e.g. ad libitum): public supply, ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20°C +- 1°C
- Humidity: 60% +- 5%
- Air changes (per hr): 15 air changes / hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1988-02-23 To: 1988-03.15

Vehicle:

unchanged (no vehicle)

Controls:

other: same animals, left eye as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0,1 mL
- Concentration (if solution): 70% Diisoctylsulfosuccinat-Natriumsalz

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

1, 24, 48 and 72 hours; 6, 8, 10, 13, 17 and 21 days

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE (eye irritation 1206)
- Washing (if done): warm physiological NaCl solution
- Time after start of exposure: 72 hours

SCORING SYSTEM: after Draize

TOOL USED TO ASSESS SCORE: sodium fluorescein solution and eye lamp

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1h, 24h, 48h, 72h

Score:

ca. 47

Max. score:

110

Reversibility:

not reversible

Remarks on result:

other: MARLINAT DF 8

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 17 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 17 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: mean of 17 and 21 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: mean of 17 and 21 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritant / corrosive response data:

See Tables 1, 2 and 3.

Table 1: Cornea evaluation

Rabbit   Ear No.	Sex	Response	1 hour	24 hours	48 hours	72 hours	6 days	8 days	10 days	13 days	17 and 21days
51197	M	T	1	1	2	2	2	2	2	3	3
		R	4	4	4	4	3	3	2	1	1
		TxRx5	20	20	40	40	30	30	20	15	15
51251	M	T	1	1	2	2	2	2-	2	3	3
		R	4	4	4	4	3	2	2	1	1
		TxRx5	20	20	40	40	30	20	20	15	15
51255	M	T	1	1	2	2	2	2 *	2 *	2	3
		R	4	4	4	4	4	4	4	4	3
		TxRx5	20	20	40	40	40	40	40	40	45
		x absolut	20,00	20,00	40,00	40,00	33,33	30,00	26,67	23,33	25,00

T= Turbidity

R= Range of turbidity

* clear white ring on the pupil

 

Table 2: Iris evaluation

Rabbit   Ear No.	Sex	Response	1 hour	24 hours	48 hours	72 hours	6 days	8 days	10 and 13 days	17 and 21 days
51197	M	T	1 x	1*	1 x	1 x	1 xc	1c	1c	1c
		Tx5	5	5	5	5	5	5	5	5
51251	M	T	1 x	1 *	1 *	1 *	1 *c	1 xc	1 c	1 c st
		Tx5	5	5	5	5	5	5	5	5
51255	M	T	1 x	1 x	1 x	1 *	1 *c	1 *c	1 xc	1 c st
		Tx5	5	5	5	5	5	5	5	5
		x absolute	5,00	5,00	5,00	5,00	5,00	5,00	5,00	5,00

T= Change

x= iris turned partially red

*= iris turned clearly red

c= circumcorneal injection

st= strong

 

Table 3: Conjunctiva evaluation

Rabbit   Ear No.	Sex	Response	1 hour	24 hours	48 hours	72 hours	6 days	8 days	10 days	13 days	17 and 21 days
51197	M	A	2	3	3 +b	3 +b	2	2	1	1	0
		B	1	1	1	1	1	1	0	0	0
		C	3	3	2	2	0	0	0	0	0
		(A+B+C)x2	12	14	12	12	6	6	2	2	0
51251	M	A	2	3	3 +	3 +	2	2	2	2	0
		B	1	1	1	1	1	1	1	1	0
		C	2	2	0	0	1	0	0	0	0
		(A+B+C)x2	10	12	8	8	8	6	6	6	0
51255	M	A	2	3	3 +	3 +	2	2	2	1	1
		B	1	1	1	1	1	1	0	0	0
		C	3	3	2	3	0	0	0	0	0
		(A+B+C)x2	12	14	12	14	6	6	4	2	2
		x absolut	11,33	13,33	10,67	11,33	6,67	6,00	4,00	3,33	0,67

A= Erythema

B= Oedema

C= Exsudation

b=bloody secretion

+= epidermis and mucosa hemorrhagic, slightly corroded

 

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Criteria used for interpretation of results: other: EU GHS

Conclusions:

Irritation index = 46,67/110.

Executive summary:

A volume of 0.1 mL Docusate sodium (70% solution in ethanol/methanol and water) was applied unilaterally in the eyes of 3 male rabbits according to OECD 405 method. After 72 hours, fluorescein solution was applied for cornea evaluation and rinsing was performed with warm physiological solution. Evalution after 1, 24, 48 and 72 hours and 6, 8, 10, 13, 17 and 21 days after application showed irriversible damage (including turbidity of the cornea). The mean overall irritation score for 1 -72 hours was 46,67/110.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A key study for skin irritation was performed in rats according to OECD 404 test guideline, which was considered to be reliable, adequate and relevant (Elementis, Mürmann 1988). A volume of 0.5 mL Docusate sodium (70% solution in ethanol/methanol and water) was applied on 6 cm2 shaved skin of 3 male rabbits by occlusive application. After this period, the skin area was washed with warm water and observed after 1, 24, 48, 72 hours and 6, 8, 10 and 14 days. The results showed that there was an irritation index of 7.8/8 over the 1 -72 hour period and some effects were still visible at 14 days.

A support study was conducted by application of 0.5 mL Docusate sodium 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 (Cytec, McGinty 1977a). 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. There was one other exploratory study in 2 rabbits which were exposed for 24 hours and evaluated after 24 and 72 hours, also showing eye irritating up to 72 hours (Dow, Rohm & Haas1974). As the latter study was exploratory, this was disregarded for the safety evaluation.

A key study for eye irritation was conducted with Docusate sodium according to OECD 405 test guideline, which was considered to be reliable, adequate and relevant (Elementis, Mürmann 1988). A volume of 0.1 mL Docusate sodium (mixture of 70% docusate sodium, ethanol in methanol, water) was applied to the eyes of 3 male rabbits. After 72 hours, fluorescein solution was applied for cornea evaluation and rinsing was performed with warm physiological solution. Evaluation after 1, 24, 48 and 72 hours and 6, 8, 10, 13, 17 and 21 days after application showed irreversible damage (including turbidity of the cornea). The mean overall irritation score for 1 -72 hours was 46,67/110.

A support study was conducted by application of a volume of 0.1 mL (0.1g) Docusate sodium to the eyes of 6 rabbits according to FHSA (Federal Hazard Substance Act) and CFR 1500.41 method. 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 (Cytec, McGinty 1977a). There was one other exploratory study in 2 rabbits which were evaluated after 24, 48 and 72 hours, also showing eye irritating up to 72 hours (Dow, Rohm & Haas 1974). As the latter study was exploratory, this was disregarded for the safety evaluation.

In summary, both skin and eye irritation studies were available showing that Docusate sodium is irritating to skin and resulting in irreversible eye damage, resulting in the need for classification and labeling.

Effects on skin irritation/corrosion: highly irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

Based on the strong skin irritation (EU GHS category 2) and irreversible eye damage (EU GHS category 1), classification is warranted.