Dodecanoic acid, 1-methyl-2-sulfoethyl ester, sodium salt (1:1)

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Guideline:

other: In house method

Principles of method if other than guideline:

Eight animals were exposed to each of the test materials applied under individual semi occlusive patches for 4 hours after which the area was wiped clean of any excess material. Treatments were sited in a randomised manner.
Irritation reactions were assessed immediately after removal of the patch and at 24, 48 and 72 hours.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8-12 weeks

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

Test material was applied as supplied or diluted in distilled water to give concentrations of 10, 25, 40, 55 and 70% active substance.
0.2 g solid test substance (i.e. substance as supplied) was applied to moistened pad or 0.5 ml of test solution applied to dry pad.

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

8 rabbits used in study. Six test groups investigated. Each rabbit received all six test groups.

Details on study design:

TEST SITE
- Area of exposure: A 2.5 cm square of 8 ply cotton gauze folded in was laid on the polythene such that the edges of the pad were attached to the zinc oxide plaster. The patches were firmly attached to ensure good contact between the skin and test substance.
- % coverage:
- Type of wrap if used: Thin flexible polythene (3 x 3 cm) was attached to a piece of zinc oxide plaster (9 x 2.5 cm).


REMOVAL OF TEST SUBSTANCE
When the test patches are removed the treatment sites are wiped clean of excess material.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
cracking using an 8 point scale, ranging from very slight (1) to severe (8).
-: no reaction
a : marginal/very slight
b : slight
c: fairly distinct
d: quite distinct
e: becoming well developed
f: well developed
g: becoming severe
h: severe

An overall irritation score was calculated as follows:

0: normal skin -
1: marginal slight erythema and oedema (grade a) at 24 hours but no effects at 72 hours
2: slight slight erythema and oedmema (grades up to bbbb) at 24 and 72 hours
3: slight/moderate slight/moderate erythema and oedema (grades ca /cc) at 24 hours. The reaction generally reduces to slight at 72 hours but sometimes the slight/moderate reaction may be maintained.
4: moderate moderate erythema and oedema (grades c and d) with slight cracking and scaling at 24 hours with the erythema and oedema being maintained at least at slight/moderate level with cracking and scaling developed at 72 hours
5: Strong As for 4 above or greater erythema and oedema with evidence of up to ¼ of the site affected by necrosis.
6: Severe Most of the site affected by suspected necrosis
7: Extreme Deep necrosis over the whole site identified by depressed, hard scab/ tissue and surrounding inflammatory reaction.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

Treatment Group A

Time point:

24/48/72 h

Score:

1.21

Irritation parameter:

erythema score

Basis:

mean

Remarks:

Treatment Group B

Time point:

24/48/72 h

Score:

1.79

Irritation parameter:

erythema score

Basis:

mean

Remarks:

Treatment Group C

Time point:

24/48/72 h

Score:

1.83

Irritation parameter:

erythema score

Basis:

mean

Remarks:

Treatment Group D

Time point:

24/48/72 h

Score:

0.96

Irritation parameter:

erythema score

Basis:

mean

Remarks:

Treatment Group E

Time point:

24/48/72 h

Score:

0.92

Irritation parameter:

erythema score

Basis:

mean

Remarks:

Treatment Group F

Time point:

24/48/72 h

Score:

1.375

Irritation parameter:

edema score

Basis:

mean

Remarks:

Treatment Group A

Time point:

24/48/72 h

Score:

0.96

Irritation parameter:

edema score

Basis:

mean

Remarks:

Treatment Group B

Time point:

24/48/72 h

Score:

1.25

Irritation parameter:

edema score

Basis:

mean

Remarks:

Treatment Group C

Time point:

24/48/72 h

Score:

1.5

Irritation parameter:

edema score

Basis:

mean

Remarks:

Treatment Group D

Time point:

24/48/72 h

Score:

0.79

Irritation parameter:

edema score

Basis:

mean

Remarks:

Treatment Group E

Time point:

24/48/72 h

Score:

0.66

Irritation parameter:

edema score

Basis:

mean

Remarks:

Treatment Group F

Time point:

24/48/72 h

Score:

1

Exposure to the test material as supplied, resulted in only marginal/very slight to slight erythema and oedema in the most animals and time points.

At the 24 hour time point, one animal (351) showed quite distinct erythema and one animal (404) fairly distinct erythema.  At 48 hours this was reduced to slight erythema in both of these animals, with all other animals either showing marginal/slight effects or no reaction.   At 72 hours all animals except 351 (which showed slight erythema) had either no reaction or marginal/very slight erythema or oedema. Marginal/ slight cracking  and scaling was observed in three animals and was still evident in two of these at the 72 hour time point

When the test substance was diluted in water to give a 70% a.i. concentration, only marginal/very slight or slight erythema and oedema was observed in all animals at 4 hours and 24 hours (apart from animal 404 where fairly distinct erythema was observed at 24 hours).   After 48 and 72  hours skin was normal in the majority of cases, with only two animals exhibiting marginal/slight erythema and oedema.  In these animals marginal/slight cracking and scaling was observed at the 72 hours time point

The study was not extended past the 72 hour time point, and therefore it is not possible to determine how long the reactions still evident at 72 hours would have persisted

An interpolation of the recorded results to the Draize scale gives the following results. The totals presented are mean scores from the treatment groups.

Treatment Group	24 hours		48 hours		72 hours		Mean 24 -72 hours
	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema	Erythema	Oedema
A= 10% ai	1.75	1.125	1.125	1	0.75	0.75	1.21	0.96
B= 25% ai	1.875	1.375	1.75	1.125	1.75	1.25	1.79	1.25
C= 40% ai	1.75	1.625	2	1.375	1.75	1.5	1.83	1.5
D= 55% ai	1.375	1	0.875	0.875	0.625	0.5	0.96	0.79
E= 70% ai	1.375	1.125	0.625	0.375	0.75	0.5	0.92	0.66
F= as supplied	1.75	1.25	1.25	1	1.125	0.75	1.375	1

These scores indicate that the solutions of SCI are mildly irritating.

Interpretation of results:

slightly irritating

Remarks:

Migrated information

Conclusions:

The results of the study indicate that the test substance produced some irritation to rabbit skin, which was reversible. However, the test was not extended past 72 hours, so it is not possible to demonstrate conclusively when the oedema, erythema, cracking and scaling was resolved. These effects were only scored as slight by the 72 hour time point and therefore it is likely that skin would have returned to normal should the test have been continued to 14 days.

Reference 2

Endpoint:

skin irritation / corrosion

Remarks:

other: Review report

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Principles of method if other than guideline:

Review of available data on SCI

GLP compliance:

no

Irritation / corrosion parameter:

other: Primary irritation (PDII) score

Value:

2.24

Irritation / corrosion parameter:

other: Primary irritation (PDII) score

Value:

2.4

Irritation / corrosion parameter:

other: Primary irritation (PDII) score

Value:

> 0.4 - < 0.5

Irritation / corrosion parameter:

other: Primary irritation (PDII) score

Value:

1.38

Irritation / corrosion parameter:

other: Primary irritation (PDII) score

Value:

4.5

In a study by Wo and Shapiro (1984), the resultant primary irritation (PDII) score was 2.24 (moderately irritating). 

The studies by van Baaren, Baszcak and Nitka and Palanker, resulted in moderate, mild, and mild irritation and PDII scores of 2.4, 0.4-0.5, and 1.38 for the three studies, respectively. 

The study by Lodestedt had a PDII score of 4.5 (see full summary provided separately).

Interpretation of results:

other: mildly to moderating irritating

Remarks:

Criteria used for interpretation of results: US EPA pesticides

Conclusions:

The authors concluded that the sum total of these five studies demonstrate that SCI is only mildly to moderately irritating to the skin.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Guideline:

other: In house method

Principles of method if other than guideline:

0.5 g of the test substance was applied to the intact and abraded skin of New Zealand white rabbits for a period of 24 hours. Skin was evaluated at 24 and 72 hours and scored for erythema/eschar and oedema.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

not specified

Preparation of test site:

abraded

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

24 hours

Observation period:

Up to 14 days

Number of animals:

6

Irritation parameter:

overall irritation score

Remarks:

Abraded skin

Basis:

mean

Time point:

24 h

Score:

2.7

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of mild irritation

Irritation parameter:

overall irritation score

Remarks:

Intact skin

Basis:

mean

Time point:

24 h

Score:

1.8

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of mild irritation

Irritation parameter:

erythema score

Remarks:

Intact skin

Basis:

mean

Time point:

24/48/72 h

Score:

2.15

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of mild irritation

Irritation parameter:

erythema score

Remarks:

Abraded skin

Basis:

mean

Time point:

24/48/72 h

Score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of mild irritation

Irritation parameter:

edema score

Remarks:

Intact skin

Basis:

mean

Time point:

24/48/72 h

Score:

1.5

Irritation parameter:

edema score

Remarks:

Abraded skin

Basis:

mean

Time point:

24/48/72 h

Score:

2.3

	Exposure time (hours)	Average value
Erythema and Eschar Formation
Intact Skin	24	2.3
	72	2.0
Abraded Skin	24	3.0
	72	3.0
Edema Formation
Intact Skin	24	1.7
	72	1.3
Abraded Skin	24	2.3
	72	2.3
Total Score ¿ Intact Skin		1.8
Total Score ¿ Abraded Skin		2.7
Combined Score		4.5

Interpretation of results:

slightly irritating

Remarks:

Criteria used for interpretation of results: US EPA pesticides

Conclusions:

The report concludes that the test substance was moderately irritating (Primary Irritation Index 4.5) and that severe effects found in one animal were reversed by 14 days.  However, two things are noted
1) the exposure period is 24 hours rather than the current OECD recommendation of 4 hours.  Therefore, exposure was much more severe than the current OECD guideline recommendation of 4 hours. 
2) total score for Primary Irritation Index is based on intact and abraded skin.  The total score for Intact skin only was 1.8 and therefore slightly irritating.

Reference 4

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Principles of method if other than guideline:

Approximately 0.1-0.15g of each test article was placed onto a Parke-Davis Readi-Bandage occlusive patch that measured 2cm by 2cm. The patch was then applied to the back of each subject between the scapulae and the waist, adjacent to the spinal mid line. Patching occurred for 14 consecutive days. Each day following application, the patches were removed, the sites were evaluated and identical patches were reapplied to the same test sites. Evaluations were made according to a 6 point scale.

GLP compliance:

no

Species:

human

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

water

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.15 g per day

Duration of treatment / exposure:

14 days . Fresh treatment applied each day.

Number of animals:

22 volunteers

Details on study design:

A 14 day cummulative irritation study using 14 test articles on 22 subjects. 0.1-0.15 g per day of each test item was applied to the back of each test subject. The irritant reponses were quantified by visual clinical evaluation

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

14 d

Score:

20

Max. score:

56

Remarks on result:

probability of mild irritation

For SLMI the total cummulative irritancy score was 400 with a mean score of 20. The highest potential mean irritation score was 56. This indicates that SLMI is mildly-moderately irritating with pink/red erythema covering the contact site.

SLMI was ranked lower in irritancy than SCI, which is also not classified for skin irritancy

Interpretation of results:

other: mildly-moderately irritating

Remarks:

Criteria used for interpretation of results: expert judgment

Conclusions:

For SLMI the total cummulative irritancy score was 400 with a mean score of 20. The highest potential mean irritation score was 56. This indicates that SLMI is mildly-moderately irritating with pink/red erythema covering the contact site.

SLMI was ranked lower in irritancy than SCI, which is also not classified for skin irritancy

Reference 5

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Guideline:

other: Study conducted according to MatTek EpiDerm in vitro toxicity system

Principles of method if other than guideline:

MatTek's EpiDerm Skin Model consists of normal, human-derived epidermal keratinocytes (NHEK) which have been cultured to form a multilayered, highly differentiated model of the human epidermis.

GLP compliance:

yes

Species:

human

Details on test animals or test system and environmental conditions:

TEST Cells
- Source: Human-derived epidermal keratinocytes (NHEK) which have been cultured to form a multilayered, highly differentiated model of the human epidermis.

Type of coverage:

other: EpiDerm Skin Model consists of normal, human-derived epidermal keratinocytes (NHEK) which have been cultured to form a multilayered, highly differentiated model of the human epidermis

Vehicle:

unchanged (no vehicle)

Duration of treatment / exposure:

1-20 hours
The exposure period for the negative controls was 4.5 hours.

Details on study design:

SCORING SYSTEM:
ET-50 hrs Expected in vivo irritancy Example
>0.5 Severe, Probably corrosive, Conc Nitric acid
0.5-4 Moderate 1% Sodium Dodecyl sulphate
4-12 Moderate - mild 1% Triton X-100
12-24 Very mild Baby shampoo
24 Non irritating 10% Tween 20

Irritation / corrosion parameter:

other: Expected in vivo irritancy response

Run / experiment:

ET-50 (estimated time for 50% cellular dysfunction) in hours

Value:

2.6

Remarks on result:

other:

Remarks:

Remarks: Tauranol I-78 Flakes 5% solution is classified as a moderate irritant. (migrated information)

Test substance	Conc	Exposure	Average% viability	ET50 (hr)	Classification
Tauranol 1-78-E	5%	20 hr	7	2.6	moderate
		4.5 hr	27
		1 hr	86
Triton X-100	1%	20 hr	8	7	mild/moderate
		4.5 hr	67
		1 hr	94
Water	100%	4.5 hr	100	NA	NA

Under the conditions of the study, Tauranol I-78 Flakes 5% solution, elicited in vitro results which indicate an ET-50 of approximately 2.6 hours.  This corresponds to an estimated dermal irritancy potential in the moderate range.

Interpretation of results:

moderately irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Under the conditions of the study, Tauranol I-78 Flakes 5% solution elicited an in vitro response that corresponded to an in vivo dermal irritancy potential in the moderate range.

Reference 6

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study conducted following the MatTek EpiDerm invitro toxicity system.

Principles of method if other than guideline:

Study conducted according to MatTek EpiDerm in vitro toxicity system

GLP compliance:

yes

Species:

human

Type of coverage:

other: EpiDerm Skin Model consists of normal, human-derived epidermal keratinocytes (NHEK) which have been cultured to form a multilayered, highly differentiated model of the human epidermis

Controls:

yes

Duration of treatment / exposure:

1-20 hours

Observation period:

1-20 hours

Number of animals:

Not applicable

Irritation / corrosion parameter:

other: Expected in vivo irritancy response

Run / experiment:

ET-50 (estimated time for 50% cellular dysfunction) in hours

Value:

2.5

Remarks on result:

other:

Remarks:

Remarks: Pureact SLMI-85 5% is classified as a moderate irritant. (migrated information)

The following results were obtained:

Test substance	Conc	Exposure	Average% viability	ET50(hr)	Classification
Pureact SLMI-85 5% Active Solution	5%	20 hr	12	2.5	moderate
		4.5 hr	15
		1 hr	106
Triton X-100	1%	20 hr	10	8.2	mild/moderate
		4.5 hr	77
		1 hr	96
Water	100%	NA	NA	NA	NA

 

Under the conditions of the study, Pureact SLMI-85 5% Active Solution, elicited in vitro results which indicate an ET-50 of approximately 2.5 hours. This corresponds to an estimated dermal irritancy potential in the moderate range.

Interpretation of results:

moderately irritating

Remarks:

Migrated information

Conclusions:

Under the conditions of the study, Pureact SLMI-85 5% Active Solution elicited an in vitro response that corresponded to an in vivo dermal irritancy potential in the moderate range.

Reference 7

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study performed using the MatTek EpiDerm in vitro toxicity system

Principles of method if other than guideline:

Study conducted according to MatTek EpiDerm in vitro toxicity system

GLP compliance:

yes

Species:

human

Type of coverage:

other: EpiDerm Skin Model consists of normal, human-derived epidermal keratinocytes (NHEK) which have been cultured to form a multilayered, highly differentiated model of the human epidermis

Controls:

yes

Duration of treatment / exposure:

1-20 hours

Observation period:

1-20 hours

Number of animals:

Not applicable

Irritation / corrosion parameter:

other: Expected in vivo irritancy response

Run / experiment:

ET-50 (estimated time for 50% cellular dysfunction) in hours

Value:

2.9

Remarks on result:

other:

Remarks:

Remarks: Pureact SLMI-85 10% Active Solution is classified as a moderate irritant. (migrated information)

The following results were obtained:

 

Test substance	Conc	Exposure	Average% viability	ET50(hr)	Classification
Pureact SLMI-85 10% Active Solution	5%	20 hr	10	2.9	moderate
		4.5 hr	25
		1 hr	100
Triton X-100	1%	20 hr	10	8.2	mild/moderate
		4.5 hr	77
		1 hr	96
Water	100%	NA	NA	NA	NA

 

Under the conditions of the study, Pureact SLMI-85 10% Active Solution, elicited in vitro results which indicate an ET-50 of approximately 2.9 hours. This corresponds to an estimated dermal irritancy potential in the moderate range.

Interpretation of results:

moderately irritating

Remarks:

Migrated information

Conclusions:

Under the conditions of the study, Pureact SLMI-85 10% Active Solution elicited an in vitro response that corresponded to an in vivo dermal irritancy potential in the moderate range.

Reference 8

Endpoint:

skin irritation / corrosion

Remarks:

other: Review report

Type of information:

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

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Principles of method if other than guideline:

The author provides a comprehensive review of the manufacture, properties and applications of the anionic surfactants known as taurates and isethionates (fatty acids sulphoalkyl amide and esters, respectively).  This includes a review of the toxicological properties, with emphasis on the skin irritancy.

GLP compliance:

no

In the paper, the lack of skin irritation is documented as the most noteworthy (toxicological) feature of the isethionates.  Petter refers to reviews by other authors (Frosch, 1982; Fremaux, 1982) to substantiate this.  A review by Frosch found that isethionate based bars were milder than any other product. 

Data published by Fremaux demonstrates the mildness of SCI to skin compared to other commonly used anionic and amphoteric surfactants.  In Fremaux's study the following surfactants were tested for irritancy on intact rabbit skin (various concentrations, ranging from 1.8 to 28%, kept in contact with shaved skin for 24 hours), to give an irritation rating versus concentration:

Sodium lauryl sulphate,

TEA-lauryl sulphate,

Cocounut acid cycloimidinium derivative,

ammonium laureth-3-sulphate

sodium cocoyl isethionate

Fremaux found that irritancy decreased in the order given above, with alkyl sulphates (e.g. sodium lauryl sulphate) being the most irritant and isethionate showing only negligible irritation As reported by Petter, the reduced differences in irritancy have been related to the effects of surfactants in reducing water binding capacity of the stratum corneum.  The author refers to a study by Middleton (1969), which demonstrates that sodium lauryl sulphate can extract lipid from the corneum cell walls, resulting in increasing permeability and allowing the escape of intracellular water soluble substances, responsible for much of the water binding ability.  SLI was found to extract less material from the cell wall and had little effect on water binding.  The study by Fremaux also found water binding data consistent with this for these two types of surfactants.

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Data reviewed by the author demonstrate that isethionates, including SCI have low irritancy to skin.

Reference 9

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Principles of method if other than guideline:

MatTek's EpiDerm Skin Model consists of normal, human-derived epidermal keratinocytes (NHEK) which have been cultured to form a multilayered, highly differentiated model of the human epidermis.

GLP compliance:

not specified

Species:

human

Details on test animals or test system and environmental conditions:

Human-derived epidermal keratinocytes (NHEK) which have been cultured to form a multilayered, highly differentiated model of the human epidermis.

Duration of treatment / exposure:

1-24 hours

Details on study design:

SCORING SYSTEM:
ET-50 hrs Expected in vivo irritancy Example
>0.5 Severe, Probably corrosive, Conc Nitric acid
0.5-4 Moderate 1% Sodium Dodecyl sulphate
4-12 Moderate - mild 1% Triton X-100
12-24 Very mild Baby shampoo
24 Non irritating 10% Tween 20

Irritation / corrosion parameter:

other: Expected in vivo irritancy response

Run / experiment:

ET-50 (estimated time for 50% cellular dysfunction) in hours

Value:

9.79

Remarks on result:

other:

Remarks:

Remarks: Tauranol I-78 was classified as a mild irritant. (migrated information)

Test substance	Conc	Exposure	Average% viability	ET50 (hr)	Classification
Tauranol 1-78-E	5%	1 hr	89.2	9.79	mild
		4 hr	53.3
		24 hr	8.7
Triton X-100	1%	1 hr	84.7	12.47	very mild
		4 hr	88.0
		24 hr	8.1
Water	neat	1 hr	na	na	na
		4 hr	na
		24 hr	na

Under the conditions of the study, Tauranol I-78 elicited in vitro results which indicate an ET-50 of approximately 9.79 hours.  This corresponds to an in vivo dermal irritancy potential in the mild range.

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Under the conditions of the study, Tauranol I-78 was classified as a mild irritant.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

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: see 'Remark'

Remarks:

The study was only carried out for 7 days and the effects are not fuly reversibel within that time period but the a decrease in severty was seen over a period of 7 days. Therefore the assumption is made that the effests are likely to be fully reversible within 21-days and the study may be used for C&L.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Remarks:

audited inhouse

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harald Schriever, Kaninchenfarm D -2740 Bremervorde, Neuendamm 88
- Age at study initiation: no data
- Weight at study initiation: 2.4 - 2.8 kg
- Housing: Single caging in battery of cages size: 40 cm high, 45 cm wide, 50 cm long with paper roll disposal system.
- Diet (e.g. ad libitum): ad libitum
Producer: Ssniff Spezialfutter GmbH, 4770 Soest/ Westfalen, Name: Ssniff Mu Z (Alleindiat fur Zuchtkaninchen) Type: pellets, 1.0 - 1.5 cm large, 0.5 cm diameter
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 2
- Humidity (%): 50-85
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: no data

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

0.1 g of the testmaterial was placed into the conjunctival sac of the left eye while the right eye served as I control. On animal 4- 6 the treated eye was carefully washed out 4 sec p.a. with lukewarm water.

Observation period (in vivo):

Prior to treatment, 24 hours p. a. and if necessary 7 days p. a., the eyes were examined for potential eyelesions by means of 1 % Fluorescin. The eyes were scored at 1, 2, 8 hours and 1, 2, 3, 4, 5, 6 and 7 days after treatment.

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): On animal 4- 6 the treated eye was carefully washed out
- Time after start of exposure: 4 sec p.a. with lukewarm water


SCORING SYSTEM: DRAIZE
Scoring system eye irritation

Cornea: degree of density (area most dense taken for reading)
0 No ulceration or opacity
1 Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible
2 Easily discernible translucent areas, details of iris slightly obscured
3 Nacrous areas, no details of iris visible, size of pupil barely discernible
4 Opaque cornea, iris not discernible through the opacity

Area of Cornea Involved
1 One quarter (or less) but not zero
2 Greater than one quarter but less than half
3 Greater than half but less than three quarters
4 Greater than three quarters, up to whole area

Iris
0 Normal
1 Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof) Iris still reaction to light (sluggish reaction is positive)
a x 5, total maximum = 10 No reaction to light .Hemorrhage. Gross destruction (any or all of these) (2)

Conjunctivae
Redness (refers to palpebral and bulbar conjunctivae cornea and iris)

0 Blood vessels normal
1 Some blood vessels definitely hyperaemic
(injected)
2 Diffuse, crimson colour, individual vessels not easily discernible
3 Diffuse, beefy red

Chemosis (lids and/or nictitating membranes)
0 No swelling 0
1 Any swelling above normal (includes nictitating membranes)
2 Obvious swelling with partial eversion of lids
3 Swelling with lids about half-closed
4 Swelling with lids more than half-closed

Discharge
0 No discharge
1 Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2 Discharge with moistening of the lids and hairs just adjacent to lids
3 Discharge with moistening of the lids and hairs a considerable area around the eye
Score (a + b + c ) x 2 Total maximum = 20

TOOL USED TO ASSESS SCORE: no data

Irritation parameter:

overall irritation score

Basis:

mean

Remarks:

animals 1-3

Time point:

24/48/72 h

Score:

1.2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks:

The study was terminated after 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1.3

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

2.3

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.7

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.7

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2.7

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

2

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

2.3

Irritant / corrosive response data:

After treatment none of the animals showed any effects on the cornea. One hour after treatment effects on the Iris were observed in all animals. One animal from the group where the eye was not washed out did not react to light up to 5 days after treatment. In two animals from this group effects on the Iris were not fully reversible, in one animal the effests disappeared after 5 days. In the group where the eyes were washed out after 4 seconds effects were not fully reversible in one animals and in the two other animals effects were gone on day 2 or 4. Conjunctivae were affected in all animals with 4 as the highest score in one animal for chemosis. In the first group on day 2 effects started to decrease but were only fully reversible within 7 days in one animal. In the second group the same effects were observed but only less severe with a highest score of 3. In two animals effects were fully reversible on day 4 or 5, in the third animals effects were not fully reversible after 7 days.

Without removal of the test substance

Rabbit No and sex	Region of the eye			Hours after instillation			Average 24-48-72hours
				24	48	72
1	Cornea	Degree of opacity		0	0	0	0
		Area of opacity		0	0	0	0
	Iris			2	2	2	2
	Conjunctivae		Redness	3	3	2	2.7
			Chemosis	3	3	2	2.7
			Discharge	2	2	1	1.7
2	Cornea	Degree of opacity		0	0	0	0
		Area of opacity		0	0	0	0
	Iris			1	1	1	1
	Conjunctivae		Redness	3	1	1	1.7
			Chemosis	3	2	1	2
			Discharge	2	1	1	1.7
3	Cornea	Degree of opacity		0	0	0	0
		Area of opacity		0	0	0	0
	Iris			1	1	1	1
	Conjunctivae		Redness	3	1	1	1.7
			Chemosis	4	2	2	2.7
			Discharge	2	2	1	1.7

Removal of the test substance after 4 seconds

Rabbit No and sex	Region of the eye			Hours after instillation			Average 24-48-72hours
				24	48	72
4	Cornea	Degree of opacity		0	0	0	0
		Area of opacity		0	0	0	0
	Iris			1	1	1	1
	Conjunctivae		Redness	3	3	3	3
			Chemosis	3	3	2	2.7
			Discharge	2	2	2	2
5	Cornea	Degree of opacity		0	0	0	0
		Area of opacity		0	0	0	0
	Iris			1	1	1	1
	Conjunctivae		Redness	3	1	1	1.3
			Chemosis	3	2	1	2
			Discharge	2	0	0	0.7
6	Cornea	Degree of opacity		0	0	0	0
		Area of opacity		0	0	0	0
	Iris			1	0	0	0.3
	Conjunctivae		Redness	3	2	2	2.3
			Chemosis	3	2	2	2.3
			Discharge	2	0	0	0.7

Interpretation of results:

highly irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

An eye irritation study was carried out according to OECD 405 and in-house quality assurance was in place.

The test substance causes a score of ≥ 1 for iris and a ≥ 2 score for chemosis. The effects are not fully reversible within 7 days but the a decrease in severity was seen over a period of 7 days. Therefore the assumption is made that the effects are likely to be fully reversible within 21-days and the substance is classified in category 2 (causes serious eye irritation).

Executive summary:

An eye irritation study was carried out according to OECD405 and inhouse quality assurance was in place.

0.1g of the test substance (white powder) was instilled in the eyes of 6 rabbits. In 3 rabbits the eyes were washed after 4 seconds. Prior to treatment, 24 hours post application and if necessary 7 days post application, the eyes were examined for potential eyelesions by means of 1 % Fluorescin.

The eyes were scored at 1, 2, 8 hours and 1, 2, 3, 4, 5, 6 and 7 days after treatment.

After treatment in none of the animals effects on the cornea were observed. One hour after treatment effects on the Iris were observed in all animals. One animal from the group with unwashed eyse did not react to light up to 5 days after treatment. In two animals from this group effects on the Iris were not fully reversible, in one animal the effests disappeared after 5 days.

In the group where the eyes were washed out after 4 seconds effects were not fully reversible in one animals and in the two other animals effects were gone on day 2 or 4. Conjunctivae were affected in all animals with 4 as the highest score in one animal for chemosis.

In the first group on day 2 effects started to decrease but were only fully reversible within 7 days in one animal.

In the second group the same effecst were observed but only less severe with a higest score of 3. In two animals effects were fully reversible on day 4 or 5, in the third animals effects were not fully reversible after 7 days.

The test substance causes a score of ≥ 1 for iris and a ≥ 2 score for chemosis. The effects are not fully reversible within 7 days but the a decrease in severty was seen over a period of 7 days. Therefore the assumption is made that the effests are likely to be fully reversible within 21-days and the substance is classified in category 2, causes serious eye irritation.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Not performed according to GLP or OECD guideline but conducted in a manner similar to OECD 405.

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Recover period was only 7 days after treatment

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazelton-Dutchland, Inc. Denver, Pennsylvania
- Age at study initiation: young adults
- Weight at study initiation: 2.2 to 2.7 kg
- Housing: individually housed; suspended, stainless steel cages
- Diet (e.g. ad libitum): purina lab rabbit chow HF (#5326) ad libitum
- Water (e.g. ad libitum):automatic watering system, ad libitum; municipal water supply
- Acclimation period:21 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 60-70 degrees F; monitored and recorded twice daily
- Humidity (%): 30-70% monitored and recorded once daily
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark


IN-LIFE DATES: From: 1985-02-18 To: 1985-02-25

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1mL
- Concentration (if solution): 15% active ingredient


VEHICLE
not applicable

Duration of treatment / exposure:

7 days (eyes were not washed)

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6 (4 females, 2 males)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: not applicable


SCORING SYSTEM: Draize*


TOOL USED TO ASSESS SCORE: fluorescein


*Total Draize score is the sum of the three scores obtained (cornea, iris, cunjuctivae)

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Score:

<= 23.3

Max. score:

23.3

Reversibility:

not specified

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

48 h

Score:

<= 14.3

Max. score:

14.3

Reversibility:

not specified

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

<= 7

Max. score:

7

Reversibility:

not specified

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

7 d

Score:

<= 1.7

Max. score:

1.7

Reversibility:

not specified

Other effects:

No apparent discomfort, as demonstrated by squealing, was noted at the time of instillation of the test material.
No mortality was observed during the course of the study.

The maximum average score, which occurred on Day 1, was 23.3. The test item produced moderate and transient ocular irritation. Most animals exhibited moderate conjunctival irritation (redness, chemosis, discharge), iridial changes and corneal opacities. ulceration and stippling. One animal was free of any ocular irritation within 7 days after instillation of the test material. The five remaining animals exhibited slight conjunctival irritation but were free of any corneal irritation at study termination (Day 7).

Interpretation of results:

irritating

Remarks:

Criteria used for interpretation of results: other: US 16 CFR 1500.3(c) [Consumer Product Safety Commission, Federal Hazardous Substances Act Regulations]

Conclusions:

According to the study report, the test material, 648-01 is considered to be an eye irritant as defined in 16 CFR 1500.3(c) [CONSUMER PRODUCT SAFETY COMMISSION, Federal Hazardous Substances Act Regulations (USA). Definitions].

Executive summary:

In an in vivo eye irritation study using New Zealand White rabbits conducted by Bio/dynamics Inc., the maximum average score, which occurred on Day 1, was 23.3. Test item produced moderate and transient ocular irritation. Most animals exhibited moderate conjunctival irritation (redness, chemosis, discharge), iridial changes and corneal opacities, ulceration and stippling. One animal was free of any ocular irritation within 7 days after instillation of the test material. The five remaining animals exhibited slight conjunctival irritation but were free of any corneal irritation at study termination (Day 7).

The test material. 648-01 is considered to be an eye irritant as defined in 16 CFR 1500.3(c) [CONSUMER PRODUCT SAFETY COMMISSION, Federal Hazardous Substances Act Regulations. Definitions].

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1986-09-11 to 1986-09-25

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study not conducted according to GLP; however the study was conducted in a manner equivalent to relevant OECD guideline (405). The study contains a quality assurance statement and was conducted in accordance to the methodology proposed under the United States Federal Hazardous Substances Labelling Act (Federal Register, 1964, 29 13009).

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Post-treatment observations were not performed at 14 and 21 days.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazelton Research Products, Inc.
- Age at study initiation: no data
- Weight at study initiation: >1.5kg
- Housing: Elevated wire mesh cages
- Diet (e.g. ad libitum): measured amount of Purina High Fiber Rabbit Chow (6oz/day) was offered to all rabbits rather than ad libitum feed.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >/= 7 days


ENVIRONMENTAL CONDITIONS

- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark
- Temperature: 22-27 Degrees C
- Humidity: 56-79%


IN-LIFE DATES: From: 1986-09-11 To: 1986-09-25

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100mg
- Concentration (if solution): not applicable


VEHICLE
Not applicable

Duration of treatment / exposure:

Eyes were not flushed of test material, therefore the duration of exposure was 7 days

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
not applicable - test substance was not flushed out of eyes


SCORING SYSTEM:
Draize technique

TOOL USED TO ASSESS SCORE: sodium fluorescein

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

24 h

Score:

<= 34.2

Max. score:

34.2

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

48 h

Score:

<= 31

Max. score:

31

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

72 h

Score:

<= 28.8

Max. score:

28.8

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 4 days

Score:

<= 28

Max. score:

28

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 7 days

Score:

<= 20.3

Max. score:

20.3

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24 h

Score:

2.5

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

mean

Time point:

48 h

Score:

2.7

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

mean

Time point:

72 h

Score:

2.8

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 96 hours

Score:

2.3

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

mean

Time point:

7 d

Score:

1.7

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24 h

Score:

1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

48 h

Score:

1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

72 h

Score:

1.2

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 96 hours

Score:

1.3

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

7 d

Score:

0.8

Irritation parameter:

iris score

Basis:

mean

Time point:

24 h

Score:

0.8

Irritation parameter:

iris score

Basis:

mean

Time point:

48 h

Score:

0.8

Irritation parameter:

iris score

Basis:

mean

Time point:

72 h

Score:

0.8

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 96 hours

Score:

0.7

Irritation parameter:

iris score

Basis:

mean

Time point:

7 d

Score:

0.7

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24 h

Score:

2.2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

48 h

Score:

2.5

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

72 h

Score:

2.2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 96 hours

Score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

7 d

Score:

1.5

Irritant / corrosive response data:

See table 1 below

Other effects:

None

Table 1: Average Eye Irritation Scores

Observation Period	Cornea		Iris	Conjunctivae
	Opacity	Area		Redness	Chemosis	Discharge
Day 1	1.0	3.3	0.8	2.2	2.5	2.0
Day 2	1.0	2.8	0.8	2.5	2.7	1.2
Day 3	1.2	2.2	0.8	2.2	2.8	1.5
Day 4	1.3	1.8	0.7	2.0	2.3	1.3
Day 7	0.8	1.2	0.7	1.5	1.7	1.2

Table 2: Animal Body Weights

Animal Number	Sex	Vocalisation following dosing	Animal body weights (g)
			Initiation	Day 7	Day 14
4736	M	N	2626	2860	2932
4737	M	N	2736	2862	2839
4738	M	N	2676	2636	2806
4776	F	N	2164	2432	2565
4740	F	N	2705	2886	3018
4741	F	N	2473	2668	2813

 

Interpretation of results:

irritating

Remarks:

Criteria used for interpretation of results: expert judgment

Conclusions:

In a study performed to OECD 405, based on the average scores for redness and chemosis, the substance (SCI) showed irritating properties under the conditions of this study.

Executive summary:

In this study, where 6 rabbits received a single application of 100 mg of the substance (47.5% pure), iris lesions and redness and chemosis of the conjunctivae were seen. Blanching of the conjunctivae was seen in all animals at Day 1, in two animals at Day 2, in three animals at Day 3, and one animal at Days 4 and 7. Corneal epithelial peeling was observed in all animals on Days 1 and 2, in five animals at Days 3 and 4, and in four animals at Day 7. Other signs observed in some animals included necrosis, pannus, and corneal neovascularisation. The average Draize score is determined to be 2.0, however for redness and chemosis of the conjunctivae the scores are higher. There was no pain response in any of the animals, no clinical signs were observed and all animals had healthy body weight gain.

Reference 4

Endpoint:

eye irritation: in vivo

Type of information:

other: Literature review

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Justification for type of information:

The target (SLMI) and four source substances have very similar structures and sizes, and the available physico-chemical data of all five substances are comparable (varying only as would be expected to account for different fatty acid chain lengths). All would be expected to undergo the same, rapid biotransformations in vivo. Metabolism would be expected to result in straight chain fatty acids (C8 to C18, innocuous components of the mammalian diet) and either sodium isethionate (SCI/SLI) or sodium methylisethionate (SLMI/SCMI/SDMI).

There are no functional groups novel to the target substance, and no structural alerts in the target or source compounds that are indicative of mutagenicity, carcinogenicity or skin sensitisation. Indeed, where available, the existing dataset on the five substances consistently indicate that this closely-related group is of low acute and repeated dose toxicity, and there is no evidence of skin sensitisation, genotoxic and carcinogenic activity, or of reproductive and developmental toxicity. Overall, SLMI and the four source substances are all considered of low concern for human health. However, there is evidence that SLMI, SCI and SCMI are mild-to-moderate skin irritants and SCI is an eye irritant.
Where available, the environmental data on these substances indicate a similar fate (readily biodegradable) and a comparable level of ecotoxicity to aquatic organisms.

Based on the considerations above, it can be confidently concluded that a read-across approach is appropriate and justified. Therefore, existing data on the four source compounds – SCI, SLI, SCMI and SDMI – can be used to predict the toxicity of the target compound, SLMI, where gaps in the current database remain. As such, further testing of SLMI is considered a low priority.

Principles of method if other than guideline:

Review of available data on SCI

GLP compliance:

no

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

72 h

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

72 h

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

In the van Baaren study, corneal opacity and transient iritis was observed in one animal during the first 72 hours after treatment, and was still present at day 7 but healed completely by day 14. The other two animals exhibited only slight iridal and conjunctival irritation, which completely healed by day 7. Based on the effects seen in the one animal, the test substance was classified as an irritant.

In the first Blaszcak study, most animals experienced moderate conjunctival irritation and other effects and SCI was classified as moderately irritating. The second Blaszcak study resulted in a "mildly irritating" classification.

The studies by Glaza, Nitka and Palanker and Shapiro found SCI to be moderately irritating, mildly irritating, and mildly (unwashed) or minimally (washed) irritating.

Interpretation of results:

moderately irritating

Remarks:

Criteria used for interpretation of results: US EPA pesticides

Conclusions:

Under the conditions of the studies, SCI was found to be mildly to moderately irritating to eyes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin irritation: Nine studies provide a Weight Of Evidence approach for the skin irritancy endpoint of SLMI

York (1983) concluded that the read across material SCI was slightly irritating to the skin of rabbits

Long (2007) found that SLMI was mildly(slightly)-moderately irritating to human skin. SLMI was ranked lower in irritancy than SCI, which is also not classified for skin irritancy

A keller and heckman review of 5 studies found that SCI is mildly (slightly )-moderately irritating for the skin

Lodestadt (1986), found that for the intact skin of rabbits SCI was slightly irritating

In a surfactant review paper of several studies, Petter (1984) concluded that isethionates have low irritancy for the skin

In 4 in vitro studies SCI and SLMI produced similar testing results of moderately irritating. This confirms the read-across applicability. Animal and human testing proves these in vitro results to be exaggerated.

Eyeirritation: Nine studies provide the data the eye irritancy endpoint of SLMI

An eye irritation study was carried out on the read across material SCI according to OECD 405 and in-house quality assurance was in place. The test substance causes a score of ≥ 1 for iris and a ≥ 2 score for chemosis. The effects are not fully reversible within 7 days but a decrease in severity was seen over a period of 7 days. Therefore the assumption is made that the effects are likely to be fully reversible within 21-days and the substance is classified in category 2 (causes serious eye irritation).

In a study performed to OECD 405, (Blascak, 1985) found the read across material, SCI to be severely irritating to the eye (max average score 23.3)

In a study performed to OECD 405, (Glaza, 1986) found the material to be irritating to the eye

In a review of the data on SCI, (Keller and heckman, 2006) found SCI to be mildly to moderately irritating to the eyes

3 further studies provide supporting evidence of the eye irritancy of SLMI and SCI to the eye,, (Nikta, 1982, Rachai, 1997, Nikta, 1999)

2 further in vitro studies on SLMI have been disregarded as the studies were flawed

Justification for selection of skin irritation / corrosion endpoint:
good kliminsch score 2 study according to OECD 404

Justification for selection of eye irritation endpoint:
Good kliminsch score 2 study according to OECD 405

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Animal and human studies showed some slight irritation of SLMI to skin. However A WOE approach concludes that the material is only slightly-moderately irritating to the skin and should not be labelled according to DPD and CLP as such.

Several studies on the read across substance, SCI showed eye irritation following exposure.

Therefore SLMI has been classified as a category 2 eye irritant according to CLP criteria or classified as R36 - Irritating to eyes, according to the criteria of Directive 67/548/EEC.