Sodium O-ethyl dithiocarbonate

Endpoint summary

Description of key information

-The acute eye irritation study indicates that Sodium ethyl xanthate) as a powder caused  moderate eye irritation, while it is mildly irritant in the diluted form (10% solution).
-The results of the study (Hazleton Laboratories 1951) indicate that Sodium  ethyl xanthate  is a moderate irritant to the skin while the 10% solution is non irritating to the skin. 
Based on the descriptions of the lesions it is considered that sodium O-ethyl dithiocarbonate  (the result was  from Ethyl Alcohol) is classifiable as an moderately irritant according to EU criteria
-The results of the study (Dow Chemical Company 1976) indicate that SEX (the result was read across from potassium amyl xanthate) has an adverse effect at concentration of 252mg/m3 on the central nervous system and liver in mice, the liver and kidneys in rats and the liver in dogs. 
Signs of irritation of respiratory tract and Nasal effects were observed in rats as Reddish nasal discharge.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation / corrosion, other

Remarks:

Substance was administered by occlusive application to the shaved abdomen of the rabbits either as 1.0 ml/kg of a 10% aqueous solution or as 1 gm/kg of the 100% dry material in a paste formed with water. The animals were observed for 12 days.

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

This study was conducted in 1951 and was repeated later in the same year. Exposure in both studies was for 18 hrs and was not according to the OECD Guidelines for acute dermal irritation (4 hrs) or for dermal toxicity (24 hrs). The initial study was performed to assess dermal irritation but deaths during the study led to further studies. Substance was administered by occlusive application to the shaved abdomen of the rabbits either as 1.0 ml/kg of a 10% aqueous solution or as 1 gm/kg of the 100% dry material in a paste formed with water. The animals were observed for 12 days.

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

other: 10% aqueous solution and unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

Sodium ethyl xanthate was administered by occlusive application to the shaved abdomen of the rabbits either as 1.0 ml/kg of a 10% aqueous solution or as 1 gm/kg of the 100% dry material in a paste formed with water. The animals were observed for 12 days.

Observation period:

The animals were observed for 12 days.

Number of animals:

12

Details on study design:

This study was conducted in 1951 and was repeated later in the same year. Exposure in both studies was for 18 hrs and was not according to the OECD Guidelines for acute dermal irritation (4 hrs)or for dermal toxicity (24 hrs).The initial study was performed to assess dermal irritation but deaths during the study led to further studies. Substance was administered by occlusive application to the shaved abdomen of the rabbits either as 1.0 ml/kg of a 10% aqueous solution or as 1 gm/kg of the 100% dry material in a paste formed with water. The animals were observed for 12 days.

Irritation parameter:

other: oedema and pigmentation of the skin.

Basis:

mean

Time point:

other: 24 hrs

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Application of 1 gm/kg ofsubstance in the form of a paste resulted in the death of ten out of twelve animals within 24 hrs. The surviving animals had moderate irritation with oedema and pigmentation of the skin.

Irritant / corrosive response data:

Application of 1 gm/kg of SEX in the form of a paste resulted in the death of ten out of twelve animals within 24 hrs. The surviving animals developed irritant effects including oedema and pigmentation of the skin.
Clinical Observations :surviving animal had moderate irritation with oedema and pigmentation of the skin.

Other effects:

Moderate amount of peritoneal fluid, visceral organs were normal.
Haemorrhagic lungs and peritoneal and pleural fluid. Other changes were markedly cyanotic ears (2/5), haemorrhagic conditions (2/5) and evidence of diarrhoea (3/5).
The liver appeared darkand mottled and the kidneys showed spotty haemorrhages

The dermal irritation/toxicity study in rabbits indicates that SEX powder

is a moderate irritant while the 10% solution is non irritating to the skin.

Results of the dermal application studies are summarised in Table 4.

Table 4:	Effects of sodium ethyl xanthate following dermal application
Animals	Dose	Clinical Observations	Gross pathology
3 rabbits	1 ml/kg, as 10% solution	No skin irritation.	No substance related changes.
3 rabbits	1 gm/kg, as a paste	2/3 died; surviving animal had moderate irritation with oedema and pigmentation of the skin.	Moderate amount of peritoneal fluid, visceral organs were normal.
5 male rabbits	1 gm/kg, as a paste	5/5 died following overnight exposure; oedemaof the skin with pigmentation.	Haemorrhagic lungs andperitoneal and pleural fluid. Other changes were markedly cyanotic ears (2/5), haemorrhagic conditions (2/5) and evidence of diarrhoea (3/5).
1 male rabbit	1 gm/kg, as a more liquid paste than above	Moderate oedema and pigmentation of the skin.	No substance related changes.
3 rabbits	1 gm/kg as a paste	All 3 animals died within24 hrs; retropulsion,salivation, loss of rightingreflex and haemorrhagicand oedematous areas of the skin were noted.	The liver appeared dark and mottled and the kidneysshowed spotty haemorrhages.

 

 

Interpretation of results:

other: moderately irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, application of 10% solution of SEX (pH 10.5 to 11) for 18 hrs did not cause skin irritation in rabbits. Similar application of 1 gm/kg of SEX in the form of a paste resulted in the death of ten out of twelve animals within 24 hrs. The surviving animals developed irritant effects including oedema and pigmentation of the skin. The sulphide odour noted during the study suggests that decomposition of sodium ethyl xanthate occurred. The results of the study (Hazleton Laboratories 1951) indicate that SEX is a moderate irritant while the10% solution is non irritating to the skin.

Executive summary:

The results of the study (Hazleton Laboratories 1951) indicate that SEX  is a moderate irritant while the10% solution is non irritating to the skin.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Ethanol/ Ethyl Alcohol is both reagents used in the manufacture of sodium O-ethyl dithiocarbonate . Therefore, Ethanol/ Ethyl Alcohol need to be considered in the assessment of sodium O-ethyl dithiocarbonate

Qualifier:

according to guideline

Guideline:

other: Fed. Reg. 38, No. 187, § 1500.41, Sept 27, 1973

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Mean weight at study initiation: 2.7 kg
- Diet (e.g. ad libitum): muemmel z (ssniff / Soest)
- Water (e.g. ad libitum): tap water
- Acclimation period: 7 - 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 18
- Humidity (%): ca. 40
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

occlusive

Preparation of test site:

other: intact and scarified

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:

24 hour(s)

Observation period:

8 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: dorsal skin 2.5 x 2.5 cm
- Type of wrap if used: test patches are covered with a rubber-coated linen patch (5 x 5 cm), fixed by a small strip of adhesive tape and wrapped with a gauze bandage

SCORING SYSTEM: Draize

Irritation parameter:

erythema score

Basis:

mean

Remarks:

3 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Remarks on result:

other: Intact skin

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.5

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: Intact skin

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: Intact skin

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.5

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: Intact skin

Intact Skin

Readings	Animal	Erythema	Edema
24 h	1	0	2
	2	0	3
	3	0	1
72 h	1	0	1
	2	0	3
	3	0	2
8 days	1	0	3
	2	0	2
	3	0	3
Mean (24 - 72 h)	1	0	1.5
	2	0	3.0
	3	0	1.5
Mean	1-3	0	2.0

Scarified Skin

Readings	Animals	Erythema	Edema
24 h	1	0	2
	2	1	2
	3	0	2
72 h	1	0	0
	2	0	2
	3	0	1
8 days	1	0	2
	2	0	3
	3	0	1
Mean (24 - 72 h)	1	0	1.0
	2	0.33	2.0
	3	0	1.5
Mean	1-3	0.11	1.5

 

Interpretation of results:

other: ambiguous

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Based on these results, the test substance would seem to require classification as an irritant according to directive 67/548 (R 38) and regulation 1272/2008 (Cat. 2) standards. The level of odema did not appear sufficient to trigger classification alone although there was some suggestion of a delayed reaction after day 3. However, it must be borne in mind that the exposure was for 24 hours under occlusive conditions - far longer than required for the OECD or REACH testing guideline of 4 hours for this end point and observation was for only 8 days and not the recommended 14 days. The result must be considered ambiguous or equivocal.
Ethanol/ Ethyl Alcohol is both reagents used in the manufacture of sodium O-ethyl dithiocarbonate . Therefore, Ethanol/ Ethyl Alcohol need to be considered in the assessment of sodium O-ethyl dithiocarbonate

Executive summary:

In a study to a US Federal regulations protocol, rabbits were subjected to a dermal irritation test by occluded exposure to ethanol for a period of 24 hours followed by an 8 day observation period. No erythema was seen but marked odema was observed, which persisted and, if anything appeared to be getting worse at the end of the observation period. Based on these results, the test substance would seem to require classification as an irritant according to directive 67/548 (R 38) and regulation 1272/2008 (Cat. 2) standards. The level of odema did not appear sufficient to trigger classification alone although there was some suggestion of a delayed reaction after day 3. However, it must be borne in mind that the exposure was for 24 hours under occlusive conditions - far longer than required for the OECD or REACH testing guideline of 4 hours for this end point and observation was for only 8 days and not the recommended 14 days. The result must be considered ambiguous or equivocal, particularly since similar observations are not seen in other studies with more appropriate durations of exposure.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation, other

Remarks:

The eyes were held closed for one minute, observed immediately for reaction 1 hr and 4 hrs later and then daily for 9 days.

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: other: The study was done in 1951 using Reaction mass of SEX as a 10% solution at pH 10.5 to 11 and as a fine powder. Two groups of three albino rabbits each were used in this study.
A 0.05 ml aliquot of 10% aqueous solution of Reaction mass of SEX was instilled into the conjunctival sacs of the left eyes of albino rabbits of one group. The eyes were held closed for one minute, observed immediately for reaction 1 hr and 4 hrs later and then daily for 9 days.

GLP compliance:

not specified

Species:

rabbit

Strain:

other: albino rabbits

Details on test animals or tissues and environmental conditions:

TEST ANIMALS: Rabbit
- Strain: albino rabbits
- Sex: Not reported
- Source: Not reported
- Age: Not reported
- Weight at study initiation: Not reported
- Number of animals: 6

Vehicle:

other: 10% aqueous solution and unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

-10% aqueous solution of sodium ethyl xanthate
-30 mg powder of sodium ethyl xanthate

Duration of treatment / exposure:

A 0.05 ml aliquot of 10% aqueous solution of Reaction mass of SEX was instilled into the conjunctival sacs of the left eyes of albino rabbits of one group. The eyes were held closed for one minute, observed immediately for reaction 1 hr and 4 hrs later and then daily for 9 days.
30 mg of Reaction mass of SEX powder was applied to the conjunctival sacs of the second group of rabbits.

Observation period (in vivo):

9 days

Number of animals or in vitro replicates:

6

Details on study design:

-A 0.05 ml aliquot of 10% aqueous solution of Reaction mass of SEX was instilled into the conjunctival sacs of the left eyes of albino rabbits of one group. The eyes were held closed for one minute, observed immediately for reaction 1 hr and 4 hrs later and then daily for 9 days.
-Approximately 30 mg of Reaction mass of SEX powder was applied to the conjunctival sacs of the second group of rabbits. All three animals showed immediate marked irritation, scrambling, excitement and evidence of pain. There was lacrimation in one animal and phonation in another. Moderate irritation and oedema of the lids was observed in all the animals at the end of 1 hr. The same observations were noted at 4 hrs with one animal showing exudate. Mild irritation was seen after 24 hrs and two rabbits appeared normal after three days. One rabbit showed slight irritation until day 5. There were no signs of opacity or necrosis. The symptoms seen in the animals could be due to the physical irritation caused by solid particles in the eye. The animals were sacrificed on day 9 when no gross pathology was observed at autopsy.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 hrs

Reversibility:

fully reversible

Remarks:

4 days

Remarks on result:

other: Powder is a moderate irritant to rabbit eyes while the 10% aqueous solution is mildly irritating .The eye effects produced by the powder were reversible, persisting for 24 hrs in all the animals with the effects lasting for up to 4 days in one animal.

Irritant / corrosive response data:

DESCRIPTION OF LESIONS:
-Mild irritation was observed immediately after instillation of 10% aqueous solution of Reaction mass of SEX
There were no signs of oedema or necrosis. Autopsy on day 9 did not reveal any gross pathology.
 -Moderate irritation to rabbit eyes was evident after instillation of 30 mg of Reaction mass of SEX powder to the conjunctival sacs.
All three animals showed immediate marked irritation, scrambling, excitement and evidence of pain. There was lacrimation in one animal and phonation in another. Moderate irritation and oedema of the lids was observed in all the animals at the end of 1 hr. The same observations were noted at 4 hrs with one animal showing exudate. Mild irritation was seen after 24 hrs and two rabbits appeared normal after three days. One rabbit showed slight irritation until day 5. There were no signs of opacity or necrosis. The symptoms seen in the animals could be due to the physical irritation caused by solid particles in the eye.The animals were sacrificed on day 9 when no gross pathology was observed at autopsy.

REVERSIBILITY:
-Mild irritation was evident after instillation of 10% aqueous solution but the eyes appeared normal one hour later. One animal showed slight irritation at 4 hrs but was normal on the second day.
-Moderate irritation to rabbit eyes was evident after instillation of 30 mg of Reaction mass of SEX powder.The eye effects produced by the powder were reversible, persisting for 24 hrs in all the animals with the effects lasting for up to 4 days in one animal.

The results of this study indicate that the powder is a moderate irritant to rabbit eyes while the 10% aqueous solution of Reaction mass of SEX is mildly irritating. The irritant effects of the solution disappeared 1 hr after instillation. The eye effects produced by the powder were reversible, persisting for 24 hrs in all the animals with the effects lasting for up to 4 days in one animal.

DESCRIPTION OF LESIONS:

-Mild irritation was observed immediately after instillation of 10% aqueous solution of Reaction mass of SEX

There were no signs of oedema or necrosis. Autopsy on day 9 did not reveal any gross pathology.

 -Moderate irritation to rabbit eyes was evident after instillation of 30 mg of Reaction mass of SEX powder to the conjunctival sacs.

All three animals showed immediate marked irritation, scrambling, excitement and evidence of pain. There was lacrimation in one animal and phonation in another. Moderate irritation and oedema of the lids was observed in all the animals at the end of 1 hr. The same observations were noted at 4 hrs with one animal showing exudate. Mild irritation was seen after 24 hrs and two rabbits appeared normal after three days. One rabbit showed slight irritation until day 5. There were no signs of opacity or necrosis. The symptoms seen in the animals could be due to the physical irritation caused by solid particles in the eye.The animals were sacrificed on day 9 when no gross pathology was observed at autopsy.

REVERSIBILITY:

-Mild irritation was evident after instillation of 10% aqueous solution but the eyes appeared normal one hour later. One animal showed slight irritation at 4 hrs but was normal on the second day.

-Moderate irritation to rabbit eyes was evident after instillation of 30 mg of Reaction mass of SEX powder.The eye effects produced by the powder were reversible, persisting for 24 hrs in all the animals with the effects lasting for up to 4 days in one animal.

The results of this study indicate that the powder is a moderate irritant to rabbit eyes while the 10% aqueous solution of Reaction mass of SEX is mildly irritating. The irritant effects of the solution disappeared 1 hr after instillation. The eye effects produced by the powder were reversible, persisting for 24 hrs in all the animals with the effects lasting for up to 4 days in one animal.

 

Interpretation of results:

other: moderately irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Based on the descriptions of the lesions it is considered that SEX is classifiable as an moderately irritant according to EU criteria
Classification: moderately irritating

Executive summary:

The results of this study indicate that the powder is a moderate irritant to rabbit eyes while the 10% aqueous solution of SEX is mildly irritating.The irritant effects of the solution disappeared 1 hr after instillation. The eye effects produced by the powder were reversible, persisting for 24 hrs in all the animals with the effects lasting for up to 4 days in one animal.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

other: published data

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Dithiocarbamates are related compounds to xanthates. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium or potassium hydroxide: They arise from the reaction of the amine with CS2.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: A. Smith, England
- Age at study initiation: ca. 12 weeks
- Weight at study initiation: 2.6 kg

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

n.a.

Observation period (in vivo):

24 h

Number of animals or in vitro replicates:

1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24 h

Score:

3

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24 h

Score:

2

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24 h

Score:

3

Reversibility:

not reversible

Remarks on result:

other: Necrosis and partial destruction of nictitating membrane.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24 h

Score:

4

Reversibility:

not reversible

Other effects:

Due to the severity of the response only one animal was exposed to the test substance and the study was terminated on humane grounds 24 h after instillation.

Interpretation of results:

other: irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Instillation of 0.1 ml of ziram into rabbit eyes produced severe ocular irritation.
Dithiocarbamates are related compounds to xanthates. This is organosulfur compound is obtained by treating carbon disulfide with amine in the presence of sodium or potassium hydroxide: They arise from the reaction of the amine with CS2.

Reference 3

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Ethanol/ Ethyl Alcohol is both reagents used in the manufacture of sodium O-ethyl dithiocarbonate . Therefore, Ethanol/ Ethyl Alcohol need to be considered in the assessment of sodium O-ethyl dithiocarbonate

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Concentration: 100 % active substance
- instillation of 0.1 ml

Duration of treatment / exposure:

single instillation

Observation period (in vivo):

Up to 21 days unless symptoms disappeared first.

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: Standard Draize grading scale for lesions.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1.1

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2.1

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

other: MMAS

Basis:

animal #1

Time point:

24 h

Score:

24

Max. score:

110

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4

Irritant / corrosive response data:

Individual animal observations reported. Full reversal of all symptoms in animals occurred within 14 days. Most persistent effect was conjunctival redness, still present, grade 1, at 7 daysin 2 animals (last observation time before 14 day observation). One animal showed full recovery of all symptoms by day 4.

Other effects:

none reported.

 

The MMAS (modified maximum average score is calculated per animal from the 24 hour observations based corneal effects (capacity x area x 5), iris effects (x5) and conjunctival effects (redness + chemosis + discharge scores). The total possible is 80 (cornea) + iris (10) plus conjunctivae (20), ie a maximum of 110.

Average scores (all animals)

	Day 1	Day 2	Day 3
Corneal opacity	1.33	1.33	0.66
Iritis	0.33	0.66	0.33
Conjunctival redness	2.66	2.00	1.66
Chemosis	1.66	1.66	0.66

Average scores (worst two animals)

	ANIMAL #1 (average days 1,2,3)	ANIMAL #2 (average days 1,2,3)
Corneal opacity	1.33	1.66
Iritis	1	0.33
Conjunctival redness	2.66	2.33
Chemosis	2	1.66

Based on the criteria for classification, only the conjunctival redness in animal one is meets the criteria for the definition of a significant occular lesions would be regarded as significant but such a response in only one animal is not regarded as sufficient for classification as an eye irritant under directive 67/548. The average results across all 3 animals are not sufficient either. However, the criteria for classification under GHS are more stringent and a positive response is seen under these criteria for corneal opacity (2 animals >1) and conjunctival redness (2 animals >2), hence classification as an eye irritant (category 2) is required.

 

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

Substance clearly shows reversible eye irritant properties.Ethanol/ Ethyl Alcohol is both reagents used in the manufacture of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide. Therefore, Ethanol/ Ethyl Alcohol need to be considered in the assessment of sodium O-ethyl dithiocarbonate

Executive summary:

In a reference handbook of peer reviewed, guideline GLP eye irritation study results in rabbits, ethanol was found to cause eye irritation. All symptoms reversed within 14 days. The response was not sufficiently severe to trigger classification under the criteria of directive 67/548 but was sufficient with respect to the corneal and conjunctival effects to trigger classification as a reversible eye irritant (category 2) under the EU GHS regulation.

Reference 4

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Ethanol/ Ethyl Alcohol is both reagents used in the manufacture of sodium O-ethyl dithiocarbonate . Therefore, Ethanol/ Ethyl Alcohol need to be considered in the assessment of sodium O-ethyl dithiocarbonate

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

undiluted

Amount applied: 100 other: microlitre into lower conjunctival sac.

Duration of treatment / exposure:

single instillation of 0.1ml

Observation period (in vivo):

72 hours only reported

Number of animals or in vitro replicates:

6

Details on study design:

SCORING SYSTEM: Draize method of scoring used.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1.2

Max. score:

4

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.28

Max. score:

2

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2.4

Max. score:

3

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.2

Max. score:

4

Reversibility:

not specified

Other effects:

none reported.

  Average Scores:

	24 hours	48 hours	72 hours
Conjunctivitis	2.50	2.61	2.06
Chemosis	1.67	1.17	0.83
Iritis	0.50	0.33	0.00
Corneal Opacity	1.00	1.50	1.00

It is not possible to make a definitive judgement regarding classification as results from individual animals are not available. However, based on the average results across all animals, the occular lesions are not severe enough to warrant classification as an eye irritant under under directive 67/548. However, the criteria for classification under GHS are more stringent and 'significant lesions' are seen under these criteria for corneal opacity ( likely that at least 2 animals >1 based on an average of 1.2) and conjunctival redness (likely that at least 2 animals >2 based on an average of 2.4), hence a judgement that the results from this study support

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

Classification: irritating. Ethanol/ Ethyl Alcohol is both reagents used in the manufacture of sodium O-ethyl dithiocarbonate . Therefore, Ethanol/ Ethyl Alcohol need to be considered in the assessment of sodium O-ethyl dithiocarbonate

Executive summary:

In a guideline eye irritation study results in rabbits for which only basic but key details are reported, ethanol was found to cause eye irritation. The response was not sufficiently severe to trigger classification under the criteria of directive 67/548 but, based on the available information, appears to be sufficient with respect to the corneal and conjunctival effects to trigger classification as an eye irritant (category 2) under the EU GHS regulation. The study did not include sufficient observations to be able to judge reversibility.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Eye irritation

The study (Hazleton Laboratories, 1951) was done in 1951 using sodium ethyl xanthate as a 10% solution at pH 10.5 to 11 and as a fine powder. Two groups of three albino rabbits each were used in thisstudy.

A 0.05 ml aliquot of 10% aqueous solution of SEX was instilled into the conjunctival sacs of the left eyes of albino rabbits of one group. The eyes were held closed for one minute, observed immediately for reaction 1 hr and 4 hrs laterand then daily for 9 days.

Mild irritation was observed immediately after instillation but the eyes appeared normal one hour later.One animal showed slightirritation at 4 hrs but was normal on the second day. There were no signs of oedema ornecrosis. Autopsy on day 9 did not reveal any gross pathology.

 

Approximately 30 mg of SEXpowder was applied to the conjunctival sacs of the second group of rabbits. All three animals showed immediate marked irritation, scrambling, excitement and evidence of pain. There waslacrimation in one animal and phonation in another. Moderate irritation andoedema of the lids was observed in all the animals at the end of 1 hr. The sameobservations were noted at 4 hrs with one animal showing exudate. Mild irritationwas seen after 24 hrs and two rabbits appeared normal after three days. One rabbitshowed slight irritation until day 5. There were no signs of opacity or necrosis. Thesymptoms seen in the animals could be due to the physical irritation caused by solidparticles in the eye. The animals were sacrificed on day 9 when no gross pathologywas observed at autopsy.

The results of this study indicate that the powder is a moderate irritant to rabbit eyes while the 10% aqueous solution of SEX is mildly irritating.The irritant effects of the solution disappeared 1 hr after instillation. The eye effects produced by the powder were reversible, persisting for 24 hrs in all the animals with the effects lasting for up to 4 days in one animal.

Based on the descriptions of the lesions it is considered that SEX is classifiable as a moderately irritant according to EU criteria.

Skin irritation

-The results of the study (Hazleton Laboratories 1951) indicate that SEX is a moderate irritant while the 10% solution is non irritating to the skin.

Under the conditions of the study, application of 10% solution of sodium ethyl xanthate as a main constituent of sodium O-ethyl dithiocarbonate (pH 10.5 to 11) for 18 hrs did not cause skin irritation in rabbits. Similar application of 1 gm/kg of SEX in the form of a paste resulted in the death of ten out of twelve animals within 24 hrs. The surviving animals developed irritant effects including oedema and pigmentation of the skin. The sulphide odour noted during the study suggests that decomposition of sodium ethyl xanthate occurred.

Based on the descriptions of the lesions it is considered that SEX is classifiable as a moderately irritant according to EU criteria

Respiratory irritation.

In the 30-day study, three groups of animals, each consisting of 10 male Swiss-Webster mice, 10 male Sprague-Dawley rats, 4 male New Zealand White rabbitsand 2 male beagle dogs were exposed to either filtered room air or to concentrationsof 100 or 800 mg/m3 of potassium amyl xanthate. Whole body exposure was for 6 hrsdaily, 5 days a week for a total of 20 exposures in 1 month.

Ten mice of the 800 mg/m3group died along with 5/6 replacement mice.

The animals were observed during the exposures and body weights were recordedthree times a week throughout the experiment. Body weight data, organ to bodyweight ratios and clinical laboratory parameters were analysed statistically usinganalysis of variance and Dunnett’s test.

Most of the mice died when exposed to 800 mg/m3. Five of the 16 mice that died showed convulsions and hyperactivity prior to death.

The results of the study (Dow Chemical Company 1976) indicate that SEX (the result was read across from potassium amyl xanthate) has an adverse effect at concentration of 252 mg/m3 on the central nervous system and liver in mice, the liver and kidneys in rats and the liver in dogs.

Signs of irritation of respiratory tract and Nasal effects were observed in rats as reddish nasal discharge.

 

 

Effects on skin irritation/corrosion: moderately irritating

Effects on eye irritation: moderately irritating

Effects on respiratory irritation: irritating

Justification for classification or non-classification

Based on the hazard assessment of SEX in section 2.1 and 2.2. in IUCLID 6., available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health” andaccording to the criteria described in Directive 67/548 and in the CLP Regulation:

Directive 67/548

Skin Corrosivity C R35 Causes severe burns R34 Causes burns Skin Irritation Xi R38 Irritating to skin R43 May cause sensitization by skin contact Eye Irritation (Ocular Lesions) Xi R36 Irritating to eyes R37 irritating to respiratory system R41 Risk of serious damage to eyes R36/37/38 Irritating to eyes, respiratory system and skin.

CLP

Skin Corrosivity  H314 Skin Corr 1A Causes severe skin burns and eye damage H314 Skin Corr 1B Causes severe skin burns and eye damage Skin Irritation  H315 Skin Irrit. 2 Causes skin irritation H317 Skin Sens. 1 May cause an allergic skin reaction Eye Irritation (Ocular Lesions) Xi H319 Eye Irrit. 2 Causes serious eye irritation H318 Eye Dam. 1 Causes serious eye damage H335 STOT SE 3 May cause respiratory irritation

 

 

It is concluded that the substance SEX  meet the criteria to be classified for human health hazards for Dermal-local effect and respiratory irritation:

R36/37/38 Irritating to eyes, respiratory system and skin,

H315 Skin Irrit. 2 Causes skin irritation,

H319 Eye Irrit. 2 Causes serious eye irritation,

H335 STOT SE 3 May cause respiratory irritation