Registration Dossier

Administrative data

Description of key information

-The acute eye irritation study indicates that Sodium ethyl xanthate) as a main constituent of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide  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 Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide (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 thatReaction mass of 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

Referenceopen allclose all

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
Justification for type of information:
Sodium O-ethyl dithiocarbonate (SEX) as the main constituent of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide
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 Reaction mass 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 Reaction mass of SEX powder

is a moderate irritant while the10% 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 Reaction mass of SEX (pH 10.5 to 11) for 18 hrs did not cause skin irritation in rabbits. Similar application of 1 gm/kg ofReaction mass 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 Reaction mass of 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 Reaction mass of SEX  is a moderate irritant while the10% solution is non irritating to the skin.

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 Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide. Therefore, Ethanol/ Ethyl Alcohol need to be considered in the assessment of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide.
Qualifier:
according to
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 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:
other: 24-72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: Intact skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 - 72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24 - 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:
other: 24 - 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:
other: 24 - 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 Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide. Therefore, Ethanol/ Ethyl Alcohol need to be considered in the assessment of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide
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

Referenceopen allclose all

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
Justification for type of information:
Sodium O-ethyl dithiocarbonate (SEX) as the main constituent of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide
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 Reaction mass of 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 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.

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:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
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.
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 Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide. Therefore, Ethanol/ Ethyl Alcohol need to be considered in the assessment of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide
Qualifier:
according to
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:
other: average over 24, 48, 72hr observations.
Score:
1.1
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: average over 24, 48, 72hr observations.
Score:
2.1
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: average over 24, 48, 72hr observations.
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
other: MMAS
Basis:
mean
Time point:
other: 24 hours
Score:
24
Max. score:
110
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 Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide
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.

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 Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide. Therefore, Ethanol/ Ethyl Alcohol need to be considered in the assessment of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide
Qualifier:
according to
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:
other: average across time points 24, 48, 72 hrs
Score:
1.2
Max. score:
4
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
mean
Time point:
other: average across time points 24, 48, 72 hrs
Score:
0.28
Max. score:
2
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: average across time points 24, 48, 72 hrs
Score:
2.4
Max. score:
3
Reversibility:
not specified
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: average across time points 24, 48, 72 hrs
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 Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide. Therefore, Ethanol/ Ethyl Alcohol need to be considered in the assessment of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide
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 main constituent of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide as a 10% solution at pH 10.5to 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 Reaction mass of SEXwas instilled into the conjunctival sacs of the left eyes of albino rabbits of one group. The eyes wereheld 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 Reaction mass of SEXpowder was applied to theconjunctival 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 Reaction mass of SEXis 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.

Basedon the descriptions of the lesions it is considered thatReaction mass of SEXis classifiable as a moderately irritant according to EU criteria.

Skin irritation

-The results of thestudy (Hazleton Laboratories 1951) indicate thatReaction mass of SEX is a moderate irritant while the10% 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 Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide (pH 10.5 to 11) for 18 hrs did not cause skin irritation in rabbits. Similar application of 1 gm/kg of Reaction mass of SEXin 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 Reaction mass of 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 Reaction mass of 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 effectswere 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 Reaction mass of SEX in section 2.1 and 2.2. in IUCLID6., available data for the substance and following the “Guidance on InformationRequirement 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 Reaction mass of 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