Potassium O-pentyl dithiocarbonate

Endpoint summary

Description of key information

-The acute eye irritation study indicates that Potassium amyl xanthate (the result was read across from sodium ethyl xanthate) as a powder caused mild to moderate irritation, while it is not an irritant in the diluted form (10% solution).
-The results of the study (Hazleton Laboratories 1951) indicate that Potassium amyl xanthate (the result was read across from sodium ethyl xanthate) is a moderate irritant to the skin while the 10% solution is non irritating to the skin. 
-The results of the study (Dow Chemical Company 1976) indicate that 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

Endpoint:

skin 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

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. 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.

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. 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.

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 of sodium ethyl xanthate 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 sodium ethyl xanthate 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 sodium ethyl xanthate 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 sodium ethyl xanthate (pH 10.5 to 11) for 18 hrs did not cause skin irritation in rabbits. Similar application of 1 gm/kg of sodium ethyl xanthate 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 Potassium amyl xanthate (the result was read across from sodium ethyl xanthate) 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 Potassium amyl xanthate (the result was read across from sodium ethyl xanthate) is a moderate irritant while the10% solution is non irritating to the skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

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

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: other: The study 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 this study.
A 0.05 ml aliquot of 10% aqueous solution of sodium ethyl xanthate 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 sodium ethyl xanthate 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 sodium ethyl xanthate 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 sodium ethyl xanthate 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 sodium ethyl xanthate 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 sodium ethyl xanthate
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 sodium ethyl xanthate 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 sodium ethyl xanthate 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 sodium ethyl xanthate 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 sodium ethyl xanthate

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 sodium ethyl xanthate 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 sodium ethyl xanthate 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 sodium ethyl xanthate 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 Potassium amyl xanthate (the result was read across from sodium ethyl xanthate) 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 Potassium amyl xanthate (the result was read across from sodium ethyl xanthate) 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 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 10.5to 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 sodium ethyl xanthate was 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 sodium ethyl xanthate powder 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 sodium ethyl xanthate 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 Potassium amyl xanthate (the result was read across from sodium ethyl xanthate) is classifiable as a moderately irritant according to EU criteria.

Skin irritation

-The results of thestudy (Hazleton Laboratories 1951) indicate that Potassium amyl xanthate (the result was read across from sodium ethyl xanthate) 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 (pH 10.5 to 11) for 18 hrs did not cause skin irritation in rabbits. Similar application of 1 gm/kg of sodium ethyl xanthate 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 Potassium amyl xanthate (the result was read across from

sodium ethyl xanthatе ) is classifiable as a moderately irritant according to EU criteria

-Potassium Hydroxide is used in the manufacturing process for Potassium amyl xanthate and is present in the final product. Therefore, the health effects of Potassium Hydroxide need to be considered in the assessment of potassium amyl xanthate.

The acute dermal irritation of Potassium Hydroxide 5% and 10% was examined in a 4 -hour exposurein rabbits (Nixon GA et al.1990).Potassium Hydroxide 5% and 10% is a moderately irritating in rabbits.

 Based on the descriptions of the lesions it is considered that Potassium amyl xanthate (the result was read across from of Potassium Hydroxide) is classifiable as an 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 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 Potassium amyl xanthate 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 Potassium amyl xanthate 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