Potassium O-isobutyl dithiocarbonate

Endpoint summary

Description of key information

-The acute eye irritation study indicates that Potassium isobutyl 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 isobutyl 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 acute dermal irritation of isobutanol was examined in a 4 -hour exposure . Minor to moderate erythema and edema on 6 of 6 rabbits, superficial necrosis on 2, ecchymoses on 1, fissuring on 1, desquamation on 4 and alopecia on 2 from 0.5 ml. Two rabbits had a normal appearance within 14 days; minor irritation persisted on the remaining 4 rabbits.
Based on the descriptions of the lesions it is considered that Potassium isobutyl xanthate (the result was read across from Isobutyl Alcohol) is classifiable as an moderately irritant according to EU criteria
-The results of the study (Dow Chemical Company 1976) indicate that Potassium isobutyl xanthate (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. There were no treatment-related changes in the haematological or urinalysis values in any of the animals. No signs of irritation of respiratory tract and Nasal effects were observe

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Isobutyl Alcohol is both reagents used in the manufacture, as well as decomposition products of Potassium isobutyl xanthate. Therefore, the health effects of Isobutyl Alcohol need to be considered in the assessment of potassium isobutyl xanthate. In addition, xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc. Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product.

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4470 (Acute Dermal Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Male and female New Zealand White rabbits were received from Hazleton Research Products, Inc. (Denver, PA). The strain and species were selected because of their availability and existing historical data. Rabbits were ordered to be between 2.0 and 2.3 kg (designated by the supplier to be approximately 12 to 14 weeks of age). The females were nulliparous and nonpregnant.

Periodically, a Clinical Veterinarian examined rabbits for any signs of health deficiencies. Within 1 or 2 days of receipt, all animals were assigned a unique number which was marked on the animal cage card. The rabbit number was also marked in indelible ink on 1 ear at the time of dosing.

The rabbits were housed individually in cages with wire floors (approximately 61.0 x 46.0 x 36.0 cm.). DACBQ (Deotized Animal Cage Board; Shepherd Specialty Papers, Inc.) was placed under each cage and changed regularly. An automatic timer was set to provide fluorescent lighting for a 12-hour photoperiod (approximately 0500 to 1700 hours for the light phase). Temperature and relative humidity were recorded (Cole-Parmer Hygrothermograph Seven-Day Continuous Recorder, Model No. 8368-00, Cole-Parmer Instrument Co., Chicago, IL). Temperature was routinely maintained at 61-70°F during the test period; relative humidity was routinely maintained at 40-70%. Any minor exceptions to these specified ranges were noted in the raw data.
Tap water (Municipal Authority of Westmoreland County, Greensburg, PA) was available ad libitum (except during dosing) and was delivered by an automatic watering system with demand control valves mounted on each rack. Water analyses were provided by the supplier, Halliburton NUS Environmental Laboratories, Materials Engineering & Testing Company, and Lancaster Laboratories, Inc. at regular intervals. EPA standards for maximum levels of contaminants were not exceeded. As available, water analysis reports were reviewed by the Study Director. AGWAYe PROLABe Animal Diet High Fiber Rabbit (Agway Inc.) was available ad libitum except during the actual dosing period. No analyses of chemical composition and possible contaminants of the feed were conducted by the supplier.

Animal Acclimation
The animals were acclimated for at least 5 days before dosing. Detailed clinical observations were conducted twice, at the time of receipt and during animal identification and/or dosing. In addition, rabbits were examined and weighed twice prior to dosing. Cage-side observations and mortality checks were conducted at least once daily. Animals considered unacceptable for the study, based on the clinical signs or body weights (rabbits), were rejected for use on this study.
Study Organization
The animals were weighed and inspected for health on the day of the test. Only those exhibiting a healthy state were used. Healthy animals appeared alert, active and well groomed, with no evidence of discharge, diarrhea, breathing difficulties or locomotor abnormalities. A BRRC veterinarian was available for consultation regarding any animal health concerns. Animals were randomly assigned to cages and were designated for dosing according to need and availability.

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

Readings were made at 1, 24, 48 and 72 hours and at 7 and 14 days, after the end of the contact period.

Number of animals:

3 males and 3 females

Details on study design:

The fur was removed from the dorsal area of the trunk of each rabbit using veterinary clippers a few days before dosing and the dose area was trimmed carefully (avoiding skin abrasion), as necessary, up to the day before application of the test substance. A 1-inch square gauze patch was placed over 1 intact (nonabraded) site/rabbit and secured by adhesive tape. A volume of 0.5 ml was then applied under the patch. Polyethylene sheeting was placed loosely around the trunk and secured. The animal was placed in a restraining device for the 4-hour contact period after which the coverings and as much excess test substance as possible were removed.

The test substance was applied to each of 6 rabbits (3 males, 3 females). Readings were made at 1, 24, 48 and 72 hours and at 7 and 14 days, after the end of the contact period according to the method of Draize, 1959. All rabbits were sacrificed at 14 days (ear vein injection using Euthanasia-6 Solution).

Reference
Draize, J. H. (1959). The Appraisal of Chemicals in Foods, Drugs and Cosmetics. Tbe Association of Food and Drug Officials of the United States.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

1.2

Max. score:

2

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Maximum score observed. One animal had a score of 1 on day 14.

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Maximum score observed. One animal had a score of 1 on day 14.

Irritant / corrosive response data:

Application of 0.5 ml of isobutanol to covered rabbit skin for a 4-hour contact period produced minor to moderate erythema and edema on 6 of 6 rabbits within 1 day. (Maximum score noted on any animal for erythema or edema was 2). One rabbit had a light brown discoloration on the dose site at 1 hour. Superficial necrosis developed on this animal by 1 day; another rabbit had superficial necrosis at 7 days. Ecchymoses were apparent on 1 animal within 1 day. At 7 days, fissuring was observed on 1 animal. Four rabbits had desquamation at this time. By 14 days, alopecia was observed on 2 rabbits. Erythema and edema subsided on 5 of 6 rabbits within 14 days; minor erythema and edema persisted on 1 rabbit. Two rabbits had a normal appearance at this time.

Other effects:

No additional information available.

Interpretation of results:

moderately irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Minor to moderate erythema and edema on 6 of 6 rabbits, superficial necrosis on 2, ecchymoses on 1, fissuring on 1, desquamation on 4 and alopecia on 2 from 0.5 ml. Two rabbits had a normal appearance within 14 days; minor irritation persisted on the remaining 4 rabbits.
Isobutyl Alcohol is both reagents used in the manufacture, as well as decomposition products of Potassium isobutyl xanthate. Therefore, the health effects of Isobutyl Alcohol need to be considered in the assessment of potassium isobutyl xanthate.

Executive summary:

Isobutyl Alcohol is both reagents used in the manufacture, as well as decomposition products of Potassium isobutyl xanthate. Therefore, the health effects of Isobutyl Alcohol need to be considered in the assessment of potassium isobutyl xanthate.

 In addition, xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc. Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product.

The acute dermal irritation of isobutanol was examined in a 4 -hour exposure. Minor to moderate erythema and edema on 6 of 6 rabbits, superficial necrosis on 2, ecchymoses on 1, fissuring on 1, desquamation on 4 and alopecia on 2 from 0.5 ml. Two rabbits had a normal appearance within 14 days; minor irritation persisted on the remaining 4 rabbits.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reasonably documented

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:

moderately irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the descriptions of the lesions it is considered that Potassium isobutyl 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 isobutyl 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:

no adverse effect observed (not 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 isobutyl 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 isobutyl 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.

-Isobutyl Alcohol is both reagents used in the manufacture, as well as decomposition products of Potassium isobutyl xanthate. Therefore, the health effects of Isobutyl Alcohol need to be considered in the assessment of potassium isobutyl xanthate.

In addition,xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc.Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product.

The acute dermal irritation of isobutanol was examined in a 4 -hour exposure (Christopher, S.M.1993). Minor to moderate erythema and edema on 6 of 6 rabbits, superficial necrosis on 2, ecchymoses on 1, fissuring on 1, desquamation on 4 and alopecia on 2 from 0.5 ml. Two rabbits had a normal appearance within 14 days; minor irritation persisted on the remaining 4 rabbits.

Based on the descriptions of the lesions it is considered that Potassium isobutyl xanthate (the result was read across from

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

-Potassium Hydroxide is used in the manufacturing process for Potassium isobutyl xanthate and is present in the final product. Therefore, the health effects of Potassium Hydroxide need to be considered in the assessment of potassium isobutyl 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 isobutyl xanthate (the result was read across fromofPotassium 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 diedshowed convulsions and hyperactivity prior to death.

The results of the study (Dow Chemical Company 1976) indicate that Potassium isobutyl xanthate (the result was read across from potassium amyl xanthate) has an adverseeffect at concentration of 252 mg/m3on the central nervous system and liver in mice, the liver and kidneys in ratsand the liver in dogs. There were no treatment-related changes in the haematological or urinalysis values in any of the animals.No signs of irritation of respiratory tract and Nasal effects were observed.

Effects on skin irritation/corrosion: moderately irritating

Effects on eye irritation: moderately irritating

Justification for classification or non-classification

Based on the hazard assessment of Potassium isobutyl xanthate in section 2.1 and 2.2. in IUCLID 5.4., 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

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 isobutyl xanthate meet the criteria to be classified for human health hazards for Dermal-local effect:  R36 Irritating to eyes,  H319 Eye Irrit. 2 Causes serious eye irritation

 

It is concluded that the substance Potassium isobutyl xanthate meet the criteria to be classified for human health hazards for Dermal-local effect R38 Irritating to skin, H315 Skin Irrit. 2 Causes skin irritation

 

It is concluded that the substance Potassium isobutyl xanthate does not meet the criteria to be classified for human health hazards for respiratory irritation