Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (LLNA)
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:
Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates.Reaction mass of SEX readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of Reaction mass of SEX. 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:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS: Mice, CBA/CaOlaHsd
- Source: Harlan Laboratories B.V., Postbus 6174, 5960 AD Horst / The Netherlands
- Age at study initiation: 8 - 12 weeks (beginning of treatment)
- Weight at study initiation: 18.3 - 23.3 g
- Housing:single caging
- Diet: pelleted standard diet (Harlan Laboratories B.V., 5960 AD Horst / Netherlands), ad libidum
- Water: tap water, (Gemeindewerke, 64380 Rossdorf), ad libitum
- Bedding: granulated soft wood bedding (Rettenmaier & Söhne GmbH + Co. KG, 73494 Rosenberg)
- Acclimation period: At least 5 days prior to the start of dosing under test conditions after health examination. Only animals without any visible signs of illness were used for the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): relative humidity 45-65%
- Photoperiod (hrs dark / hrs light): artificial light 6:00 a.m. - 6:00 p.m.
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
The highest test item concentration which can be technically used was 100% of the undiluted test item. The dilutions were formulated in acetone/olive oil (4:1 v/v).
In the pre-test, two mice were treated with test item concentrations of 50 or 100%.
The test item in the main study was assayed at 25, 50, and 100%.
No. of animals per dose:
4
Details on study design:
RANGE FINDING TESTS:
- Compound solubility: The highest test item concentration which can be technically used was 100% of the undiluted test item. The dilutions were formulated in acetone/olive oil (4:1 v/v).
In the pre-test, two mice were treated by topical application to the dorsal surface of each ear with test item concentrations of 50 or 100% once daily each on three consecutive days. At those concentrations the animals did not show signs of systemic toxicity or local irritation.

MAIN STUDY:

TOPICAL APPLICATION:
Each test group of mice was treated by topical (epidermal) application to the dorsal surface of each ear (left and right) with different test item concentrations of 25, 50, and 100% (w/v) in acetone:olive oil (4:1). The application volume, 25 µl, was spread over the entire dorsal surface (~ 8 mm) of each ear once daily for three consecutive days. A further group of mice was treated with an equivalent volume of the relevant vehicle alone (control animals).
ADMINISTRATION OF ³H-METHYL THYMIDINE AND DETERMINATION OF INCORPORATED ³H-METHYL THYMIDINE

Five days after the first topical application, all mice were intraveneously injected into a tail vein with radio-labelled thymidine (³H-methyl thymidine). Approximately five hours after treatment with ³HTdR all mice were sacrificed and the draining lymph nodes were excised and pooled per group. Single cell suspensions lymph node cells were prepared from pooled lymph nodes, which were subsequently washed with phosphate buffered saline and incubated with trichloroacetic acid overnight. The proliferative capacity of pooled lymph node cells was determined by the incorporation of ³H-methyl thymidine measured in a ß-scintillation counter.

INTERPRETATION OF RAW DATA

The proliferative response of lymph node cells is expressed as the number of radioactive disintegrations per minute per lymph node (DPM/node) and as the ratio of ³HTdR incorporated into lymph node cells of test lymph nodes relative to that recorded for control lymph nodes (stimulation index). Before DPM/node values were determined, mean scintillation-background DPM was subtracted from test and control raw data. A test item is regarded as a sensitiser in the LLNA if the following criteria are fulfilled:
- First, that exposure to at least one concentration of the test item resulted in an incorporation of ³HTdR at least 3-fold or greater than that recorded in control mice, as indicated by the stimulation index.
- Second, that the data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression.
OBSERVATIONS

In addition to the sensitising reactions the following observations and data were recorded during the test and observation period:
- Mortality / Viability: Once daily (week day) from experimental start to necropsy.
- Body weights: In the pre-test prior to the first application and prior to sacrifice; in the main experiment prior to the first application and prior to treatment with 3HTdR.
- Clinical signs (local / systemic): In the pre-test clinical signs were recorded within 1 hour and 24 ± 4 hours after each application as well as on day 7. In the main experiment clinical signs were recorded within 1 hour each application, and 24 ± 4 hours after the first and second application as well as on the day of preparation. Especially the treatment sites were observed carefully.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
The mean values and standard deviations were calculated in the body weight tables.
Positive control results:
Experiment performend in November 2009:
5, 10, and 25% alpha-hexyl cinnamic aldehyde in acetone:olibe oil (4:1) yielded a S.I. of 1.78, 2.54, and 4.88, respectively. The EC3 value calculated was 12.9%.
The positive control substance alpha-hexyl cinnamic aldehyde was found to be a skin sensitizer under the described conditions, demonstrating the validity of the study.
Parameter:
SI
Remarks on result:
other: see Remark
Remarks:
In this study Stimulation Indices of 1.22, 0.99, and 3.46 were determined with the test item at concentrations of 25, 50, and 100% in acetone/olive oil (4:1 v/v), respectively. A conventional dose response curve could not be established and an EC3 value was not calculated because of the odd dose response.
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: As depicted in the table below.

Calculation and results of individual data; Vehicle: acetone/olive oil (4:1 v/v)

Test item concentration % (w/v)

Group

Measurement DPM

Calculation

Result

DPM-BGa)

number of lymph nodes

DPM per lymph nodeb )

S.I.

---

BG I

17

---

---

---

---

---

BG II

17

---

---

---

---

---

1

3517

3500

8

437.5

---

25

2

4282

4265

8

533.1

1.22

50

3

3479

3462

8

432.8

0.99

100

4

12129

12112

8

1514.0

3.46

VIABILITY / MORTALITY

No deaths occurred during the study period.

CLINICAL SIGNS

No symptoms of local toxicity at the ears of the animals and no systemic findings were observed during the study period.

BODY WEIGHTS

The body weight of the animals, recorded prior to the first application and prior to treatment with 3HTdR, was within the range commonly recorded for animals of this strain and age.

 

Interpretation of results:
other: not sensitising
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Based on the numerical values of the stimulation indices one of which is slightly above 3, the test item Carbon disulfide has to be considered a skin sensitizer under the test condidions of this study. However, a conventional dose-response curve could not be established. An EC3 value was not calculated because of the odd dose-response.These factors contribute also in determining whether a borderline result shall be deemed as positive. In the opinion of the applicant this is a false positive and CS2 cannot be considered as a skin sensitizer base don this study.
Carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates.Reaction mass of SEX readily decomposes to carbon disulphide, especially in the presence of moisture/water. Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of Reaction mass of SEX.
Executive summary:

In this study carbon disulfide dissolved in acetone/olive oil (4:1 v/v) was assessed for its possible contact allergenic potential. For this purpose a local lymph node assay according to OECD guideline 429 was performed using test item concentrations of 25, 50, and 100%. All treated animals survived the scheduled study period and no signs of systemic toxicity or local irritation were observed. A test item is regarded as a sensitiser in the LLNA if the exposure to one or more test concentration results in a 3-fold or greater increase in incorporation of ³HTdR compared with concurrent controls, as indicated by the Stimulation Index (S.I.). The estimated concentration of test item required to produce a S.I. of 3 is referred to as the EC3 value. In this study Stimulation Indices of 1.22, 0.99, and 3.46 were determined with the test item at concentrations of 25, 50, and 100% in acetone/olive oil (4:1). Based on the numerical values of these stimulation indices, the test item carbon disulfide has to be considered a skin sensitizer under the test conditions of this study. However, a conventional dose-response curve could not be established. An EC3 value was not calculated because of the odd dose-response. These factors contribute also in determining whether a borderline result shall be deemed as positive. In the opinion of the applicant this is a false positive and CS2 cannot be considered as a skin sensitizer base don this study.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
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 hydroxide is both reagents used in the manufacture of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide. Therefore, sodium hydroxide need to be considered in the assessment of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide
Qualifier:
no guideline followed
Principles of method if other than guideline:
Patch testing for 24 hours with visual scoring being recorded by the subjective evaluation method and by the transepidermal water loss method. After the seventh day reading sodium hydroxide (0.125%) was re-applied to all pretested sites and reading was performed on the next day.
GLP compliance:
not specified
Type of study:
not specified
Justification for non-LLNA method:
Patch testing for 24 hours with visual scoring being recorded by the subjective evaluation method and by the transepidermal water loss method. After the seventh day reading sodium hydroxide (0.125%) was re-applied to all pretested sites and reading was performed on the next day.
Species:
human
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
HUMAN VOLUNTEERS
- Age at study initiation: between 20 and 25
Route:
other: no data
Vehicle:
no data
Concentration / amount:
Concentrations used for induction: 50 µl, 1.0, 0.5, 0.25, 0.125 and 0.063%
Route:
other: no data
Vehicle:
no data
Concentration / amount:
Concentrations used for induction: 50 µl, 1.0, 0.5, 0.25, 0.125 and 0.063%
No. of animals per dose:
Number of volunteers: 15 without any previous history of atopy
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- Control group: yes, distilled water and empty chambers
- Site: back
- Duration: 24 hours (induction and challenge)
- Concentrations: 50 µl, 1.0, 0.5, 0.25, 0.125 and 0.063%


B. CHALLENGE EXPOSURE
- No. of exposures: on day 7, NaOH was reapplied
- Day(s) of challenge: 1
- Concentrations: 0.125%
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50 µl, 1.0, 0.5, 0.25, 0.125 and 0.063%
Total no. in group:
15
Clinical observations:
The irritant response was well correlated to the concentration of the irritant. However, increased response was not observed when subclinical doses were rechallenged on the previously patch tested sites.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50 µl, 1.0, 0.5, 0.25, 0.125 and 0.063%. Total no. in groups: 15.0. Clinical observations: The irritant response was well correlated to the concentration of the irritant. However, increased response was not observed when subclinical doses were rechallenged on the previously patch tested sites..

The irritant response was well correlated to the concentration of the irritant. However, increased response was not observed when subclinical doses were rechallenged on the previously patch tested sites.

Interpretation of results:
other: not sensitising
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Sodium hydroxide is both reagents used in the manufacture of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide. Therefore, sodium hydroxide need to be considered in the assessment of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide.
The irritant response was well correlated to the concentration of the irritant. However, increased response was not observed when subclinical doses were rechallenged on the previously patch tested sites.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1988
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 hydroxide is both reagents used in the manufacture of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide. Therefore, sodium hydroxide need to be considered in the assessment of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide
Qualifier:
no guideline available
Principles of method if other than guideline:
Mouse ear swelling test. Substance applied to mouse ear with adjuvant with measure of subsequent swelling used to indicate hypersensitivity.
GLP compliance:
not specified
Type of study:
mouse ear swelling test
Justification for non-LLNA method:
An ear swelling study was used to examine the skin sensitising potential of ethanol. Ethanol was applied twice on the right ear after an induction procedure involving two scapular subcutaneous injection of adjuvant and multiple topical ethanol applications to the abdomen over a period of 14 days.
Species:
mouse
Strain:
Swiss
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: IFFA-CREDO, L'Arbresle, France
- Age at study initiation: 6 - 8 weeks
- Housing: polyethylene cages
- Food and water ad libitum
- Acclimation period: 7 days
Route:
intradermal and epicutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
neat
Route:
intradermal and epicutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
neat
No. of animals per dose:
23
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
Anaesthetised animals received subcutaneous injection of 0.05ml of ethanol and complete Freund' adjuvant (CFA) into scapular region plus topical application to shaved abdomen (amount not specified - referred to as day 0).

B. CHALLENGE EXPOSURE
- No. of exposures: 7
- Day(s) of challenge: days 3, 5, 7, 10, 12 and 14 and 27
- Topical application on the shaved abdomen (amount not specified) on days above and a 2nd subcutaneous injection of CFA (0.05ml) on day 7 only.

OTHER: Mice were allowed to rest between days 14-26. On day 26, the thickness of the ear was measured before another topical application of the test substance to both sides of the ear. Ear thickness was measured again on days 27 and 28 (24 and 48 hours later). Thickness measurements were carried out with a mobile-disk dial caliper with an accuracy of 0.01mm.
Positive control substance(s):
yes
Remarks:
Penicillin, paraphenylene diamine and nickel chloride
Remarks on result:
no indication of skin sensitisation

Measurements of 94 untreated mice showed an ear thickness of 0.214 mm with a typical variation of 0.002 mm. 

Results on sensitisation and challenge with ethanol:

 Sex

 Number

 Before

 24 hour

 48 hour

 Male

 9

 26.94 +/-1.02

27.22 +/-1.58

(101.0%) 

 27.78 +/-1.86

(103.1%)

 Female

 10

 24.30 +/-1.38

 24.95 +/-1.44

(102.7%)

23.55 +/-1.46

(96.9%) 

Known moderate and strong sensitizers applied as controls produced significant swelling in this study.

Induction and challenge with the three positive controls all produced statistically significant increases in ear thickness.

 

Interpretation of results:
other: not sensitising
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Classification: not sensitizing.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:

An ear swelling study was used to examine the skin sensitising potential of ethanol. Ethanol was applied twice on the right ear after an induction procedure involving two scapular subcutaneous injection of adjuvant and multiple topical ethanol applications to the abdomen over a period of 14 days. The degree of contact hypersensitivity is deduced from easr swelling measured 24 and 48 hours after application. Ethanol was found not to cause any statistical increase in ear swelling, in contrast to 3 positive controls which all caused a statistically significant increase.

Endpoint:
skin sensitisation: in chemico
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitisation

No evidence of sensitisation in the study of of Vogel 2010.Based on the numerical values of the stimulation indices one of which is slightly above 3, the test item Carbon disulfide has to be considered a skin sensitizer under the test condidions of this study.

 However, a conventional dose-response curve could not be established. An EC3 value was not calculated because of the odd dose-response.These factors contribute also in determining whether a borderline result shall be deemed as positive. In the opinion of the applicant this is a false positive andCS2 cannot be considered as a skin sensitizer base don this study.

 

Because carbon disulphide is both a reagent in the manufacture, as well as a decomposition product of xanthates. Reaction mass of SEX readily decomposes to carbon disulphide, especially in the presence of moisture/water.Therefore, the health effects of carbon disulphide (CS2) need to be considered in the assessment of Reaction mass of SEX .

This result can be reliably be read across to the substanceReaction mass of SEX 

 

Synopsis

Not sensitising

 

-In other study Ethyl Alcohol was tested for skin sensitisation .

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.

Ethanol was applied twice on the right ear after an induction procedure involving two scapular subcutaneous injection of adjuvant and multiple topical ethanol applications to the abdomen over a period of 14 days. The degree of contact hypersensitivity is deduced from easr swelling measured 24 and 48 hours after application. Ethanol was found not to cause any statistical increase in ear swelling, in contrast to 3 positive controls which all caused a statistically significant increase.

 

 Synopsis

Not sensitising

 

-In other study Sodium Hydroxide was tested for skin sensitisation

Sodium hydroxideis both reagents used in the manufacture of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide. Therefore,sodium hydroxideneed to be considered in the assessment of Reaction mass of ethanol and sodium O-ethyl dithiocarbonate and sodium hydroxide

The irritant response was well correlated to the concentration of the irritant. However, increased response was not observed when subclinical doses were rechallenged on the previously patch tested sites.

Synopsis

Not sensitising

 

 


Migrated from Short description of key information:
No evidence of skin sensitisation. It is concluded that the substance Reaction mass of SEX  does not meet the criteria to be classified for human health hazards for Inhalation - local effect: skin sensitisation.

Respiratory sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
respiratory sensitisation: in vivo
Type of information:
other: published data
Adequacy of study:
key study
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:
Reaction mass of SEX are related compound to PAX
Qualifier:
no guideline followed
Principles of method if other than guideline:
A 30-day repeated inhalation study for potassium amyl xanthate was conducted in 1976. Animals were exposed to potassium amyl xanthate as an aqueous aerosol. Attempts at dust exposure were unsuccessful as potassium amyl xanthate is hygroscopic.
Animals were exposed to concentrations of 0, 100 and 800 mg/m3 of potassium amyl xanthate. These concentrations were equivalent to actual doses of 0, 23 and 252 mg/m3. Analysis of the particle size indicated that all the particles at the lower dose of 100 mg/m3 were less than 10μm in diameter while approximately 80% of the particles had a diameter of 10μm or less at a dose of 800 mg/m3. It is not possible to state from the description of the exposure method whether air flow was dynamic or static.
GLP compliance:
not specified
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Route of induction exposure:
inhalation
Route of challenge exposure:
inhalation
Vehicle:
other: aqueous aerosol
Concentration:
10 male Sprague-Dawley rats were exposed to concentrations of 0, 200 or 800 mg/m3 of potassium amyl xanthate, 6 hrs daily for 10 exposures in 2 weeks.
No. of animals per dose:
10
Details on study design:
Animals were exposed to concentrations of 0, 100 and 800 mg/m3 of potassium amyl xanthate. These concentrations were equivalent to actual doses of 0, 23 and 252 mg/m3. Analysis of the particle size indicated that all the particles at the lower dose of 100 mg/m3 were less than 10μm in diameter while approximately 80% of the particles had a diameter of 10μm or less at a dose of 800 mg/m3. It is not possible to state from the description of the exposure method whether air flow was dynamic or static.
Exposure levels for the study were established by a preliminary experiment. In the preliminary experiment, three groups of 10 male Sprague-Dawley rats were exposed to concentrations of 0, 200 or 800 mg/m3 of potassium amyl xanthate, 6 hrs daily for 10 exposures in 2 weeks.
Positive control substance(s):
not specified
Negative control substance(s):
not specified
Results:
The results of the study (Dow Chemical Company 1976) indicate that Sodium ethyl 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. Only Signs of irritation of respiratory tract and Nasal effects were observed in rats as reddish nasal discharge but not respiratory sensitisation.

Table 5 Results of repeated inhalation study with potassium amyl xanthate in laboratory animals

 

 

 

Dogs

(2 animals)

 

Rabbits

(4 animals)

 

Rats

(10 animals)

 

Mice

(10,6 animals)

 

100 mg/m3

 

Eyes

 

No irritation

 

No irritation

 

No irritation

 

No irritation

 

 

Nasal effects and irritation of respiratory tract

 

No effects

 

No effects

 

No effects

 

No effects

 

 

Hair coat

 

Yellow brown staining.

 

Progressive yellow brown staining

 

Yellow brown stainingof

the hair coat of the rats.

 

No staining

 

 

Other effects

 

Staining of the appendages

and scrotum; ulceration of the

skin in the scrotal region.

 

None

 

None

 

None

 

 

Body weight

 

No change

 

No change

 

No change

 

No change

 

 

Organ weight

 

No change

 

No change

 

No change

 

Higher liver to body weight

ratio than controls

 

 

Liver enzyme changes

 

Marked elevation of serum

alanine aminotransferase and

alkaline phosphatase activities

 

No change

 

No change

 

No change

 

 

Histopathology

changes

 

Hepatocellular degeneration,

necrosis and inflammation

 

No treatment related change

 

No treatment related change

 

No treatment related change

 

 

Deaths

 

None

 

None

 

None

 

None

 

800 mg/m3

 

Eye changes

 

Excessive lacrimation

 

Conjunctival redness

 

No irritation

 

No changes

 

 

Nasal effects and irritation of respiratory tract

 

None

 

None

 

Reddish nasal discharge

 

None

 

 

Hair coat

 

Yellow brown staining

 

A more intense yellow brown

 

Yellow brown staining

 

No effects

 

 

Skin

 

Ulceration of the skin

 

No effect

 

No effect

 

No effect

 

 

Body weight

 

No effect

 

No effect

 

No effect

 

No effect

 

 

Organ weight

 

No change

 

No change

 

Higher liver to body weight

ratio than controls

 

Higher liver to body weight

ratio than controls

 

 

Liver enzyme changes

 

Marked elevations of serum

alanine aminotransferase and alkaline phosphatase activities.

 

 

No changes

 

High serum alanine

aminotransferase activity

 

No changes

 

 

Histopathology

changes

 

Hepatocellular degeneration,

necrosis and inflammation

 

No changes

 

Microscopically visible

granular degeneration

 

No changes

 

 

Deaths

 

None

 

None

 

One, but not related to

exposure

 

10 from the original group

and 5/6 replacement animals

died. Convulsions hyperactivity

in 5/16 prior to death.

 

 

Interpretation of results:
other: not sensitising
Conclusions:
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 252mg/m3 on the central nervous system and liver in mice, the liver and kidneys in rats and the liver in dogs. Only Signs of irritation of respiratory tract and Nasal effects were observed in rats as reddish nasal discharge but not respiratory sensitisation.
Executive summary:

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 rabbits and 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 adverse effects produced by the two doses of potassium amyl xanthate are shown in Table1.

  

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 252mg/m3 on the central nervous system and liver in mice, the liver and kidneys in rats and the liver in dogs.

Only Signs of irritation of respiratory tract and Nasal effects were observed in rats as reddish nasal discharge but not respiratory sensitisation.

Endpoint:
respiratory sensitisation: in chemico
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Respiratory sensitisation.

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 Reaction 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.

Only Signs of irritation of respiratory tract and Nasal effects were observed in rats as reddish nasal discharge but not respiratory sensitisation.

Synopsis

Not Sensitising


Migrated from Short description of key information:
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 252mg/m3 on the central nervous system and liver in mice, the liver and kidneys in rats and the liver in dogs. Only Signs of irritation of respiratory tract and Nasal effects were observed in rats as reddish nasal discharge but not respiratory sensitisation.

Justification for classification or non-classification

Based on the hazard assessment ofReaction mass of SEX 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

Respiratory Sensitisation Xn

R42 May cause sensitization by inhalation

Respiratory Irritation Xi

R37 irritating to respiratory system

CLP

Respiratory Sensitisation

H334 Resp. Sens. 1 May cause allergy or asthma symptoms or breath-ing difficulties if inhaled

Respiratory Irritation

H335 STOT SE 3 May cause respiratory irritation

It is concluded that the substance Reaction mass of SEX does notmeet the criteria to be classified for human health hazards for Inhalation - local effect: respiratory sensitisation