Pentapotassium bis(peroxymonosulphate) bis(sulphate)

Endpoint summary

Description of key information

Acute toxitity test results
KMPS (triple salt) was tested in a number of studies for acute toxicity on oral, dermal, and inhalation exposure.

The acute oral LD50 and LOAEL for KMPS (triple salt) was determined to be 500 mg/kg bw in the rat.

 

The acute dermal LD50 and LOAEL was determined to be greater than 2000 mg/kg bw and 2000 mg/kg bw in the rat respectively.

 

The acute inhalation LC50 (4 h) and LOAEL was determined to be 1850 mg KMPS (triple salt)/m³ and 1250 mg/m³ respectively.

In another acute inhalation study the obtained LC50 (4 h) was > 5 mg/L with KMPS (Oxone Monopersulfate).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001-01-04 - 2001-09-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

March 1996

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

September 1996

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan U. K. Ltd., Bicester, Oxon, UK
- Age at study initiation: 5 - 7 weeks
- Weight at study initiation: 108 g (males); 88.5 g (females)

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2 % w/v and 20 % w/v (corresponding to 20 mg/mL and 200 mg/mL, respectively)
- Total volume applied: 10 mL/kg bw

Doses:

200 mg/kg bw (3 males; 3 females) + 2000 mg/kg bw (3 females)

No. of animals per sex per dose:

3 rats per sex and group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Examinations:
* clinical observations: at frequent intervals during test day 1, twice daily during days 2 – 15; all abnormalities were recorded
* mortality/viability: at least twice daily
* body weight: on test day 1 (prior to administration), 8 and 15
* necropsy (day 15): macroscopical examination of all animals (survivors and decedents) which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.

Statistics:

Toxicity was estimated without use of a statistical model.
Further more, when applying OECD 423 (Acute Toxic Class Method) for the determination of the acute oral LD50, a statistical method is not considered to be required, as this particular method does not yield the determination of an accurate LD50 figure but apart from specific situations gives rather an estimate on the range of the LD50.

Preliminary study:

not indicated

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

500 mg/kg bw

Based on:

test mat.

Mortality:

Since no deaths occurred at a dose level of 200 mg/kg bw and all animals died after the administration of 2000 mg/kg bw the LD50 (oral) was determined to be 500 mg/kg bw according to OECD 423 Annex 2c.

Clinical signs:

other: - Both dosages/all rats: piloerection, first noted approximately one hour after dosing - 200 mg/kg bw: no further signs of toxicity observed - 2000 mg/kg bw: all females showed hunched posture, lethargy, abnormal gait, reduced body temperature, body tremo

Gross pathology:

- All females treated with 2000 mg/kg bw died (two animals were found dead 6 h after administration, one on day 2). The animals revealed congestion in the subcutaneous tissue, brain, heart, lungs and spleen with pallor of the kidneys and pale patches on the liver and red fluid contents of the urinary bladder in one or more animals. Congestion and fluid contents were noted in the stomach and along the alimentary tract and in the urinary tract with enlarged, swollen or thickened tissues and dark and pale discolouration of the lining also seen in the stomach for all animals.
- No abnormalities were revealed for surviving animals.

Other findings:

not indicated

 

Table 1: Mortality data

Dose (mg/kg bw)	No. of deaths in group of 3	Day*
-	-	1 6 hours	2 a             b	3 to 14 a             b
200	0/3 Male 0/3 Female	0 0	0             0 0             0	0             0 0             0
2000	3/3 Female	2	1             -	-             -

*     The day/time indicated is the time that the animal was observed to die or found dead.

a    First observation
b    Second observation
-    Not applicable

 

Table 2: Signs of reaction to treatment

Clinical signs	No. of rats in groups of 3 showing signs Dose (mg/kg)
	200		2000
	Male	Female	Female
Piloerection	3	3	3
Hunched posture	0	0	3
Lethargy	0	0	3
Abnormal gait	0	0	3
Reduced body temperature	0	0	3
Body tremors	0	0	3
Shallow respiration	0	0	3
Pallor of the skin	0	0	3
Dull eyes	0	0	2
Partially closed eyelids	0	0	1
Red staining around the uro/genital area	0	0	1

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability). Since no deaths occurred at a dose level of 200 mg/kg bw and all animals died after the administration of 2000 mg/kg bw the LD50 (oral) was determined to be 500 mg/kg bw according to OECD 423 Annex 2c. Based on Regulation 1272/2008/EC (CLP), KMPS triple salt is classified as harmful if swallowed (cat. 4 (H302)).

Executive summary:

Materials and methods

Six (three male and three female) Sprague Dawley (CD) rats received a single dose of 200 mg KMPS triple salt/kg bw and another group of three females received 2000 mg KMPS triple salt/kg bw. The substance was administered by gavage at a constant volume of 10 mL/kg bw in distilled water as the vehicle. Animals were fastened over night prior to administration of the test material. Post-observation period was 14 days. A regular examination on clinical signs of toxicity and mortality/viability was performed. Body weights were determined pre-treatment on day 1, on days 8 and 15, or at death. All animals were subjected to a macroscopic examination on day 15.

 

Results and discussion

Please refer to tables 1 and 2, which are presented under "Remarks on results including tables and figures".

Following a single oral administration of KMPS triple salt by gavage to male and female Sprague Dawley (CD) rats at dose levels of 200 + 2000 mg/kg bw, all three females dosed with 2000 mg/kg bw died (two approximately 6 hours after dosing and one within 22 hours of dosing). A body weight loss was recorded for two of the decedents. Clinical signs at the 2000 mg/kg bw dosage were characterised by hunched posture, lethargy, abnormal gait, reduced body temperature, body tremors, shallow respiration and pallor of skin with dull eyes in two females and partially closed eyelids and red staining around the uro/genital area in one female. The animals revealed congestion in the subcutaneous tissue, brain, heart, lungs and spleen with pallor of the kidneys and pale patches on the liver and red fluid contents of the urinary bladder in one or more animals. Congestion and fluid contents were noted in the stomach and along the alimentary tract and in the urinary tract with enlarged, swollen or thickened tissues and dark and pale discolouration of the lining also seen in the stomach for all animals. No signs of toxicity (except of piloerection) observed were observed in animals of the 200 mg/kg bw dose group.

Recovery of surviving rats, as judged by external appearance and behaviour, was complete by day 3. No abnormalities were revealed for surviving animals.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

500 mg/kg bw

Quality of whole database:

Guideline conform study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980-09-12 - 1980-12-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Only male rats were used in this investigation. This is not considered to have comprised the study results as in a comparable investigation performed with Virkon S dust in male and female rats of the same strain and source, male rats were demonstrated to be slightly more sensitive than female rats (please refer to the Endpoint summary record Sect. 7.2.2; Doc. No. 528-002). Thus, the inhalation study reliably reflects and does not underestimate the acute inhalation toxicity potential of KMPS triple salt dust.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

Deviations:

no

Principles of method if other than guideline:

The 4-hour LC50 of KMPS triple salt dust was determined in male rats. Groups of 10 male rats were exposed to atmospheres of KMPS triple salt dust for single 4-hour periods. The concentrations ranged from 1.5 to 5.0 mg/L, higher atmospheric concentrations could not be generated under the given experimental conditions.

GLP compliance:

no

Remarks:

, GLP was not compulsory at the time of study conduct. In addition, laboratories in the USA are not certified by any governmental agency, but are subject to official inspections.

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Crl:CD

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Not indicated; rats used at Haskell laboratories were acquired from Charles River Laboratories Inc., Raleigh, North Carolina; U.S.A
- Age at study initiation: 8 weeks
- Weight at study initiation: 228 – 298 g

Route of administration:

inhalation: dust

Type of inhalation exposure:

head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
A dust aerosol of Oxone® (Potassium Peroxymonosulfate/KMPS triple salt) was generated with a 3-stage glass generator composed of dust reservoir, cyclone generator, and elutriator. A stirring rod with plastic paddles agitated the dust in the first 2 stages. Air introduced at the reservoir carried dust particles up to the generator and elutriator. Additional houseline air swept airborne dust from the elutriator stage into the chamber


VEHICLE
- Composition of vehicle: dilution with clean air (“houseline air”) only


TEST ATMOSPHERE
- Particle size distribution: The mass median aerodynamic diameter (MMAD) of the dust generated ranged from 1.7 to 4.0 µm (please refer to table 1, presented under "Any other information on materials and methods incl. tables").

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1.5, 3.9, 4.2, 5.0 mg/L (higher atmospheric concentrations could not be generated under the conditions used in the study)
Please refer to table 1, presented under “Any other information on materials and methods incl. tables”.

No. of animals per sex per dose:

10 animals (males) per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days post-observation

-Examinations performed:
* Rats were quarantined in pairs, in stainless-steel wire mesh cages for 1 week prior to use. During this period, rats were weighed and observed for normal weight gain and overt manifestations of disease. Food and water were provided ad libitum.
* During exposure, all rats were observed and clinical signs noted.
* Following exposure, rats were weighed and observed daily (excluding weekends) for a 14-day observation period.

Statistics:

In the absence of any deaths occurring at any exposure levels, a statistical method was not required for the determination of acute inhalation LC50.

Preliminary study:

not indicated

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 5 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: no deaths occured

Mortality:

No deaths were reported at any exposure level during exposure and during the 14-day observation period.
Please refer to the table presented under “Remarks on results including tables and figures”.

Clinical signs:

other: During exposure: In all exposures animals exhibited reduced response to sound and moderate to severe, ocular and nasal discharge increasing with concentration. Rats exposed at 1.5 mg/L exhibited moderate lung nouse immediately post exposure. This was not

Body weight:

not indicated

Gross pathology:

No pathological findings reported.

Other findings:

One rat at the highest exposure level of 5.0 mg/L was injured upon removal from the wire mesh restrainer. It was subsequently sacrificed.

 

Mortality

-	Mean Atmospheric Concentration (mg/L)	Mortality (No. deaths /No. exposed)	Time of death (day of death/no. of animals)
Male rats	1.5	0/10	-
-	3.9	0/10	-
-	4.2	0/10	-
-	5.0	0/9*	-

*:           One rat was injured upon removal from the wire mesh restrainer. It was subsequently sacrificed

Interpretation of results:

GHS criteria not met

Conclusions:

The study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability). When male Crl:CD rats were exposed head-only for a single 4-hour exposure period towards Oxone® (KMPS triple salt) dust at particle sizes lying well within the respirable range for rats, no deaths occurred up to and including the highest exposure level of 5.0 mg/L tested. Thus, Oxone (KMPS triple salt) does not have to be classified and labelled with respect to acute inhalation toxicity.

Executive summary:

Materials and methods

The purpose of this investigation was to determine the 4-hour LC50 of Oxone ® (KMPS triple salt) dust in male Crl:CD rats.

Groups of 10 male Crl:CD rats were exposed head-only for a single 4-hour period to dust atmospheres of KMPS triple salt at concentrations of 1.5, 3.9, 4.2 and 5.0 mg/L. Higher atmospheric concentrations could not be generated under these conditions. Except during exposure, rats were housed in pairs, in stainless-steel wire mesh cages. Food and water was provided ad libitum. Rats were quarantined under these conditions for 1 week prior to use. During this period, rats were weighed and observed for normal weight gain and overt manifestations of disease. During exposure, all rats were observed and clinical signs noted. Following exposure, rats were weighed and observed daily (excluding weekends) for a 14-day observation period.

Dust atmospheres were generated with a 3-stage glass generator. Chamber concentrations were gravimetrically verified at 30 min intervals. Particle size measurements were performed once during each exposure.

 

Results and discussion

A single 4-hour head-only exposure of male rats to chamber concentrations of 1.5, 3.9, 4.2 and 5.0 mg/L caused no mortalities during exposure and the following 14-day post-observation period. During exposure, clinical signs were characterised by moderate to severe ocular and nasal discharge increasing with concentration. Lung noise was reported for the low exposure level only. Slight to severe weight loss during days 1 through 4 and alopecia around the eyes, cloudy eyes as well as severe discharge from eyes and nose was evident at the three highest exposure levels. Weight gain returned to normal during the remainder of the observation period at these exposure levels.

An LC50 could not be determined since no deaths occurred at any exposure concentration.

The MMAD of the dust was determined to be 1.7 to 4.0 µm. Thus, the MMAD was well within the respirable range for rats at all exposure levels.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-03-07 - 1995-06-21

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Version / remarks:

1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

Version / remarks:

1984

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Crl:CD BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Inc., Raleigh, North Carolina; U.S.A
- Age at study initiation: 7 – 10 weeks
- Weight at study initiation:
males: 238 – 305 g
females: 170 – 242 g

Route of administration:

other: dust aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
System of generating particulates/aerosols: A dust aerosol of KMPS triple salt was generated by suspending the test substance in air with a Fluid Energy Model 00 Jet-O-Mizer Jetmill.


TEST ATMOSPHERE
MMAD (Mass median aerodynamic diameter): The MMAD of the dust generated ranged from 3.1 to 3.8 µm, with 1 to 2.1 % of the particles less than 1 µm, 34 to 48 % of the particles less than 3 µm, and 92 to 99 % of the particles less than 10 µm (please refer to table 1 presented under "Remarks on results including tables and figures").

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The atmospheric concentration of the test substance was determined by gravimetric analysis at approximately 30 min. intervals during the exposure.

Duration of exposure:

4 h

Concentrations:

2.5, 3.1 and 4.8 mg/L

No. of animals per sex per dose:

5 rats per sex and group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- The following examinations were made:
* clinical observations, mortality/viability: during and immediately after exposure and daily thereafter (except for test days 12 and 13 for the 2.5 mg/L group and days 13 and 14 for the 3.1 mg/L group)
* body weight: daily (except for test days 12 and 13 for the 2.5 mg/L group and days 13 and 14 for the 3.1 mg/L group)
* necropsy: at the end of the observation period all animals were examined macroscopically.

Statistics:

The acute inhalation toxicity LC50 was estimated by employing Probit analysis.

Preliminary study:

not indicated

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

3.7 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: related to Virkon S/L

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.85 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: related to Oxone Monopersulfate Compound

Sex:

male/female

Dose descriptor:

other: LOAEL

Effect level:

1.25 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No deaths in the 2.5 mg/L group, 60 % of male rats and 20 % of female rats died in the 3.1 mg/L group, all male rats and 60 % of the females of the 4.8 mg/L group died (please refer to table A6.1.3/01-2 presented under "Remarks on results including tables and figures").

Clinical signs:

other: Please refer to tables 3 and 4 presented under "Remarks on results including tables and figures". All surviving rats experienced severe body weight losses up to five days following exposure. All males and most females had an overall weight gain by the end

Body weight:

Please refer to "Executive summary: Results and discussion"

Gross pathology:

No treatment-related gross lesions were noted.

Other findings:

Characterisation of the chamber atmosphere during exposure showed the mean total particulate concentration to be 2.5, 3.1, or 4.8 mg/L (please refer to table 1 presented under "Remarks on results including tables and figures").

Table 1: Summary of Virkon S concentration and particle size distribution

Atmospheric concentration (mg/L)			MMAD* (µm)a	Geometric S.D.b	% Particle by Mass
Mean	S.D.	Range			1 µm	3 µm	10 µm
2.5	1.1	0.75-4.0	3.8	1.8	2.1	34	92
3.1	1.2	0.83-4.2	3.6	1.6	1.0	40	97
4.8	1.5	2.0-6.6	3.1	1.7	1.4	48	99

*    MMAD: mass median aerodynamic diameter
a     One sample taken during each exposure
b     S.D.: standard deviation

 

 

Table 2: Mortality

-	Mean Atmospheric Concentration (mg/L)	Mortality (No. deaths /No. exposed)	Time of death (day of death/no. of animals)
Male rats	2.5	0/5	-
"	3.1	3/5	1/1; 2/2
"	4.8	5/5	1/3; 2/2
Female rats	2.5	0/5	-
"	3.1	1/5	2/1
"	4.8	3/5	1/1; 2/1; 4/1

 

 

Table 3: Summary of clinical observations in male rats

-	Number of rat with given sign
Concentration (mg/L)	2.5	3.1	4.8
Observation	-
Coloured discharge Eye(s)	5	1	4
Coloured discharge Nose	4	0	4
Diarrhea	1	0	0
Enopthalmus	1	0	0
Gasping	5	4	0
Hunched over	5	4	0
Irregular respiration	5	4	2
Lethargy	0	0	1
Ruffled fur	3	0	0
Stained fur	5	4	1
Weakness	5	4	0
Wet fur	2	0	1

Interpretation of results:

GHS criteria not met

Conclusions:

The study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability). The LC50 (4-hour inhalation) of a dust aerosol of Virkon S (KMPS triple salt - 50 %) was determined to be 3.7 mg/L, corresponding to 1.85 mg/L KMPS triple salt/L after linear extrapolation taking into account the content of KMPS in Virkon S.
As only a low proportion of the particles of KMPS triple salt is in the respirable range under real case conditions and taking into consideration the available particle size distribution data, KMPS triple salt does not present an acute inhalation hazard. For this reason, no classification and labelling with respect to acute inhalation toxicity is proposed for KMPS triple salt. The absence for a need to classify KMPS triple salt with respect to acute inhalation is further substantiated by the availability of an older, but valid acute inhalation toxicity study (please refer to Section 7.2.2 ) performed with Oxone® Monopersulfate compound (identical to KMPS triple salt). In this study, male rats which appeared to be the more sensitive gender when the results of the acute inhalation toxicity study performed with Virkon S are considered, were exposed for 4 hours to a dust aerosol consisting of particles in the respirable range (MMADs < 4 µm). The results obtained showed that KMPS triple salt did not reveal an inhalation hazard up to and including the highest exposure level of 5 mg/L tested. Thus, no C&L with respect to acute inhalation toxicity is required for KMPS triple salt.

Executive summary:

Materials and methods

Three groups of five male and five female Crl:CD BR rats were exposed nose-only to a KMPS triple salt (50 %) atmosphere for a duration of 4 hours at chamber concentrations of 2.5, 3.1 and 4.8 mg/L. Chamber concentrations were determined twice per hour, sampling for particle size distribution was also performed. During exposure and the following 14-day observation period, rats were regularly inspected for clinical signs of toxicity and mortality/viability. Body weights were determined daily. On termination of the study after 14 days, all rats were subjected to a gross pathological examination.

MMAD of the dust was determined to be 3.1 to 3.8 µm, with 1 to 2.1 % of the particles less than 1 µm, 34 to 48 % of the particles less than 3 µm, and 92 to 99 % of the particles less than 10 µm. The MMAD was well within the respirable range for rats.

 

Results and discussion

Exposure to 2.5, 3.1, or 4.8 mg/L KMPS triple salt (50 %) produced mortalities of 0/10, 4/10, and 8/10, respectively. Deaths were observed on day 1 (one male) and day 2 (two males and one female) in the 3.1 mg/L group and on day 1 (three males and one female), day 2 (two males and one female), and day 4 (one female) in the 4.8 mg/L group. All surviving rats experienced severe body weight loss up to five days following exposure. Although some surviving rats had transient body weight losses during the remainder of the recovery period, most gained weight, exceeding their initial body weight by the end of the recovery period.

Clinical signs of toxicity observed in male and female rats that survived exposure to KMPS triple salt (50 %) included gasping, nasal and ocular discharges, hunched posture, lethargy weakness, diarrhea, enophthalmus, irregular respiration, lung noise, and ruffled fur. Gross pathological examination revealed no evidence of organ-specific toxicity in rats found dead during the study or sacrificed by design at the end of the 14‑day observation period.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

1 850 mg/m³ air

Quality of whole database:

Guideline conform study

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001-01-04 - 2001-09-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan U. K. Ltd, Bicester, Oxon, UK
- Age at study initiation: 8 11 weeks
- Weight at study initiation: 234 g (males); 216 g (females)

Type of coverage:

occlusive

Vehicle:

other: distilled water

Details on dermal exposure:

TEST SITE
Area of exposure: approx. 10 % of the total body surface

REMOVAL OF TEST SUBSTANCE
Removal of dressing 24 hours after topical application of test substance. Skin was washed with warm water. The treated area was blotted dry with absorbent paper.

TEST MATERIAL
- Amount(s) applied: 1.20 mL test substance dilution/kg bw (corresponding to 2000 mg/kg bw)
- Concentration (in vehicle): 166.7 % w/v (corresponding to 1.667 g/mL)

Duration of exposure:

24 hours

Doses:

1.20 mL test substance dilution/kg bw (corresponding to 2000 mg/kg bw)

No. of animals per sex per dose:

5 per sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

Statistics:

Toxicity was estimated without use of a statistic model

Preliminary study:

not indicated

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Sex:

male/female

Dose descriptor:

other: LOAEL

Effect level:

2 000 mg/kg bw

Mortality:

No lethal effect at maximal dose.
LD50: > 2000 mg/kg bw

Clinical signs:

other: No deaths and no systemic response to treatment (please refer to Table 1, which is presented under "Remarks on results including tables and figures"). Severe dermal irritation was seen in three animals following removal of the dressings persisting until s

Gross pathology:

Macroscopic examination revealed a necrotic area on the dose site of three animals and scabbing on the dose site of two animals. No abnormalities were recorded for the remaining animals.

Other findings:

- No deaths occurred during the entire study period
- Loss of body weight was recorded for one female and low body weight gains were recorded for two females on day 8

Table 1: Summary of Acute Dermal Toxicity

ose [mg/kg bw]	Sex	Number of dead / number of investigated	Time of death (range)	Observations
2000	male	0/5	n.a.	-        No clinical signs of systemic toxicity, local irritations at the application site, no effect on body weights and necrotic area or scabbing on the dose site in some animals
2000	female	0/5	n.a.	-        No clinical signs of systemic toxicity, local irritations at the application site, loss of body weight in one and low body weight gains in two animals and necrotic area or scabbing on the dose site in some animals
LD50 value	> 2000 mg/kg bw

 

Table 2: Dermal reactions

Dose (mg/kg)

Sex

Animal No.

Erythema / Oedema

Day

2

3

4

5

6

7

8

9

10

11

12

13

14

15

2000

male

1

E O

ef 0

bf 2

bf 1

bf 1

bf 1

bf 1

bf 1

bf 1

bf 1

bf 1

bf 1

bf 1

bf 1

bf 1

2

E O

2ac 1f

0a 1

0a 1

0a 1

0a 1

0a 1

0c 0

0c 0

0c 0

0c 0

0c 0

0c 0

0c 0

0c 0

3

E O

1c 0

1c 0

1c 0

0c 0

0c 0

0 0

0 0

0 0

0 0

0 0

0 0

0 0

0 0

0 0

4

E O

1d 1

0 0

0 0

0 0

0 0

0 0

0 0

0 0

0 0

0 0

0 0

0 0

0 0

0 0

5

E O

ef 4

bf 4

bf 3

bf 2

bf 2

bf 1

bf 2

bf 1

bf 1

bf 1

bf 1

bf 1

bf 1

bf 1

female

6

E O

1c 1

1a 1

1a 1

0a 1

0a 1

0a 1

0c 0

0c 0

0c 0

0c 0

0c 0

0c 0

0 0

0 0

7

E O

2d 2

b 2

b 2

bf 2

bf 2

bf 1

bf 1

bf 1

bf 1

bf 1

bf 1

bf 1

bf 1

bg 1

8

E O

2a 2d

1a 2

1a 1

0a 1

0a 1

0a 1

0a 0

0a 0

0a 0

0a 0

0a 0

0a 0

0a 0

0c 0

9

E O

0d 0

0 0

0 0

0 0

0 0

0 0

0 0

0 0

0 0

0 0

0 0

0 0

0 0

0 0

10

E O

2d 2

1a 2

1a 2

0a 1

0a 1

0a 1

0d 0

0d 0

0d 0

0d 0

0d 0

0d 0

0d 0

0 0

E = Erythema; O = Oedema
a   Localised necrosis (assessment of erythema not impaired)
b   Necrosis over majority of treatment site (assessment of erythema precluded)
c   Localised spots and/or scabbing
d   Spots and/or scabbing over the majority of the treatment site
e   Blanching over majority of treatment site
f    Cracking of the skin at edge of blanched area
g   Wet ulceration on dose site

Interpretation of results:

GHS criteria not met

Conclusions:

The study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability). LD50: > 2000 mg/kg bw. No classification and labelling with respect to acute dermal toxicity is required according to Regulation 1272/2008/EC (CLP).

Executive summary:

Materials and methods

A single dose of 2000 mg of KMPS triple salt/kg bw was topically applied under occlusive conditions onto the clipped dorsal skin of 5 male and 5 female Sprague Dawley (CD) rats for a period of 24 hours. Animals were regularly observed for clinical signs of toxicity, mortality/viability and local reactions. Body weights were recorded on day 1, 8 and 15, respectively. Following a 24 hour exposure period, the test material was removed and animals observed for another 14 days. Thereafter, animals were necropsied and examined macroscopically.

 

Results and discussion

No deaths and no clinical signs of systemic toxicity were reported following administration of a single dermal dose of 2000 mg KMPS triple salt/kg bw to 5 male and 5 female Sprague Dawley (CD) rats. Severe dermal irritation was seen in three animals following removal of the dressings persisting until study termination. Slight to well‑defined dermal irritation was observed in six animals following removal dressings. These reactions had resolved completely by Day 3 in one animal, Day  5 in one animal and Day 8 in four animals. In addition, localised necrosis, localised spots and/or scabbing, spots and/or scabbing over the majority of the treatment site, blanching over the majority of the treatment site, cracking of the skin at the edge of the blanched area and wet ulceration on the dose site were noted in a number of animals during the study. Loss of body weight was recorded for one female and low body weight gains were recorded for two females on day 8. Macroscopic examination revealed a necrotic area on the dose site of three animals and scabbing on the dose site of two animals. No abnormalities were recorded for the remaining animals.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Guideline conform study

Additional information

Oral toxicity

KMPS triple salt was tested in an acute oral toxicity study in rats (EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method). Six (three male and three female) Sprague Dawley (CD) rats received a single dose of 200 mg KMPS triple salt/kg bw and another group of three females received 2000 mg KMPS triple salt/kg bw. The substance was administered by gavage at a constant volume of 10 mL/kg bw in distilled water as the vehicle. Animals were fastened over night prior to administration of the test material. Post-observation period was 14 days. A regular examination on clinical signs of toxicity and mortality/viability was performed. Body weights were determined pre-treatment on day 1, on days 8 and 15, or at death. All animals were subjected to a macroscopic examination on day 15.

No deaths occurred at a dose level of 200 mg/kg bw. All animals died following administration of 2000 mg/kg bw. The LD50 (oral) was determined at 500 mg/kg bw.

Inhalation toxicity

KMPS triple salt was tested in an acute inhalation toxicity study in rats (EU Method B.2 (Acute Toxicity - Inhalation). Three groups of five male and five female Crl:CD BR rats were exposed nose-only to an atmosphere with a test substance containing 50 % KMPS for a duration of 4 hours at chamber concentrations of 2.5, 3.1 and 4.8 mg/L. Chamber concentrations were determined twice per hour, sampling for particle size distribution was also performed. During exposure and the following 14-day observation period, rats were regularly inspected for clinical signs of toxicity and mortality/viability. Body weights were determined daily. On termination of the study after 14 days, all rats were subjected to a gross pathological examination. MMAD of the dust was determined to be 3.1 to 3.8 µm, with 1 to 2.1 % of the particles less than 1 µm, 34 to 48 % of the particles less than 3 µm, and 92 to 99 % of the particles less than 10 µm. The MMAD was well within the respirable range for rats.

The LC50 (4-hour inhalation) of a dust aerosol of was determined at 3.7 mg/L, corresponding to 1.85 mg/L pure KMPS triple salt/L, after linear extrapolation and taking the KMPS triple salt content of the test substance into account (50 %).

As only a low proportion of the particles of KMPS triple salt is in the respirable range under real case conditions and taking into consideration the available particle size distribution data, KMPS triple salt does not present an acute inhalation hazard. For this reason, no classification and labelling with respect to acute inhalation toxicity is proposed for KMPS triple salt.

The absence for a need to classify KMPS triple salt with respect to acute inhalation is further substantiated by the availability of an older, but valid acute inhalation toxicity study performed with Oxone Monopersulfate compound (identical to KMPS triple salt). In this study, male rats which appeared to be the more sensitive gender when the results of the acute inhalation toxicity study performed with KMPS triple salt are considered, were exposed for 4 hours to a dust aerosol consisting of particles in the respirable range (MMADs < 4µm) The results obtained showed that KMPS triple salt did not reveal an inhalation hazard up to and including the highest exposure level of 5 mg/L tested. Thus, no C&L with respect to acute inhalation toxicity is required for KMPS triple salt.

Dermal toxicity

KMPS triple salt was tested in an acute dermal toxicity study in rats (EU Method B.3 (Acute Toxicity - Dermal). A single dose of 2000 mg of KMPS/kg bw was topically applied under occlusive conditions onto the clipped dorsal skin of 5 male and 5 female Sprague Dawley (CD) rats for a period of 24 hours. Animals were regularly observed for clinical signs of toxicity, mortality/viability and local reactions. Body weights were recorded on day 1, 8 and 15, respectively. Following a 24 hour exposure period, the test material was removed and animals observed for another 14 days. Thereafter, animals were necropsied and examined macroscopically.

No deaths and no clinical signs of systemic toxicity were reported following administration of a single dermal dose of 2000 mg KMPS/kg bw to 5 male and 5 female Sprague Dawley (CD) rats.

Severe dermal irritation was seen in three animals following removal of the dressings persisting until study termination. Slight to well‑defined dermal irritation was observed in six animals following removal dressings. These reactions had resolved completely by Day 3 in one animal, Day 5 in one animal and Day 8 in four animals. In addition, localised necrosis, localised spots and/or scabbing, spots and/or scabbing over the majority of the treatment site, blanching over the majority of the treatment site, cracking of the skin at the edge of the blanched area and wet ulceration on the dose site were noted in a number of animals during the study.

Loss of body weight was recorded for one female and low body weight gains were recorded for two females on day 8. Macroscopic examination revealed a necrotic area on the dose site of three animals and scabbing on the dose site of two animals.No abnormalities were recorded for the remaining animals.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. Based on the available data, the substance is not considered not to be classified for acute dermal or inhalative toxicity under Regulation (EC) No 1272/2008, as amended for the seventeenth time in Regulation (EU) 2021/849.

 

KMPS triple salt is classified as harmful if swallowed (cat 4, H302) according to Regulation (EC) No 1272/2008, as amended for the seventeenth time in Regulation (EU) 2021/849.