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Description of key information

Oral repeated dose toxicity 
Potassium chloride (KCl) is the most common source of Potassium oxide (K2O). Therefore, the health effects of potassium chloride need to be considered in the assessment of Potassium oxide
Groups of male F344/Slc rats received 110, 450, 1820 mg/kg bw/day of KCl in feed over a period of 2 years and were observed for clinical signs and mortality and were examined for gross and histopathological changes at the end of the treatment period (Imai 1961) The NOAEL was set 1820 mg/kg bw/day since nephritis was reported in all treatment groups as well as in the control group. With respect to the observed gastritis which is regarded to be a local effect a LOAEL(local) of 110 mg/kg bw/d was determined (Imai 1961, UNEP 2003).
NOAEL -1820 mg/kg bw/day

Dermal repeated dose toxicity
There are no dermal repeated studies available.
For dermal exposure we taken that:
-the average weight of rats is 250g (200-300g),
-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg
corrected dermal NOAEL= oral NOAEL
1820 mg/kg bw/day x 0.025 kg =
NOAELrat = 45.5 mg/kg bw/day

Inhalation repeated dose toxicity
There are no Inhalation Repeated studies available.
The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.
NOAEL rat
1820 mg/kg bw/day
÷1.15 m3/kgbw
÷20m3/rat
NOAECrat 79.13 mg/m3

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: oral
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
Principles of method if other than guideline:
Groups of male F344/Slc rats received different doses of KCl in feed over a period of 2 years and were observed for clinical signs and mortality and were examined for gross and histopathological changes at the end of the treatment period
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
other: F344/Slc
Sex:
male
Details on test animals and environmental conditions:
no data to be identified because only abstract available
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Groups of male F344/Slc rats received different doses of KCl in feed over a period of 2 years
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
2 years
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
0, 0.25, 1, 5 % in diet (corresponding to 0, 110, 450, 1820 mg/kg bw/day
Basis:
nominal in diet
No. of animals per sex per dose:
50
Control animals:
yes, concurrent no treatment
Details on study design:
Groups of male F344/Slc rats received different doses of KCl in feed over a period of 2 years and were observed for clinical signs and mortality and were examined for gross and histopathological changes at the end of the treatment period
Positive control:
no
Observations and examinations performed and frequency:
survival, food consumption, blood pressure, body weight development
urinalysis: protein, glucose, keton, bilirubin, urobilinogen, pH
hematology: RBC, HB, Ht, MCV, HCH, MCHC, Pt, WBC
biochemical analysis: GOT, GPT, ALP, LDH, Ch-E, Na, K, Cl, Nu, Clu, Tp, Glu
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
absolue and relative organ weight: brain, pituitary, thymus, heart, right and leftlungs, linver, spleen, pancreas, right and left kidneys, right and leftadernals. right and left testes, seminal vesicles, prostrate
HISTOPATHOLOGY: Yes
heart, lung, liver, kidney, stomach, aorta
(grading of nephrosis +, ++, +++)
Other examinations:
no data
Statistics:
no data
Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
effects observed, treatment-related
Details on results:
MORTALITY:
after termination of the 2 year treatment period_
110, 450, 1820 mg/kg bw/day versus control:
18/50, 21/50, 8/50 versus 26/50
survival rate:
32/50, 29/50, 42/50 versus 24/50

HISTOPATHOLOGY: NON-NEOPLASTIC
KIDNEYS. nephritis
110, 450, 1820 mg/kg bw/day versus control:
32/32, 29/29, 42/42 versus 24/24
grading:
110 mg/kg: 23/32: +; 6/32: ++; 3/32: +++
450 mg/kg: 11/29:+; 6/29: ++; 12/29: +++;
1820 mg/kg: 28/42: +; 13/42: ++; 1/42: +++
control: 14/24: +; 6/24: ++; 4/24: +++

STOMACH.:
110, 450, 1820 mg/kg bw/day versus control:
gastritis
18/32, 18/29; 30/42 versus 6/24
ulcer
0/32, 2/29 , 2/42 versus 0/24

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
HISTORICAL CONTROL DATA (if applicable)
In tumerous lesions, testicular tumor developed with a high incidence in all groups and the incidence of pheochromocytoma in the adrenals was moderately high in all groups.
However the incidence and type of tumour in experimental and control group were comparable to those of spontaneous tumours in F344/Slc rats (data not shown). Therefore the tumours observed in this study were thought to be spontaneous in origin
OTHER FINDINGS
Dose descriptor:
NOAEL
Effect level:
ca. 1 820 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: The high mortality in all groups including controls (>50%) . nephritits was reported in all treatment groups as well as in the control group (UNEP 2003)
Dose descriptor:
LOAEL
Remarks:
local
Effect level:
ca. 110 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: With respect to gastritis which is regarded to be a local effect; UNEP 2003
Critical effects observed:
not specified
Conclusions:
Groups of male F344/Slc rats received 110, 450, 1820 mg/kg bw/day of KCl in feed over a period of 2 years and were observed for clinical signs and mortality and were examined for gross and histopathological changes at the end of the treatment period (Imai 1961) The NOAEL was set 1820 mg/kg bw/day since nephritis was reported in all treatment groups as well as in the control group. With respect to the observed gastritis which is regarded to be a local effect a LOAEL(local) of 110 mg/kg bw/d was determined (Imai 1961, UNEP 2003).
Executive summary:

Groups of male F344/Slc rats received 110, 450, 1820 mg/kg bw/day of KCl in feed over a period of 2 years and were observed for clinical signs and mortality and were examined for gross and histopathological changes at the end of the treatment period (Imai 1961) The NOAEL was set 1820 mg/kg bw/day since nephritis was reported in all treatment groups as well as in the control group. With respect to the observed gastritis which is regarded to be a local effect a LOAEL(local) of 110 mg/kg bw/d was determined (Imai 1961, UNEP 2003).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 820 mg/kg bw/day
Study duration:
chronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
79.13 mg/m³
Study duration:
chronic
Species:
rat
Quality of whole database:
Inhalation exposure:
The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.
NOAEL rat
1820 mg/kg bw/day
÷1.15 m3/kgbw
÷20m3/rat
NOAECrat 79.13 mg/m3

Repeated dose toxicity: inhalation - local effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
79.13 mg/m³
Study duration:
subacute
Species:
rat
Quality of whole database:
Inhalation exposure:
There are no Inhalation Repeated studies available.
The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.
NOAEL rat
1820 mg/kg bw/day
÷1.15 m3/kgbw
÷20m3/rat
NOAECrat 79.13 mg/m3

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: dermal
Data waiving:
other justification
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
45.5 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
Dermal repeated dose toxicity
There are no dermal repeated studies available.
For dermal exposure we taken that:
-the average weight of rats is 250g (200-300g),
-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg
corrected dermal NOAEL= oral NOAEL
1820 mg/kg bw/day x 0.025 kg =
NOAELrat = 45.5 mg/kg bw/day

Repeated dose toxicity: dermal - local effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: dermal
Data waiving:
other justification
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
5.62 mg/cm²
Study duration:
subacute
Species:
rat

Additional information

Oral repeated dose toxicity

Potassium chloride (KCl)is the most common sourceofPotassium oxide(K2O).Therefore, the health effects of potassium chloride need to be considered in the assessment of Potassium oxide

Groups of male F344/Slc rats received 110, 450, 1820 mg/kg bw/day of KCl in feed over a period of 2 years and were observed for clinical signs and mortality and were examined for gross and histopathological changes at the end of the treatment period (Imai 1961) The NOAEL was set 1820 mg/kg bw/day since nephritis was reported in all treatment groups as well as in the control group. With respect to the observed gastritis which is regarded to be a local effect a LOAEL(local) of 110 mg/kg bw/d was determined (Imai 1961, UNEP 2003).

NOAEL -1820 mg/kg bw/day

 

 

Dermal repeated dose toxicity

 

There are no dermal repeated studies available.

For dermal exposure we taken that:

-the average weight of rats is 250g (200-300g),

-the dose is applied over an area which is approximately 10% of the total body surface=0.025 kg

 corrected dermal NOAEL=   oral NOAEL

1820 mg/kg bw/dayx0.025 kg =                  

 NOAELrat  = 45.5 mg/kg bw/day

 

Inhalation repeated dose toxicity

 

There are no Inhalation Repeated studies available.

The oral dose for the rat is converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m3/kg for 24 hours exposure. The resulting air concentration needs to be additionally corrected for 24 hlight activity (20 m3), assuming 100 % absorption for both routes.

NOAEL rat

1820 mg/kg bw/day

÷1.15 m3/kgbw

÷20m3/rat

NOAECrat    79.13 mg/m3


Justification for selection of repeated dose toxicity dermal - local effects endpoint:
The generic modification from the NOAELtest (in mg/kg of body weight) to NOAELmodified (in mg/cm2/day) will be
NOAELin mg/cm2 = ((dose in mg/kg bw)x (average animal weight in kg)) / Treated surface in cm2)
NOAELtest* 0.25/44.5= NOAELmodified

The highest dose not causing irritation/corrosion was 1000 mg/kg bw in dermal toxicity study in rats of Merkel, D.J., N. 2000.
the modified dose descriptor would be
NOAELmodified =1000 mg/kg*0.25 kg/44.5cm2=5.62 mg/cm2

Repeated dose toxicity: via oral route - systemic effects (target organ) urogenital: kidneys; other: all gross lesions and masses

Repeated dose toxicity: inhalation - systemic effects (target organ) urogenital: kidneys; other: all gross lesions and masses

Repeated dose toxicity: dermal - systemic effects (target organ) other: all gross lesions and masses

Justification for classification or non-classification

Based on the hazard assessment of Potassium oxide/Dipotassium oxide in section 2.1 and 2.2. in IUCLID 5.4., available data for the substance and following the “Guidance onInformation Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health”, according to the EU’s list of dangerous substances (OJEC No L200/130.7.99) and according to the criteria described in Directive 67/548 and in the CLP Regulation:

 

Directive 67/548

Repeated dose toxicity

R33 Danger of cumulative effects.

T; R48/23 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation.

T; R48/23/24 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation and in contact with skin.

T; R48/23/24/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed.

T; R48/23/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed.

T; R48/24 Toxic; Toxic: danger of serious damage to health by prolonged exposure in contact with skin.

T; R48/24/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure in contact with skin and if swallowed.

T; R48/25 Toxic; Toxic: danger of serious damage to health by prolonged exposure if swallowed.

Xn; R48/20 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation.

Xn; R48/20/21 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation and in contact with skin.

Xn; R48/20/21/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation, in contact with skin and if swallowed.

Xn; R48/20/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure through inhalation and if swallowed.

Xn; R48/21 Harmful; Harmful: danger of serious damage to health by prolonged exposure in contact with skin.

Xn; R48/21/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure in contact with skin and if swallowed.

Xn; R48/22 Harmful; Harmful: danger of serious damage to health by prolonged exposure if swallowed.

 

CLP

Repeated dose toxicity

STOT Rep. Exp. 1

STOT Rep. Exp. 2

H372: Causes damage to organs <or state all organs affected, if known> through prolonged or repeated exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

H373: May cause damage to organs <or state all organs affected, if known> through prolonged or repeated exposure <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

 

 

It is concluded that the substance Potassium oxide/Dipotassium oxide does not meet the criteria to be classified for human health hazards for Repeated dose toxicity