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Toxicological information

Repeated dose toxicity: oral

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Administrative data

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

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Chronic toxicity test of KCl abd NaCl in F344/Slc rat
Author:
Imai, Sh, Morimoto J, Sekiya N, Shima M, Kiyozuka Y, Nakamori K, Tsubura Y
Year:
1961
Bibliographic source:
J Nara Med Ass 37, 115-127
Reference Type:
review article or handbook
Title:
Potassium chloride (CAS-Nr. 7447-40-7)
Author:
UNEP
Year:
2003
Bibliographic source:
United Nations Environmental Program

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
purity commercial grade

Test animals

Species:
rat
Strain:
other: F344/Slc
Sex:
male
Details on test animals and environmental conditions:
no data to be identified because only abstract available

Administration / exposure

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
Doses / concentrations
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

Examinations

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

Results and discussion

Results of examinations

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

Effect levels

open allclose all
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

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

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).