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Toxicity to reproduction: other studies

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Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
other: Published data
Adequacy of study:
supporting 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:
Toxicity and carcinogenicity of acidogenic or alkalogenic diets in rats; effects of feeding NH4Cl, KHCO3 or KCl
Author:
Lina BAR, Juijpers MHM
Year:
2004
Bibliographic source:
Food Chem Toxicol 42,135-153
Reference Type:
publication
Title:
The role of akalizing and neutral potassium salts in urinary bladder carcinogenesis in rats
Author:
Lina BAR, Hollanders VMH, Kuijpers MHM
Year:
1994
Bibliographic source:
Carcinogenesis 15, 523-527

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD TG 453
Deviations:
yes
Remarks:
prolongation of treatment time up to 30 months and only one dose used
GLP compliance:
not specified
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
purity :>99.5 %

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 5 weeks
- Housing: groups of 5 of same sex and same treatment group
- Diet ad libitum
- Water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 35-70
- Air changes (per hr):10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
male and female rats were fed diets containing 0 or 3 % KCL over a total period of 30 months
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
no details given

Duration of treatment / exposure:
10 rats/sex/group: 13 weeks
15 rats/sex/group; 18 months
50 rats/sex/group: 30 months
Frequency of treatment:
coninuously in diet
Duration of test:
30 months
Doses / concentrations
Remarks:
Doses / Concentrations:
3 % in diet
Basis:
nominal in diet
No. of animals per sex per dose:
10 rats/sex/group: 13 weeks
15 rats/sex/group; 18 months
50 rats/sex/group: 30 months
Control animals:
yes, concurrent no treatment
Details on study design:
male and female rats were fed diets containing 0 or 3 % KCL over a total period of 30 months: after 13 weeks 10 rats/sex/group were examined , after 18 months 15 rats/sex/group were examined and after 30 months 50 rats/sex / group were examined
Statistics:
ANOVA /LSD test, Mann-Whitney U-test. two-sided Fisher exactprobability test

Results and discussion

Effect levels

Dose descriptor:
conc. level:
Effect level:
ca. 3 other: % in diet
Based on:
other: nominal
Sex:
male/female
Basis for effect level:
other: no effects on reproductive organs were reported

Observed effects

for general toxicity see section Repeated dose toxicity
No effects on reproductive organs were reported

Any other information on results incl. tables

BODY WEIGHT AND WEIGHT GAIN (graphic only)

30 months: mean body weights were decreased in males and females compared to controls

18 months: mean body weights in males were decreased when compared to controls

13 weeks no growth depression was observed

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)

due to the reduction of feed intake the mean test substance intake decreased in time:

--13 w treatment males 29.9 mmol/kg bw , females: 35.2 mmol/kg bw

--18 month treatment, males: 20.8 mmol/kg bw , females 24.7 mmol/kg bw

--30 months treatment, males:19.5 mmol/kg bw , females:.22,6 mmol/kg bw

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)

water intake was increased throughout the studies by ca 25 % in males and females

HAEMATOLOGY

blood gas analysis: base exess was not affected by feeding KCl

there were no consistent or treatment related effects on red blood cell variables , clotting potential or total and differential blood cell count

CLINICAL CHEMISTRY

Potassium levels in plasma were generally increased although the difference to the concurrent control was not significant (data not shown)

URINALYSIS

Urinary pH was not influenced by the feeding of KCl

the volume of the urine collected during 24 hours was generally increased in rats fed KCL

urinary potassium excretion was significantly increased in all groups that were fed KCl

GROSS PATHOLOGY/ ORGAN WEIGHTS

-With KCl the relative kidney weights tended to be increased but were not consistent

-there was no consistent or treatment related changes in the weights of the liver, spleen, ovaries , pituitary, thyroid, thymus or heart

-The analysis of femur ath the end of the studies did not reveal any effects of femur weight, calcium content or on total bone substance

-macroscopic examinations at necropsy did not reveal significant differences among the treatment group and the control group,

HISTOPATHOLOGY: NON-NEOPLASTIC

30 month-treatment:

in the adrenals, zona glomerulosa: hypertrophy in 24/50 treated rats versus 4/50 in controls,

in the urinary bladder: cystitis (males: 3/59; females 3/50) and single epithelial hyperplasia (males 3/50; females 2/50)

Applicant's summary and conclusion

Conclusions:
Male and female Wistar rats were fed diets containing 0 or 3 % KCL over a total period of 30 months: Examination after 13 weeks (10 rats/sex/group), after 18 months (15 rats/sex/group) and after 30 months (50 rats/sex /group). Due to the reduction of feed intake the mean test substance intake and mean body weight decreased in time. After 30 months treatment, reproductive organs on males and females were not affected by treatment.
Executive summary:

Male and female Wistar rats were fed diets containing 0 or 3 % KCL over a total period of 30 months: Examination after 13 weeks (10 rats/sex/group), after 18 months (15 rats/sex/group) and after 30 months (50 rats/sex /group). Due to the reduction of feed intake the mean test substance intake and mean body weight decreased in time. After 30 months treatment, reproductive organs on males and females were not affected by treatment.