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Diss Factsheets

Administrative data

Description of key information

Rats received KBr in food for 104 weeks in a testing regime approximating OECD guideline 453.
No detrimental changes were seen in the clinical signs, mortality, food and water consumption, ophthalmoscopic examination, haematology, clinical chemistry, urinalysis or organ weights of the treated animals. There is no evidence for potential carcinogenicity.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990
Reliability:
2 (reliable with restrictions)
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
GLP compliance:
not specified
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
104 weeks
Frequency of treatment:
Daily
Post exposure period:
N/A
Remarks:
Doses / Concentrations:
500 ppm
Basis:

Remarks:
Doses / Concentrations:
500 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
60 rats/sex/dose
Control animals:
yes, plain diet
Statistics:
The multiple comparison test (Dunnett’s or Scheffé’s method) was used to analyse data on body weight, food consumption, water consumption, urinalysis (specific gravity and urine volume), haematology, blood biochemistry and organ weights in order to determine the significance of the results. Mortality was evaluated by life-table analysis. The Mann-Whitney U test was applied to the urinalysis data except for those on specific gravity and urine volume. Fisher’s exact probability test was used for the analysis of data on ophthalmology and gross histopathology. The significance of the differences between the basal diet and treated groups was estimated at 5 and 1% levels of probability
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
No effects were observed on the behaviour of the rats treated with KBr.
Mortality:
mortality observed, treatment-related
Description (incidence):
No effects were observed on the behaviour of the rats treated with KBr.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Higher body weights than those in the basal diet group were noted in the KBr group at weeks 1-6 (males) and at weeks 1, 10, 16, 24-36 and 44 (females).
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Higher food consumption was seen at weeks 3 and 4 (males) and at weeks 1-4 (females) of the KBr treated group. The compound intake was equivalent to 16.5 mg/kg bw/day (males) and 20.0 mg/kg bw/day (females).
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Description (incidence and severity):
Water consumption was statistically significantly higher in the treated group than in the control group at weeks 1-2, 7-8, 10, 13 and 24 in females).
Ophthalmological findings:
effects observed, treatment-related
Description (incidence and severity):
Several of the lesions observed in the treated and control groups were considered to be spontaneous. There was no lesion that showed a statistically significantly increased incidence.
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
There were no significant differences between groups in haematological indices.
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
Treated males showed a slightly increased concentration in calcium at week 52. However, this result was within the normal range seen in historical data, and there were no statistically significantly different differences between the treated and control gr
Urinalysis findings:
effects observed, treatment-related
Description (incidence and severity):
Urinalysis revealed statistically significant increases in mean values of specific gravity and in the number of rats showing a moderate degree of urobilinogen in males of the treated group at week 52 in comparison with the control. However, these changes
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Liver, kidneys, adrenals, testes, ovaries, spleen, brain, heart, pituitary, thyroids with parathyroids - There were no significant changes in the absolute weights of any organ in any of the treated groups in comparison with the control group.
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
No abnormal observations (not including tumour formation) were noted by the author.
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
The overall incidence of prostatitis (20/60) was significantly increased in comparison with the control group (10/60). This lesion is described by the author as a focal inflammatory lesion characterised by neutrophilic infiltration into the glandular spac
Histopathological findings: neoplastic:
effects observed, treatment-related
Details on results:
No detrimental changes were seen in the clinical signs, mortality, food and water consumption, ophthalmoscopic examination, haematology, clinical chemistry, urinalysis or organ weights of the treated animals.
Histologically, all tumours observed in this study were similar to those that are known to occur spontaneously in this strain of rats. Although the incidences of prostatitis (20/60) in males, and mononuclear cell leukaemia in treated females (11/60) were significantly increased, historical control data indicate that these increases were within the ranges of incidence previously observed for control animals at the testing laboratory and so neither increased incidence was considered to be treatment related.
Dose descriptor:
NOAEL
Basis for effect level:
other: see 'Remark'
Remarks on result:
not determinable
Remarks:
no NOAEL identified
Conclusions:
Rats received KBr in food for 104 weeks in a testing regime approximating OECD guideline 453. Animals were assessed regularly for signs of toxicity, and standard biochemical and urinalysis changes. Tissues were examined for tumour formation at interim, terminal sacrifice and when any other unplanned deaths occurred.
No detrimental changes were seen in the clinical signs, mortality, food and water consumption, ophthalmoscopic examination, haematology, clinical chemistry, urinalysis or organ weights of the treated animals.
Histologically, all tumours observed in this study were similar to those that are known to occur spontaneously in this strain of rats. Although the incidences of prostatitis (20/60) in males, and mononuclear cell leukaemia in treated females (11/60) were significantly increased, historical control data indicate that these increases were within the ranges of incidence previously observed for control animals at the testing laboratory and so neither increased incidence was considered to be treatment related.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Justification for classification or non-classification

Based on the conclusions from outlined above from subchronic toxicity studies and human dietary experience, it is considered unnecessary to conduct further carcinogenicity studies or additional repeat dose toxicity studies.

Additional information

Rats received KBr in food for 104 weeks in a testing regime approximating OECD guideline 453.

No detrimental changes were seen in the clinical signs, mortality, food and water consumption, ophthalmoscopic examination, haematology, clinical chemistry, urinalysis or organ weights of the treated animals.

Histologically, all tumours observed in this study were similar to those that are known to occur spontaneously in this strain of rats. Although the incidences of prostatitis (20/60) in males, and mononuclear cell leukaemia in treated females (11/60) were significantly increased, historical control data indicate that these increases were within the ranges of incidence previously observed for control animals at the testing laboratory and so neither increased incidence was considered to be treatment related.

Potassium bromide is an inorganic salt that dissociates to its composite ions in aqueous solutions at environmental pH and temperature. Comparison of the available data on the various bromide salts have shown that the bromide ion is the relevant ion for determination of the toxicological profile with simple cations such as potassium, sodium or ammonium, that are ubiquitous in nature, having little or no influence on the bromide ion properties. It is therefore justified to read-across data from other inorganic bromide salts to potassium bromide.

The results from in vitro genotoxicity studies showed that sodium bromide was not genotoxic under the test conditions. Furthermore, the repeated dose studies did not show any evidence of cellular change, even in potential target tissues such as the endocrine (thyroid) or neural systems, that could be considered preneoplastic change (e.g. hyperplasia or metaplasia). No reports were found to indicate potential neoplastic change as a consequence of normal human exposure to bromide in the diet. Therapeutic exposure has not been associated with neoplastic change.