Sodium hydrogencarbonate

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

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

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

carcinogenicity: oral

Type of information:

experimental study

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

Remarks:

Taken from OECD SIDS on Sodium bicarbonate (2002), where a similar reliability was assigned.

GLP compliance:

not specified

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ORGANISM
- Age: 6 weeks.
- Weight at study initiation: Approximately 120 g.
- Number of animals: 216 in total, 31 in group 1-6 and 30 in group 7.

Route of administration:

oral: feed

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

104 weeks

Frequency of treatment:

continously

Dose / conc.:

0.64 other: %

Remarks:

Exposure to 0.64% NaHCO3 only.

Dose / conc.:

0.64 other: %

Remarks:

Combined exposure: 0.64% NaHCO3 + 1.25% sodium o-phenylphenol

Dose / conc.:

0.32 other: %

Remarks:

Combined exposure: 0.32% NaHCO3 + 1.25% sodium o-phenylphenol

Dose / conc.:

0.16 other: %

Remarks:

Combined exposure: 0.16% NaHCO3 + 1.25% sodium o-phenylphenol

Dose / conc.:

0 other: %

Remarks:

Exposure to 2% sodium o-phenylphenol only.

Dose / conc.:

0 other: %

Remarks:

Exposure to 1.25% sodium o-phenylphenol only.

Control animals:

yes

Details on results:

Result (carcinogenicity): negative

Dose descriptor:

other:

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

no significant increase in the number of tumours in comparison to the control group

The study assessed the carcinogenic potential of OPP-Na and OPP in combination with NaHCO3. NaHCO3 alone did not have a carcinogenic effect on the urinary bladder of rats. Papillary or nodular hyperplasia and papilloma incidence did not differ from the control group incidence.

MORTALITY AND TIME TO DEATH: The percentage of survival in week 104 was: NaHCO3-exposed animals: 84% (26/31); control group: 73% (22/30). Time of death is not reported.

BODY WEIGHT GAIN: The final body weight was significantly lower in all treated groups than in the control group.

URINALYSIS: The urinary Na+ concentrations increased significantly with NaHCO3 exposure, compared to the control group 7. Potassium levels were increased significantly compared to the control group. NaHCO3 exposure also caused significantly elevated urinary pH concentrations.

ORGAN WEIGHTS: The relative weight (organ/body weight %) of kidneys and liver was significantly increased compared to the control.

GROSS PATHOLOGY: NaHCO3-exposed animals did not have a significant increase in the number of tumours, in comparison to the control group.

TIME TO TUMOURS: The first bladder tumour was found in a rat that died in week 49. It is not known how many rats survived the full experimental period of 104 weeks.

Data source

Reference

Reference Type:

publication

Title:

Co-carcinogenic effects of NaHCO3 on o-phenylphenol-induced rat bladder carcinogenesis

Author:

Fukushima, S. et al.

Year:

1989

Bibliographic source:

Carcinogenesis vol.10, no.9: 1635-1640

Materials and methods

Principles of method if other than guideline:

Male F344 rats were dosed with diet to which 0.64% of sodium bicarbonate was added for a duration of 104 weeks. Body weights were measured and urinalysis was performed throughout the duration of the experiment. At study termination, all surviving animals were killed and underwent gross examination. The liver, kidney and tissues with macroscopic lesions were removed and fixed. The relative organ/body weight was determined for the bladder, kidneys and liver. Histopathology was performed on the bladder.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium hydrogencarbonate

EC Number:

205-633-8

EC Name:

Sodium hydrogencarbonate

Cas Number:

144-55-8

Molecular formula:

CH2O3.Na

IUPAC Name:

sodium hydrogen carbonate

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan, Inc., Atsugi, Japan
- Age at study initiation: 6 weeks
- Weight at study initiation: not reported
- Housing: 5 or 6 rats per plastic cage with wood chips bedding
- Diet (e.g. ad libitum): powdered diet (Oriental MF, Oriental Yeast Co., Tokyo, Japan), ad libitum, except during urine collection.
- Water (e.g. ad libitum): ad libitum, except during urine collection.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 10%
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Details on oral exposure:

Animals were given powdered diet supplemented with 0.64% NaHCO3.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

104 weeks

Frequency of treatment:

daily

Doses / concentrations

Dose / conc.:

0.64 other: %

Remarks:

Dose group 6 received diet supplemented with NaHCO3. Other dose groups received a combination of NaHCO3 and o-phenylphenol or sodium o-phenylphenate via the diet.

No. of animals per sex per dose:

31 male rats in dose group 6
30 male rats in the control group, who received plain diet

Control animals:

yes, plain diet

Positive control:

No

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Not specified

DETAILED CLINICAL OBSERVATIONS: Not specified

BODY WEIGHT: Yes
- Time schedule for examinations: weekly up to week 14 and monthly thereafter.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
Food consumption was stated to be measured monthly up to week 16 and every 3 months thereafter. The amounts of food consumed on 2 consecutive days of a week were measured on a per cage basis.

FOOD EFFICIENCY: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: Yes
For urine pH determinations, fresh urine samples were obtained from 4 to 6 rats in each group by forced urination in the morning (09-10h). The pH was measured with a pH meter 10 times during the experiment.
For urinary electrolyte analysis, samples of urine were obtained from 3 or 4 rats in each group housed individually in metal metabolic cages without food or water for 4h in the morning (08-12h) during weeks 58, 80 and 96. The urine samples were analysed for sodium, potassium, calcium, chloride, phosphorus and magnesium.

NEUROBEHAVIOURAL EXAMINATION: No

IMMUNOLOGY: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

HISTOPATHOLOGY: Yes, on the bladder.

Statistics:

Not specified.

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

no mortality observed

Description (incidence):

Percent survival in the dose group receiving NaHCO3 was 84%. Percent survival in the control group receiving plain diet was 73%.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Starting after 24 weeks, the average body weights in the group dosed with NaHCO3 were lower than those of the control group.

The average final body weight of the group dosed with NaHCO3 was 409.5 +/- 22.7g as compared to 443.7 +/- 36.9g in the control group. Student t-test p < 0.001.

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

effects observed, treatment-related

Description (incidence and severity):

The urinary pH was significantly elevated in the group dosed (7.47 +/- 0.39) with NaHCO3 as compared to the control group (6.35 +/- 0.37); Student's t-test p < 0.01.

Electrolyte analysis revealed that Na+ and K+ concentrations were significantly higher in the group dosed with NaHCO3 (160 +/- 43 mEq/L and 192 +/- 39 mEq/L, respectively) as compared to the control group (66 +/- 27 mEq/L and 140 +/- 42 mEq/L, respectively); Student's t-test p < 0.001 and p < 0.05 mEq/L, respectively.
No significant increases or decreases were observed in the levels of the other electrolytes: Ca2+, Cl-, P, Mg2+.

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Relative bladder, kidney and liver weights in the group dosed with NaHCO3 were increased (0.037 +/- 0.008 %, 0.73 +/- 0.10 % and 3.60 +/- 0.42%, respectively) when compared to the control group (0.031 +/- 0.006%, 0.67 +/- 0.07 % and 3.30 +/- 0.29%, respectively). Student t-test p < 0.01, p < 0.05 and p < 0.01, respectively.

Gross pathological findings:

not specified

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

One rat in the group dosed with NaHCO3 had a moderate-sized tumor of the bladder (carcinoma), but this is not significantly different from the control group.

Other effects:

not specified

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

6 400 mg/kg diet

Remarks on result:

other: =0.64%

Applicant's summary and conclusion

Conclusions:

Sodium hydrogen carbonate was found to be not carcinogenic when administered to Fisher 344 rats via the diet in a concentration of 0.64% for a period of 104 weeks.