Potassium hydrogencarbonate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test procedure according to national standards, test performed in governmental laboratory

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

Remarks:

not tested up to current limit dose

GLP compliance:

no

Remarks:

study performed before implementation of GLP

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Potassium carbonate

EC Number:

209-529-3

EC Name:

Potassium carbonate

Cas Number:

584-08-7

Molecular formula:

CH2O3.2K

IUPAC Name:

dipotassium carbonate

Test animals

Species:

mouse

Strain:

CD-1

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: virgin adult
- Weight at study initiation: 75 - 78 g
- Fasting period before study: no data
- Housing: gang-housed in disposable plastic cages
- Diet: ad libitum
- Water: tap water, ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled, record available in study report
- Humidity (%): controlled, record available in study report
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on mating procedure:

Females were mated with young adult males, observation of the vaginal plug was considered day 0 of gestation. One male was not permitted to impregnate more than one female per group.

Duration of treatment / exposure:

day 6 to 15 of gestation

Frequency of treatment:

once daily

Duration of test:

until day 17 of gestation

No. of animals per sex per dose:

22 to 25 animals

Control animals:

yes, sham-exposed

other: second control group treated with 150 mg Aspirin/kg bw

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least once daily
- Cage side observations were included.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
All animals observed daily for appearance and behavior, with particular attention to food consumption and weight, in order to rule out any abnormalities which may have occurred as a result of anorexic effect in the pregnant animal.

BODY WEIGHT: Yes
- Time schedule for examinations: on days 0, 6, 11, 15, and 17 of gestation

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 17
- Organs examined: urogenital tract of each dam was examined in detail for anatomical normality

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number resorptions: Yes
- Number of live and dead fetuses: yes
- Sex ratio of fetuses: yes

Fetal examinations:

- External examinations: Yes: all per litter for congenital abnormalities
- Soft tissue examinations: Yes: 1/3 per litter (Wilson technique)
- Skeletal examinations: Yes: 2/3 per litter
- Head examinations: Yes
- Body weights of live pups were recorded.

Statistics:

Not reported

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
Refer to remarks on results

Effect levels (maternal animals)

Dose descriptor:

NOEL

Effect level:

290 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Maternal abnormalities

Abnormalities:

no effects observed

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Refer to remarks on results

Effect levels (fetuses)

1

Dose descriptor:

NOEL

Effect level:

290 mg/kg bw/day

Basis for effect level:

other: teratogenicity

2

Dose descriptor:

NOEL

Effect level:

290 mg/kg bw/day

Basis for effect level:

other: fetotoxicity

Fetal abnormalities

Abnormalities:

no effects observed

Overall developmental toxicity

Developmental effects observed:

no

Any other information on results incl. tables

NOEL for maternal and developmental effects = 290 mg/kg bw/day (highest dose tested)

TOXIC RESPONSE / EFFECTS BY DOSE LEVEL:
- Maternal data:
-- Mortality: no dam died until final sacrifice
-- Number of pregnants: 20/22, 21/24, 21/24, 20/22, 22/25, and 22/25

  femals were pregnant in the dose groups 2.9, 13.5, 62.5 and 290 mg

  potassium carbonate (K2CO3)/kg bw/day, the negative control group, and

  the positive control group, respectively.
-- Number aborting: zero
-- Body weight gain: no dose related effects
-- Macroscopy: uroginital tract examined, no alterations reported

-Fetal data:
-- Corpora lutea: no dose related effects; the average numbers of corpora

  lutea/dam were 10.2, 9.58, 11.2, 10.3, 10.6, and 10.7 in the dose groups

  2.9, 13.5, 62.5 and 290 mg K2CO3/kg bw/day, the negative control group,

  and the positive control group, respectively; total numbers of corpora

  lutea were 225, 230, 268, 227, 266, and 268, respectively
-- Live liters: no dose related effects; total numbers of live liters

  were 20, 21, 21, 20, 22, and 22 in the dose groups 2.9, 13.5, 62.5 and

  290 mg K2CO3/kg bw/day, the negative control group, and the positive

  control group, respectively
-- Implantations: no dose related effects; the total numbers of implantations

 were 208, 212, 246, 208, 251, and 253 in the dose groups 2.9, 13.5, 62.5

 and 290 mg K2CO3/kg bw/day, the negative control group, and the positive

 control group, respectively; the average numbers of implantations/dam were

 10.4, 10.1, 11.7, 10.4, 11.4, and 11.5, respectively
-- Resorptions: no dose related effects; total numbers of resorptions

  were 1, 12, 12, 4, 5, and 5 in the dose groups 2.9, 13.5, 62.5 and 290 mg

  K2CO3/kg bw/day, the negative control group, and the positive control group,

 respectively; numbers (%) of dams with one or more resorptions  were 1(5%),

 10 (47.6%), 9 (42.9%), 4 (20%), 5 (22.7%), and 4 (18.2%), respectively; there

 was no dam with all sites resorbed in any treatment group
-- Life fetuses: no dose related effects; total numbers of live fetuses

  were 203, 200, 234, 203, 245, and 245 in the dose groups 2.9, 13.5, 62.5

  and 290 mg K2CO3/kg bw/day, the negative control group, and the positive

  control group, respectively; average numbers of life fetuses/dam were

  10.2, 9.52, 11.1, 10.2, 11.1, and 11.1, respectively
-- Sex ratio: no dose related effects; sex ratio (M/F) of live fetuses

  were 0.93, 0.94, 0.80, 1.03, 1.01, and 0.96 in the dose groups 2.9, 13.5,

  62.5 and 290 mg K2CO3/kg bw/day, the negative control group, and the

  positive control group, respectively
-- Dead fetuses: no dose related effects; total numbers of dead fetuses

  were, 4, 0, 0, 1, 1, and 3 in the dose groups 2.9, 13.5, 62.5 and 290 mg

  K2CO3/kg bw/day, the negative control group, and the positive control

  group, respectively; numbers (%) of dams with one or more dead fetuses

  were 3 (15%), 0 (0%), 0 (0%), 1 (5%), 1 (4.55%), and 3 (13.6%), respectively;

 there was no dam with all fetuses dead in any treatment group
-- Average fetus weight: no dose related effects; average fetus weights(g)

 were 0.85, 0.87, 0.81, 0.91, 0.90, and 0.85 in the dose groups 2.9,

  13.5, 62.5 and 290 mg K2CO3/kg bw/day, the negative control group, and

  the positive control group, respectively
-- Skeletal findings: no dose related effects; 

                    SUMMARY OF SKELETAL FINDINGS
-----------------------------------------------------------
               negative positive    potassium carbonate 
               control  control       (mg/kg bw/day)
Findings       sham     Aspirin*  2.9   13.5   62.5  290.0
-----------------------------------------------------------
Live fetuses   171/22** 174/22  146/20 141/21 164/21 141/20
examined
(at term)

Sternebrae:
- incom. oss    32/14*** 45/16   74/20  42/15  45/15  64/15
- scrambled       -        -       -      -      -      -
- bipartite      1/1       -       -      -      -      -
- fused           -        -       -      -      -      -
- extra           -        -       -      -      -     2/1
- missing        8/4     34/11   33/17  20/8   25/9   32/12
- other           -        -       -      -      -      -
 
Ribs:
- incom. oss.     -        -       -      -      -      -
- fused/split     -        -       -      -      -      - 
- wavy            -        -       -      -      -      -
- less than 12    -        -       -      -      -      -
- more than 13  35/14    43/10   38/16  36/11  55/17  21/11
- other           -        -       -      -      -      -
 
Vertebrae:
- incom. oss.     -      11/5     3/3    9/3    1/1    3/2
- scrabbled       -        -       -      -      -      -
- fused           -        -       -      -      -      -
- extra ctrs.     -        -       -      -      -      -
  oss.
- scoliosis       -        -       -      -      -      -
- tail defects    -        -       -      -      -      -

Skull:            -       2/1      -     4/2      -      -
-incom. closure   -        -       -      -      -      -
- missing         -        -       -      -      -      -
- craniostosis    -        -       -      -      -      -
- other           -        -       -      -      -      -

Ectremities:
- incom. oss.     -       4/3     2/2    7/3    1/1    3/2
- missing         -        -       -      -      -      -
- extra           -        -       -      -      -      -
Miscellaneous:    -        -       -      -      -      -
- hyoid missing 23/9     45/18  49/18  50/16   50/16   48/13
- hyoid reduced 20/11    25/13  23/15  24/12   28/15   12/7
------------------------------------------------------------
*   positive control: 150 mg Aspirin/kg bw/day
**  Numerator = number of fetuses examined; 
    Denominator = number of liters examined
*** Numerator = number of fetuses affected; 
    Denominator = number of liters affected

-- Soft tissue abnormalities: no dose related effects; in total only fife

  pups with soft tissue abnormalities were listed: one pup with

   exophthalmos and one pup with encephalomyelocele in the positive control

  group, and one pup with exophthalmos and two pups with encephalomyelocele

  in the 290 mg K2CO3/kg bw/day dose group

Applicant's summary and conclusion

Conclusions:

There were no treatment-related maternal or developmental toxic effects observed in this study when potassium carbonate was administrated up to and including the highest tested dose of 290 mg/kg bw/day. In conclusion, no teratogenicity potential by the results of this study have been documented for potassium carbonate.

Executive summary:

In a developmental toxicity study similar to OECD Guideline 414 (Prenatal Developmental Toxicity Study) potassium carbonate (no data on a.i.) was administered to groups of 22-25 female CD-1 mice/dose by gavage at dose levels of 0, 2.9, 13.5, 62.5 or 290.0 mg/kg bw per day from days 6  through 15 of gestation. On day 17 all dams were subjected to ceasarian section, and the sex, numbers of corpora lutea, implantation sites, resorption sites, and live and dead fetuses as well as the body weights of live pups were recorded. The urogenital tract of each dam was examined in detail for anatomical normality. All fetuses were examined grossly for presence of external congenital abnormalities. One-third of the fetuses of each litter underwent detailed visceral examinations, the remaining two-thirds were examined for skeletal defects.

There were no effects on mortality, body weight gain and the urogenital tracts of dams.

 

NOEL maternal toxicity: 290 mg/kg bw/day (highest dose tested)

 

There were no effects on numbers of corpora lutea, live liters, implantations, resorptions, live and dead fetuses, the sex ratio of the fetuses or the average fetus weight. Soft tissue and skeletal anomalies noted in the groups treated with potassium carbonate did not differ from anomalies occurring in sham-treated controls.

NOEL developmental toxicity/teratogenicity: 290 mg/kg bw/day (highest dose tested)

There were no treatment-related maternal or developmental toxic effects observed in this study when potassium carbonate was administrated up to and including the highest tested dose of 290 mg/kg bw/day.