Potassium carbonate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

A study on fertility, e. g. a 1- or 2- generation study, is not available for potassium carbonate. However, a study on fertility is scientifically unjustified. There are no indications on an intrinsic toxicity to reproduction of potassium carbonate from the results of reliable developmental toxicity and teratogenicity studies performed on potassium carbonate itself, reliable repeated dose toxicity studies with macroscopic and histological examination of the male and female reproductive organs (epididymides, testes, ovaries, and uterus) performed with closely related read across substance potassium hydrogencarbonate and available information from assessments carried out within the OECD work on investigation of high production volume chemicals on compounds which have a carbonate or a potassium moiety. Further on, based on chemistry considerations of the structure of potassium carbonate, no reproductive toxicity is expected to occur because potassium carbonate will not influence the natural K+ or CO32- level in the body and will not reach the foetus nor reach male and female reproductive organs under normal handling and use conditions.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

A study on fertility, e. g. a 1- or 2- generation study, is not available for potassium carbonate. However, a study on fertility is scientifically unjustified. Long-term studies on the closely related read across substance potassium hydrogencarbonate are available, in which reproduction organs have been evaluated. A justification for read-across is attached to Iuclid section 13. In these studies the macroscopically and histopathologically evaluated reproductive organs epididymides, testes, ovaries, and uterus were free of treatment related effects, even at lifetime (30 months) treatment with dose levels far exceeding the guideline limit dose for one or two generation studies of 1000 mg/kg body weight/day (for details see Chapter 5.6. Repeated dose toxicity).

Absence of intrinsic toxic properties of potassium carbonate is generally taken for granted, which is proved by its long-standing safe use in food - including foodstuffs for infants and children - and pharmaceuticals and its GRAS (generally recognized as safe) status in the USA. In addition, available information from assessments carried out within the OECD work on investigation of high production volume chemicals on compounds which have a carbonate or a potassium moiety gives no indication on an intrinsic toxicity to reproduction of potassium or carbonate either. OECD SIDS Initial Assessment Reports are e. g. available for Bicarbonate special, Sodium carbonate, Sodium bicarbonate, Ammonium hydrogencarbonate which have a carbonate moiety and on Potassium chloride, Potassium hydroxide or Potassium methanolate, which have a potassium moiety (reports are published via internet (http: //www. oecd. org/document/63/0,3343, en_2649_34379_1897983_1_1_1_1,00. html). None of these compounds are considered to have the potency to be toxic to reproduction.

Further on, based on chemistry considerations of the structure of potassium carbonate, no reproductive toxicity is expected to occur because potassium carbonate will not influence the natural K⁺or CO₃^2- level in the body and will not reach the foetus nor reach male and female reproductive organs under normal handling and use conditions.

Potassium and carbonate are essential constituents and two of the most abundant ions in all animal species. In adult humans, the total body potassium is approx. 3.5 mol (135 g). 98 % of this is located intracellular (150 mmol/l), the extracellular potassium concentration is approx. 4 mmol/l.

 

The metabolism and mechanisms of action of potassium and carbonate are well reviewed in standard textbooks on pharmacology and physiology.

 

About 90 % of the ingested dose of potassium is absorbed by passive diffusion in the membrane of the upper intestine. Potassium is distributed to all tissues where it is the principal intracellular cation. Insulin, acid-base status, aldosterone, and adrenergic activity regulate cellular uptake of potassium.

The majority of ingested potassium is excreted in the urine via glomelural filtration. The distal tubules are able to secrete as well as reabsorb potassium, so they are able to produce a net secretion of potassium to achieve homeostasis in the face of a potassium load due to abnormally high levels of

ingested potassium. About 15 % of the total amount of potassium excreted is found in faeces.

Excretion and retention of potassium is mainly regulated by the main adrenal cortical hormones.

Normal homeostatic mechanisms controlling the serum potassium levels allow a wide range of dietary intake. The renal excretory mechanism is designed for efficient removal of excess K, rather for its conservation during deficiency. Even with no intake of K, humans lose a minimum of 585-1170 mg K per day. However, the distribution of potassium between the intracellular and the extracellular fluids can markedly affect the serum potassium level without a change in total body potassium. K+ is the principal cation mediating the osmotic balance of the body fluids. In animals, the

maintenance of normal cell volume and pressure depends on Na+ and K+ pumping. The K+/Na+ separation has allowed for evolution of reversible transmembrane electrical potentials essential for nerve and muscle action in animals, and both potassium and chloride are important in transmission of nerve impulses to the muscle fibers.

Potassium transport through the hydrophobic interior of a membrane can be facilitated by a number of natural compounds that form lipid-soluble alkali metal cation complexes. Potassium serves the critical role as counterion for various carboxylates, phosphates and sulphates, and stabilizes macromolecular structures (OECD SIDS, 2001).

 

The bicarbonate buffer system described by the following equation:

H2O + CO2 <=> H2CO3 <=> H+ + (HCO3)-

is the major extracellular buffer in the blood and the interstitial fluid of vertebrates. The blood plasma of man normally has a pH of 7.40. Should the pH fall below 7.0 or rise above 7.8, irreversible damage may occur. Compensatory mechanisms for acid-base disturbances function to alter the ratio of (HCO3)- to PCO2, returning the pH of the blood to normal. Thus, metabolic acidosis may be compensated for by hyperventilation and increased renal absorption of (HCO3)-. Metabolic alkalosis may be compensated for by hypoventilation and the excess of (HCO3)- in the urine. Renal mechanisms are usually sufficient to restore the acid-base balance (OECD SIDS, 2002).

 

No fertility study has been localised for potassium carbonate or related substances. However, the maximum plasma concentration of potassium and carbonate is efficiently and tightly regulated by renal elimination. A significant increase in the potassium concentration in the extracellular fluid will only occur after high potassium intake or in patients with severely reduced kidney function.

 

No effects of exposure potassium carbonate on gonadal function can be expected if the plasma concentrations are within the normal range, as neither potassium nor carbonate accumulates in the body. Based on the extensive amount of knowledge on regulation and effects of potassium and carbonate in the human body, no further testing of fertility is required.

 

References

OECD SIDS, 2001. Potassium chloride.SIDS Initial Assessment Report for 13th SIAM. UNEP Publications.

 

OECD SIDS, 2002. Sodium bicarbonate.SIDS Initial Assessment Report for 15th SIAM. UNEP Publications.

 

 

 

Effects on developmental toxicity

Description of key information

Prenatal developmental toxicity studies with potassium carbonate in rats and mice by oral route are available. Although the studies have been performed prior to implication of the guidelines they are well performed and documented and comparable to recent guideline studies with the exception that the nowadays required highest dose of 1000 mg/kg bw was not included. Further on the developmental toxicity potential of a aqueous potassium carbonate-based scrubbing solution was evaluated in a inhalation study in rats. None of these studies gave indications on intrinsic toxic effects of potassium carbonate on reproduction.

Link to relevant study records

Reference

Reference 1

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication which meets basic scientific principles

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)

Qualifier:

according to guideline

Guideline:

EPA OPP 83-3 (Prenatal Developmental Toxicity Study)

Qualifier:

according to guideline

Guideline:

other: U.S. Environmental Protection Agency (1986) Guidelines for Health Assessment of Suspect Developmental Toxicants. Fed. Reg. 51 (185):34028-34034

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Portage, MI, USA (Virgin female Sprague-Dawley Crl:CD VAF/plus)
- Age at study initiation: approximately 12 weeks (female rats)
- Weight at arrival at study laboratory: Females: 223 - 278 g
- Fasting period before exposure: no
- Housing: All animals were individually housed in wire-mesh cages
- Diet: PMI Feeds, Inc., certified rodent lab diet 5002, ad libitum during nonexposure periods, ad libitum
- Water: tap water, ad libitum during nonexposure periods
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (C°): 22-24
- Humidity (%): 40-60 %
- Air changes (per hr): at least 12
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark cycle

Route of administration:

inhalation

Type of inhalation exposure (if applicable):

whole body

Vehicle:

other: The aerosol concentration was reduced to the target concentrations by dilution with the chamber ventilation air flow.

Details on exposure:

Female rats were exposed, 6 h/d, from implantation to termination (GD 6-19/ inclusive U.S. EPA/ 1994) for a total of 14 consecutive days. All animals were caged individually in the exposure chambers, which were maintained at 72-75°F (22-24°C), 40-60 % relative humidity, and at least 12 air changes per hour.

Respirable aerosols were generated with stainless-steel atomizers (Spraying Systems, Inc., Wheaton, lL) fitted with a no. 1650 fluid nozzle and a no. 64 air eap. The atomizer sprayed into a 6-L glass atomization chamber to collect large droplets produced during the atomization process. The resulting aerosol was piped to the exposure chamber inlets, where the aerosol concentration was reduced to the target concentrations of 0.05, 0.1, 0.2, or 0.3 mg/L by dilution with the chamber ventilation air flow.

Respirable aerosol was generated, similar in all exposure groups (mean MMAD of all samples ranged from 1.6 to 2.8 µm)

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Target concentrations (mg/L): control (filtered air), 0.05, 0.1, 0.2, or 0.3; aerosol concentrations were very near the target concentrations and were
approximately +14 % to - 7 % of the target exposure concentrations.
The actual exposure concentrations were determined by standard gravimetric methods after collecting samples on 25-mm Teflon filters (Millipore type FG, 0.2 µm). Analytical confirmation of exposure concentrations was performed by ion-exchange chromatography using electrochemical conductivity detection for potassium.

Details on mating procedure:

Individual breeding pairs were cohabited overnight. Detection of mating was confirmed the next morning by the presence of a copulatory plug or by a vaginal lavage for the presence of sperm. After confirmation of mating, females were returned to their cages and considered to be at day 0 of gestation (GD 0). If no sperm or vaginal plug was observed, the female remained with the same male the next evening. The study was designed such that 24 pregnant females per group were used. Bred females were consecutively assigned in a block design to exposure groups on a daily basis until 24 females were placed in each group.

Duration of treatment / exposure:

day 6 to 19 of gestation

Frequency of treatment:

daily, 6 hours per day

Duration of test:

until day 20 of gestation

No. of animals per sex per dose:

24 animals

Control animals:

yes, sham-exposed

Details on study design:

Aerosol particle size was determined twice weekly for each exposure chamber by utilizing an INTOX Products, Inc. (Albuquerque, NM) model 02-140/1B seven-stage cascade impactor with cutoff diameters ranging from 0.26 to 5.27 µm. Air-exposed animals served as controls.

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule:
All animals were observed twice daily for moribundity and mortality from GD 0 through 20.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:
All animals were observed regularly during exposure periods and again 1 hour following completion of each exposure for treatment-related clinical signs.

BODY WEIGHT: Yes
- Time schedule for examinations: on gestation day (GD) 0 and daily from GD 6 to 20

FOOD CONSUMPTION : Yes
- Time schedule for examinations: on gestation day (GD) 0 and daily from GD 6 to 20

WATER CONSUMPTION: No data

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20, all dams were euthanized by intravenous injection of sodium pentobarbital.
- Organs examined: The maternal body and intact uterus were weighed.

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes

- Other: Number and sex of viable and nonviable fetuses, as well as body weight of viable and nonviable fetuses, and crown-rump length of nonviable fetuses were recorded. Live fetuses were euthanized by an intrathoracic injection of sodium pentobarbital.
- Uteri that had no macroscopic implantation sites were stained with ammonium sulfide (19%) to detect very early resorptions.

Fetal examinations:

- External examinations: Yes: all per litter were examined grossly for the presence of external morphological abnormalities

- Soft tissue examinations: Yes: all per litter were dissected for visceral examination using a fresh tissue dissection technique (Stuckhard and Poppe, 1984), which included examination of the heart and major blood vessels.

- Skeletal examinations: Yes: half per litter
- Head examinations: Yes: half per litter

Half of the fetuses were decapitated prior to dissection, and the heads from these fetuses were fixed in Bouin´s solution for examination by a free-hand section technique (Wilson, 1965). The heads from the remaining half of the fetuses were examined by a mid-coronal slice. All fetal carcasses were eviscerated, fixed in 100% ethyl alcohol, macerated in potassium hydroxide, stained with alizarin red S by a method similar to that described by Dawson (1926), and then examined for skeletal abnormalities

Statistics:

All analyses were two-tailed for a significance level of 5%. One-way analyses of variance (ANOVA) were applied for continuous maternal and fetal variables comparing the treated groups to the control group using Dunnett's test (1955). Analysis of fetal sex ratios used the
chi-square test with Yates's correction factor. The numbers of early and late resorptions, dead fetuses, and implantations were analyzed by the Mann-Whitney U-test. The numbers of litters with malformations and developmental variations were analyzed by Fisher's exact test. The mean litter proportions of fetal malformations and developmental variations were analyzed by the Kruskal-Wallis test to determine intragroup differences. If significant differences were observed, comparison of each treated group to the control was performed using the Mann-Whitney U-test.

Historical control data:

(WIL Research Laboratories, unpublished; CharIes River, 1993)

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
-- Mortality:
--- Dose groups 0.05, 0.1, and 0.2 mg/l: no animal died
--- Dose group 0.3 mg/l: One animal died on GD 17. For further details refer to "remarks on results"

Dose descriptor:

NOAEC

Effect level:

0.2 mg/L air (analytical)

Basis for effect level:

other: maternal toxicity

Dose descriptor:

NOAEC

Effect level:

0.062 mg/L air

Basis for effect level:

other: maternal toxicity

Abnormalities:

no effects observed

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
For further details refer to "remarks on results"

Dose descriptor:

NOEC

Effect level:

0.3 mg/L air (analytical)

Basis for effect level:

other: teratogenicity

Dose descriptor:

NOEC

Effect level:

0.092 mg/L air

Basis for effect level:

other: teratogenicity

Dose descriptor:

NOEC

Effect level:

0.2 mg/L air (analytical)

Basis for effect level:

other: embryotoxicity

Dose descriptor:

NOEC

Effect level:

0.062 mg/L air

Basis for effect level:

other: embryotoxicity

Abnormalities:

no effects observed

Developmental effects observed:

no

EXPOSURE PARAMETERS:
- Target concentrations (mg/l): control (filtered air), 0.05, 0.1, 0.2,  0.3
- Mean gravimetric concentrations (mg/l): control, 0.057, 0.093, 0.206,  0.329
- Mean analytical concentrations (mg/l): control, 0.054, 0.086, 0.189,  0.313
- Mean mass median aerodynamic diameter of the aerosols +/- standard  deviation (µm): control, 2.5 +/- 0.38, 2.8 +/- 0.20,

2.1 +/- 0.31, 1.6 +/- 0.19
- Mean chamber temperature (°C): 21 +/- 0.6 to 23 +/- 1.1  
- Mean relative humidity (%): 51 +/- 4.5 to 64 +/-6.3

Aerosol concentrations were very near the target concentrations and were approximately +14% to -7% of the target exposure concentrations. This level of agreement was considered acceptable considering the low concentrations and close spacing to the target levels.

TOXIC RESPONSE / EFFECTS BY DOSE LEVEL:

Maternal data:
-- Mortality:  
--- Dose groups 0.05, 0.1, and 0.2 mg/l: no animal died

--- Dose group 0.3 mg/l: One animal died on GD 17. Rales and gasping were noted for this female for 4 consecutive days prior to

death, but no abnormal changes were seen in the lungs at necropsy.
-- Clinical signs: Rales (noted in all treated groups) and gasping (observed only in the 0.3 mg/l group) was observed primarily during

the week 2 of exposure. The occurrence of rales was presumably a localized effect in the respiratory tract and likely due to the

irritating properties of the alkaline solution rather than an indication of systemic toxicity.

-- Number of pregnants: 23/24, 23/24, 24/24, 23/24, and 22/24 were pregnant in the control group and the dose groups 0.05, 0.1,

0.2, and 0.3 mg/l, respectively.
-- Number aborting: zero
-- Body weight gain and food consumption:  
--- Dose groups 0.05, 0.1, and 0.2 mg/l: no dose related effects
--- Dose group 0.3 mg/l: Maternal corrected body weight, weight gains and  corrected gestational weight gain were significantly lower at this exposure level in conjunction with a significant decrease in food consumption throughout the entire exposure period.
-- Mean gravid uterine weights: no dose related effects
-- Macroscopy: no treatment-related findings; two females in the 0.3 mg/l group had pale and dark red lungs, but these changes were not considered to be treatment related.

Fetal data:
-- Corpora lutea: no dose related effects; average numbers of corpora  lutea were 16.2 +/- 2.39, 17.5 +/- 2.81, 17.0 +/- 2.06,

16.5 +/- 2.35,  and 16.2 +/- 1.66 in the control group and the dose groups 0.05, 0.1,  0.2, and 0.3 mg/l, respectively

-- Implantations: no dose related effects; average numbers of  implantations were 14.4 +/- 2.52, 14.5 +/- 3.98, 15.0 +/- 2.00,

14.2 +/-  3.37, and 14.6 +/- 3.83 in the control group and the dose groups 0.05,  0.1, 0.2, and 0.3 mg/l, respectively

-- Pre-implantation loss: no dose related effects; average numbers of  pre-implantation loss were 1.7 +/- 2.14, 3.0 +/- 3.28,

2.0 +/- 1.96, 2.3  +/- 3.08, and 1.6 +/- 3.03 in the control group and the dose groups 0.05,  0.1, 0.2, and 0.3 mg/l, respectively

-- Early resorptions: no dose related effects; average numbers of early  resorptions were 1.0 +/- 1.36, 1.0 +/- 0.08, 1.4 +/- 1.35,

0.6 +/- 0.84,  and 0.7 +/- 0.89 in the control group and the dose groups 0.05, 0.1, 0.2,  and 0.3 mg/l, respectively

-- Late resorptions: no dose related effects; average numbers of late  resorptions were 0.0 +/- 0.00, 1.0 +/- 0.29, 0.0 +/- 0.00,

0.0 +/- 0.00,  and 0.0 +/- 0.00 in the control group and the dose groups 0.05, 0.1, 0.2,  and 0.3 mg/l, respectively

-- Live liter size: no dose related effects; average numbers of live  liter size were 13.4 +/- 2.54, 13.4 +/- 3.87, 13.6 +/- 2.20,

13.6 +/-  3.45, and 13.9 +/- 3.78 in the control group and the dose groups 0.05,  0.1, 0.2, and 0.3 mg/l, respectively

-- Fetal weight: no dose related effects; average fetal weights (g) were  3.5 +/- 0.14, 3.4 +/- 0.29, 3.5 +/- 0.17, 3.5 +/- 0.19, and 3.3 +/- 0.50  in the control group and the dose groups 0.05, 0.1, 0.2, and 0.3 mg/l,  respectively

-- Sex ratio: no dose related effects; the percentages of male fetuses ranged from 48 to 54.6 and were within the normal distribution

for this species and strain.

-- Dead fetuses: no dose related effects (ascertained numbers not reported)

-- Visceral and skeletal malformations: no dose related effects; No structural malformations were noted in the concurrent control group. The total number of fetuses with malformations was 2, 3, 3, and 1 for the 0.05, 0.1, 0.2, and 0.3 mg/l groups, respectively. None of these findings were considered as treatment related since no dose-response relationship was found and the litter and fetal incidences of malformations were within the historical control range for this species and strain. The mean litter proportions of malformations in the exposed groups were neither biologically nor statistically different from controls.

SUMMARY OF SKELETAL and VISCERAL MALFORMATIONS

Findings	Control	potassium carbonate mg/L
		0.05	0.1	0.2	0.3
Fetuses examined*	308/23	309/23	327/24	313/23	306/22
External observations:
Fetal anasarca	0	0	0	1	0
Micromelia	0	0	0	1	0
Mandibular micrognathia	0	0	1	0	0
Aglossia	0	0	1	0	0
Microphthalmia	0	0	0	1	0
Vertebral agenesia	0	2	0	0	0
Visceral observations:
Sinus inversus	0	0	1	0	1
Heart and/or great vessel anomaly	0	0	1	0	0
Retroesophageal aortic arch	0	0	1	0	0
Lungs, lobular agenesis	0	0	1	0	0
Skeletal observations:
Atlas occipital defect	0	0	1	0	0
Vertebral anomaly with or without associated rib anomaly	0	0	1	1	0
Total number with malformations:**
- External	0/0	2/2	1/1	2/2	0/0
Visceral	0/0	0/0	3/3	0/0	1/1
Skeletal	0/0	2/2	1/1	1/1	0/0
Combined	0/0	2/2	3/3	3/3	1/1

*   Numerator = number of fetuses examined; 
    Denominator = number of liters examined
**  Numerator = number of fetuses affected; 
    Denominator = number of liters affected

- Visceral variations: no dose related effects; Soft-tissue variations  were observed only in the 0.1 and 0.2 mg/L  groups, affecting 2 fetuses  each. 
- Skeletal variations: The incidence of fetuses with sternebrae 5 and/or 6 unossified was increased in the 0.3 mg/l group (14 fetuses vs. 6 fetuses in control), but no differences in litter incidence (4/22 litters vs. 5/23 litters in control) or percent per litter with total variations were detected. The incidences of fetuses with skeletal variations involving the sternum were clustered in two litters with atypically low term fetal body weights conceived by the two most severely affected mothers in this group. The corrected gestational weight gain in both dams  was remarkably lower (2.2 g and - 2.2 g) in comparison with the group  mean value (47.4 g) for this exposure concentration. The variation of sternal elements is most probably a consequence of the maternal toxicity and no indication on an intrinsic developmental toxic activity of the substance.
No treatment-related variations were noted in the other groups. 

SUMMARY OF SKELETAL and VISCERAL VARIATIONS

Findings	Control	potassium carbonate mg/L
		0.05	0.1	0.2	0.3
Fetuses examined*	308/23	309/23	327/24	313/23	306/22
Visceral variations:**
Major blood vessel variation	0/0	0/0	2/2	1/1	0/0
Thymus hemorrhagic	0/0	0/0	0/0	1/1	0/0
Skeletal observations:**
Sternebrae 5 and/or 6 unossified	6/5	11/5	4/3	8/5	14/4
Entire sternum unossified	0/0	0/0	0/0	0/0	16/1
Sternebrae malaligned (slight or moderate)	0/0	0/0	3/3	1/1	2/2
Sternebrae 1,2,3, and/or 4 unossified	0/0	1/1	0/0	0/0	0/0
Reduced ossification of vertebral arches	0/0	1/1	0/0	0/0	2/1
14th Rudimentary rib(s)	6/4	0/0	3/2	0/0	0/0
7th Cervical rib(s)	1/1	5/3	3/2	0/0	3/2
Reduced ossification of the13th rib(s)	8/6	7/6	10/5	12/5	17/9
Bent rib(s)	5/3	1/1	2/2	3/2	4/2
Hyoid unossified	2/2	1/1	0/0	2/2	6/4
Pubis unossified	0/0	1/1	0/0	0/0	0/0

Note: None significantly different from control group using Fisher´s exact test.

*   Numerator = number of fetuses examined; Denominator = number of liters examined
** Numerator = number of fetuses affected; Denominator = number of liters affected

   

Conclusions:

Under the conditions of this investigation, potassium carbonate scrubbing solution “Cartacab” (main active ingredient 30.8 % potassium carbonate) is not a selective developmental toxicant.

Executive summary:

In a developmental toxicity study similar to OECD guideline 414 an aerosol of a used scrubbing solution “Catacarb” (with main active ingredient 30.8% potassium carbonate; further ingredients: 65.1% water, 1.6% diethanolamine, 0.4% potassium borate (as boron), 0.3% potassium metavanadate (as vanadium), and 6.7 ppm chromium, 8.4 ppm molybdenum and 4.5 ppm nickel) was administered to groups of 24 female Sprangue-Dawley rats/dose by whole body exposure at dose levels of 0, 0.05, 0.1, 0.2 and 0.3 mg/mL for 6 hours per day, from days 6  through 19 of gestation. Animals were sacrificed on gestation day 20.

One female died in the 0.3 mg/L group. Rales and gasping were noted, but no abnormal changes were seen in the lungs at necropsy.

Signs of respiratory tract impairment, rales all test groups and gasping) were observed and considered to be a local response to the high alkalinity of the test substance. Reduced body weights in conjunction with decreased food consumption were observed in the high dose group (0.3 mg/mL).

NOAEC maternal toxicity: 0.2 mg/L 

The only observed effect in the developmental parameters was a delayed mineralization of sternal elements in the maternal toxic dose group of 0.3 mg/L. The incidence of fetuses (14 fetuses vs. 6 fetuses in control) but not the litter incidence (2/22 litters vs. 5/23 litters in control) with sternebrae 5 and/or 6 unossified was increased in this group. The increase in fetuses with delayed mineralization of sternal elements in this dose group was primarily attributable to two litters assigned to the two most severely affected dams in the group. Thus, the variation of sternal elements is most probably a consequence of the maternal toxicity and no indication on an intrinsic developmental toxic activity of the substance.

NOEC developmental toxicity: 0.2 mg/L 

There were no treatment related external, visceral, or skeletal malformations. Isolated incidences of external, visceral, or skeletal malformations noted in the treated groups, were within the normal ranges for this species and strain (Charles River, 1993).

NOEC teratogenicity: 0.3 mg/l (highest dose tested)

Under the conditions of this investigation, potassium carbonate scrubbing solution “Cartacab” (main active ingredient 30.8 % potassium carbonate) is not a selective developmental toxicant.

Reference 2

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

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

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

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

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

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
Refer to remarks on results

Dose descriptor:

NOEL

Effect level:

290 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Abnormalities:

no effects observed

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

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

Dose descriptor:

NOEL

Effect level:

290 mg/kg bw/day

Basis for effect level:

other: teratogenicity

Dose descriptor:

NOEL

Effect level:

290 mg/kg bw/day

Basis for effect level:

other: fetotoxicity

Abnormalities:

no effects observed

Developmental effects observed:

no

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

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.

Reference 3

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

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

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation: virgin adult females
- Weight at study initiation: 221 to 232 g
- Fasting period before study: no data
- Housing: individually in mesh bottom 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

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

Volume administered: 1 ml/kg bw/day

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 20 of gestation

No. of animals per sex per dose:

22 to 25 animals

Control animals:

yes, sham-exposed

other: second control group treated with 250 mg Aspirin/kg bw

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: no data
- 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 20 of gestation

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- 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

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
Refer to remarks on results

Dose descriptor:

NOEL

Effect level:

180 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Abnormalities:

no effects observed

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

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

Dose descriptor:

NOEL

Effect level:

180 mg/kg bw/day

Basis for effect level:

other: teratogenicity

Dose descriptor:

NOEL

Effect level:

180 mg/kg bw/day

Basis for effect level:

other: fetotoxicity

Abnormalities:

no effects observed

Developmental effects observed:

no

NOEL for maternal and developmental effects = 180 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: 19/25, 20/24, 21/22, 21/24, 22/24, and 22/23  

females were pregnant in the dose groups 1.8, 8.4, 38.8 and 180.0 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; final body weight in  

positive control group (301 g) lower than in negative control group (339 g)
-- Macroscopy: uroginital tract examined, no alterations reported

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

lutea/dam were 9.92, 10.4, 12.6, 10.8, 11.7, and 11.9 in the dose groups  

1.8, 8.4, 38.8 and 180.0 mg K2CO3/kg bw/day, the negative control group,  

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

lutea were 248, 249, 278, 259, 280, and 273, respectively
-- Live liters: no dose related effects; total numbers of live liters

   were 19, 20, 21, 21, 22, and 19 in the dose groups 1.8, 8.4, 38.8 and

   180.0 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 223, 225, 262, 223, 265, and 230 in the dose groups

   1.8, 8.4, 38.8 and 180.0 mg K2CO3/kg bw/day, the negative control group,

   and the positive control group, respectively; the average numbers of

  implantations/dam were 11.7, 11.3, 12.5, 10.6, 12.0, and 10.5,

  respectively
-- Resorptions: no dose related effects; total numbers of resorptions

  were 6, 1, 7, 1, 3, and 78 in the dose groups 1.8, 8.4, 38.8 and 180.0 mg

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

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

  were 3 (15.8%), 1 (5%), 4 (19.1%), 1 (4.76%), 3 (13.6%), and 15 (62.2%),

  respectively; there were three dams (13.6%) with all sites resorbed in

  the positive control group
-- Life fetuses: no dose related effects; total numbers of live fetuses

   were 216, 224, 255, 221, 262, and 151 in the dose groups 1.8, 8.4, 38.8

   and 180.0 mg K2CO3/kg bw/day, the negative control group, and the

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

   were 11.4, 11.2, 12.1, 10.5, 11.9, and 6.68, respectively
-- Sex ratio: no dose related effects; sex ratio (M/F) of live fetuses

  were 1.00, 0.81, 0.90, 0.91, 1.17, and 1.19 in the dose groups 1.8, 8.4,

38.8 and 180.0 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, 1, 0, 0, 1, 0, and 1 in the dose groups 1.8, 8.4, 38.8 and 180.0 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 1 (5.26%), 0 (0%), 0 (0%), 1 (4.76%), 0 (0%), and 1 (4.55%),

  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 3.88, 3.98, 3.84, 3.93, 3.89, and 2.40 in the dose groups 

1.8,8.4, 38.8 and 180.0 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*  1.8    8.4   38.8  180.0
-----------------------------------------------------------
Live fetuses   182/22** 107/19  149/19 158/20 176/21 154/21
examined
(at term)

Sternebrae:
- incom. oss    44/15*** 72/18   54/16  23/11  47/16  30/10
- scrambled       -        -       -      -      -      -
- bipartite      1/1      5/3      -      -     4/3     -
- fused           -        -       -      -      -      -
- extra           -        -       -      -      -      -
- missing        3/2     96/19   23/10    -    12/5    6/3
- other           -        -       -      -      -      -
 
Ribs:
- incom. oss.     -        -       -      -      -     2/1
- fused/split     -       9/6      -      -      -      -
- wavy          18/10    48/15   11/6    9/4    9/5   16/7
- less than 12    -        -       -      -      -      -
- more than 13   2/2     95/19    1/1     -     4/2     -
- other           -        -       -      -      -      -
 
Vertebrae:
- incom. oss.    5/4     70/19    8/5    2/2    4/3   11/5
- scrabbled       -        -       -      -      -      -
- fused           -        -       -      -      -      -
- extra ctrs.     -        -       -      -      -      -
  oss.
- scoliosis       -        -       -      -      -      -
- tail defects    -        -       -      -      -      -

Skull:          28/12    49/16   20/11  15/7   20/10  39/11
-incom. closure   -       2/1      -      -      -      -
- missing         -        -       -      -      -      -
- craniostosis    -        -       -      -      -      -
- other           -        -       -      -      -      -

Extremities:
- incom. oss.     -       4/3     1/1     -      -      -
- missing         -        -       -      -      -      -
- extra           -        -       -      -      -      -
Miscellaneous:    -        -       -      -      -      -
- hyoid missing  3/3     67/19   23/10    -    21/9    10/7
- hyoid reduced 66/18     8/6    21/12  32/11  19/11   50/15
------------------------------------------------------------
*   positive control: 250 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 ten

   pups with soft tissue abnormalities were listed: one pup with cleft

palate, harelip and exophthalmos in the 1.8 mg K2CO3/kg bw dose group,

   one pup with umbilical hernia each in the 38.8 and the 180 mg K2CO3/kg bw

   dose group, each, and in 7 pups of the positive control group (two with

   abdominal hernia, one with hydrocephalus, one with exocephalus, one with

   cleft palate and harelip, and one with encephalomyelocele and

   gatroschisis)

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 180 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 Wistar rats/dose by gavage at dose levels of 0, 1.8, 8.4, 38.8 or 180.0 mg/kg bw per day from days 6  through 15 of gestation. On day 20 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: 180 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 experimental group did not differ from anomalies occurring in sham-treated controls.

 

NOEL developmental toxicity/teratogenicity: 180 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 180 mg/kg bw/day.

In conclusion, no teratogenicity potential by the results of this study have been documented for potassium carbonate.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no adverse effect observed

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Oral teratogenicity studies on potassium carbonate performed on two species (rat and mouse) and an inhalative teratogenicity study on a potassium carbonate-based technical formulation performed on rats available. In these studies there were no indications on any reproductive effects.

Potassium carbonate was administered daily via oral intubation to pregnant mice and rats at doses ranging from 2.9 to 290 mg/kg bw and 1.8 to 180 mg/kg bw respectively during days 6-15 of gestation. The test substance had neither effects on mortality, body weight gain and the macroscopy of the urogenital tracts of the dams nor effects on numbers of corpora lutea, live litters, 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 experimental group did not differ from anomalies occurring in sham-treated controls. Therefore, the NOEL for maternal toxicity, developmental toxicity and teratogenicity in these studies is 290 mg/kg bw for mice and 180 mg/kg bw for rats (highest doses tested) (Food and Drug Research Laboratories, 1975). Also, a potassium carbonate-based scrubbing solution as used in petroleum refineries did not appear to be a developmental toxicant in rats. Sprague-Dawley rats were whole body exposed to the used scrubbing solution “Cartacarb” at concentrations of 0.05, 01.0.2 and 0.3 mg/L for 6 h/d on days 6 to 19 of pregnancy. “Catacarb” is an alkaline solution consisting primarily of potassium carbonate and low concentrations of borate, diethanolamine, and metavanadate salts, used to remove acidic gases from refinery gas streams by chemical absorption (analytical composition of the used “Catacarb” solution collected from a hydrotreating unit of a refinery: pH 9.9, 30.8% potassium carbonate, 65.1% water, 1.6% diethanolamine, 0.4% potassium borate (as boron), 0.3% potassium metavanadate (as vanadium), and 6.7 ppm chromium, 8.4 ppm molybdenum and 4.5 ppm nickel).

Maternal toxicity was exhibited in the 0.3 mg/L group, including signs of respiratory tract impairment, reduced body weight and food consumption, and one animal died. The only fetal effect seen was a delayed mineralization of sternal elements at the maternal toxic concentration of 0.3 mg/L. The incidence of fetuses (14 fetuses vs. 6 fetuses in control) but not the litter incidence (2/22 litters vs. 5/23 litters in control) with sternebrae 5 and/or 6 unossified was increased in this group. The increase in fetuses with delayed mineralization of sternal elements in this dose group was primarily attributable to two litters conceived by the two most severely affected mothers in the group. The delayed mineralization is most probably a consequence of the maternal toxicity and no indication on an intrinsic developmental toxic activity of the formulation. The NOAEC for maternal toxicity and the NOEC for developmental toxicity is 200 mg scrubbing solution (corresponding to 62 mg potassium carbonate) /m³ and the NOEC for teratogenicity is 300 mg scrubbing solution (corresponding to 92 mg potassium carbonate) /m³ (highest concentration tested) (Bui et al., 1998b).

Although potassium carbonate was not tested up to the limit dose of current guidelines, no potential for teratogenicity is expected, since Potassium and carbonate are essential constituents and two of the most abundant ions in all animal species. In adult humans, the total body potassium is approx. 3.5 mol (135 g). 98 % of this is located intracellular (150 mmol/l), the extracellular potassium concentration is approx. 4 mmol/l.

 

The metabolism and mechanisms of action of potassium and carbonate are well reviewed in standard textbooks on pharmacology and physiology.

 

About 90 % of the ingested dose of potassium is absorbed by passive diffusion in the membrane of the upper intestine. Potassium is distributed to all tissues where it is the principal intracellular cation. Insulin, acid-base status, aldosterone, and adrenergic activity regulate cellular uptake of potassium. The majority of ingested potassium is excreted in the urine via glomelural filtration. The distal tubules are able to secrete as well as reabsorb potassium, so they are able to produce a net secretion of potassium to achieve homeostasis in the face of a potassium load due to abnormally high levels of ingested potassium. About 15 % of the total amount of potassium excreted is found in faeces.

Excretion and retention of potassium is mainly regulated by the main adrenal cortical hormones.

Normal homeostatic mechanisms controlling the serum potassium levels allow a wide range of dietary intake. The renal excretory mechanism is designed for efficient removal of excess K, rather for its conservation during deficiency. Even with no intake of K, humans lose a minimum of 585-1170 mg K per day. However, the distribution of potassium between the intracellular and the extracellular fluids can markedly affect the serum potassium level without a change in total body potassium. K+ is the principal cation mediating the osmotic balance of the body fluids. In animals, the maintenance of normal cell volume and pressure depends on Na+ and K+ pumping. The K+/Na+ separation has allowed for evolution of reversible transmembrane electrical potentials essential for nerve and muscle action in animals, and both potassium and chloride are important in transmission of nerve impulses to the muscle fibers.

Potassium transport through the hydrophobic interior of a membrane can be facilitated by a number of natural compounds that form lipid-soluble alkali metal cation complexes. Potassium serves the critical role as counterion for various carboxylates, phosphates and sulphates, and stabilizes macromolecular structures (OECD SIDS, 2001).

 

The bicarbonate buffer system described by the following equation:

H2O + CO2 <=> H2CO3 <=> H+ + (HCO3)-

is the major extracellular buffer in the blood and the interstitial fluid of vertebrates. The blood plasma of man normally has a pH of 7.40. Should the pH fall below 7.0 or rise above 7.8, irreversible damage may occur. Compensatory mechanisms for acid-base disturbances function to alter the ratio of (HCO3)- to PCO2, returning the pH of the blood to normal. Thus, metabolic acidosis may be compensated for by hyperventilation and increased renal absorption of (HCO3)-. Metabolic alkalosis may be compensated for by hypoventilation and the excess of (HCO3)- in the urine. Renal mechanisms are usually sufficient to restore the acid-base balance (OECD SIDS, 2002).

 

No fertility study has been localised for potassium carbonate or related substances. However, the maximum plasma concentration of potassium and carbonate is efficiently and tightly regulated by renal elimination. A significant increase in the potassium concentration in the extracellular fluid will only occur after high potassium intake or in patients with severely reduced kidney function.

 

No effects of exposure potassium carbonate on gonadal function can be expected if the plasma concentrations are within the normal range, as neither potassium nor carbonate accumulates in the body. Based on the extensive amount of knowledge on regulation and effects of potassium and carbonate in the human body, no further testing of developmental toxicity is required.

 

References

OECD SIDS, 2001. Potassium chloride.SIDS Initial Assessment Report for 13th SIAM. UNEP Publications.

 

OECD SIDS, 2002. Sodium bicarbonate.SIDS Initial Assessment Report for 15th SIAM. UNEP Publications.

 

 

Justification for classification or non-classification

There is no evidence for an intrinsic toxicity to reproduction of potassium carbonate from the results of reliable developmental toxicity and teratogenicity studies on mice and rats performed with potassium carbonate itself, reliable repeated dose toxicity studies with macroscopic and histological examination of the male and female reproductive organs (epididymides, testes, ovaries, and uterus) performed with closely related read across substance potassium hydrogencarbonate and available information from assessments carried out within the OECD work on investigation of high production volume chemicals on compounds which have a carbonate or a potassium moiety. Further on, based on chemistry considerations on the structure of potassium carbonate and potassium hydrogencarbonate, no toxicity to reproduction is expected.

Therefore, no classification is required for toxicity to reproduction according to CLP, EU GHS (Regulation (EC) No 1272/2008).