Potassium superoxide

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No reproductive or developmental toxicity studies with potassium superoxide are available. The summary only provides evidence from the degradation product hydrogen peroxide. Overall, due to rapid in vivo degradation of KO2, no toxicity to the reproductive system is anticipated. Also, in practice, exposure of workers and consumers to KO2 is not expected and is completely confined to closed containers or articles. Therefore, reproductive-developmental toxicity of KO2 is expected to be of low concern.

No significant exposure occurs at the level of industrial/professional handling: KO2 is not manufactured in the EU. The substance is imported in the form of low dust tablets which are sealed and packed. Upon opening and before use, dust reduction measures are taken to avoid exposure via inhalation. The tablets are transferred from the barrels/bags into cartridges that are integrated into sealed Oxygen Self Rescuer units.

No significant exposure occurs at the level of consumer use: The self-rescuer device serves as a rescue device in emergency situations e.g. in mines or aircrafts. The user puts on the device and breathes through a mouthpiece and breathing tube. The moisture and CO2 from the breath react with KO2 to generate oxygen, potassium hydroxide and potassium carbonate in the cartridge. Due to the specific design of the device, the user is protected from any contact with KO2 or inhaling KO2 dust. When spent, the cartridges are sent back for recycling or waste incineration. Unused devices are disposed of in a similar way.

Link to relevant study records

Reference

Reference 1

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Justification for type of information:

Refer to the section 13 for details on the read across justification. The toxicity to reproduction study with the degradation product is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Principles of method if other than guideline:

Reproductive toxicity study in rats

GLP compliance:

no

Limit test:

yes

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Route of administration:

oral: drinking water

Details on exposure:

0.45% test substance in drinking water (ad lib.)

Duration of treatment / exposure:

Exposure period: 5 months (females), 9 months (male offspring)
Premating exposure period (males): 5 months
Premating exposure period (females): 5 months
Duration of test: ca. 14 months

Frequency of treatment:

Daily

Dose / conc.:

0.45 other: %

Remarks:

in drinking water

Control animals:

yes, concurrent vehicle

Key result

Dose descriptor:

NOEL

Effect level:

0.45 other: %

Based on:

test mat. (dissolved fraction)

Sex:

female

Basis for effect level:

other: no treatment-related adverse effect

No effects on reproduction in rats

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Body weight for male offspring on H2O2 is lower than those on tap water
Difference in body weight of the six male offspring followed for 9 months (an average of 521g for those on tap water against 411g for those on the test substance).

Beside the effect on F1 body weight, normal litters were produced.

Key result

Dose descriptor:

LOAEL

Generation:

F1

Effect level:

0.45 other: %

Based on:

test mat. (dissolved fraction)

Sex:

male/female

Basis for effect level:

other: no adverse effect except decrease in body weight

Key result

Reproductive effects observed:

no

Conclusions:

Under the study conditions, long term administration of the substance did not affect reporduction in female rats.

Executive summary:

A study was conducted to determine the potential reproductive toxicity of the degradation product hydrogen peroxide in female rats. The substance was admnistered to the rats through drinking water at 0.45% for 5 months and mated with normal males. Upon production of normal litters, they were maintained under the treated drinking water for nine months. The only noticeable effect observed was a difference in body weight of the male offsprings which they gained after they were given normal water. Under the study conditions, long term administration of the substance did not affect reporduction in female rats at 0.45% of the substance (Hankin, 1958).

Reference 2

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

other: evidence based on degradation product

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Justification for type of information:

Justification for type of information: Refer to the section 13 for details. The toxicity to reproduction study with the degradation product is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.

Principles of method if other than guideline:

Male reproductive toxicity study

GLP compliance:

no

Limit test:

yes

Species:

mouse

Strain:

not specified

Sex:

male

Route of administration:

oral: drinking water

Duration of treatment / exposure:

Exposure period: 7, 21 or 28 days
Premating exposure period (males): 7, 21 or 28 days

Frequency of treatment:

Daily

Details on study schedule:

Exposure period: 7, 21 or 28 days
Premating exposure period (males): 7, 21 or 28 days

Dose / conc.:

0 other: %

Remarks:

in drinking water

Dose / conc.:

0.33 other: %

Remarks:

in drinking water

Dose / conc.:

1 other: %

Remarks:

in drinking water

Dose / conc.:

3 other: %

Remarks:

in drinking water

No. of animals per sex per dose:

12 males per dose

Control animals:

no

Key result

Dose descriptor:

LOAEL

Effect level:

0.33 other: %

Based on:

test mat. (dissolved fraction)

Sex:

male

Basis for effect level:

other: no treatment-related adverse effects except body weight gain

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

3 other: %

Based on:

test mat. (dissolved fraction)

Sex:

male/female

Basis for effect level:

other: no treatment-related adverse effect

Key result

Reproductive effects observed:

no

Conclusions:

Under the study conditions, the substance had no significant effects on the reproductive capacity of male mice.

Executive summary:

A study was conducted to determine the potential reprotoxicity of the degradation product hydrogen peroxide. Male mice were administered the substance in drinking water at 0, 0.33, 1 and 3% for 7, 21 or 28 days before the mating period and then mated with normal females. The test substance treatment continued through the mating period. All female mice mated to treated males became pregnant within a few days and in each case healthy pups were born in litters of normal size. Pregnant mice that continued to consume 1% test substance in water until near term showed some delays in parturition compared to dams consuming untreated tap water, although the effect was small and inconsistent. The concentration, morphology and motility of the mouse spermatozoa after 3 weeks of treatment appeared normal. Under the study conditions, the substance had no significant effects on the reproductive capacity of male mice (Wales, 1959).

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Evidence based on the studies with the degradation product hydrogen peroxide:

A study was conducted to determine the potential reproductive toxicity of the degradation product hydrogen peroxide in female rats. The substance was admnistered to the rats through drinking water at 0.45% for 5 months and mated with normal males. Upon production of normal litters, they were maintained under the treated drinking water for nine months. The only noticeable effect observed was a difference in body weight of the male offsprings which they gained after they were given normal water. Under the study conditions, long term administration of the substance did not affect reporduction in female rats at 0.45% of the substance (Hankin, 1958).

A study was conducted to determine the potential reprotoxicity of the degradation product hydrogen peroxide. Male mice were administered the substance in drinking water at 0, 0.33, 1 and 3% for 7, 21 or 28 days before the mating period and then mated with normal females. The test substance treatment continued through the mating period. All female mice mated to treated males became pregnant within a few days and in each case healthy pups were born in litters of normal size. Pregnant mice that continued to consume 1% test substance in water until near term showed some delays in parturition compared to dams consuming untreated tap water, although the effect was small and inconsistent. The concentration, morphology and motility of the mouse spermatozoa after 3 weeks of treatment appeared normal. Under the study conditions, the substance had no significant effects on the reproductive capacity of male mice (Wales, 1959).

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Mode of Action Analysis / Human Relevance Framework

In vivo, potassium superoxide reacts rapidly with water to produce potassium hydroxide (KOH), oxygen (O2) and potassium hydrogen peroxide (KHO2), which slowly degrades to KOH, H2O2 (hydrogen peroxide) and O2. KOH further dissociates into potassium and hydroxyl ions which constitute normal physiological ion pool. On the other hand, hydrogen peroxide is likely to degrade within a short time in in vivo conditions due to many alternative and competitive degradation pathways. Especially, in alkaline medium and in the presence of heavy and transition metals it is degraded rapidly.

No appropriate animal studies were available for a complete evaluation of reproductive and developmental toxicity with H2O2. Two limited studies with mice and rats exposed to hydrogen peroxide in drinking water suggested no grave disturbances on the male or female reproductive functions (Wales et al., 1959; Hankin, 1958).

Thus there is a clear data gap regarding studies of developmental toxicity for hydrogen peroxide. Industry had however requested a derogation for reproductive toxicity screening which was consented at the Technical Meeting level. The decision was reached on the presumption that conventional study protocols (e.g. administration in drinking water) were unlikely to show specific embryonal or foetal effects firstly, because it is doubtful whether hydrogen peroxide (as opposed to its degradation products oxygen and water) would reach the foetus and secondly, because local effects in the mother, possibly causing nutritional disturbances and general toxicity, are expected (European Chemicals Bureau, 2003).

No significant exposure occurs at the level of industrial/professional handling or consumer use. In practice, KO2 is completely confined to closed containers or articles and hence not expected to come in contact with humans during normal use conditions.

Therefore, overall considering the in vivo degradation of KO2 and inaccessibility to human beings under normal use conditions, reproductive toxicity of KO2 is expected to be of low concern.

Justification for classification or non-classification

Based on the information presented above, potassium superoxide does not warrant classification for reproductive toxicity according to EU CLP (1272/2008) criteria.