Potassium tert-butanolate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 mg/m³

DNEL related information

DNEL derivation method:

other: based on local effects of potassium hydroxid

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 mg/m³

DNEL related information

DNEL derivation method:

other: based on local effects of potassium hydroxid

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 mg/m³

DNEL related information

DNEL derivation method:

other: based on local effects of potassium hydroxid

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 mg/m³

DNEL related information

DNEL derivation method:

other: based on local effects of potassium hydroxid

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

Potassium tert-butanolate is the salt of tert-butyl alcohol ion and the potassium metal cation. In the presence of water it reacts under formation of tert-butyl alcohol and potassium hydroxide (KOH). Several data are available for tert-butyl alcohol. Defined NOAELs that were based on repeated dose studies were set at 590 mg/kg (oral) and at 540 ppm (inhalative). Potassium tert-butanolate is highly corrosive, therefore the NOAELs received from the respective repeated dose studies are too high (for the oral route they lie in the range of the LD50 values) and not suitable for the derivation of a DNEL. Local corroding and irritating effects are expected to occur before systemic effects from tert-butyl alcohol can arise. For tert-butyl alcohol, it was shown to have a low bioaccumulation. After inhalation or oral uptake, the levels in the blood increase linearly and are distributed quickly through the bloodstream in the organism. The structural analogue MTBA showed a rapid and complete absorption (tmax 15 min) across the gastrointestinal tract and after intravenous application, distribution half-life was only 3 min. The elimination half-life was between 3.8 and 5 h in rats. Only high doses lead to saturation and accumulation. These cannot be reached due to corrosive properties of Potassium tert-butanolate. Therefore, the DNEL was derived based on KOH which as one of the reaction products is characterized by its corrosivity.

KOH is not expected to become systemically available under normal handling conditions. Potassium is a mineral necessary for balancing the pH-value of the body and for keeping fluids in balance as well, so it's important for normal blood pressure regulation. Potassium is also needed for normal muscle growth, for the nervous system, brain function and for many enzymatic reactions, especially those involved in energy transfer.The normal plasmatic concentration is approximately 140 – 200 mg/l. The K+ concentration in blood is regulated by renal excretion and reabsorption. An increase of the K+ concentration in the extra cellular liquid stimulates strongly aldosterone liberation, which increases K+ excretion (Marieb, 1992). 24 – 27 g K+ ions can be filtered daily by the kidneys whereupon 90 % is excreted into the urine and 10% through the faeces (Saxena, 1989).Neither the concentration of potassium in the blood nor the pH of the blood will be increased above normal limits and therefore absorbed KOH is not expected to cause systemically toxic levels in the blood. The renal excretion of K+ can be elevated and the OH-ion is neutralized by the bicarbonate buffer system in the blood(OECD SIDS KOH 2004).As no systemic effects are expected, the local DNEL covers the systemic DNEL.

For the determination of the DNEL, a study was used where subjects had been exposed to NaOH mist (Fritschi et al., 2001). A read-across from NaOH to determine the DNEL for KOH is suitable because the hydroxyl ion is responsible for the respiratory irritation effects. In addition, both NaOH and KOH exhibit the same legal classification with the same concentration limits regarding skin corrosion (Cat 1A: C ≥ 5 %; Cat 1B: 2 % ≤ C < 5 %, Cat 2: 0,5 % ≤ C < 2 %). In the described study, a cross-sectional survey of 2404 employees from three aluminium refineries was published where 1045 of the subjects had been exposed to NaOH mist, 1359 subjects were unexposed. The exposure had been assessed on a semi-quantitative basis and concentrations calculated were: low (<0.05 mg/m3), medium (0.05 – 1.0 mg/m3) or high (>1.0 mg/m3). The authors concluded that exposure to high levels of NaOH mist (>1.0 mg/m3) was associated with an increased prevalence of work-related wheeze and rhinitis, but lung function was not impaired. These symptoms of respiratory tract irritation, in the lack of any measured functional change in lung performance, suggest that any effects were minimal. Such reporting is also subject to recall bias, which can lead to over-reporting of symptomatology. No increase of respiratory symptoms was shown for the subjects in the medium exposure group.

This data suggests that the NOEL for respiratory irritation due to exposure to NaOH mist in a large sample of subjects from three factories was 1 mg/m3. This value is likely to be a conservative estimate due to the study design.

As the study was in human subjects, no interspecies assessment factor is required. Similarly, assessment factors to take account of differences in exposure duration, dose-response or quality of the database are not required. It is noted that more than 40% of the subjects were reported to be atopic, suggesting that the study population were towards the more sensitive end of the overall population in terms of their response to respiratory irritants. This fact, coupled with the facts that a relatively large random sample of workers had been studied and irritation is not expected to be related to enzymatic differences within a species, suggest also that no assessment factor is required to account for intraspecies differences in the human population.

In addition, it is noted that the OEL (8-hour TWA) for NaOH is 2.0 mg/m3, (Belgium, NIOSH, ACGIH). This OEL value is broadly consistent with a NOEL in humans for respiratory irritation of 1.0 mg/m3.

 

1 mg/m3 is considered to be the NOEL for KOH in humans for respiratory irritation. An uptake of 1 mg/m3 results for a worker in an overall uptake during a working day of 10 mg. 10 mg KOH consist of 6.7 mg potassium based on the molecular weight and clearly lye below the daily amount of K+ that are filtered by the kidneys. For the reasons stated above, it is proposed that no assessment factors are required for the derivation of the DNEL. In addition, no calculation will be performed on the molar ratio due to the instability and high reactivity of potassium tert-butanolate. For that reason, DNEL derivation is based on the quantifiable reaction product KOH.

Regarding tert-butanol, a systemic DNEL could be derived considering the female LOAEL of < 180 mg/kg (based on organ weights) of the 2-year drinking water study as a point of departure. Since no concentrations without effects could be detected, a BMDL of 68 mg/kg is calculated using the BMDS-Software. The following extrapolation factors need to be adopted: a factor of 4 has to be added for allometric scaling, a standard human body weight of 70 kg and default human breathing volume of 10 m3 for workers in 8h and light activity, a time extrapolation factor of 0.7 has to adopted based on the ratio of 5 days for worker and 7 days of exposure in the rat and finally oral and inhalative resorption rates of 100 % need to be added. These factors lead to a value of 166 mg/m3. This value exceeds the defined DNEL of KOH, hence, no relevant systemic uptake of tert-butanol is possible from potassium butanolate inhalation.

As a result, the DNEL for inhalation (local and systemic) for workers is 1.0 mg /m3.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure

DNEL related information