Sodium ethanolate

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 sodium 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 sodium 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 sodium 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 sodium 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

The predominant adverse effect of sodium ethanolate is corrosivity to skin and mucous membranes due to the immediate exothermic reaction with tissue water at the port of entry which leads to the development of heat and burn from a strong alkaline impact. The hydrolysis of sodium ethanolate results in sodium hydroxide (NaOH) formation and ethanol. Non-irritating concentrations of sodium ethanolate are not known and expectedly extreme low. Sodium ethanolate is instable in aqueous solutions and thus, a non-irritating concentration would not be feasible to describe. For that reason, the toxicological assessment should take the hydrolysis products into account. Several data are available for ethanol. Defined NOAELs that were based on repeated dose studies were between 1730 mg/kg and 6200 mg/kg (oral) and at 16000 ppm (inhalative). Due to the high corrosivity of sodium ethanolate, the NOAELs received from the respective repeated dose studies are too high and not suitable for the derivation of a DNEL when considering that the NOAELs are at least 4-fold higher than the LD50 of sodium ethanolate with 406 mg of ethanol/kg (calculated on the molecular weights). Local corroding and irritating effects are expected to occur before systemic effects from ethanol can arise. Ethanol is immediately absorbed following ingestion with more than 90% of the consumed dose being absorbed by the GI tract. The concentration of ethanol in blood rapidly declines, reaching endogenous levels after several hours. Ethanol can also be absorbed by inhalation. An approximate amount of 60 - 80 % absorption of inhaled ethanol is supported by human studies with levels ranging from 25 to 10,000 ppm ethanol (Lester, 1951). The maximum amount of ethanol that can be metabolised per hour has been estimated to be between 83 – 127 mg/kg/hr (or 8 – 9 g ethanol/hr). Due to the rapid absorption and the short half-life of ethanol and the high corrosivity of sodium ethanolate which avoids the uptake of high amounts, systemic effects of ethanol are unlikely to occur. Therefore, the DNEL was derived based on NaOH which as one of the reaction products is characterized by its corrosivity.

NaOH is not expected to become systemically available under normal handling conditions. Sodium is a normal constituent of the blood and an excess is excreted in the urine. It also is needed for energy mechanisms including sodium-potassium pump. Significant amounts of sodium are taken up via the food and lie between 3.1-6 g/day (Fodor et al., 1999). Exposure to NaOH could potentially increase the pH of the blood but via urinary excretion of bicarbonate and via exhalation of carbon dioxide, the pH is maintained at the normal value of 7.4-7.5 (EU RAR, 2007, section 4.1.2.1, page 63). The mean daily intake of sodium is approximately 3-5 g (ca. 8 -11 g sodium hydroxide) and are well in excess of dietary needs (about 1.5 g sodium/day in adults) (EFSA, 2006). The major effect of increased sodium intake is elevated blood pressure. Evidence that high sodium intake may have a direct effect on heart function is not conclusive so that the Panel (EFSA, 2006) concluded that the available data are not sufficient to establish an upper level (UL) for sodium from dietary sources.

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 (Fritschiet al., 2001). 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 NaOH 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 NaOH consist of 5.8 mg sodium based on the molecular weight and clearly lye below the daily amount of sodium that are taken up via food. The OEL in Germany for ethanol is 960 mg/m3. Hence, no relevant systemic uptake of ethanol is possible from sodium ethanolate inhalation.

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 sodium ethanolate. For that reason, DNEL derivation is based on the quantifiable reaction product NaOH.

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

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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

Additional information - General Population

Since exposure for the general public is precluded, DNELs for the general population are not relevant and thus not derived.