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Administrative data

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

Sodium tert-butanolate is the salt of tert-butyl alcohol ion and the sodium metal cation. In the presence of water it reacts under formation of tert-butyl alcohol and sodium hydroxide (NaOH). 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). Sodium 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 determined for potassium tert-butanolate) 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 sodium tert-butanolate. 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 (Fodoret 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. 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 tert-butanolate. For that reason, DNEL derivation is based on the quantifiable reaction product NaOH.

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 (NTP, 1995). 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 NaOH, hence, no relevant systemic uptake of tert-butanol is possible from sodium 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

General Population - Hazard for the eyes

Additional information - General Population