Feropur

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.93 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

Overall assessment factor (AF):

1

Dose descriptor:

NOAEC

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

Additional information - workers

When in contact with water, the constituents of Feropur will be degraded within seconds to Na⁺,OH^-and H₂. Consequently, Na₂O and NaH are considered to be too short-living and hence irrelevant for the assessment of environmental and toxicological effects. Based on the very quick and complete degradation of Na₂O and NaH to NaOH, the risk assessments for the environment and humans are based on the properties of NaOH and Na₂CO₃.

This approach was discussed with ECHA (see attached document: "Strategy paper Feropur ECHA 090813.pdf"). ECHA agreed on this approach (see attached document "reply ECHA 090902.pdf").

The hazards of NaOH and Na₂CO₃ for the environment are caused by the hydroxyl ion and carbonate ion, respectively, and hence by an effect on the pH, i.e., both ions will increase the pH. However, the impact on the pH-effect of the carbonate ion is much weaker than the impact of the hydroxyl ion. In the SIDS dossier of sodium carbonate (SIDS dossier for sodium carbonate, 2002, Table 1, page 10, see attached document) it is outlined that 603 mg sodium carbonate/L are needed to increase the pH of distilled water to a pH of 11. To cause the same effect with sodium hydroxide, only 40 mg sodium hydroxide/L is needed (SIDS dossier for sodium hydroxide, 2002, Table 1, page 10, see attached document). Hence, the effects of sodium carbonate are about 15 times weaker than for sodium hydroxide. In addition, the concentration of sodium carbonate is only about 5% in Feropur. When in contact with water, the degradation products consists to about 95 % of sodium hydroxide and about 5% of sodium carbonate (see attached document "Strategy paper Feropur ECHA 090813.pdf"). When multiplying the concentration with the efficiency of sodium carbonate relative to sodium hydroxide (1/15th), i.e., 5%*1/15, the impact of sodium carbonate in Feropur would be about 0.3% when compared to the effect of sodium hydroxide in Feropur. Na₂CO₃ is registered as food additive E500i and may be added quantum satis to food and is therefore considered to be a substance of “low priority".

Based on the same mode of action and the much weaker effect of sodium carbonate in combination with the much lower content of sodium carbonate in Feropur when compared to sodium hydroxide, it can be concluded that the risk of Feropur is sufficiently described by the risk resulting from sodium hydroxide alone.

The focus is the occurrence of local effects after acute and repeated exposure at those places where NaOH is produced and/or used. This is because NaOH is not expected to become systemically available in the body under normal handling and use conditions, i.e. neither the concentration of sodium in the blood nor the pH of the blood will be increased (EU RAR of sodium hydroxide, 2007; section 4.1.3.1, page 73).

Acute exposure

Acute / short-term exposure and long-term exposure - systemic effects

NaOH is not expected to become systemically available in the body under normal handling and use conditions, i.e. neither the concentration of sodium in the blood nor the pH of the blood will be increased (EU RAR of sodium hydroxide, 2007; section 4.1.3.1, page 73). Therefore, it is not useful to derive a DNEL for acute exposure, systemic effects.

Acute - short-term exposure - local effects (dermal)

According to the CLP Regulation No 1272/2008 Annex VI Table 3.1, the concentration limit for corrosivity of NaOH is considered to be 2%.

Considering that 1 g Feropur will be degraded to 1.07 g NaOH when in contact with water (see attached documents "Strategy paper Feropur ECHA 090813.pdf" and "reply ECHA 090902.pdf"), this results in a concentration limit for corrosivity of 1.86% for Feropur.

Acute - short-term exposure - local effects (inhalation)

According to chapter R8 of the ECHA "Guidance on information requirements and chemical safety assessment' a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified. Sodium hydroxide is not classified regarding acute inhalation toxicity. In addition, a DNEL for acute toxicity should be derived if there is a potential for high peak exposures, for instance when sampling or connecting/disconnecting vessels. This is not the case for sodium hydroxide. High peak exposure does not occur during the manufacturing or use.

Long-term exposure

Long-term exposure - local effects (dermal DNEL in mg/kg bw):

No DNEL long-term exposure - local effects could be derived as no reliable dose descriptors were available for that route of exposure.

Long-term exposure - local effects (inhalation DNEL in mg/m³):

The most relevant starting point from the available data is the study of Fritschi et al (2001), which is a cross-sectional survey of 2404 employees from three aluminium refineries. Of these subjects, 1045 had been exposed to sodium hydroxide mist, leaving 1553 unexposed subjects.

Exposure to sodium hydroxide mist had been assessed on a semi-quantitative basis and the exposed subjects had been assigned to one of three exposure groups: low (<0.05 mg/m³), medium (0.05 – 1.0 mg/m³) or high (>1.0 mg/m³) based on an assessment of peak exposures over a 15 -minute period. The authors concluded that exposure to high levels of sodium hydroxide mist (>1.0 mg/m³) was associated with an increased prevalence of reporting work-related wheeze and rhinitis, but not impairment of lung function. These symptomatic reports 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 increased prevalence of respiratory symptoms was reported for the subjects in the medium exposure group.

This data suggests that the NOEL for respiratory irritation due to exposure to sodium hydroxide mist in a large sample of subjects from three factories was 1.0 mg/m³. This value is likely to be a conservative estimate due to the study design.

As the study was conducted 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 in excess of 40% of the study subjects were reported to be atopic. This distribution suggests 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 fact that a relatively large random sample of workers had been studied, suggest also that no assessment factor is required to account for intraspecies differences in the human population.

In addition, it is noted that in many EU countries, the OEL (8-hour TWA) for sodium hydroxide is 2.0 mg/m³, with a few exceptions (Czech Republic - 1.0 mg/m³; Poland – 0.5 mg/m³) (see Table 1). In the UK, a Workplace Exposure Limit (15 -minute STEL) of 2.0 mg/m³ exists. This value is most probably based on the ACGIH TLV Ceiling Limit of 2.0 mg/m³, which itself is based on “noticeable, but not excessive, ocular and upper respiratory tract irritation” (ACGIH, 1997). This latter statement is attributed to Patty, 1947. These OEL values are 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 sodium hydroxide mist in humans for respiratory irritation For the reasons stated above, it is proposed that no assessment factors are required to derive the DNEL.

As a result, the DNEL for sodium hydroxide for long-term inhalation, workers = 1.0 mg/m³.

Considering that 1 g Feropur will be degraded to 1.07 g NaOH when in contact with water (see attached documents "Strategy paper Feropur ECHA 090813.pdf" and "reply ECHA 090902.pdf"), this results in a DNEL for long term inhalation, workers = 0.93 mg Feropur/m³.

Table 25. Occupational Exposure Limits (OELs) in the EU and Norway (ACGIH, 2006)

 

EU Member State	Unit	TW	ST	Ceiling	Reference
Austria	mg/m³	2	4
Belgium	mg/m³			2	ACGIH, 2006
Czech Republic	mg/m³	1	2		ACGIH, 2006
Denmark	mg/m³	2
Finland	mg/m³	2			ACGIH, 2006
France	mg/m³	2
Hungary	mg/m³	2	2
Ireland	mg/m³		2		ACGIH, 2006
Norway	mg/m³			2	ACGIH, 2006
Poland	mg/m³	0.5	1		ACGIH, 2006
Portugal	mg/m³		2
Spain	mg/m³		2		ACGIH, 2006
Sweden	mg/m³	1		2	ACGIH, 2006
United Kingdom	mg/m³		2		ACGIH, 2006

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.93 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

Overall assessment factor (AF):

1

Dose descriptor:

NOAEC

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

When in contact with water, the constituents of Feropur will be degraded within seconds to Na⁺,OH^-and H₂. Consequently, Na₂O and NaH are considered to be too short-living and hence irrelevant for the assessment of environmental and toxicological effects. Based on the very quick and complete degradation of Na₂O and NaH to NaOH, the risk assessments for the environment and humans are based on the properties of NaOH and Na₂CO₃.

This approach was discussed with ECHA (see attached document: "Strategy paper Feropur ECHA 090813.pdf"). ECHA agreed on this approach (see attached document "reply ECHA 090902.pdf").

The hazards of NaOH and Na₂CO₃ for the environment are caused by the hydroxyl ion and carbonate ion, respectively, and hence by an effect on the pH, i.e., both ions will increase the pH. However, the impact on the pH-effect of the carbonate ion is much weaker than the impact of the hydroxyl ion. In the SIDS dossier of sodium carbonate (SIDS dossier for sodium carbonate, 2002, Table 1, page 10, see attached document) it is outlined that 603 mg sodium carbonate/L are needed to increase the pH of distilled water to a pH of 11. To cause the same effect with sodium hydroxide, only 40 mg sodium hydroxide/L is needed (SIDS dossier for sodium hydroxide, 2002, Table 1, page 10, see attached document). Hence, the effects of sodium carbonate are about 15 times weaker than for sodium hydroxide. In addition, the concentration of sodium carbonate is only about 5% in Feropur. When in contact with water, the degradation products consists to about 95 % of sodium hydroxide and about 5% of sodium carbonate (see attached document "Strategy paper Feropur ECHA 090813.pdf"). When multiplying the concentration with the efficiency of sodium carbonate relative to sodium hydroxide (1/15th), i.e., 5%*1/15, the impact of sodium carbonate in Feropur would be about 0.3% when compared to the effect of sodium hydroxide in Feropur. Na₂CO₃ is registered as food additive E500i and may be added quantum satis to food and is therefore considered to be a substance of “low priority".

Based on the same mode of action and the much weaker effect of sodium carbonate in combination with the much lower content of sodium carbonate in Feropur when compared to sodium hydroxide, it can be concluded that the risk of Feropur is sufficiently described by the risk resulting from sodium hydroxide alone.

As sodium hydroxide is not expected to become systemically available in the body under normal handling and use conditions, the focus is on possible risks from acute exposure (local effects) (EU RAR of Sodium Hydroxide, 2007; section 4.1.3.2.4.1; page 77).

Acute exposure

Acute / short-term exposure and long-term exposure - systemic effects

As sodium hydroxide is not expected to become systemically available in the body under normal handling and use conditions, the focus is on possible risks from acute exposure (local effects) (EU RAR of Sodium Hydroxide, 2007; section 4.1.3.2.4.1; page 77).

Therefore, it is not useful to derive a DNEL for acute exposure, systemic effects.

Acute - short-term exposure - local effects - dermal

According to the CLP Regulation No 1272/2008 Annex VI Table 3.1, the concentration limit for corrosivity of NaOH is considered to be 2%.

Acute - short-term exposure - local effects - inhalation

According to chapter R8 of the ECHA "Guidance on information requirements and chemical safety assessment' a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified. Sodium hydroxide is not classified regarding acute dermal toxicity.

Long-term exposure

DNEL - long term exposure - local effects - dermal:

No DNEL long-term exposure - local effects could be derived as no reliable dose descriptors were available for that route of exposure.

DNEL - long term exposure - local effects - inhalation

The same point of departure is relevant for deriving a DNEL for the general population, i.e. the study by Fritschi et al (2001). The following comments apply in the assessment of the need for further Assessment Factors in deriving a local DNEL for the general population.

1. The assessment of exposure to sodium hydroxide conducted by Fritschi et al was based on peak exposures over a 15-minute period. The same assessment of duration of exposure would be relevant for both the working population and the general population, given that the effect being assessed to derive the NOAEL is local irritation of the respiratory tract. No further modification is therefore required to the NOAEL to take account of potential differences in the duration of exposure of the general population.
2. In the population studied by Fritschi et al, in excess of 40% of the subjects were reported to be atopic. This distribution suggests that the study population were towards the more sensitive end of the overall population in terms of their response to respiratory irritants and, as such, could be regarded as an adequate representation of the general population in terms of their response to sodium hydroxide. It is concluded, therefore, that no additional assessment factor is required to take account of further intraspecies differences in the general human population.

As a result, the DNEL for sodium hydroxide for long-term inhalation, general population = 1.0 mg/m³.

Considering that 1 g Feropur will be degraded to 1.07 g NaOH when in contact with water (see attached documents "Strategy paper Feropur ECHA 090813.pdf" and "reply ECHA 090902.pdf"), this results in a DNEL for long term inhalation = 0.93 mg Feropur/m³.