Zinc selenite

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.12 mg/m³

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

17.05 mg/kg bw/day

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

Rationale for and derivation of worker DNELs (Derived No Effect Level) for Selenium and its inorganic compounds

In 1999 (and confirmed in 2001) the German MAK Commission derived its Maximum Workplace Concentration (MAK: Maximale Arbeitsplatz-Konzentration) on the basis of the Yang et al (1989) study, but also taking into account the relevant NOAEL of 0.15 mg/kg bw/day from a two-generation study on rats and a LOAEL of <0;1 mg/kg bw/day from a 4-generation study on mice (Rosenfeld and Beath, 1954; Schroeder and Mitchener, 1971; Schroeder and Mitchener, 1972).

 

Inhalation:

The MAK that was put forward in in 1999/2001 was 0.05 mg Se/m³ (Göen et al, 2019), equivalent to 7 µg Se/kg bw/day (for an 8-hour shift). This MAK value covers all relevant systemic toxicological endpoints (acute toxicity, toxicity after repeated dosing, for reproduction, genotoxicity and carcinogenicity). 

 

Dermal:

For the dermal route the low absorption of 0.1 % has to be taken into account, that means, that the dermal DNEL is set to 7 mg Se/kg bw/day.

 

For zinc selenite a factor of 2.436 is used to account for molecular weight differences, resulting in the following DNELs for workers:

 

• DNEL_dermal: 17.05 mg ZnSeO₃/kg bw/day


• DNEL_inhalation: 0.12 mg ZnSeO₃/m³ (for an 8-hour shift)

 

It is worth noting that the TLV in the United Kingdom for workplace exposure and its compounds (excl. hydrogen selenide) for an 8-hour shift is 0.1 mg/m3 (Health and Safety Executive: EH40/2005 Workplace exposure limits, Merseyside UK, 2011. Available at: www.hse.gov.uk).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.036 mg/m³

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10.47 mg/kg bw/day

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10.47 µg/kg bw/day

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

Rationale for and derivation of DNELs (Derived No Effect Level) for Selenium and its inorganic compounds 

According to ECHA guidance, the traditional default AF of 10 should be considered on a human-based NOAEL in order to take intra-species variability into account.  This AF represents two different components: a toxicokinetic parameter and a toxicodynamic parameter. However, when the observed effect in humans is associated with biomonitoring data such as urinary or blood level – as is the case For Se in the Yang et al (1989)-study – the toxicokinetic factor of intraspecies variation is accounted for and the AF could be reduced as it would only have to cover for toxicodynamic variability. Biomonitoring data reflect the internal exposure and thus, toxicokinetic parameters influencing the internal/systemic bioavailability do not play a role.

 

Taking the information of this data quality assessment information into account, an AF of 3 (instead of the default AF of 10) is proposed for the derivation of a DNEL that is based on Yang et al (1989) (based on a NOAEL of 900 µg Se/day).

 

It should be noted that the Scientific Committee on Food (SCF, 2000) for inorganic selenium compounds determined a Tolerable Upper Intake Level (UL) of 300 μg/day for adults (including pregnant and lactating women), on the basis of the No Observed Adverse Effect Level (NOAEL) of 850 μg/day for clinical selenosis and applying a comparable uncertainty factor of 3. They also referred three studies that reporting no adverse effects for selenium intake between about 200 and 500 μg/day. This UL was recently fully acknowledged by the Office of Dietary Supplements of the US National Institutes of Health (available at:http://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/). Similarly, in a document from the World Health Organization (WHO) for drinking water quality, the human NOAEL for Selenium uptake was stated to be 4 µg/kg bw per day.

Finally the US Environmental Protection Agency has defined a Reference Dose (RfD) for Selenium to be 5 µg/kg bw per day (available at:http://www.epa.gov/iris/subst/0472.htm).

 

Normalising the DNEL of 300 µg/day for body weight (average of 70 kg), a DNEL of 4.3 µg Se/kg/day is determined.

It is worth mentioning that the EFSA-panel (2009; Scientific opinion on L-selenomethionine as a source for selenium added for nutritional purposes to food supplements) concluded that the toxicity of L-selenomethionine is comparable to other forms of selenium, in terms of equivalent amounts of bioavailable selenium. As with other selenium compounds, the results of toxicological studies with L-selenomethionine in animals are indicative of a steep dose-response curve, with a threshold for onset of toxicity in the range of 100–400 μg selenium/kg bw/day, dependent on the species. These thresholds are approximately a factor of 20-100 higher than the DNEL of 4.3 µg/kg bw/day that is derived from Yang et al (1989).

The derived human NOAEL (equivalent to the DNEL) seems to cover the general population for all routes of exposure.

Oral:

The DNEL of 300 µg Se/person/day or 4.3 µg/kg bw/day is directly used for the oral route.

 

Dermal:

For the dermal route the low absorption of 0.1 % has to be taken into account, that means, that the dermal DNEL is set to 4.3 mg/kg per day.

 

Inhalation:

The corresponding DNEL for inhalation expressed as concentration in the air is calculated by:

Daily respiratory volume = 20 m³ according to ECHA guidance R.8 for 24 hours of exposure.

DNEL = 300 µg per person per day,

DNEL_inh= 0.3 mg Se/20 m³ = 0.015 mg Se/m³ or 15 µg Se/m³

For zinc selenite a factor of 2.436 is used to account for molecular weight differences, resulting in the following DNELs:

• DNEL_oral: 10.47 µg ZnSeO₃/kg bw/day


• DNEL_dermal: 10.47 mg ZnSeO₃/kg bw/day


• DNEL_inhalation: 0.0365 mg ZnSeO₃/m³ (or 36.54 µg ZnSeO₃/m³)