Potassium 2-ethylhexanoate

Endpoint summary

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

Species:

other: animal and human data

Additional information

Introduction to read-across matrix

A comprehensive data gap analysis was conducted for the entire substance portfolio of the Metal carboxylates REACH Consortium (MCRC), covering 10 metal carboxylates in total. This literature screening effort included:

 

• all available proprietary studies from the Metal carboxylates REACH Consortium (MCRC)
• detailed literature searches in online databases
• screening of human health review articles
• rigorous quality and reliability screening according to Klimisch criteria, where those criteria apply

 

During the literature search and data gap analysis it became obvious that the overall database on substance-specific human health hazard data for the metal carboxylates is too scant to cover all REACH endpoints. Therefore, the remaining data gaps had to be covered by either experimental testing or read-across from similar substances.

 

Selected endpoints for the human health hazard assessment are addressed by read-across, using a combination of data on the organic acid counterion and the metal (or one of its readily soluble salts). This way forward is acceptable, since metal carboxylates dissociate to the organic anion and the metal cation upon dissolution in aqueous media. No indications of complexation or masking of the metal ion through the organic acid were apparent during the water solubility tests (please refer to the water solubility data in section of the IUCLID and chapter of the CSR). Once the individual constituents of the metal carboxylate become bioavailable (i.e. in the acidic environment in the gastric passage or after phagocytosis by pulmonary macrophages), the “overall” toxicity of the dissociated metal carboxylate can be described by the toxicity of the “individual” constituents. Since synergistic effects are not expected for this group of metal carboxylates, the human health hazard assessment consists of an individual assessment of the metal cation and the organic anion.

 

The hazard information of the individual constituents was obtained from existing REACH registration dossiers via a license-to-use obtained by the lead registrant. These registration dossiers were submitted to ECHA in 2010 as full registration dossiers, and are thus considered to contain relevant and reliable information for all human health endpoints. All lead-registrant dossiers were checked for completeness and accepted by ECHA, i.e. a registration number was assigned.

 

Potassium 2-ethylhexanoate is the potassium metal salt of 2-ethylhexanoic acid, which readily dissociates to the corresponding monovalent potassium cation and 2-ethylhexanoic acid anions. The potassium cation and the 2-ethylhexanoic acid anion are considered to represent the overall toxicity of the potassium 2-ethylhexanoate in a manner proportionate to the free acid and the metal (represented by one of its readily soluble salts). Based on the above information, unrestricted read-across is considered feasible and justified.

Although the term „constituent“ within the REACH context is defined as substance (also being part of a mixture), the term constituent within this hazard assessment is meant to describe either part of the metal carboxylate salt, i.e. anion or cation.

Repeated dose toxicity

No repeated dose toxicity study with potassium 2-ethylhexanoate is available, thus the repeated dose toxicity will be addressed with existing data on the dissociation products potassium and 2-ethylhexanoic acid as detailed in the table below.

 

Table: Summary of repeated dose toxicity data of the potassium 2-ethylhexanoate and the individual constituents.

	potassium substances	2-ethylhexanoic acid (CAS# 149-57-5)	Potassium 2-ethylhexanoate (CAS# 3164 -85 -0)
Repeated dose oral toxicity	NOAEL(human data)= 85 mg K/kg bw/day*	NOAEL(rat;90d)= 300 mg/kg bw/day   NOAEL(mice;90d)= 200 mg/kg bw/day	no data

* Identified as most sensitive endpoint in the registration dossier for potassium, thus has been used for the DNEL derivation of this substance.

 

Potassium

Assessment of potential systemic risks after prolonged oral exposure of humans to potassium is considered feasible on the basis of the comprehensive evaluation of all available human data on potassium as published in the Opinion of the Scientific Panel on Dietetic Products, Nutrition and Allergies (EFSA 2005), the EGVM publication on safe upper levels for vitamins and minerals (EVM 2003) and the report of the European Food Safety Authority on nutrient and energy intake for the EC (EFSA 1993).

 

According to the EFSA report (2005) "potassium intakes from foods have not been associated with adverse effects in normal, healthy children and adults. The average intake in adults from the diet is 3-4 g and the intake generally does not exceed 5-6 g per day. A long-term intake of potassium supplements as potassium chloride of about 3 g per day in addition to intakes from foods has been showed not to have adverse effects. Supplemental potassium in doses of 5-7 g/day in addition to dietary intake has in a few cases, however, been reported to cause conductive effects and compromised heart function in apparently healthy

adults" (EFSA 2005). A NOAEL of 6000 mg/day, which corresponds to a dose of approximately 85 mg potassium/kg bw/day taking into account an average body weight of 70 kg/person is therefore taken forward in the hazard assessment.

 

2-Ethylhexanoic acid

In a 90-day repeated dose toxicity study in rats and mice with 2-ethylhexanoic acid, adiet containing 0.5% 2-ethylhexanoic acid caused no adverse effect in rats in a 13 week feeding study (dose levels were 0, 0.1, 0.5, or 1.5%, calculated NOAEL ca. 300 mg/kg bw/day). No adverse effect was observed in mice receiving a diet containing 0.5 % 2-ethylhexanoic acid in a 13 week feeding study (dose levels were 0, 0.1, 0.5, or 1.5%). The NOAEL was calculated to be 200 mg/kg bw/day. Both NOAELs were based on reduced food consumption and a decreased rate of body weight gain in the high dose groups.For further information on the toxicity of 2-ethylhexanoic acid, please refer to the relevant sections in the IUCLID and CSR.

 

Potassium 2-ethylhexanoate

Since no repeated dose toxicity study is available specifically for potassium 2-ethylhexanoate, information on the individual constituents potassium and 2-ethylhexanoic acid will be used for the hazard assessment and when applicable for the risk characterisation of potassium 2-ethylhexanoate. For the purpose of hazard assessment of potassium 2-ethylhexanoate, the point of departure for the most sensitive endpoint of each constituent will be used for the DNEL derivation. In case of potassium in potassium 2-ethylhexanoate, the NOAEL of 85 mg/kg bw/day in repeated dose toxicity (human data) will be used.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Information from read-across substances:
human data for potassium: NOAEL=85mg/kg bw/day
animal data for 2-ethylhexanoic acid: NOAEL(rat)=300mg/kg bw/day, NOAEL(mice)=200mg/kg bw/day