Hexanoic acid, 2-ethyl-, zinc salt, basic

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.

 

Hexanoic acid, 2-ethyl-, zinc salt, basic is the zinc metal salt of 2-ethylhexanoic acid, which readily dissociates to the corresponding divalent zinc cation and 2-ethylhexanoic acid anions. The zinc cation and the 2-ethylhexanoic acid anion are considered to represent the overall toxicity of the hexanoic acid, 2-ethyl-, zinc salt, basic 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 hexanoic acid, 2-ethyl-, zinc salt, basic is available, thus the repeated dose toxicity will be addressed with existing data on the dissociation products zinc and 2-ethylhexanoic acid as detailed in the table below.

 

Table: Summary of repeated dose toxicity data of the hexanoic acid, 2-ethyl-, zinc salt, basic and the individual constituents.

	(slightly soluble) zinc substances	2-ethylhexanoic acid (CAS# 149-57-5)	Hexanoic acid, 2-ethyl-, zinc salt, basic (CAS# 85203-81-2)
Repeated dose oral toxicity	NOAEL(human data)= 0.83 mg Zn/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 zinc, thus has been used for the DNEL derivation of this substance.

 

Zinc

From studies in which humans were supplemented with zinc (as zinc gluconate)it was concludedthat women are more sensitive to the effects of high zinc intake and that a dose of 50 mg Zn/day is the human NOAEL. This corresponds to a daily exposure of 0.83 mg Zn/kg bw. At the LOAEL of 150 mg Zn/day, clinical signs and indications for disturbance of copper homeostasis have been observed. Studies conducted on animals are not discussed here, since information on human experience are considered of higher relevance for risk assessment purposes and should take precedence over animal studies.For further information on the toxicity of zinc, please refer to the relevant sections in the IUCLID and CSR.

 

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.

 

Hexanoic acid, 2-ethyl-, zinc salt, basic

Since no repeated dose toxicity study is available specifically for hexanoic acid, 2-ethyl-, zinc salt, basic, information on the individual constituents zinc and 2-ethylhexanoic acid will be used for the hazard assessment and when applicable for the risk characterisation of hexanoic acid, 2-ethyl-, zinc salt, basic. For the purpose of hazard assessment of hexanoic acid, 2-ethyl-, zinc salt, basic, the point of departure for the most sensitive endpoint of each constituent will be used for the DNEL derivation. In case of zinc in hexanoic acid, 2-ethyl-, zinc salt, basic, the NOAEL of 0.83 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 zinc: NOAEL=0.83mg/kg bw/day

animal data for 2-ethylhexanoic acid: NOAEL(rat)=300mg/kg bw/day, NOAEL(mice)=200mg/kg bw/day