Barium bis(2-ethylhexanoate)

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June - July 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

issued 2012-07-18

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2.018g/10mL (high dose), 0.3005 and 0.3004g/10mL (low dose)
- MAXIMUM DOSE VOLUME APPLIED: 10mL/kg bw

Doses:

300, 2000 mg/kg bw

No. of animals per sex per dose:

Dose group 2000mg/kg bw: 3 animals
Dose group 300mg/kg bw: 6 animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: behavioural or toxic effects on the major physiological functions

Statistics:

not performed

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - <= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

3/3 in 2000mg/kg bw dose group, 1h post dose
1/6 in 300mg/kg bw dose group, 23h 15min post dose

Clinical signs:

other: 2000mg/kg bw dose group: absence of spontaneous activity (3/3), Preyer's reflex (3/3), righting reflex (3/3), muscle tone (3/3), bradypnoea (3/3), salvation (1/3) 300mg/kg bw dose group: decrease of spontaneous activity (2/5), salvation (2/5), piloerectio

Gross pathology:

2000mg/kg bw dose group: white colouration of the forestomach (3/3), red spots on the corpus (3/3)
300mg/kg bw dose group: rigor mortis before necropsy, marked lysis prevented macroscopic examination, surviving animals did not reveal treatment related changes

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test item barium bis(2-ethylhexanoate) is higher than 300mg/kg bw and lower than 2000mg/kg bw by oral route in the rat.
In accordance with directive 67/548/EEC, the test item barium bis(2-ethylhexanoate) has to be classified with Xn, R22 (Harmful if swallowed).
In accordance with regulation (EC) 1272/2008 the test item barium bis(2-ethylhexanoate) has to be classified in category 4, H302 (Harmful if swallowed) and the signal word "Warning" be assigned.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

One key study available (according to OECD 423, under GLP) which is reliable without restrictions (RL=1). The overall quality of the database is therefore high.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Introduction

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.

 

Barium bis(2-ethylhexanoate) is the barium metal salt of 2-ethylhexanoic acid, which readily dissociates to the corresponding metal barium cation and 2-ethylhexanoic anions. The barium cation and the 2-ethylhexanoic acid anion are considered to represent the overall toxicity of barium bis (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.

Acute toxicity

No acute toxicity studies via inhalation and dermal route with barium bis(2-ethylhexanoate) are available. Acute inhalative and dermal acute toxicity will be addressed with existing data on the dissociation products as detailed in the table below. Further details on the acute toxicity of the individual constituents within the framework of regulation (EC) 1907/2006 are given below.

 

Table: Summary of acute toxicity data of barium bis(2-ethylhexanoate) and the individual constituents.

	BaCl2 (CAS# 10361-37-2)	2-ethylhexanoic acid (CAS# 149-57-5)	Barium bis(2-ethylhexanoate) (CAS# 2457-01-4)
Acute inhalation toxicity	LC50>1mg/L Acute Tox 4 (H332)	LD0= 0.11 mg/L air (nominal)	waived, since the substance is used and placed on the market in a non-inhalable form
Acute dermal toxicity	LD50(rat)>2,000 mg/kg bw	LD50> 2,000 mg/kg bw	LD50>2,000 mg/kg bw (calculated)

 

The acute dermal toxicity for barium bis(2-ethylhexanoate) is > 2000mg/kg bw, since both constituents have shown no sign of acute dermal toxicity. Hence the substance is not to be classified according to regulation (EC) 1272/2008 for acute dermal toxicity.

 

In a study according to OECD 423 and under GLP, the LD50 of the test item barium bis(2-ethylhexanoate) was determined to be higher than 300mg/kg bw and lower than 2000mg/kg bw by oral route in the rat.

 

Further testing is not required. For further information on the toxicity of the individual constituents, please refer to the relevant sections in the IUCLID and CSR.

Justification for selection of acute toxicity – oral endpoint
Key study

Justification for selection of acute toxicity – inhalation endpoint
Endpoint waived, since the substance is used and placed on the market in a non-inhalable form.

Justification for selection of acute toxicity – dermal endpoint
Read-across information.

Justification for classification or non-classification

The calculated dermal LD50 for barium bis(2 -ethylhexanoate) is > 2000mg/kg, hence the substance is not to be classified according to regulation (EC) 1272/2008 and directive 67/548/EEC for acute dermal toxicity.

Furthermore, no classification for specific target organ toxicity, single exposure (STOT SE) is required based on the acute dermal toxicity data.

 

In a study according to OECD 423 and under GLP, the LD50 of the test item barium bis(2-ethylhexanoate) was determined to be higher than 300mg/kg bw and lower than 2000mg/kg bw by oral route in the rat.

In accordance with directive 67/548/EEC, the test item barium bis(2-ethylhexanoate) has to be classified with Xn, R22 (Harmful if swallowed).

In accordance with regulation (EC) 1272/2008 the test item barium bis(2-ethylhexanoate) has to be classified in category 4, H302 (Harmful if swallowed) and the signal word "Warning" be assigned.

 

This classification is in accordance with tables 3.1 and 3.2 REGULATION (EC) No 1272/2008, Index No: 056-002-7 (barium salts in general) for acute oral and inhalative toxicity (Cat 4/H302, H332; Xn R20/22).