2-ethylhexanoic acid, molybdenum salt

Endpoint summary

Additional information

Read-across approach

Selected endpoints for the human health hazard assessment are addressed by read-across, using a combination of data on the metal cation and the organic acid anion. This way forward is acceptable, since metal carboxylates are shown to 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 and dissociation tests (please refer to the water solubility and dissociation in sections 4.8 and 4.21 of IUCLID). Once the individual transformation products 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 a combination of the toxicity of these transformation products, i.e. the metal cation and carboxylate anion according to an additivity approach.

 

2-ethylhexanoic, molybdenum salt is the molybdenum metal salt of 2-ethylhexanoic acid, which readily dissociates to the corresponding molybdenum and 2-ethylhexanoate ions. These ions are considered to represent the overall toxicity of 2-ethylhexanoic, molybdenum salt in a manner proportionate to the free acid and the metal (represented by one of its readily soluble salts). 

 

A detailed justification for the read-across approach is added as a separate document in section 13 of IUCLID.

 

Repeated dose toxicity

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

 

Table: Summary of repeated dose toxicity data of 2-ethylhexanoic acid, molybdenum salt and the individual constituents.

	Disodium molybdate (CAS# 7631-95-0)	2-ethylhexanoic acid (CAS# 149-57-5)	2-ethylhexanoic acid, molybdenum salt (CAS# 34041-09-3)
Repeated dose oral toxicity	NOAEL(subchronic, rat)=17 mg Mo/kg bw/day*	NOAEL(rat;90d)= 300 mg/kg bw/day   NOAEL(mice;90d)= 200 mg/kg bw/day	No data
Repeated dose inhalation toxicity	NOAEC(subchronic, rat)= 100 mg MoO3/m³   NOAEC(subchronic, rat)= 66.7 mg Mo/m³**	No data	No data

* Identified as most sensitive endpoint in the registration dossier for disodium molybdate for the oral route, thus has been used for the DNEL derivation of 2-ethylhexanoic acid, molybdenum salt.

** Identified as most sensitive endpoint in the registration dossier for disodium molybdate for the oral route, thus has been used for the DNEL derivation of 2-ethylhexanoic acid, molybdenum salt.

 

Disodium molybdate

The dietary administration of 5, 17 or 60 mg/kg bw/day of Mo (molybdenum in sodium molybdate dihydrate) to rats for at least 90 days resulted in reduced bodyweight gain in the 60 mg Mo/kg bw/day animals. The effect was more severe in males. In males, this may have been due in part to slightly reduced food intake. Light microscopy evaluation of control and 60 mg Mo/kg bw/day animals identified test substance-related findings in the kidneys (slight diffuse hyperplasia of the proximal tubules) of two 60 mg Mo/kg bw/day females which recovered following up to 60 days after completion of dosing. No adverse effects were observed on the gonads, oestrous cycles or sperm analyses in any of the treated animals.

A NOAEL was determined to be 17 mg Mo/kg bw/day based on the effects on body weights and kidneys seen at 60 mg Mo/kg bw/day. The NOAEL for testicular (or gonadal) and sperm and oestrous cycle effects is > 60mg Mo/kg bw/day.

 

13-weeks, rats: No treatment-related effects on mortality, clinical signs, final mean body weights, organ weights, haematology or clinical chemistry parameters, sperm counts or motility and liver copper concentrations were observed. No treatment-related gross or microscopic lesions were observed. Thus, the concentration of 100 mg/m³ represents a NOEC in this 13-week inhalation study on rats because no adverse effects were seen up to and including the highest concentration tested.

 

2-Ethylhexanoic acid

In a 90-day repeated dose toxicity study in rats and mice with 2-ethylhexanoic acid, a diet 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.

 

2-ethylhexanoic acid, molybdenum salt

Since no repeated dose toxicity study is available specifically for2-ethylhexanoic acid, molybdenum salt, information on the individual constituents molybdate and 2-ethylhexanoic acid will be used for the hazard assessment and when applicable for the risk characterisation of 2-ethylhexanoic acid, molybdenum salt.

 

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Information from read-across substances:
animal data for molybdenum: NOAEL(rat)=17 mg Mo/kg bw/day
animal data for 2-ethylhexanoic acid: NOAEL(rat)=300 mg/kg bw/day, NOAEL(mice)=200 mg/kg bw/day

Justification for classification or non-classification

Considering the read-across principles as detailed above for 2-ethylhexanoic acid, molybdenum salt based on the toxicological assessment of the individual constituents, 2-ethylhexanoic acid, molybdenum salt does not need classification for Specific target organ toxicity-repeated exposure.