Barium neodecanoate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

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.

 

Barium neodecanoate is the barium metal salt of neodecanoic acid, which readily dissociates to the corresponding divalent barium cation and neodecanoic acid anions. The barium cation and the neodecanoic acid anion are considered to represent the overall toxicity of the barium neodecanoate 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.

 

Introduction to the neoacids hazard assessment

The carboxylic acids “neodecanoic acid” and “fatty acid C9 to C13 neo” are considered similar in their toxicological profile and are therefore grouped together. Both neoacids originate from the same production process in which a branched olefin is reacted with carbon monoxide and water at elevated temperature and pressure in th1e presence of an acid as catalytic component. The dossiers for neodecanoic acid and fatty acid C9 to C13 neo contain human health hazard information on both substances indicating that the toxicological profile is similar. This approach was also used and accepted in the US EPA HPV programme, even for a wider range of neo-acid substances (US EPA, April 2009: http://www.epa.gov/chemrtk/pubs/summaries/neoc528/c13335tc.htm).

Based on the above information “neodecanoic acid” and “fatty acid C9 to C13 neo” will be assessed for their hazardous properties, using the same dataset for both substances.

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.

Toxicity for reproduction– effects on fertility

No toxicity data on adverse effects on sexual function and fertility with barium neodecanoate are available, thus the reproductive toxicity will be addressed with existing data on the dissociation products as detailed in the table below. Further details on the reproductive toxicity of the individual constituents are given below.

 

Table: Summary of toxicity data on adverse effects on sexual function and fertility of barium neodecanoate and the individual constituents.

	BaCl2 (CAS# 10361-37-2)	Neodecanoic acid (CAS# 26896-20-8)	Barium neodecanoate (CAS# 55172-98-0)
Screening for repro./dev. toxicity (OECD 421/422)	NOAEL(rat; P) = 4000 ppm NOAEL(rat; F1) = 100 mg/kg bw/day	No data	No data
Two-generation reproductive toxicity study	Test proposal	NOAEL(3-gen;rat, P, F1 and F2)= 75 mg/kg bw/day* (read-across)   not classified	No data

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

 

Barium

Only two studies (NTP and Dietz) exist in which a dose-response relationship of different adverse effects after oral administration of barium chloride was investigated. Thus, the studies which were published in peer-reviewed journals were examined with respect to their adequacy for the derivation of NOAEL/LOAEL values for fertility impairment.

Based on these limited investigations with barium chloride as described above, a lack of adequate, guideline conform data must be noted. Tentatively, the premating study by Dietz et al. (1992) on rats and mice may be considered as the only acceptable study for the derivation of a preliminary NOAEL for fertility effects of soluble barium compounds. This study investigated the occurrence of different adverse effects in male and female rats and mice and their offspring related to barium chloride exposure via drinking water. A tentative NOAEL for fertility impairment of 4,000ppm in rats and 2,000 ppm in mice can be derived.

 

Neodecanoic acid

In a modified three-generation reproductive toxicity study, male and female Sprague-Dawley rats were administered neodecanoic acid at 0, 100, 500 and 1500 ppm (approximately 0, 5, 25 and 75 mg/kg-bw/day, respectively) in the diet. No adverse effects were observed on survival, appearance, behaviour, body-weight gain and food consumption in the parental, F1 or F2 generations. The reproductive performance of the parents was not affected. No treatment-related gross or microscopic pathological findings were observed at any of the dietary levels.

 

Barium neodecanoate

Since no study on the reproductive toxicity for barium neodecanoate is available, information on the individual constituents barium and neodecanoic acid will be used for the hazard assessment and when applicable for the risk characterisation of barium neodecanoate. For the purpose of hazard assessment of barium neodecanoate, the point of departure for the most sensitive endpoint of each constituent will be used for the DNEL derivation. In case of neodecanoic acid in barium neodecanoate, the NOAEL of 75 mg/kg bw/day obtained out of a 3-generation reproductive toxicity study will be used.

 

No information for barium on adverse effects on sexual function and fertility is available, adequate for risk assessment and classification and labelling purposes. A test proposal was issued by the lead registrant for a readily bioavailable barium substance.Upon availability of the testing results for barium chloride, the registrant ensures that the dossier for barium neodecanoate and the risk assessment will be updated without undue delay.

 

For the purpose of hazard assessment of barium neodecanoate, the point of departure for the most sensitive endpoint of each constituent will be used for the DNEL derivation. In case of neodecanoic acid in barium neodecanoate, the NOAEL of 75 mg/kg bw/day for the reproductive toxicity will be used.

Short description of key information:
A testing proposal for a two generation study was issued by the lead registrant for a readily bioavailable barium substance. The dossier for barium neodecanoate will be updated, when the testing result for barium chloride is available.

Justification for selection of Effect on fertility via oral route:
Information from read-across substances:
No data available for barium: a testing proposal for a two-generation study is included in the reference dossier.
Animal data for neodecanoic acid: NOAEL(rat, P)=75mg/kg bw/day

Effects on developmental toxicity

Description of key information

A testing proposal for a developmental toxicity study was issued by the lead registrant for a readily bioavailable barium substance. The dossier for barium neodecanoate will be updated, when the testing result for barium chloride is available.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

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.

 

Barium neodecanoate is the barium metal salt of neodecanoic acid, which readily dissociates to the corresponding divalent barium cation and neodecanoic acid anions. The barium cation and the neodecanoic acid anion are considered to represent the overall toxicity of the barium neodecanoate 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.

 

Introduction to the neoacids hazard assessment

The carboxylic acids “neodecanoic acid” and “fatty acid C9 to C13 neo” are considered similar in their toxicological profile and are therefore grouped together. Both neoacids originate from the same production process in which a branched olefin is reacted with carbon monoxide and water at elevated temperature and pressure in th1e presence of an acid as catalytic component. The dossiers for neodecanoic acid and fatty acid C9 to C13 neo contain human health hazard information on both substances indicating that the toxicological profile is similar. This approach was also used and accepted in the US EPA HPV programme, even for a wider range of neo-acid substances (US EPA, April 2009: http://www.epa.gov/chemrtk/pubs/summaries/neoc528/c13335tc.htm).

Based on the above information “neodecanoic acid” and “fatty acid C9 to C13 neo” will be assessed for their hazardous properties, using the same dataset for both substances.

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.

Toxicity for reproduction – developmental toxicity

No toxicity data on adverse effects on development of the offspring with barium neodecanoate are available, thus the reproductive toxicity will be addressed with existing data on the dissociation products as detailed in the table below. Further details on the reproductive toxicity of the individual constituents are given below.

 

Table: Summary of toxicity data on adverse effects on development of the offspring of barium neodecanoate and the individual constituents.

	BaCl2 (CAS# 10361-37-2)	Neodecanoic acid (CAS# 26896-20-8)	Barium neodecanoate (CAS# 55172-98-0)
Screening for repro./dev. toxicity (OECD 421/422)	NOAEL(rat; P) = 4000 ppm NOAEL(rat; F1) = 100 mg/kg bw/day	No data	No data
Pre-natal developmental toxicity study	Test proposal	NOAEL(rat)=250mg/kg bw/day   not classified	No data
Two-generation reproductive toxicity study	Test proposal	NOAEL(3-gen;rat, P, F1 and F2)= 75 mg/kg bw/day* (read-across)   not classified	No data

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

 

Barium

Guideline-conform prenatal developmental toxicity studies (according to OECD TG 414) via the oral route in any species are not available.

Tentative NOAEL values for developmental toxicity of 4,000 ppm and 2,000 ppm for rats and mice, respectively, are reported in the study by Dietz et al. (1992). However, these NOAELs are of limited value to evaluate the potential for barium to induce developmental effects because the study design did not include prenatal exposure of the female animals to barium chloride. Therefore, this study has to be considered as inadequate for the assessment of the potential to induce developmental toxicity and cannot be used in a regulatory context.

 

Neodecanoic acid

In developmental toxicity study, pregnant rats, n=22 per dose, were treated by oral gavage to 50, 250, 600 or 800 mg/kg/day neoheptanoic acid, a substance similar in structure to neodecanoic acid, during gestation days 6-15. On gestation day 21, the dams were euthanized and the pups were examined for signs of developmental toxicity. Under the conditions of the experimental methods, the test material produced maternal toxicity at dose levels of 600 and 800 mg/kg with maternal lethality at 800 mg/kg. The test material was severely embryotoxic at 800 mg/kg with less than 20% of embryos surviving. Offspring of the 800 mg/kg group had reduced body weight, reduced crown-rump distance, displayed variations signifying delayed development, and a significant percentage (25%) were malformed. In the 600 mg/kg group, there was an increase number of dams with 3 or more resorptions. Offspring of the 600 mg/kg group displayed significant incidences of major (hydrocephalus) and minor (knobby or angular ribs, extra lumbar vertebrae) malformations but showed few signs of delayed development and were not runted. There was no statistically significant evidence of maternal toxicity at dose levels of 50 or 250 mg/kg. There was a slight, but not statistically significant, increase in embryonic resorption noted for the 250 mg/kg group. There was no statistically significant evidence of developmental toxicity at doses for 50 or 250 mg/kg. The NOAEL for maternal toxicity is 250 mg/kg and the NOAEL for developmental toxicity is 250 mg/kg. 

 

Barium neodecanoate

No information for barium on adverse effects on development of the offspring is available, adequate for risk assessment and classification and labelling purposes. A test proposal was issued by the lead registrant for a readily bioavailable barium substance.Upon availability of the testing results for barium chloride, the registrant ensures that the dossier for barium neodecanoate and the risk assessment will be updated without undue delay.

 

Information on the individual constituents barium and neodecanoic acid will be used for the hazard assessment and, when applicable, for the risk characterisation of barium neodecanoate. For the purpose of hazard assessment of barium neodecanoate, the point of departure for the most sensitive endpoint of each constituent will be used for the DNEL derivation. In case of neodecanoic acid in barium neodecanoate, the NOAEL of 75 mg/kg bw/day for the reproductive toxicity will be used.

Justification for selection of Effect on developmental toxicity: via oral route:
Information from read-across substances:
No data available for barium: a testing proposal for a prenatal developmental toxicity study is included in the reference dossier.
Animal data for neodecanoic acid: NOAEL(rat)=250mg/kg bw/day

Justification for classification or non-classification

The classification and labelling will be postponed till the results of the two generation study and the developmental toxicity study are available.