Registration Dossier
Registration Dossier
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EC number: 305-998-4 | CAS number: 95465-85-3
Endpoint summary
Administrative data
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
- 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
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:
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.
Fatty acids, C14-18 and C16-18, unsatd. barium salts is the barium metal salt of Fatty acids, C14-18 and C16-18, unsatd, which readily dissociates to the corresponding metal barium cation and Fatty acids, C14-18 and C16-18, unsatd, anions. The barium cation and the Fatty acids, C14-18 and C16-18, unsatd anion are considered to represent the overall toxicity of Fatty acids, C14-18 and C16-18, unsatd. barium salts 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.
Toxicity for reproduction – effects on fertility
No toxicity data on adverse effects on sexual function and fertility withfatty acids, C14-18 and C16-18, unsatd. barium salts 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 offatty acids, C14-18 and C16-18, unsatd. barium salts and the individual constituents.
|
BaCl2 |
Fatty acids, C14-18 and C16-18-unsatd. |
Fatty acids, C14-18 and C16-18, unsatd. barium salts |
Screening for repro./dev. toxicity (OECD 421/422) |
NOAEL(rat; P) |
not reprotoxic (weight of evidence, human data) not classified |
no data |
Two-generation reproductive toxicity study |
Test proposal |
no data |
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.
Fatty acids, C14-18 and C16-18-unsatd.
(1) A large part of human nutrition consists of oils and fats of vegetable and animal origin. The oils and fats contain a mixture of fatty acids with a chainlength distribution of C6-C24 (vegetable sources) and C4-C22 (animal origin). The oleic acid (C18:1) content of widely used oils and fats makes up to: 36-44% (palm oil), 45.8% (beef fat), 26.6% (cow milk), 45.1% (bacon fat) (Beare-Rogers J,2001)
(2) The Scientific Committee on GRAS Substances (SCOGS) of the U.S. FDA concluded on oleic acid: “There is no evidence in the available information on coconut oil, peanut oil, and oleic acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public as they are now used in paper and cotton packaging material for food at levels now current or as they might reasonably be expected to be used for such purposes in the future. There is no evidence in the available information on linoleic acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used as a nutrient or dietary supplement at levels now current or that might reasonably be expected in the future.” (SCOGS, 1975)
(3) Exposure of breast-fed babies to oleic acid via mother milk: A breast-fed of 3 months age has an average weight of 6.5 kg (WHO 2013) and the infant ingests approx. 180mL/kg bw of milk per day (Riordan 2001), being 1170 mL for a baby at an age of 3 months. The fat content of mother milk is approx. 4.2% (United Nations 1996), with a content of oleic acid of approx. 32% (total content of C18 fatty acids: C18:0, C18:1, C18:2 and C18:3 = 58.2%) (Finley et al. 1985). This results in a total “exposure” for a 3 month old baby of 15.7 g oleic acid per day, being 2400 mg/kg bw/day.
(4) Substances obtained from natural sources are exempt from the obligation to register (in accordance with Annex V, Section 9). Sincefatty acids, C14-18 and C16-18, unsatdis a substance obtained from natural sources (see point 1 above), thus the chemically unmodified substance is exempt from registration.
Based on the above given arguments, one may safely assume that human exposure towardsfatty acids, C14-18 and C16-18, unsatd.exerts any adverse effects of toxicological relevance after acute or chronic exposure is grossly implausible.
Fatty acids, C14-18 and C16-18, unsatd. barium salts
Since notoxicity data on adverse effects on sexual function and fertilityis available for fatty acids, C14-18 and C16-18, unsatd. barium salts, information on the individual constituents barium and fatty acids, C14-18 and C16-18-unsatd. will be used for the hazard assessment and, when applicable, for the risk characterisation of fatty acids, C14-18 and C16-18, unsatd. barium salts. Based on the hazard profile of fatty acids, C14-18 and C16-18-unsatd, effects on the reproductive organs can safely be excluded.
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 fatty acids, C14-18 and C16-18, unsatd. barium salts and the risk assessment will be updated without undue delay.
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 fatty acids, C14-18 and C16-18, unsatd. barium salts 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.
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 fatty acids, C14-18 and C16-18, unsatd. barium salts 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
- 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
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:
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.
Fatty acids, C14-18 and C16-18, unsatd. barium salts is the barium metal salt of Fatty acids, C14-18 and C16-18, unsatd, which readily dissociates to the corresponding metal barium cation and Fatty acids, C14-18 and C16-18, unsatd, anions. The barium cation and the Fatty acids, C14-18 and C16-18, unsatd anion are considered to represent the overall toxicity of Fatty acids, C14-18 and C16-18, unsatd. barium salts 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.
Toxicity for reproduction – developmental toxicity
No toxicity data on adverse effects on development of the offspring with fatty acids, C14-18 and C16-18, unsatd. barium salts 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 genetic toxicity of the individual constituents are given below.
Table: Summary of toxicity data on adverse effects on development of the offspring of fatty acids, C14-18 and C16-18, unsatd. barium salts and the individual constituents.
|
BaCl2 |
Fatty acids, C14-18 and C16-18-unsatd. |
Fatty acids, C14-18 and C16-18, unsatd. barium salts |
Screening for repro./dev. toxicity (OECD 421/422) |
NOAEL(rat; P) |
not reprotoxic (weight of evidence, human data) not classified |
no data |
Pre-natal developmental toxicity study |
Test proposal |
no data |
|
Two-generation reproductive toxicity study |
Test proposal |
no data |
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.
Fatty acids, C14-18 and C16-18-unsatd.
(1) A large part of human nutrition consists of oils and fats of vegetable and animal origin. The oils and fats contain a mixture of fatty acids with a chainlength distribution of C6-C24 (vegetable sources) and C4-C22 (animal origin). The oleic acid (C18:1) content of widely used oils and fats makes up to: 36-44% (palm oil), 45.8% (beef fat), 26.6% (cow milk), 45.1% (bacon fat) (Beare-Rogers J,2001)
(2) The Scientific Committee on GRAS Substances (SCOGS) of the U.S. FDA concluded on oleic acid: “There is no evidence in the available information on coconut oil, peanut oil, and oleic acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public as they are now used in paper and cotton packaging material for food at levels now current or as they might reasonably be expected to be used for such purposes in the future. There is no evidence in the available information on linoleic acid that demonstrates, or suggests reasonable grounds to suspect, a hazard to the public when it is used as a nutrient or dietary supplement at levels now current or that might reasonably be expected in the future.” (SCOGS, 1975)
(3) Exposure of breast-fed babies to oleic acid via mother milk: A breast-fed of 3 months age has an average weight of 6.5 kg (WHO 2013) and the infant ingests approx. 180mL/kg bw of milk per day (Riordan 2001), being 1170 mL for a baby at an age of 3 months. The fat content of mother milk is approx. 4.2% (United Nations 1996), with a content of oleic acid of approx. 32% (total content of C18 fatty acids: C18:0, C18:1, C18:2 and C18:3 = 58.2%) (Finley et al. 1985). This results in a total “exposure” for a 3 month old baby of 15.7 g oleic acid per day, being 2400 mg/kg bw/day.
(4) Substances obtained from natural sources are exempt from the obligation to register (in accordance with Annex V, Section 9). Sincefatty acids, C14-18 and C16-18, unsatdis a substance obtained from natural sources (see point 1 above), thus the chemically unmodified substance is exempt from registration.
Based on the above given arguments, one may safely assume that human exposure towardsfatty acids, C14-18 and C16-18, unsatdexerts any adverse effects of toxicological relevance after acute or chronic exposure is grossly implausible.
Fatty acids, C14-18 and C16-18, unsatd. barium salts
Since no toxicity data on adverse effects on development of the offspring is available for fatty acids, C14-18 and C16-18, unsatd. barium salts, information on the individual constituents barium and fatty acids, C14-18 and C16-18-unsatd. will be used for the hazard assessment and, when applicable, for the risk characterisation of fatty acids, C14-18 and C16-18, unsatd. barium salts. Based on the hazard profile of fatty acids, C14-18 and C16-18-unsatd, effects on the unborn child can safely be excluded.
No information on adverse effects on development of the offspring for barium 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 fatty acids, C14-18 and C16-18, unsatd. barium salts and the risk assessment will be updated without undue delay.
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.
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.
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
