Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: Expert review and assessment
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Not assignable as the result is from expert assessment.

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Objective of study:
other: Basic toxicokinetic assessment to support REACH registration
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Expert review of available data.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Test material form:
liquid
Remarks:
clear colourless
Details on test material:
UVCB
At room temperature protected from light
31 March 2018 (expiry date)

Results and discussion

Any other information on results incl. tables

Toxicokinetic Assessment ofReaction products of monoethanolamine and boric acid (1:3)EC#701-024-0.

 

The following assessment of the toxicokinetic profile of Reaction products of monoethanolamine and boric acid (1:3), EC#701-024-0 is based on the physical chemical properties and toxicity data on the substance. No experimentally derived ADME data are available for this substance.

 

Substance Characterization

Analytical characterizations show that this substance meets the definition of a UVCB. This substance is a clear colorless to pale yellow liquid at ambient laboratory temperature (20°C)andonly exists in aqueous solution. It exists in a constant state of equilibrium and attempts to remove the water result in a shift of equilibrium, and a change in the nature of the molecule.The idealized molecular formula is given as C2H7NO.xBH3O3 and the MW is a minimum of 122.92, but the reality is too complex to define. Further information about the chemical species potentially present at any one time is appended in the Category Justification Document.

 

Physical Chemical Properties

Molecular weight, water solubility, log Kow, and vapour pressure are key physical chemical properties for assessing the toxicokinetics of a substance. This substance is a liquid. The substance is highly soluble in water (infinite according to OECD 202 study) and the partition coefficient (log Pow) of Reaction products of monoethanolamine and boric acid (1:3) in an OECD 107 study under GLP conditions at 19.7°C, pH 7 was -0.9 for the polyborate moiety and -2.5 for the organic moiety. The determined log Pow values were within the acceptable range of ± 0.3 log units. The substance has a negligible vapour pressure (< 1.3 x 10(-8) Pa and < 3.9 x 10(-8) Pa at 20°C (293K) and 25°C (298K) respectively).

 

Exposure Routes

The dermal contact route is considered to be the primary route of occupational exposure due to its use and physico-chemical properties. Inhalation exposure is expected to be limited because this substance has a negligible vapour pressure. The potential for oral exposure is very limited due to the majority of the volume being used in either an industrial or professional setting with the lead dossier supporting only a single consumer use (fertilizers).

 

Absorption

Dermal

The dermal absorption of the main components of this UVCB substance is expected to be very limited because of the high solubility in water and low lipid solubility. ECHA endpoint specific guidance chapter R.7C indicates that substances with a MW <100 are favored for absorption (this substance has a MW >100), and given that water solubility is >10g/L and a Log PoW <0, the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Consequently, absorption via the dermal route is expected to be very low, which is supported by the toxicity data.

 

Based on read-across to the Reaction products of monoethanolamine and boric acid (1:1), in a skin irritation study with an exposure period of 4 hours there was no evidence of skin irritation in either of three female rabbits. In an eye irritation study the substance itself was shown to be non-irritant. The results of an acute dermal toxicity study in rats indicate that dermal absorption of this substance is, as expected, very limited. Animals were given a single dermal dose of 2000 mg/kg for a 24-hour exposure period and observed for systemic and local effects for 14 days. No evidence of systemic toxicity was observed and there were no premature deaths. Slight to moderate erythema was noted at the test sites of the animals up to 3 days after exposure and all signs of irritation has disappeared by day 8. Animals showed expected gains in bodyweight over the study period, except for one female which showed no bodyweight gain during the first week but the expected gain in bodyweight during the second week, and another female which showed the expected bodyweight gain during the first week but a slight loss in bodyweight during the second week. In a Buehler sensitisation test the substance was shown to be a non-sensitizer when tested at 100% (induction concentration) and 100% in PEG400 (challenge concentration).

 

Based on the toxicological evidence, the test substance is not likely to be absorbed following dermal application.

 

Oral

Absorption in the gastrointestinal tract is predominantly influenced by the water solubility, ionization state, lipophilicity, and molecular weight of a chemical. This UVCB substance is highly soluble in water and has a very low lipid solubility (log Kow -0.9 to -2.5), which is outside the range of -1 to 4 that is considered favorable for absorption, even though the molecular weight is below that which may permit passage through aqueous pores (e.g., <200). The results of an acute oral toxicity study indicate no evidence of systemic toxic effects at a dose level of 2,000 mg/kg, which may be because the substance is not absorbed or because of low intrinsic toxicity. The physicochemical properties suggest low absorption is probable, and thein vitromammalian cell assays suggest that the substance has low intrinsic toxicity.In vitrostudies with five strains of bacteria show that the substance is not toxic toSalmonella typhimuriumandEscherichia coliat the highest concentration 5,000 ug/plate, either with or without metabolic activation. In vitro studies with mammalian cells showed that the substance was not significantly toxic to human lymphocytes at the highest recommended concentration of 5,000 ug/mL in the presence of S9.

 

It is therefore considered that absorption via the oral route is likely to be very low.

 

Inhalation  

The substance is a liquid and has a negligible vapour, therefore the potential for inhalation exposure via vapour is highly unlikely.

 

 

Distribution

Once this UVCB substance (or at least the absorbable components) is absorbed, it is expected to be circulated via the blood to the liver and other tissues. Due to its strong hydrophilic nature it is predicted not to be absorbed by cells of the organs and tissues that it contacts except for the kidney. Therefore, the substance is highly unlikely to bioaccumulate because of its very low lipid solubility.

 

Metabolism

The absorbed components of this UVCB substance are expected to be unlikely to be metabolised by intracellular enzymes because the low lipophilicity of the substance will limit entry to cells. Metabolism is therefore expected to be minimal.

 

Elimination

Because of the physicochemical characteristics of this substance any absorbed material is expected to be excreted rapidly via the kidneys and non-absorbed material will be excreted via the feces.

Applicant's summary and conclusion

Conclusions:
No toxicokinetic (absorption, metabolism, distribution, elimination) data is available for MEA-Polyborate. Available data is primarily physico-chemical properties that influence the absorption and distribution of the substance in the body. Both 1:1 and 1:3 mole ratios of MEA to boric acid are infinitely soluble in water with log Pow of -0.9 for the polyborate moiety by ICP-MS and log Pow of -2.5 for the organic moiety by LC-MS. The log P values indicate that both ratios of MEA-Polyborate will likely be 100% absorbed in the gastrointestinal track, primarily found in the blood serum and excreted primarily via the kidneys in the urine. The log P values also indicate that both ratios of MEA-Polyborate is poorly absorbed through the skin with dermal absorption rates similar to monoethanolamine. No data is available on the metabolism of MEA-Polyborate.