Reaction products of boric acid and calcium dihydroxide and lithium hydroxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

A toxicokinetic assessment was performed based on data available for dilithium tetraborate as well as for calcium metaborate. Based on the physical/chemical properties of dilithium tetraborate as well as for calcium metaborate, absorption factors for this substance are derived to be 100% (oral), 100% (inhalation of aqueous aerosols) and 0.5% (dermal absorption from aqueous solutions) for risk assessment purposes. The bioaccumulation potential is expected to be low.
As Reaction products of boric acid and calcium dihydroxide and lithium hydroxide has similar physicochemical properties ie. low vapour pressure and soluble in water then it is expected that the toxicokinetics assessment would be similar for Reaction products of boric acid and calcium dihydroxide and lithium hydroxide especially since all absorption factors derived were based on evidence for boric compounds such as boric acid. The inorganic borates, will be converted to boric acid at physiological pH in the aqueous layer on the surfaces of the mucosa. Boric acid is known to be readily taken up from the gastrointestinal tract in rats and humans, as demonstrated by experimental evidence in both human and animal studies, where more than 90% of the administered dose of borate was excreted as boric acid.
The target UVCB substance has a higher precursor molar ratio for lithium hydroxide than for calcium hydroxide, and therefore the precautionary principle should be applied and read across from dilithium tetraborate where relevant to consider the worst case.
Sufficient evidence therefore exists to propose the same absorption factors for the toxicokinetics assessment. Read-across to dilithium tetraborate is proposed.

Cross-reference

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

Expert report

Type of information:

other: Expert report

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

no guideline followed

Principles of method if other than guideline:

Theoretical statement based on literature data.

Specific details on test material used for the study:

Identification: Dilithium tetraborate
Molecular formula: B4Li2O7
Molecular weight: 169.12
Chemical structure
CAS Number: 12007-60-2
EC number 234-514-3
Purity: 99.3%

Details on test animals or test system and environmental conditions:

Not applicable.

Duration and frequency of treatment / exposure:

Not applicable.

No. of animals per sex per dose / concentration:

Not applicable.

Positive control reference chemical:

Not applicable.

Details on study design:

Not applicable.

Details on dosing and sampling:

Not applicable.

Statistics:

Not applicable.

Details on absorption:

ORAL EXPOSURE - Dilithium tetraborate is very soluble in water (141.2 g/L) and is therefore expected to readily dissolve into the gastrointestinal fluids. Upon solution, the substance is expected to dissociate into lithium ions and a tetraborate ion. Before being absorbed, inorganic borates can be converted to boric acid at physiological pH in the aqueous layer on the surfaces of the mucosa. Boric acid is known to be readily taken up from the gastrointestinal tract in rats and humans, as demonstrated by experimental evidence in both human and animal studies, where more than 90% of the administered dose of borate was excreted as boric acid. Taking all aspects into account, for risk assessment purposes, oral absorption of dilithium tetraborate is set at 100%.Absorbed lithium ions are expected to be excreted unchanged via urine.
DERMAL EXPOSURE - Based on existing evidence related to the very low uptake through intact skin of boric compounds, dermal absorption rate of 0.5% has been put forward for risk assessment purposes. However, it has been suggested that for borates, the absorption could be lower than 0.5%. Furthermore, since the substance is not corrosive or irritating to the skin, it is likely that skin integrity will remain intact upon exposure. The dermal absorption of dilithium tetraborate for risk assessment purposes is therefore set at 0.5%.
INHALATION EXPOSURE -It is possible that aerosols are formed which can enter the lungs. The deposition pattern in the lung can be determined based on its distribution, although shape and electrostatic properties can influence this as well. Since aerosols are expected to be very small, they may reach the thoracic region and the alveolar region of the respiratory tract. Overall it is expected that the exposure via inhalation will be very limited. However, if an aqueous aerosol of the substance reaches the lung regions, dilithium tetraborate is likely to dissolve in the mucus lining the respiratory tract and to get absorbed due to its high water solubility and moderate molecular weight. Based on the above data, for risk assessment purposes the inhalation absorption of aqueous dilithium tetraborate aerosols is set at 100%.

Details on distribution in tissues:

Based on the fact that the boron will be present uncharged and as a small molecule, even distribution of the ions throughout the soft tissues of the body is expected. Due to its water solubility, small size and inorganic nature, significant accumulation in adipose tissue is not expected.

Details on excretion:

Absorbed lithium ions are expected to be excreted unchanged via urine.

Metabolites identified:

not measured

Details on metabolites:

Not applicable.

Bioaccessibility (or Bioavailability) testing results:

Not applicable.

Conclusions:

A toxicokinetic assessment was performed based on the available data of dilithium tetraborate. Based on the physical/chemical properties of dilithium tetraborate, absorption factors for this substance are derived to be 100% (oral), 100% (inhalation of aqueous aerosols) and 0.5% (dermal absorption from aqueous solutions) for risk assessment purposes. The bioaccumulation potential is expected to be low.

Executive summary:

A toxicokinetic assessment was performed based on the available data of dilithium tetraborate. Based on the physical/chemical properties of dilithium tetraborate, absorption factors for this substance are derived to be 100% (oral), 100% (inhalation of aqueous aerosols) and 0.5 % (dermal absorption from aqueous solutions) for risk assessment purposes. The bioaccumulation potential is expected to be low.

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of boric acid and calcium dihydroxide and lithium hydroxide

IUPAC Name:

Reaction products of boric acid and calcium dihydroxide and lithium hydroxide

Applicant's summary and conclusion

Conclusions:

A toxicokinetics assessment was performed using the available data for diltihium tetraborate.
Reaction products of boric acid and calcium dihydroxide and lithium hydroxide is sufficiently similar in terms of physicochemical properties and behaviour upon absorption that the same absorption factors can be used.

Executive summary:

A toxicokinetic assessment was performed based on data available for dilithium tetraborate as well as for calcium metaborate.   Based on the physical/chemical properties of dilithium tetraborate as well as for calcium metaborate, absorption factors for this substance are derived to be 100% (oral), 100% (inhalation of aqueous aerosols) and 0.5% (dermal absorption from aqueous solutions) for risk assessment purposes. The bioaccumulation potential is expected to be low

 

 As Reaction products of boric acid and calcium dihydroxide and lithium hydroxide has similar physicochemical properties ie. low vapour pressure and soluble in water then it is expected that the toxicokinetics assessment would be similar for Reaction products of boric acid and calcium dihydroxide and lithium hydroxide especially since all absorption factors derived were based on evidence for boric compounds such as boric acid.  The inorganic borates, will be converted to boric acid at physiological pH in the aqueous layer on the surfaces of the mucosa. Boric acid is known to be readily taken up from the gastrointestinal tract in rats and humans, as demonstrated by experimental evidence in both human and animal studies, where more than 90% of the administered dose of borate was excreted as boric acid. 

The target UVCB substance has a higher precursor molar ratio for lithium hydroxide than for calcium hydroxide, and therefore the precautionary principle should be applied and read across from dilithium tetraborate where relevant to consider the worst case.

Sufficient evidence therefore exists to propose the same absorption factors for the toxicokinetics assessment. Read-across to dilithium tetraborate is proposed.