Reaction product of mixed inorganic base and acid resulting in complex boron, potassium, fluoride and potassium fluoride constituents

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

other: Case study

Adequacy of study:

supporting study

Study period:

No data

Reliability:

other: Case study

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Not applicable as this is a case study. This study is conducted on an analogue substance. Read-across is justified on the following basis: In aqueous solutions at physiological and acidic pH, low concentrations of simple inorganic borates such as boric acid, disodium tetraborate decahydrate, disodium tetraborate pentahydrate, boric oxide and disodium octaborate tetrahydrate will predominantly exist as undissociated boric acid. At about pH 10 the metaborate anion (B(OH)4-) becomes the main species in solution (WHO, 1998). This leads to the conclusion that the main species in the plasma of mammals and in the environment is un-dissociated boric acid. Since other borates dissociate to form boric acid in aqueous solutions, they too can be considered to exist as un-dissociated boric acid under the same conditions. For comparative purposes, exposures to borates are often expressed in terms of boron (B) equivalents based on the fraction of boron in the source substance on a molecular weight basis. Some studies express dose in terms of B, whereas other studies express the dose in units of boric acid. Since the systemic effects and some of the local effects can be traced back to boric acid, results from one substance can be transferred to also evaluate the another substance on the basis of boron equivalents. Therefore data obtained from studies with these borates can be read across in the human health assessment for each individual substance. Conversion factors are given in the table below. Conversion factor for equivalent dose of B Boric acid H3BO3 0.175 Boric Oxide B2O3 0.311 Disodium tetraborate anhydrous Na2B4O7 0.215 Disodium tetraborate pentahydrate Na2B4O7•5H2O 0.148 Disodium tetraborate decahydrate Na2B4O7•10H2O 0.113 Disodium octaborate tetrahydrate Na2B8O13•4H2O 0.210 Sodium metaborate (anhydrous) NaBO2 0.1643 Sodium metaborate (dihydrate) NaBO2•2H2O 0.1062 Sodium metaborate (tetrahydrate) NaBO2•4H2O 0.0784 Sodium pentaborate (anhydrous) NaB5O8 0.2636 Sodium pentaborate (pentahydrate) NaB5O8∙5H2O 0.1832 References: WHO. Guidelines for drinking-water quality, Addendum to Volume 1, 1998.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Enquiries to a centre for information on poisoning during a period of 12 years (Boraks er de farlight (12 ars foresporgslert il giftinformationscentralen).

Author:

Abelhardt & Fogh A

Year:

1983

Bibliographic source:

Ugeskr. Laeger 145: 3808 - 3810.

Reference 2

Reference Type:

publication

Title:

Poisoning: Toxicology, symptoms, treatments.

Author:

Arena JM & Drew RH

Year:

1986

Bibliographic source:

Thomas Springfield, IL: P131.

Reference 3

Reference Type:

publication

Title:

Ingestion of boric acid by infants.

Author:

Baker MD & Bogema SC

Year:

1986

Bibliographic source:

Am. J. Emerg. Med. 4: 358.

Reference 4

Reference Type:

publication

Title:

Boric acid poisoning treated by exchange transfusion; report of a case.

Author:

Boggs TR & Anrode HG

Year:

1955

Bibliographic source:

Pediatrics 16: 109.

Reference 5

Reference Type:

publication

Title:

Boric acid poisoning in an infant.

Author:

Connelly JP, Crawford JD & Soloway AH

Year:

1958

Bibliographic source:

New England Journal of Medicine. 259: 1123.

Reference 6

Reference Type:

publication

Title:

Hazard assessment of boric acid in toys.

Author:

Craan AG, Myers AW & Green DW

Year:

1997

Bibliographic source:

Reg. Tox. Pharmacol. 26: 271 - 280.

Reference 7

Reference Type:

publication

Title:

Inorganic boron health effects in humans: An aid to risk assessment and clinical judgement.

Author:

Culver BD & Hubbard SA

Year:

1996

Bibliographic source:

J. Trace. Elements in Experimental Medicine 9: 175 - 184.

Reference 8

Reference Type:

publication

Title:

Un cas de dermatite exfoliante palmaire condsecutivea l'inestion d'acide borique.

Author:

Desage M

Bibliographic source:

Societe des Sciences Medicales et Biologique de Montpellier et du Languedoc Mediteranneen, Archives (bull. Soc. Sci. Med. Biol. (Montpellier) 4: 154.

Reference 9

Reference Type:

publication

Title:

Reevaluation de la toxicite des sodium borates. A propos de 134 observations au CAP de Paris.

Author:

Elmalem J, Efthymious ML & Fournier E

Year:

1984

Bibliographic source:

Toxicol. Med. 4: 317 - 325.

Reference 10

Reference Type:

publication

Title:

Boric acid poisoning in infants; cases observed at the Rome Pediatric Centre from 1958 - 1968.

Author:

Giadini O & Cardi E

Year:

1970

Bibliographic source:

Minerva Pediatr. 22: 1723 - 1726.

Materials and methods

Study type:

poisoning incident

Endpoint addressed:

not applicable

Test guideline

Qualifier:

according to guideline

Guideline:

other: No data

Deviations:

not specified

Principles of method if other than guideline:

This is a summary of accidental or intentional poisoning incidents for humans.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

boric acid and sodium borates

IUPAC Name:

boric acid and sodium borates

Details on test material:

- Name of test material: Boric acid and sodium borates

Method

Subjects:

Males and females of various ages.

Route of exposure:

other: Not specified

Reason of exposure:

other: Accidental misuse as an antiseptic or as a treatment for conditions such as epilepsy. Also, misuse in the preparation of baby formula and the topical use of boric acid powder in infant has led to poisonings.

Exposure assessment:

not specified

Results and discussion

Clinical signs:

A review was carried out of 784 cases of boric acid ingestions from two poison control centres in the USA for the period 1981-1985. No patients developed severe toxicity symptoms, and 88 % of these cases were asymptomatic. Less severe common symptoms were vomiting, lethargy and diarrhoea. The authors concluded that acute boric acid ingestions produced minimal or no toxicity and that aggressive treatment is not necessary in most patients. No fatalities or severe manifestations of toxicity were observed, despite ingestions of up to 89 g.

All the case studies for both acute and chronic (adults and children) show a common range of symptoms that occur on exposure to boric acid and sodium borates. The most commonly seen symptoms are nausea, diarrhoea, vomiting and skin rashes (dermatitis). Acutely, in adults, as administered dose increases from a dose of 2 – 3 g boric acid (29 – 43 mg boric acid/kg), or more, symptoms may include nausea, vomiting, diarrhoea, gastric discomfort, skin flushing, excitation, convulsions, depression and vascular collapse. In addition, cases where no real estimate of dose can be made, similar symptoms have been noted and especially vomiting and GI tract effects as the first symptom. In an extensive review by Kliegel (1980), single doses as low as 2-4 g have produced symptoms of vomiting and/or diarrhoea. In children, similar doses seem to produce the same symptoms. In the literature, the oral lethal dose is regularly quoted as of 2-3 g boric acid for infants, 5-6 g boric acid for children and 15-30 gm boric acid for to adults. Doses of 1-3 g have been reported as producing severe symptoms in infants (origin possibly McNally and Rust, 1928, McNally, and Rukstinat, 1947). However, there are cases where higher levels do not cause any serious effects, although medical intervention may have helped prevent the more severe symptoms (e.g. 88.8 g reported in Litovitz et al, 1988).

With chronic exposure in adults the symptoms seen most frequently at doses below around 3 g/day were dermatitis, nausea and in many cases vomiting, diarrhoea and indigestion. Doses above 3 –5 g/day regularly caused vomiting and/or diarrhoea in the first instance often accompanied by dermatitis and appetite suppression. As the dose became higher and the dosing period longer, symptoms of alopecia, disseminated maculopapular eruption followed by widespread desquamation and focal or generalised central nervous system irritation or convulsions occurred. The symptoms of dermatitis, nausea, diarrhoea and vomiting symptoms also occurred in some patients receiving doses of 2 g boric acid/day (29 mg boric acid/kg/day) and above. In one such case, reduction of the dose from 2 g/day of boric (29 mg boric acid/kg/day) acid to 1g/day (14 mg boric acid/kg/day) resulted in resolution of the effects (vomiting and dermatitis). In all cases where withdrawal of treatment was reported, recovery occurred with no lasting effects. The lowest recorded adult dose causing symptoms was 2 g/day boric acid.

In children, where low levels can be estimated, (Gordon et al, 1973 and O'Sullivan and Taylor, 1983), infants aged from 6 to 19.5 weeks ingested borax (as a honey-borax mixture which had been applied to pacifiers) for periods of 4 to 12 weeks. The mean intake was 0.98 g boric acid/day (range 0.55g to 2 g) for a 10 kg child. The effects seen, which disappeared on withdrawal of the honey-borax mixture, were of central nervous system signs, convulsions, generalized seizures and focal seizures. There were no dermal effects. Minor occurrences of vomiting and loose stools were also described. Further support for the initial symptoms of diarrhoea, vomiting, nausea as a result of exposure to boric acid or sodium borates comes from cases where patients have had sodium borates used as antiseptics for wound and body washes. The absorbed dose cannot be estimated. The first symptoms seen are GI effects including vomiting and diarrhoea indicating that the early effects of absorption of boric acid or sodium borates are vomiting. Similarly, in cases where infants have been liberally treated with neat boric acid powder on severe nappy rash or eczema (reviewed in Valdes-Dapena & Arey, 1962 and Gold 1949) which resulted in death in many cases, the early symptoms included vomiting and diarrhoea.

Results of examinations:

A review was carried out of 784 cases of boric acid ingestion from two poison control centres in the USA for the period 1981-1985. No patients developed severe toxicity symptoms, and 88 % of these cases were asymptomatic. Less severe common symptoms were vomiting, lethargy and diarrhoea. The authors concluded that acute boric acid ingestion produced minimal or no toxicity and that aggressive treatment is not necessary in most patients. No fatalities or severe manifestations of toxicity were observed, despite ingestion of up to 89 g.

All the case studies for both acute and chronic (adults and children) show a common range of symptoms that occur on exposure to boric acid and sodium borates. The most commonly seen symptoms are nausea, diarrhoea, vomiting and skin rashes (dermatitis). Acutely, in adults, as administered dose increases from a dose of 2 – 3 g boric acid (29 – 43 mg boric acid/kg), or more, symptoms may include nausea, vomiting, diarrhoea, gastric discomfort, skin flushing, excitation, convulsions, depression and vascular collapse. In addition, cases where no real estimate of dose can be made, similar symptoms have been noted and especially vomiting and GI tract effects as the first symptom. In an extensive review by Kliegel (1980), single doses as low as 2-4 g have produced symptoms of vomiting and/or diarrhoea. In children, similar doses seem to produce the same symptoms. In the literature, the oral lethal dose is regularly quoted as of 2-3 g boric acid for infants, 5-6 g boric acid for children and 15-30 gm boric acid for to adults. Doses of 1-3 g have been reported as producing severe symptoms in infants (origin possibly McNally and Rust, 1928, McNally, and Rukstinat, 1947). However, there are cases where higher levels do not cause any serious effects, although medical intervention may have helped prevent the more severe symptoms (e.g. 88.8 g reported in Litovitz et al, 1988).

With chronic exposure in adults the symptoms seen most frequently at doses below around 3 g/day were dermatitis, nausea and in many cases vomiting, diarrhoea and indigestion. Doses above 3 –5 g/day regularly caused vomiting and/or diarrhoea in the first instance often accompanied by dermatitis and appetite suppression. As the dose became higher and the dosing period longer, symptoms of alopecia, disseminated maculopapular eruption followed by widespread desquamation and focal or generalised central nervous system irritation or convulsions occurred. The symptoms of dermatitis, nausea, diarrhoea and vomiting symptoms also occurred in some patients receiving doses of 2 g boric acid/day (29 mg boric acid/kg/day) and above. In one such case, reduction of the dose from 2 g/day of boric (29 mg boric acid/kg/day) acid to 1g/day (14 mg boric acid/kg/day) resulted in resolution of the effects (vomiting and dermatitis). In all cases where withdrawal of treatment was reported, recovery occurred with no lasting effects. The lowest recorded adult dose causing symptoms was 2 g/day boric acid.

In children, where low levels can be estimated, (Gordon et al, 1973 and O'Sullivan and Taylor, 1983), infants aged from 6 to 19.5 weeks ingested borax (as a honey-borax mixture which had been applied to pacifiers) for periods of 4 to 12 weeks. The mean intake was 0.98 g boric acid/day (range 0.55g to 2 g) for a 10 kg child. The effects seen, which disappeared on withdrawal of the honey-borax mixture, were of central nervous system signs, convulsions, generalized seizures and focal seizures. There were no dermal effects. Minor occurrences of vomiting and loose stools were also described. Further support for the initial symptoms of diarrhoea, vomiting, nausea as a result of exposure to boric acid or sodium borates comes from cases where patients have had sodium borates used as antiseptics for wound and body washes. The absorbed dose cannot be estimated. The first symptoms seen are GI effects including vomiting and diarrhoea indicating that the early effects of absorption of boric acid or sodium borates are vomiting. Similarly, in cases where infants have been liberally treated with neat boric acid powder on severe nappy rash or eczema (reviewed in Valdes-Dapena & Arey, 1962 and Gold 1949) which resulted in death in many cases, the early symptoms included vomiting and diarrhoea.

Applicant's summary and conclusion

Conclusions:

All the case studies for both acute and chronic (adults and children) show a common range of symptoms that occur on exposure to boric acid and sodium borates. The most commonly seen symptoms are nausea, diarrhoea, vomiting and skin rashes (dermatitis). Acutely, in adults, as administered dose increases from a dose of 2 – 3 g boric acid (29 – 43 mg boric acid/kg), or more, symptoms may include nausea, vomiting, diarrhoea, gastric discomfort, skin flushing, excitation, convulsions, depression and vascular collapse. In addition, cases where no real estimate of dose can be made, similar symptoms have been noted and especially vomiting and GI tract effects as the first symptom.
Read-across is justified on the basis detailed in the rationale for reliability above. This study is therefore considered to be of sufficient adequacy and reliability to be used as a supporting study and no further testing is justified.