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Toxicological information

Direct observations: clinical cases, poisoning incidents and other

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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: Not applicable as this is a 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. 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 Type:
publication
Title:
Boric acid poisoning: A report of fatal adult case from cutaneous use. A critical evaluation of the use of this drug in dermatologic practice.
Author:
Jordon JW & Crissey JT
Year:
1957
Bibliographic source:
AMA Archives of Dermatology 75: 720 – 728.

Materials and methods

Study type:
poisoning incident
Endpoint addressed:
repeated dose toxicity: dermal
Test guideline
Qualifier:
according to
Guideline:
other: No data
Deviations:
not specified
Principles of method if other than guideline:
The reference describes a poisoning incident in humans.
GLP compliance:
no
Remarks:
Study pre-dates GLP

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Subjects:
- Number of subjects exposed: 1
- Sex: Female
- Age: 35
Route of exposure:
dermal
Reason of exposure:
intentional
Exposure assessment:
estimated

Results and discussion

Clinical signs:
Except for the discomfort of the skin eruption the patient was otherwise well until shortly before admission when she had become lethargic, chose to remain in bed and became comatose 24 h before admission. On examination the patient was in deep coma. On the entire skin surface there was a generalised erythema with some scaling. There was a cyanotic flush to her face; the extremities exhibited pallor, cyanosis and were cold to the touch. The pupils failed to react to light and accommodation; the tongue was dry and coated. The heart exhibited no murmurs; the blood pressure was unobtainable; the pulse was 120; respirations were 40; the chest was clear; the extremities spastic. The patient was obviously moribund. Laboratory tests performed at the time of admission were as follows. Spinal fluid examination clear, pressure 120 – 140; spinal fluid protein 0.029 g per 100 cc; spinal fluid. Wassermann and colloidal gold test negative. Blood glucose170 mg. Blood Wassermann reaction negative; red blood cell count 4100000; white blood cell count 34000; myelocytes 1; juvenile forms 2; band forms 38; basophils 1, eosinophils 1; lymphocytes 1. Death occurred 14 h after admission to hospital. Post mortem examination showed the following positive findings. The liver and lungs were hyperaemic; microscopic examination of the kidneys showed the glomerular loops to be dilated and filled with blood. The tubules showed degeneration and necrosis. The bone a marrow was hyperplastic, with predominance of the eosinophilic series. Analysis of various organs and fluids for boric acid showed the following per 100 g: Liver, 79 mg; brain 69 mg; urine 525 mg; spinal fluid 95 mg and blood 350 mg.

Applicant's summary and conclusion

Conclusions:
The reference reports a fatal case of boric acid poisoning following the use of the drug in the treatment of a skin condition.
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.