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Toxicological information

Direct observations: clinical cases, poisoning incidents and other

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direct observations: clinical cases, poisoning incidents and other
Type of information:
experimental study
Adequacy of study:
key study
2 (reliable with restrictions)

Data source

Reference Type:
Neonatal hypotonia secondary to transplacental bromism
Mangurten H.H. and Ban R.
Bibliographic source:
The Journal of Pediatrics, Vol. 85, No. 3, pp. 426-428.

Materials and methods

Study type:
clinical case study

Test material

Constituent 1
Reference substance name:
Liquid bromide mixture
Liquid bromide mixture
Details on test material:
Mother ingested a liquid bromide mixture which contained 72 g ammonium bromide and 72 g potassium bromide per pint which is stated as being 0.3 g total bromide per mL.
This dose calculation may be incorrect as only by including the ammonium and potassium cations can the dose ingested be calculated to be 0.3 g/mL:
72 g/pt (NH4Br) + 72 g/pt (KBr) = 144 g/pt (total bromide salts)
144 g/pt ÷ 473 mL/pt (US) = 0.30 g/mL.

Using molecular weights, the following calculation may be made:
72 g NH4Br (MW = 97.9 g/mol) is equivalent to 58.7 g Br-.
72 g KBr (MW = 118.9 g/mol) is equivalent to 48.4 g Br-.
72 g/pt (NH4Br) + 72 g/pt (KBr) = 107.1 g(Br-)/pt (i.e. total bromide).
107.1 g(Br-)/pt ÷ 473 mL/pt (US) = 0.23 g(Br-)/mL.
Thus, the true dosage of bromide ingested may be lower than that indicated in the published article.

Results and discussion

Clinical signs:
A pregnant mother was prescribed bromide-containing drugs (0.3 g total bromide per mL) for psychiatric treatment and took them (6 g/day) daily for 4 days until the day prior to delivery. The infant was born by caesarean section after 37 weeks gestation and described as large, puffy and quiet but in no distress. Neurological examination revealed an infant with a weak, high pitched cry, poor sucking and partial Moro reflex and diminished tone; deep tendon reflexes were absent. After exposure in the womb of up to 5 days prior to birth, the infant was born exhibiting signs of hypotonia and neurological depression. Maternal diabetes was suspected but serial determinations of concentrations of blood glucose, calcium and magnesium were all within normal limits. The serum bromide levels, first determined on the fifth day, were: 200 mg/100 mL (infant) and 310 mg/100 mL (mother) Urinary concentration: 166 mg/100 mL (infant - by this time the infant was more alert and was taking all feedings by nipple) Serial determinations of serum bromide concentrations revealed significant decrease over subsequent days. No treatment for bromide was administered as the discovery of high bromide levels was preceded by signs of improvement in the infant's condition. The patient was discharged after 15 days and by 5 months showed no residual manifestations of bromism. The serum bromide level was found to be 23 mg/100 mL at 69 days of age confirming the known slow clearance and increased renal tubular reabsorption of this ion.

Applicant's summary and conclusion

Bromism intoxication shows signs compatible with a variety of causes, e.g. hypotonia and neurologic depression. In the case presented, once dosing had ceased the patient showed a steady improvement in general condition with no specific treatment from bromism. The serum bromide level found at 69 days of age confirms the known slow clearance and increased renal tubular reabsorption of this ion.