Spinflam MF 83 PP-25

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: A case reported. Justification for read across approach is explained in the endpoint summary of acute toxicity.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1976

Reference 2

Reference Type:

secondary source

Title:

Unnamed

Year:

2005

Materials and methods

Study type:

clinical case study

Endpoint addressed:

acute toxicity: oral

Principles of method if other than guideline:

Neurotoxic side-effects - a case reported.

GLP compliance:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Method

Type of population:

other: a 12-year-old girl

Subjects:

A 12-year-old girl weighing 30 kg

Ethical approval:

not applicable

Route of exposure:

oral

Reason of exposure:

intentional

Details on exposure:

Girl was given 3.0 g of test item at bedtime for ascariasis.

Results and discussion

Clinical signs:

The morning following the administration she was reported to be unable to sit up in the bed without support.
Her respiration rate was 10 per minute; other vital signs and blood pressure were normal.
Neurological examination revealed horizontal nystagmus, generalized diminution of muscle power (she was quite unable to stand or sit without support), hypotonia and diminished tendon reflexes. Plantars were flexor. There was no previous history suggestive of any neurological, renal or hepatic disease. Her blood urea was 25 mg %.
Cerebrospinal fluid examination revealed no abnormality.
Later the patient gradually improved and became perfectly well after 24 hours.
Review of the available literature shows that neurotoxic side effects occur mainly in patients with predisposing neurological or renal disease or after administration of an over dose.

In the present case none of these factors were operating and two possibilities can be considered:
(1) that this patient may be lacking or deficient in an enzyme which metabolizes or helps in the excretion of test item and
(2) that the patient’s nervous system was hypersensitive to test item.

Applicant's summary and conclusion

Conclusions:

Horizontal nystagmus, generalised diminution of muscle power, hypotonia and diminished tendon reflexes were observed in a 12-year-old girl given a single dose of test item as citrate, corresponding to 24 mg/kg base.

Executive summary:

A 12-year-old girl weighing 30 kg was given 3.0 g of test item citrate at bedtime for ascariasis. Next morning she was reported to be unable to sit up in the bed without support. Her respiration was 10 per minute; other vital signs and blood pressure were normal. Neurological examination revealed horizontal nystagmus, generalized diminution of muscle power, hypotonia and diminished tendon reflexes. Plantars were flexor. There was no previous history suggestive of any neurological, renal or hepatic disease. Cerebrospinal fluid examination revealed no abnormality.

Review of the available literature shows that neurotoxic side effects occur mainly in patients who either had some predisposing neurological or renal disease or to whom an overdose was administered.

In the present case none of these factors were operating and two possibilities can be considered:

(1) that this patient may be lacking or deficient in an enzyme which metabolizes or helps in the excretion of piperazine and

(2) that the patient’s nervous system was hypersensitive to piperazine.

Conclusion

Horizontal nystagmus, generalised diminution of muscle power, hypotonia and diminished tendon reflexes were observed in a 12-year-old girl given a single dose of test item citrate, corresponding to 24 mg/kg base.