Mecoprop

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

other: Literature report of poisoning incident

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Treatment of severe 2,4-D and Mecoprop Intoxication with Alkaline Diuresis.

Author:

Prescott LF, Park J, Darrien I.

Year:

1979

Bibliographic source:

Br. J. Clin. Pharmac. (1979) 7: 111 – 116

Materials and methods

Study type:

poisoning incident

Endpoint addressed:

acute toxicity: oral

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Report of a self-poisoning incident with a selective weedkiller in a 39 year old man.

GLP compliance:

no

Remarks:

Not applicable

Test material

Test material information

Constituent 1

Reference substance name:

Mecoprop

EC Number:

230-386-8

EC Name:

Mecoprop

Cas Number:

7085-19-0

Molecular formula:

C10H11ClO3

IUPAC Name:

2-(4-chloro-2-methylphenoxy)propanoic acid

Test material form:

not specified

Specific details on test material used for the study:

Weedkiller containing 20 % test material.

Method

Type of population:

general

Subjects:

- Number of subjects exposed: One
- Sex: Male
- Age: 39

Ethical approval:

not applicable

Route of exposure:

oral

Reason of exposure:

intentional

Exposure assessment:

estimated

Details on exposure:

A 39 year old male was admitted to hospital 2 h after the deliberate ingestion of the contents of a lemonade bottle half full of weedkiller which was later shown to contain 20 % of the target material and 10 % 2,4-D.

Examinations:

Pulse rate
Blood pressure
Respiratory rate
Pupil reactivity
Muscle tone and tendon reflexes
Arterial blood analysis
Stimulation to pain
Clinical and radiological chest examination
Arterial oxygen
ECG
Electromyography

Analytical Methods:
Plasma and urine were acidified with 1 N HCl and the herbicides were extracted into 5 mL ether containing 2,4,5-trichlorophenoxyacetic acid as internal standard. The aqueous phase was discarded and the chlorophenoxy acids extracted back into 100 μL 0.1 < trimethylanilinium hydroxide in 50 % aqueous methanol. Aliquots 2 (μL) were injected into a HP Model 402 gas chromatograph fitted with a 4 ft x 1/4 in glass column packed with 10 % OV17 on Gaschrom Q. the injection port and oven temperature were 310 °C and 200 °C respectively and the carrier gas (nitrogen) flow rate was 60 mL/min. The chlorophenoxy acids were chromatographed as methyl esters formed by thermal decomposition in the injection port. The mean standard deviation of replicate assays of plasma and urine containing 10 – 100 μg/mL of test material was 5.3 %.
Total unchanged and conjugated chlorophenoxy acids in urine were estimated as above after hydrolysis with 3 N HCl at 80 °C for 1 h. The pKa of the test material was determined by titration.

Dose Absorbed:
The total amount of the test material recovered in the urine was 7.64 g. About 65 % of the test material was excreted as acid-labile conjugates.

Medical treatment:

Gastric aspiration and lavage were performed on admission.
Cooled with fans and tepid sponging.

An alkaline diuresis was induced after 40 h and over the next 48 h 14L fluid containing 69.3 g sodium bicarbonate was given intravenously while the central venous pressure was monitored.

Results and discussion

Clinical signs:

Soon after ingestion the patient vomited, became aggressive and confused and then rapidly lost consciousness. On admission the pulse rate and blood pressure were normal but the respiratory rate was 35/min with a minute volume of 121. The pupils were small but reactive, muscle tone was increased and tendon reflexes were normal. Arterial blood analysis showed mild metabolic acidosis and hypoxia (H+ 47 nmol, pCO2 3.6 kPa, bicarbonate 14 mmol/L and pO2 8.7 kPa).
Over the next few hours his condition deteriorated. He became unresponsive to painful stimuli, the tendon reflexes disappeared, the pulse rate increased to 140/min and the temperature rose to 39 °C. He was vasodilated and sweating profusely. Cyanosis was evident despite a respiratory rate of 40 – 50/ min and the chest was clear clinically and radiologically. A normal arterial oxygen tension could only be maintained with an M.C. mask and the temperature remained at 39 °C despite the use of fans and tepid sponging.
40 h after admission the patient was still deeply unconscious. Arterial blood analysis showed H+ 37 nmol/L, pCO2 5/1 kPa, pO2 5.4 kPa and bicarbonate 25.5 mmol/L with a minute volume of 141 and respiratory rate of 45/min. The chest was still clear and an ECG showed sinus tachycardia with T wave flattening in the standard leads and marked T wave inversion in the chest leads. The plasma urea had risen to 28.4 mmol/L despite good peripheral perfusion, as systolic blood pressure of 90 – 100 mmHg and a urine output of 2 - 3L/24 h.

Within a few hours of starting the alkaline diuresis the pulse rate, respiration rate and temperature began to fall and 18 h later he was responding readily to painful stimuli, deep tendon reflexes were brisk and marked myotonia was present. Consciousness was regained 4 days after admission, but he remained confused and disorientated for a further 4 days. The myotonia persisted for several days and there was marked proximal muscle weakness which lasted for several weeks.
By the 5th day the plasma urea had fallen to 5.6 mmol/L and the ECG reverted to normal. The creatinine clearance was 139 mL/min on the ninth day. There was biochemical evidence of severe muscle injury. The plasma creatinine phosphokinase (CPK) rose to > 3 000 u/L (normal < 180) and remained above this for several days and the urine gave a strongly positive test for haemoglobin. The plasma aminotransferase and lactic dehydrogenase activities were also elevated but the alkaline phosphatase and bilirubin remained within normal limits. Electromyography performed 6 days after ingestion showed changes consistent with mild myopathy. The patient was discharged to a psychiatric ward 11 days after admission and at follow up 2 months later was well but still complaining of some weakness of the legs.

Results of examinations:

As listed in Clinical Signs.

Effectivity of medical treatment:

The plasma concentration of the test material on admission was 751 μg/mL. Over the next two days the concentration declined slowly with a half-life of about 40 h. There was a delay before the urine became alkaline after diuresis was started. The half life values just before, during and after the urine became alkaline was 24, 11 and 28 h respectively.
The measured pKa value was 2.8.
Muscle damage with myotonia was a major complication and the striking elevation of plasma CPK could not be attributed to coma alone. The generalised T wave abnormalities on the ECG suggest myocardial as well as skeletal muscle damage.
The patient remained gravely ill with no signs of improvement after two days of supportive therapy. The test material was extensively metabolised and although alkaline diuresis while worthwhile was less effective in enhancing its elimination than for 2,4-D. The pKA of the test material is 2.8, which is just below the critical value of 3.0 proposed for pH-dependent renal excretion of organic acids.

Outcome of incidence:

The patient was discharged to a psychiatric ward 11 days after admission and at follow up 2 months later was well but still complaining of some weakness of the legs.

Applicant's summary and conclusion

Conclusions:

Self-poisoning with a selective weedkiller containing 20 % of the target material and 10 % 2,4-D in a 39 year old man resulted in prolonged deep coma, pyrexia, hyperventilation, hypoxia, myotonia, skeletal muscle damage and electrocardiographic changes consistent with cardiomyopathy. On admission, the plasma concentration of the target substance was 751 μg/L. The patient remained gravely ill with no sign of improvement for two days with supportive therapy, followed by induction of alkaline diuresis. The target substance was extensively metabolised and although alkaline diuresis was worthwhile it was less effective in enhancing its elimination than for 2,4-D. The pKA of the test material is 2.8, which is just below the critical value of 3.0 proposed for pH-dependent renal excretion of organic acids. The patient was discharged to a psychiatric ward 11 days after admission and at follow up 2 months later was well but still complaining of some weakness of the legs.

Executive summary:

Self-poisoning with a selective weedkiller containing 20 % of the target material and 10 % 2,4-D in a 39 year old man resulted in prolonged deep coma, pyrexia, hyperventilation, hypoxia, myotonia, skeletal muscle damage and electrocardiographic changes consistent with cardiomyopathy. On admission, the plasma concentration of the target substance was 751 μg/L. The patient remained gravely ill with no sign of improvement for two days with supportive therapy. The target substance was extensively metabolised and although alkaline diuresis was worthwhile it was less effective in enhancing its elimination than for 2,4D. The pKA of the test material is 2.8, which is just below the critical value of 3.0 proposed for pH-dependent renal excretion of organic acids.

Consciousness was regained 4 days after admission, but he remained confused and disorientated for a further 4 days. The myotonia persisted for several days and there was marked proximal muscle weakness which lasted for several weeks.
By the 5th day the plasma urea had fallen to 5.6 mmol/L and the ECG reverted to normal. The creatinine clearance was 139 mL/min on the ninth day. There was biochemical evidence of severe muscle injury. The plasma creatinine phosphokinase (CPK) rose to > 3 000 u/L (normal < 180) and remained above this for several days and the urine gave a strongly positive test for haemoglobin. The plasma aminotransferase and lactic dehydrogenase activities were also elevated but the alkaline phosphatase and bilirubin remained within normal limits. Electromyography performed 6 days after ingestion showed changes consistent with mild myopathy. The patient was discharged to a psychiatric ward 11 days after admission and at follow up 2 months later was well but still complaining of some weakness of the legs.