Ammonium 2-amino-4-(hydroxymethylphosphinyl)butyrate

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

other: observational case series study

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: poisoning cases with different formulations of Glufosinate-ammonium, not with the pure substance.

Data source

Reference

Reference Type:

publication

Title:

Acute human Glufosinate-containing herbicide poisoning

Author:

Yan-Chiao Mao et al.

Year:

2012

Bibliographic source:

Clinical Toxicology (2012), 50, 396-402

Materials and methods

Study type:

poisoning incident

Principles of method if other than guideline:

Retrospective review of the medical records of all glufosinate poisoned cases reported to the Taiwan National Poison Control Center and two medical centers in Taiwan from August 1993 through February 2010. Their demographic and clinical data were then analyzed to identify potential predictors of severe effects following acute glufosinate poisoning.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ammonium 2-amino-4-(hydroxymethylphosphinyl)butyrate

EC Number:

278-636-5

EC Name:

Ammonium 2-amino-4-(hydroxymethylphosphinyl)butyrate

Cas Number:

77182-82-2

Molecular formula:

C5H12NO4P.H3N

IUPAC Name:

ammonium 2-amino-4-[hydroxy(methyl)phosphoryl]butanoate

Specific details on test material used for the study:

Reported GA concentration of the formulations: 13.5% and 18.5%

Method

Type of population:

general

Subjects:

90 male and 41 female patients; median age was 46 years (interquartile range 33--63 years). Most patients (n = 115) were orally exposed to glufosinate-containing herbicides, and the majority of them (n = 98) ingested the herbicide in a suicide attempt. Concomitant ingestion
of other mildly toxic substances was recorded in 29 (25.2 % ) out of the 115 patients with oral exposure. Most of them drank ethanol (n = 22); two ingested benzodiazepines without manifesting overt CNS depression; and five co-ingested small amount of glyphosate-surfactant herbicide that was judged to be of minimal toxicity.

Reason of exposure:

other: accidental and intentional

Exposure assessment:

estimated

Details on exposure:

Since the ingested amount was usually reported in a descriptive term, such as "a mouthful", "a cup", or "a bottle", arbitrary volumes were assigned to the phrase that occurred frequently. "A mouthful" (n = 32) was assigned to 25 mL in adults and was 5 mL in children; "a bowl" or "a
glass" (n = 5) was 200 mL; and "a bottle" (n = 2) was 1000 mL, the size of the most commonly available glufosinate bottle in Taiwan. An estimated ingested amount was assumed to be the mean of the range ( e.g. 2--4 mouthfuls were estimated to be 3 mouthfuls). Because there are two glufosinate formulations (13.5% and 18.5% ammonium salt of glufosinate) available in Taiwan, for ingestions with unknown concentration of
glufosinate-containing herbicide, the most commonly marketed formulation of glufosinate (13.5% w/v) was assumed to be the ingested substance (n = 30).

Results and discussion

Clinical signs:

gastrointestinal, neurological, cardiovascular, and/or respiratory manifestations.

Outcome of incidence:

Among patients with oral exposure to GA, 25 were asymptomatic, while the others developed gastrointestinal, neurological, cardiovascular, and/or respiratory manifestations. Seven patients died following deliberate glufosinate ingestion, yielding a case fatality rate of 6.1 %.
The first patient was a 41-year-old male who experienced out-of-hospital cardiac arrest after taking unknown amount of glufosinate-containing herbicide 6 hours prior to presentation. Another two males, aged 58 years and 75 years respectively, manifested shock ( with a systolic blood pressure of 63 mmHg and 79 mmHg) and tachycardia (with a pulse rate of 150/min and 170/min) when they arrived at the emergency
department 1 hour post-ingestion. The 58-year-old patient died 12 hours later, while the 75-year-old patient died during inter-hospital transfer some 24 hours post-ingestion. The remaining four patients included three men and one woman whose age ranged from 41 to 94 years. All of them had profound shock, coma and bradycardia progressing to asystole that developed between 12 and 48 hours post-ingestion despite receiving intensive care. Life support was withdrawn against medical advice upon the request ofthe patients' family because of religious beliefs, which led to the death of the four patients.

Any other information on results incl. tables

The median dose of glufosinate ingestion was 30.4 grams in the severe/fatal group compared to 6.8 grams in the non-severe group. Older age and larger amount of glufosinate ingestion were positively associated with the development of severe toxicity, whereas ethanol consumption was inversely associated with the risk of severe toxicity.