2,4-dinitrophenol

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

other: exposure observation in humans: clinical study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data have been obtained from secondary source.

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

Unnamed

Year:

1995

Reference 2

Reference Type:

other: original reference

Title:

Dangerous Properties of Industrial Materials

Author:

Tainter ML, Wood DA.

Year:

1934

Bibliographic source:

A case of fatal dinitrophenol poisoning. JAMA 102:1147, 1934

Materials and methods

Study type:

poisoning incident

Principles of method if other than guideline:

Data have been obtained from an observation of a poisoning in a clinical study on human exposure to 2,4-dinitrophenol. Details on method have not been specified.

Test material

Test material information

Constituent 1

Reference substance name:

2,4-dinitrophenol

EC Number:

200-087-7

EC Name:

2,4-dinitrophenol

Cas Number:

51-28-5

Molecular formula:

C6H4N2O5

IUPAC Name:

2,4-dinitrophenol

Test material form:

other: sodium salt

Method

Subjects:

weight of man: 80 Kg

Route of exposure:

oral

Results and discussion

Clinical signs:

The first dose of 2,4-dinitrophenol sodium salt produced a high fever. The second dose resulted in admission to the hospital 6.5 hours later because of hyperpnea and chest pain. The rectal temperature was 105 °F, and pulse (as high as 146 beats per minute) and respiratory rate were rapid. This increase in respiration is secondary to 2,4-DNP-induced uncoupling of oxidative phosphorylation, leading to elevation of basal metabolic rate and body temperature.
Despite the administration of aspirin, the temperature rose to 105.7 °F by 10.5 hours following ingestion of the drug. Death occurred 0.5 hours later, with rigor mortis setting in 10 minutes after death and the temperature rising to ≈115 °F by 20 minutes after death. The clinical signs and the autopsy and histological findings were considered by the authors to be similar to those seen in heat stroke. Mild nephrotic changes and slight detachment of liver cells were seen during histopathological examination of tissues.

Applicant's summary and conclusion

Conclusions:

In this clinical observation 2,4-dinitrophenol sodium salt caused death of a 80 Kg man at a first dose of c.a 46 mg plus another 46 mg dose 1 week later. 2,4-DNP appears to be readily absorbed from the respiratory and gastrointestinal tracts. It showed toxic effect, and the most significant simptoms were high fever, hyperpnea and chest pain, high rectal temperature and rapid pulse and respiratory rate. This increase in respiration is secondary to 2,4-DNP-induced uncoupling of oxidative phosphorylation, leading to elevation of basal metabolic rate and body temperature. The clinical signs, the autopsy and histological findings were considered by the authors to be similar to those seen in heat stroke.
Mild nephrotic changes and slight detachment of liver cells were seen during histopathological examination of tissues.
LOAEL in mg/kg/day was set at 46.

Executive summary:

Data have been obtained from secondary source that mentions Tainter ML, Wood DA. 1934. A case of fatal dinitrophenol poisoning. JAMA 102:1147.

In this clinical study on human exposure, a first dose of 46 mg of 2,4-dinitrophenol sodium salt has been taken by an 80 Kg-man, followed by another 46 mg dose 1 week later. Details on method has not been specified. 2,4-DNP appears to be readily absorbed from the respiratory and gastrointestinal tracts. The first dose produced a high fever. The second dose resulted in admission to the hospital 6.5 hours later because of hyperpnea and chest pain. The rectal temperature was 105 °F, and pulse (as high as 146 beats per minute) and respiratory rate were rapid. This increase in respiration is secondary to 2,4-DNP-induced uncoupling of oxidative phosphorylation, leading to elevation of basal metabolic rate and body temperature. Despite the administration of aspirin, the temperature rose to 105.7 °F by 10.5 hours following ingestion of the drug. Death occurred 0.5 hours later, with rigor mortis setting in 10 minutes after death and the temperature rising to ≈115 F by 20 minutes after death. The clinical signs and the autopsy and histological findings were considered by the authors to be similar to those seen in heat stroke.

Mild nephrotic changes and slight detachment of liver cells were seen during histopathological examination of tissues. LOAEL in mg/kg/day was set at 46.