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Administrative data

Description of key information

 ORAL ACUTE TOXICITY
LD50 on animals could be defined in the range of 20 (rat) - 81 (rabbit) mg/kg of 2,4-dinitrophenol. More specifically, in a fairly reliable study 30 > LD50 < 100 mg/kg (Spencer et al., 1948). Anyway, the most conservative value of LD50 is on dog 20 mg/kg (CNR, Drinking Water and Health, Volume 4, 1981).
Data on human exposure, as a poisoning clinical studies are available.

INHALATION ACUTE TOXICITY
The LCLo (lowest published lethal concentration) on dog, tested in 30 months is 300 mg/m^3 of 2,4-dinitrophenol. LD50 could be setted as discriminating dose > 300 mg/kg of 2,4-dinitrophenol.

DERMAL ACUTE TOXICITY
LD20 (and LOAEL) has been defined on 300 mg/kg on guinea pigs. LD50 could be set as discriminating dose at > 300 mg/kg of 2,4-dinitrophenol.
Data on human, as a occupational exposure, on supporting the inhalation route are available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental 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.
Principles of method if other than guideline:
The method has not been specified.
GLP compliance:
not specified
Species:
dog
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Doses:
20 to 30 mg/kg
Sex:
not specified
Dose descriptor:
LD50
Effect level:
ca. 20 - 30 other: mg/kg

The lethal dose LD50 on dog is 20 to 30 mg/kg. This value has been taken from table. Details of toxic effects have not been reported other than lethal dose value.

Conclusions:
The acute oral toxicity test defined a lethal dose LD50 on cat of 20 - 30 mg/kg, but details of toxic effects have not been reported other than lethal dose value. This value has been taken from table.
Executive summary:

Data have been obtained from secondary source that mentions National Research Council. Drinking Water &amp; Health, Volume 4. Washington, DC: National Academy Press, 1981., p. 236. The method used has not been specified and data have been taken from table.

The lethal dose LD50 on dog is 20 to 30 mg/kg, but details of toxic effects have not been reported other than lethal dose value.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
20 mg/kg bw
Quality of whole database:
Different animals were tested, but details on methods are not specified. Data on human oral acute toxicity are also available from clinical cases, performed on normal, obese and ill patients, that could support the evaluation of 2,4-DNP tocixity.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data have been obtained from secoundary source.
Principles of method if other than guideline:
The method has not been specified.
GLP compliance:
not specified
Species:
dog
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Duration of exposure:
30
Remarks on duration:
Months
Concentrations:
300 mg/m3
Sex:
not specified
Dose descriptor:
LCLo
Effect level:
300 other: mg/m^3
Remarks on result:
other: Duration: 30 M (months)

The LCLo-Lowest published lethal concentration on dog of 2,4 -dinitrophenol is 300 mg/m3. Details of toxic effects have not been reported other than lethal dose value.

Conclusions:
The LCLo-Lowest published lethal concentration on dog , tested in 30 Months of 2,4 -dinitrophenol is 300 mg/m^3. Details of toxic effects have not been reported other than lethal dose value.
Executive summary:

Data have been obtained from secoundary source taht mentions 85GMAT "Toxicometric Parameters of Industrial Toxic Chemicals Under Single Exposure," Izmerov, N.F., et al., Moscow, Centre of International Projects, GKNT, 1982 Volume(issue)/page/year: -,62,1982. The method has not been specified. The LCLo-Lowest published lethal concentration on dog of 2,4 -dinitrophenol is 300 mg/m3 for 30 months but details of toxic effects have not been reported other than lethal dose value.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating conc.
Value:
300 mg/m³
Quality of whole database:
Data on human acute inhalation toxicity are also available from occupational exposure cases on workers that could support the evaluation of 2,4-DNP tocixity.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data have been obtained from secondary source.
Principles of method if other than guideline:
Guinea pigs were exposed dermally to 100-1,000 mg/kg 2,4-dinitrophenol for 4 hours.
GLP compliance:
not specified
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Duration of exposure:
4 hours
Doses:
To 100-1000 mg/kg of 2,4-dinitrophenol
Sex:
not specified
Dose descriptor:
LD0
Effect level:
ca. 100 - 200 other: mg/kg
Sex:
not specified
Dose descriptor:
other: LD20
Effect level:
300 other: mg/kg
Sex:
not specified
Dose descriptor:
LD100
Effect level:
700 other: mg/kg
Sex:
not specified
Dose descriptor:
other: LOAEL
Effect level:
300 other: mg/kg

No mortality was observed at 100 -200 mg/kg.

The lowest dose causing mortality LD20 was 300 mg/kg (20 %)

The lowest dose causing totally the mortality LD100 was 700 mg/kg (100%).

Due to the local effect it might be possible to identify a LOAEL of 300 mg/kg.

Conclusions:
No mortality was observed at 100 or 200 mg/kg. LD20 was 300 mg/kg (20% mortallity ), and the lowest dose causing 100% mortality was 700 mg/kg.
Due to the local effect it might be possible to identify a LOAEL of 300 mg/kg.
Executive summary:

Data have been obtained from secondary source tha mentions Spencer HC, Rowe VK, Irish DD. 1948. Toxicological studies on laboratory animals of certain alkyldinitrophenols used in agriculture. J Ind Hyg Toxicol 30:10-25.Guinea pigs were exposed dermally to 100-1,000 mg/kg 2,4-DNP for 4 hours. No mortality was observed at 100 or 200 mg/kg. The lowest dose causing mortality at 20% was 300 mg/kg, and the lowest dose causing 100% mortality was 700 mg/kg. Due to the local effect it might be possible to identify a LOAEL of 300 mg/kg.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
300 mg/kg bw
Quality of whole database:
Data on human acute inhalation toxicity are also available from occupational exposure cases on workers that could support the evaluation of 2,4-DNP toxicity.
 

Additional information

Many studies on animals assessed the oral acute toxicity of 2,4 -dinitrophenol, anyway details of the method have not been specified.

The oral LD50 could be defined in the range 20 (rat) - 81 (rabbit) mg/kg of 2,4-dinitrophenol. Anyway, the most conservative value of LD50 is on dog 20 mg/kg (CNR, Drinking Water and Health, Volume 4, 1981).

For the inhalation route of exposure, an LCLo (lowest published lethal concentration) on dog, tested in 30 months is available. The relative LD50 is > 300 mg/kg.

LD50 could be setted as discriminating dose > 300 mg/kg of 2,4-dinitrophenol.

LD20 for dermal exposure on guinea pigs has been defined at 300 mg/kg. LD50 could be set as discriminating dose > 300 mg/kg of 2,4-dinitrophenol.


Justification for selection of acute toxicity – oral endpoint
Despite the presence of a fairly reliable study of Spencer et al., 1948 (30 mg/kg), the most conservative valute of oral acute toxicity LD50 is 20 mg/kg on dog.

Justification for classification or non-classification

ACUTE ORAL TOXICITY

Acute toxicity data collected from many secondary sources of 2,4 -dinitrophenol, DL50 could be setted in the range 20 - 81 mg/kg. In a fairly reliable study 30 > LD50 < 100 mg/kg (Spencer et al., 1948) and the most conservative value of LD50 is on dog 20 mg/kg (CNR, Drinking Water and Health, Volume 4, 1981).

Despite the presence of studies with values that fall in the Category 2 range (< 5 - <=50), 2,4 -dinitrophenol could be classified in Category 3, according to the European Commission Decision, H301: toxic if swallowed. This classification has been assigned considering an unknown but legal evaluation for the inclusion in annex VI of Regulation 1272/2008/EC and annex I of Directive 67/548/EEC.

This classification can include the possible rilevant human exposure by oral assumption, and its important clinical signs.

ACUTE INHALATION TOXICITY

Despite the data available for inhalation end point, 300 mg/m^3 (0.3 mg/L), the classification in according to the European Commission Decision is H331: toxic if inhaled. This classification has been assigned considering an unknown but legal evaluation for the inclusion in annex VI of Regulation 1272/2008 and annex I of Directive 67/548/EEC. This classification can include the possible rilevant worker exposure by inhalation.

ACUTE DERMAL TOXICITY

From the two studies available the ones choosen (300 mg/kg), classifies 2,4 -dinitrophenol H311: Toxic in contact with skin, Category 3, according to the European Commission Decision for the inclusion of 2,4 -DNP in annex VI of Regulation 1272/2008 and annex I of Directive 67/548/EEC.