4-pyridylamine

Endpoint summary

Description of key information

4-AP has high acute toxicity to mammals via the oral route of exposure (Category I) and the dermal and inhalation routes of exposure (Category II). The acute and subchronic toxicological effects of 4-AP are manifested as hyperexcitability, hyperirritability, salivation, tremors, and muscular incoordination. 4-AP acts by blocking potassium ion channels in nerve fibers. Adverse effects in humans ingesting low levels of 4-AP (5-30 mg/day) were nervousness, giddiness or dizziness, memory alteration, cramps, arterial vasospasm and peripheral paraesthesia. Higher doses in an accidental poisoning case (one-time estimated dose of 60 mg) produced additional effects including weakness, intense diaphoresis, feeling of impending doom, dyspnea, agitation and combative behavior, and profound thirst. Human studies demonstrated that 4-AP is eliminated quickly from the body and effects did not accumulate with continuous exposure.

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:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

no guideline followed

Principles of method if other than guideline:

Previously unpublished data from the Denver Wildlife Research Center (DWRC) were derived primarily by the po methods described by DeCino et al. (1966), Schafer (1972), and Schafer et aÍ. (1967). Other methods of oral administration included force-feeding synthetic pellets (Pan and Caslick, 1966) or treated grain. Dermal toxicity was determined by the method described by Schafer et al. (1969). All test animals were adults unless noted in the table. LD50 values and 95 % confidence limits were derived by the moving-point interpolation method described by Thompson (1948), Thompson and Weil (1952), and Weil (1952). The 4AP used was technical material of about 95% purity.
Methodology for other data can be found in the cited articles.

GLP compliance:

not specified

Test type:

other: not specified

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

not specified

Control animals:

not specified

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

20 mg/kg bw

Based on:

test mat.

Other findings:

4-Aminopyridine (4AP) is an acutely toxic substituted pyridine. In mammals, it produces the following sequence of clinical signs: hyperexcitability, salivation, tremors, muscular incoordination, clonic and tonic convulsions, cardiac or respiratory arrest, and death. At doses near the LD50, initial effects are usually noted in 10-15 min and death often occurs 15 min to 4 hr later. Occasionally, the tremor and/or convulsive stages are accompanied by audible vocalizations produced by strong, involuntary contractions of the diaphragm.

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

LD50 (rat, oral): 20 mg/kg bw

Executive summary:

LD50 (rat, oral): 20 mg/kg bw (toxikology review: EPA TSCA Inventory)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

20 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

no guideline followed

Principles of method if other than guideline:

Peer reviewed summary from US EPA

GLP compliance:

not specified

Remarks:

data from a reliable peer reviewed summary from US EPA

Test type:

other: Acute dermal

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

inhalation: dust

Type of inhalation exposure:

not specified

Vehicle:

not specified

Analytical verification of test atmosphere concentrations:

not specified

Control animals:

not specified

Key result

Sex:

not specified

Dose descriptor:

LC50

Effect level:

0.53 mg/L air

Based on:

test mat.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Acute inhalation LD50: 0.53 mg/L

Executive summary:

Acute inhalation LD50: 0.53 mg/L

(toxicology review: EPA TSCA Inventory)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

0.001 mg/m³ air

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:

data from handbook or collection of data

Qualifier:

no guideline followed

Principles of method if other than guideline:

Previously unpublished data from the Denver Wildlife Research Center (DWRC) were derived primarily by the po methods described by DeCino et al. (1966), Schafer (1972), and Schafer et aÍ. (1967). Other methods of oral administration included force-feeding synthetic pellets (Pan and Caslick, 1966) or treated grain. Dermal toxicity was determined by the method described by Schafer et al. (1969). All test animals were adults unless noted in the table. LD50 values and 95 0/0 confidence limits were derived by the moving-point interpolation method described by Thompson (1948), Thompson and Weil (1952), and Weil (1952). The 4AP used was technical material of about 95% purity.
Methodology for other data can be found in the cited articles.

GLP compliance:

not specified

Test type:

other: not specified

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

not specified

Vehicle:

water

Control animals:

not specified

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

327 mg/kg bw

Based on:

test mat.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Acute dermal - rabbit LD50 = 327 mg/kg

Executive summary:

Acute dermal - rabbit  LD50 = 327 mg/kg

(toxicology review: EPA TSCA Inventory)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

327 mg/kg bw