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Toxicological information

Acute Toxicity: other routes

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Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No OECD guideline or GLP defined.

Data source

Reference
Reference Type:
publication
Title:
Comparative acute toxicity and primary irritancy of various classes of amines
Author:
Myers R.C. et al.
Year:
1997
Bibliographic source:
Toxic Substance Mechanisms, 16: 151-193 (1997)

Materials and methods

Principles of method if other than guideline:
Three- to five month old male New Zealand white rabbits (2.0-3.0 kg) were used, and maintained ad libitum on commercial diet and municipal water, except during the skin preparation and contact periods. Fur was removed from the entire trunk using an electric clipper, avoiding abrasion. Impervious plastic sheeting was wrapped around the trunk and secured. Using a calibrated syringe, test substance was injected under the edge of the plastic sheeting and spread (through gentle massaging) over as large an area as possible (Myers, 1993). Animals were placed into a restraining apparatus for a 24-h contact period. After a dosing, the wrappings and any excess test material were removed (with cleansing tissue), and the animal was returned to its cage for the remainder of a 14-d observation period. Dosed animals were observed frequently during the time of contact, and daily for 13 d after the 24-h contact. Body weights were measured before dosing and at d 14. Necropsy was conducted on decedents and sacrificed survivors. Four male rabbits were used for each dose. Variation in dosages (by a factor of two) was achieved through adjustment of dose volume. LD50 values, and 95% confidence limits, were calculated by the method of Thompson (1947) and Weil (1983).
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Physical state: Pale yellow liquid
Molecular weight: 135.23
Specific gravity : 0.894 (27°C)
Vapor pressure : 1.82 mm Hg (25°C)

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male

Administration / exposure

Route of administration:
other: percutaneous
Vehicle:
not specified
Doses:
no data
No. of animals per sex per dose:
4
Control animals:
not specified

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
1.66 mL/kg bw
95% CL:
1.35 - 2.04
Remarks on result:
other: Time to death: 1-2d

Any other information on results incl. tables

The LD50 value was 1.66 ml/kg. Rabbits died from the test substance after 1 -2 d. Local skin lesionsincluded edema, necrosis, and scabs. At the highest dosage, there was immediate hyperactivity followed by tremors, vocalization, and pupillary dilation (by 4.5 h). The weights were decreased. Pathologic changes included congestion of the liver. In addition, the animals had gray stomachs and congested kidneys.

Applicant's summary and conclusion

Executive summary:

In an acute percutaneous study, three- to five month old male New Zealand white rabbits (2.0-3.0 kg) were used. Fur was removed from the entire trunk using an electric clipper, avoiding abrasion. Impervious plastic sheeting was wrapped around the trunk and secured. Using a calibrated syringe, test substance was injected under the edge of the plastic sheeting and spread (through gentle massaging) over as large an area as possible (Myers, 1993). Animals were placed into a restraining apparatus for a 24-h contact period. After a dosing, the wrappings and any excess test material were removed (with cleansing tissue), and the animal was returned to its cage for the remainder of a 14-d observation period. Dosed animals were observed frequently during the time of contact, and daily for 13 d after the 24-h contact. Body weights were measured before dosing and at d 14. Necropsy was conducted on decedents and sacrificed survivors. Four male rabbits were used for each dose (no data about doses used given).

Rabbits died from the test substance after 1 -2 d. Local skin lesionsincluded edema, necrosis, and scabs. At the highest dosage, there was immediate hyperactivity followed by tremors, vocalization, and pupillary dilation (by 4.5 h). The weights were decreased. Pathologic changes included congestion of the liver. In addition, the animals had gray stomachs and congested kidneys.

The LD50 value was 1.66 ml/kg.