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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study appears well conducted with limited reporting of methods and results and a single dose tested only and not a limit dose.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978

Materials and methods

Test guideline
Guideline:
other: 16 CFR 1500. 40
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Nitrilotriacetonitrile
EC Number:
230-804-9
EC Name:
Nitrilotriacetonitrile
Cas Number:
7327-60-8
Molecular formula:
C6H6N4
IUPAC Name:
2-[bis(cyanomethyl)amino]acetonitrile
Details on test material:
purity> 99%
White Crystalline material

Test animals

Species:
rabbit
Strain:
other: albino
Sex:
not specified

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Remarks:
moistened with saline
Details on dermal exposure:
The animals were prepared by clipping the skin of the trunk free of hair. Approximately one-half of the animals was further prepared by making epidermal abrasions every 2 or 3 centimeters longitudinally over the area of exposure. The abrasions were sufficiently deep to penetrate the stratum corneum (horny layer of the epidermis) but not to distrub the derma; that is, not to obtain bleeding.

The sleeve was slipped onto the animal which is then placed in a comfortable but immobilized position in a multiple animal holder. Selected doses of liquids and solutions are introduced under the sleeve. If there is slight leakage from the sleeve, which may occur during the first few hours of exposure, it is collected and reapplied. Dosage levels are adjusted in subsequent exposures (if necessary) to enable a calculation of a dose that would be fatal to 50 percent of the animals. This can be determined from mortality ratios obtained at various doses employed. At the end of 24 hours the sleeves or screens are removed, the volume of unabsorbed material (if any) is measured, and the skin reactions are noted. The subjects are cleaned by thorough wiping, observed for gross symptoms of poisoning, and then observed for 2 weeks.

In this study only one dose level was chosen.
Duration of exposure:
24 hours
Doses:
200 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
not required

Results and discussion

Effect levels
Sex:
not specified
Dose descriptor:
LD0
Effect level:
200 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortalities observed
Mortality:
No mortality observed
Clinical signs:
other: Decreased activity and some nasal discharge was observed, but not indicated in how many animals or at what stage after dosing these effects started and ceased.
Gross pathology:
No pathology reported

Applicant's summary and conclusion

Conclusions:
A dose of 200 mg/kg was not lethal to adult albino rabbits following occlusive dermal exposure (intact and abraded skin). The LD0, therefore is 200 mg/kg bw.