Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to GLP and OECD guideline 402

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Ammonium carbamate
EC Number:
214-185-2
EC Name:
Ammonium carbamate
Cas Number:
1111-78-0
Molecular formula:
CH3NO2.H3N
IUPAC Name:
ammonium carbamate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
The test substance was supplied by Smithers Viscient (SMV), LLC. As reported by SMV, the purity of the test substance was tested as 100% (composition of 43.6% as ammonia and 56.3% as carbon dioxide). The appropriate amount of test substance was ground to a fine powder and weighed into
tared weigh boats that were covered, labeled, and transported to the animal room for dosing. Sufficient deionized water (prepared on-site) was dispensed for moistening the test substance.

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
The animals were approximately 8 weeks old at the initiation of dose administration.The albino rats utilized for this study were received in good health from Charles River Laboratories, Inc., Raleigh, NC. The rats were inspected by a qualified technician upon receipt, weighed and uniquely identified by a metal eartag displaying the animal number. The rats were acclimated to laboratory conditions for a minimum of 5 days. During this period, each animal was observed twice daily for mortality and changes in general appearance or behavior.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
On the day prior to dosing, the hair was removed from the backs and flanks of the rats using an electric clipper. Individual doses of the test substance were applied to the maximum area possible on the dorsal skin. Doses covered approximately 10% of the total body surface. Each dose was applied to the unabraded skin and overwrapped with gauze binders (<8 ply) that were secured with nonirritating tape. Upon completion of exposure, the bandages were removed and the sites were wiped with disposable paper towels moistened with tepid tap water.
Duration of exposure:
24 hours
Doses:
5000 mg/kg
No. of animals per sex per dose:
5
Details on study design:
DOSING:
One group of 5 male and 5 female rats were dermally administered a single dose (24 hour semi-occluded exposure) of ammonium carbamate at a dose level of 5000 mg/kg (5.0 g/kg). Individual doses were calculated based on body weights taken just prior to dosing.
MORTALITY:
The rats were observed at approximately 1, 2, and 4 hours post-application on study day 0 and twice daily, once in the morning and once in the afternoon, thereafter for 14 days.
CLINICAL OBSERVATIONS:
The rats were observed at approximately 1, 2, and 4 hours post-application on study day 0 and once daily thereafter for 14 days. Observations included, but were not limited to, evaluation for changes in appearance of skin and fur, eyes, mucous membranes, respiratory and circulatory systems, autonomic effects, and central nervous system effects.
DERMAL OBSERVATIONS:
The application sites were examined for erythema, edema (Draize scores), and other dermal findings beginning approximately 30-60 minutes after bandage removal and daily thereafter through study day 14. The areas of application were clipped free of hair on the day prior to dosing and as needed to facilitate accurate dermal observations.
BODY WEIGHTS:
Body weights were obtained and recorded on study days 0 (initiation), 7, and 14 (termination).
NECROPSY:
Upon termination, all rats were euthanized by carbon dioxide inhalation. The major organ systems of the cranial, thoracic, and abdominal cavities were examined for all animals.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
There were no deaths during the study.
Clinical signs:
There were no clinical findings observed during the study.
Body weight:
There were no remarkable body weight changes noted during the study.
Gross pathology:
At the scheduled necropsy, macroscopic findings consisted of scabbing at the application site for 1 male and 2 females.
Other findings:
Dermal findings noted during the study consisted of very slight (grade 1) to severe (grade 4) erythema, very slight (grade 1) to moderate (grade 3) edema, eschar, pinpoint scabbing, necrosis, scabbing within dose site, exfoliation, and desquamation. Erythema, eschar, and scabbing within dose site were still present for some rats at study termination
(study day 14)

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of this study, the LD50 of ammonium carbamate was greater than 5000 mg/kg when administered once for 24 hours to the clipped, unabraded skin of male and female albino rats. Classification according to Regulation (EC) No 1272/2008 is therefore not required.
Executive summary:

The objectives of this study were to determine the acute dermal median lethal dose, evaluate potential systemic toxicity, and evaluate the local irritative effects of the ammonium carbamate when applied once to the skin of albino rats. The study was conducted according to GLP and OECD guideline 402.

The test substance, ammonium carbamate, was administered once dermally for a 24-hour period under semi-occlusive dressing to Crl:CD(SD) albino rats for the determination of a median lethal dosage (LD50). The test substance was administered to 1 group of 5 male and 5 female rats at a dose level of 5000 mg/kg (5.0 g/kg).

Mortality, clinical observations, dermal findings (Draize, 1965; Appendix C), and body weight changes were evaluated over a 14-day observation period. All animals were subjected to a gross necropsy.

There were no deaths, remarkable body weight changes, or clinical findings. Dermal findings noted during the study consisted of very slight to severe erythema, very slight to moderate edema, eschar, pinpoint scabbing, necrosis, scabbing within dose site, exfoliation, and desquamation. Scabbing at the application site was noted for 1 male and 2 females at the scheduled necropsy.

Based on the results of this study, the LD50 of ammonium carbamate was greater than 5000 mg/kg when administered once for 24 hours to the clipped, unabraded skin of male and female albino rats. Classification according to Regulation (EC) No 1272/2008 is therefore not required.