Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Feb-July, 992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Justification for type of information:
Guideline study under GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EPA OTS 798.1100 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Purity 100%, Brownish White Flaky Solid, Lot # 11202AB
Specific details on test material used for the study:
Brownish white flaked solid, Lot # 11202AB

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
Ten healthy young adult New Zealand White rabbits, five of each sex, were used in the study.
Animals were purchased from a registered commercial breeding laboratory (Eastern Rabbit Breeding laboratory, Taunton, MA)
Animals were in the weight range between 2.0 and 3.0 kilograms at the start of the study
Animals were 10-12 weeks old at the start of the study. They were quarantined for 5 days prior to the study.

Animals were all housed individually using suspended stainless steel cages marked with the corresponding animal number.
Hardwood Sani-chips were used as non-contact bedding under the cages.
Animal rooms were maintained at 68±F at 30-70% Humidity
A minimum of 10-13 complete air exchanges per house occured
12 hour light/dark cycles using full spectrum fluorescent lights were used.

Animals were supplied with a commercial rabbit ration (Agway Prolab, Waverly, NY) and municipal tap water ad libitum.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Animals were weighed prior to testing and their fur clipped 24 h prior to adminstration of test material. The test substance was introduced under gauze patches two single layers thick and applied directly to the skin of the body surface (approximately 10%) of each of the ten animals. Animals were immobilized and the patches were secured in place by wrapping the entire trunk of the animal with an impervious bandaging.
Duration of exposure:
24 hours
Doses:
2 g/kg
No. of animals per sex per dose:
5 males
5 females
Control animals:
no
Details on study design:
After the exposure period, the wrapping was removed from the animals and the site rinsed gentily with USP water to remove remaining test material. Any skin lesions found were graded 30-60 minutes after bandage removal. Animals were observed for erythema and edema for a 24 h observation period. The animals were observed daily for 14 days. Any animal found dead was necropsied within 12 hours. All animals underwent a gross necropsy. Surviving animals were euthanised with an injectable barbiturate, Euthanasia-5 (Veterinary Laboratories Inc, Lenexa , KS, USA).
Statistics:
none

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
given as > 2 g/kg
Mortality:
No animals died during the 14 day observation period
Clinical signs:
There were no overt signs of toxicity exclusive of skin irritation noted in any test animal during the observation period. There was no evidence the animals experienced pain or suffering
Body weight:
All animals gained weight when assessed at 14 days post exposure. Four animals lost weight during the first 7 days but regained weight by day 14
Gross pathology:
Necrosis was observed in the skin in all animals. Gross necropsy showed that necrosis penetrated through the skin into the underlying muscle. It also showed atrophy of the spleen and discoloration of the liver and kidneys.

Any other information on results incl. tables

LD50 > 2 g/kg bw.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance is considered nontoxic in rabbits at a dose of 2000 mg/kg bw for 24 h, occlusive exposure, based upon the absense of mortality in a 14 day limit dose acute dermal toxicity study. Necrosis of the skin was observed in all animals at necropsy but no other clinical signs were reported.