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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
SY-83

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Young adult, New Zealand White albino rabbits were obtained from Langshaw Farms, Route l, Box 256, Augusta, MI 49012. The albino rabbit is the species preferred in the EPA/OPP Guidelines (1982) for determining the dermal irritation potential of test articles. Animals were housed individually in stainless steel, wire-bottomed cages that conformed to the size standards specified in DHEW Publication (NIH) 78.23. The cages on each rack were numbered in a Standard manner and a list of random numbers was generated by computer program for each rack of cages. Upon receipt, each animal was removed from the shipping container and housed in the appropriate randomly selected cage.
Each animal was then assigned a sequential animal number unique within ToxiGenics and identified with an ear tag bearing this animal number. The sequential animal number was listed on a cage card that was affixed to the front of the animal's cage.
The animals were quarantined for 2 weeks after receipt. During the quarantine period, Veterinary Sciences' personnel observed the animals at least once each day for mortality, morbidity, and abnormal signs. Animals were examined during quarantine and only those considered to be in good health were used in this study. The quarantine and study room (241) was cleaned daily and
cages were cleaned and sanitized as specified in ToxiGenics' Standard Operating Procedures. Urine and feces feil through the wire mesh floor onto animal caging board. The cage boards were changed at least 3 times a week.
The animal room was well ventilated and air-conditioned, and the temperature and humidity were monitored daily in this room during the quarantine and study periods. The temperature ranged
from 66 to 70°F and the relative humidity varied from 37 to 64 percent except for one day when a relative humidity value of 72 percent was recorded.

The animal room was lighted from approximately 6:00 a.m. to 6:00 p.m. (12-hour light/12-hour dark cycle) using automatic timers. The test article applications were completed at 12:05 p.m. on November 8, 1983. Purina Certified Rabbit Chow 5322 was fed to the animals ad libitum during the quarantine and study periods. Filtered tap water was provided ad libitum through an automatic watering system and was analyzed periodically as specified in ToxiGenics' Standard Operating Procedures.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped and abraded.
Vehicle:
other: applied neat
Amount / concentration applied:
Concentration: 80 %
Duration of treatment / exposure:
24 hour(s)
Observation period:
60 minutes
Number of animals:
6
Details on study design:
The duration of the study was one day. One group consisting of 3 males and 3 females was used. Animals were assigned to the study by sequential animal number. However, any animal deemed unsuitable by the Study Director and any animal exhibiting dermal lesions or irritation (-24 hour evaluations) was not used, and the next acceptable sequentially numbered animal was used.
Two test sites were prepared on each side of the spinal column in the thoracic región of each animal by closely clipping the hair with Oster electric clippers equipped with a number 40 (surgical) blade. Approximately 24 (+ 2) hours after clipping, 0.5 milliliter of the test article was applied to each 2.5 centimeter square surgical gauze patch. While each animal was manually immobilized, 2 application sites on each animal After a 24-hour exposure period, the impervious binders and patches were removed. Each test site was gently wiped with gauze sponges moistened with water to remove remaining test article. All animals were observed for mortality and abnormal clinical signs twice daily during the study in the early morning and late afternoon. The skin condition of each test site was evaluated for erythema, edema, and other lesions at 30 to 60 minutes after test article removal. Dermal reaction scores were assigned using the grading system presented in Table l of this report. Representative photographs of lesions observed were taken after the 30 to 60 minute evaluations. One set of photographs were submitted to the Sponsor as an addendum report.
After the 30- to 60-minute evaluations, all animals were euthanized by administration of an intraveneus overdose of a barbiturate and discarded. The study was terminated due to the
severity of the dermal reactions observed.

Results and discussion

In vivo

Irritant / corrosive response data:
The following were observed at the evaluations done at 30 to 60 minutes after test article removal: - Severe erythema (grade 4) at 10 of the 12 abraded test sites (on 5 animals) and at 7 of the 12 intact test sites on 4 of the same animals. Moderate to severe erythema (grade 3) at the 2 remaining abraded and 5 remaining intact test sites (all sites on one animal and one or both intact sites on 2 animals).
- Severe edema (grade 4) at 11 of 12 intact and 11 of 12 abraded test sites, and slight edema (grade 2) at one intact site and one abraded site on one animal.
- Blanching at both abraded sites on each animal, and at both intact sites on 5 animals.
- Yellow-brown color of skin at all sites on 3 animals, at both abraded sites on one animal, and at one intact site and both abraded sites on a fifth animal.
- Red exudate at one intact site on one animal.
- Skin missing at all sites on one animal, at one intact site and both abraded sites on one animal, and at one intact site or one abraded site on 2 other animals. No other dermal reactions were observed at the evaluations done at 30 to 60 minutes after test article removal.
One animal (BB5196) was observed by an attending veterinarian and the following comments were noted:
Both lesions in the left lateral thoracic and abdominal wall were circular and approximately 4 cm. in diameter. Tags of necrotic skin were observed around the circumference while the entire center (greater than a 3 cm. circle) was totally denuded of all layers of skin. The peritoneum was intact, and hemorrhage from the peritoneal vessels and skin vessels around the circumference was evident. Without medical treatment, these and similar lesions were expected to become secondarily infected
resulting in the animals death. Termination of the study was recommended by the veterinarian. No abnormal clinical signs were observed and no mortalities occurred prior to sacrifice after the 30- to 60-minute evaluations.

Applicant's summary and conclusion

Interpretation of results:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Classification: irritating
Executive summary:

The test article, SY-83, was evaluated for primary dermal irritation potential when applied to 2 intact and 2 abraded test sites on the skin of each of 6 albino rabbits and covered with impervious bandages for 24 hours. These 24 test sites were evaluated for erythema, edema, and other lesions at 30 to 60 minutes after test article removal. This study was designed to comply with the procedures described in the EPA/OPP Guidelines, 1982. The following were observed at 30 to 60 minutes after test article removal: Severe erythema was observed at all test sites on 3 animals, and at both abraded sites on 2 other animals and at one intact site .on one of these 2 animals. Moderate to severe erythema was observed at all test sites on one animal, and at one or both intact sites on 2 animals. Severe edema was observed at all test sites on 5 animals and at one intact site and one abraded site on the sixth animal. Slight edema was observed at the other 2 sites on the sixth animal. Blanching was observed at both abraded sites on all animals and at both intact sites on 5 of these animals. Yellow-brown color of the skin was observed at all sites on 3 animals and at either 2 or 3 test sites on 2 animals. A red exudate was observed at one intact site on one animal. Skin was missing at all test sites on one animal, at one intact and both abraded sites on one animal, and at one intact site or one abraded site on 2 other animals. No other dermal reactions were observed during the study. This study was terminated after the 30- to 60-minute evaluations upon the recommendation of an attending veterinarian due to the severity of the reactions observed. No abnormal clinical signs were observed and no mortalities occurred prior to sacrifice after the 30- to 60-minute evaluations.