Registration Dossier

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: GLP Study

Data source

Reference
Title:
Unnamed
Year:
1983

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

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

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
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 for acute dermal toxicifey testing.
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 the number of animals of each sex received. 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 approximately 3 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 (252) was cleaned daily and the cages were cleaned and sanitized as specified in ToxiGenics1 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 68 to 70°F and the relative humidity varied from 47 to 68 percent with the following exception: a relative humidity value of 72 percent was recorded on one day during quarantine. 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 1:45 p.m. on October 19, 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 ToxiGenics1 Standard Operating Procedures.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: applied neat
Details on dermal exposure:
The dorsal trunk (approximately 10% of the body surface area) of each animal was clipped free of hair with Oster electric clippers equipped with a number 40 (surgical) blade. The areas were reclipped as needed during the study for evaluation of dermal reactions.
On the day of dosing (day 0), body weights were recorded and doses were calculated. Approximately 24 hours after the initial clipping, the prepared area of each animal was abraded. The
Ibngitudinal epidermal abrasions were spaced 2 to 3 cm. apart and were sufficiently deep to penetrate the stratum corneum but not the dermis. After abrading, a measured volume of the test arti- cle was introduced under an impervious binder, consisting of a
plastic wrap and adhesive tape secured around the trunk of each manually restrained animal, and gently spread over the applica-
tion site. After test article application, the trunk of each animal was wrapped with additional adhesive tape and masking tape.
After a 24-hour exposure period, each binder was removed, and the test site of each animal was wiped (not washed) with gauze sponges moistened with water to remove remaining test article
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Hourly on day 0, twice daily for all other days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None
Clinical signs:
No abnormal clinical signs were observed during the study.
Body weight:
Body weight gains were observed for all animals during the study. Four males and 4 females gained weight on days 7 and 14. One male and one female.lost either 50 or 60 grams of weight from day 0 to day 7, and gained weight from day 7 to day 14.

Any other information on results incl. tables

Severe erythema and severe edema were observed for all animals after test article removal on day 1. Erythema decreased in severity (to well defined or very slight) for 2 males on day 14 and for one female on day 12. Edema decreased in severity (to moderate, slight, or very slight) for all males and 3 females as early as day 2. No erythema was observed on day 14, and no edema was observed on days 12 to 14 for one female. Also, no edema was observed on day 14 for one male. Other dermal reactions observed at test sites included:

- Blanching: all animals on day l and as late as days 2, 3, or 4 for 6 animals.

- Necrosis (brown-green discoloration): all animals on days l and 2, as late as days 3, 5, or 6 for 3 males, and to day 11 for 4 females.

- Eschar formation: all animals on days 2 to 11, and for 7 animals to day 14. Eschar was present along the abrasion lines only of one female on days 7 to 11.

- Eschar peeled off: one female on day 12, and 2 males on day 14.

- Atonia: all males and 3 females from days 3 or 4 to days 11 or 14.

- Desquamation: all animals from days 10 or 11 to day 14.

- Fissures: one male and 4 females as early as day 5 and as late as day 14.

- Denuded areas along abrasion lines: one female on day 14. No other dermal reactions were observed during the study. Brown, crusted, and raised discolorations of the treated skin were observed during necropsy of 3 males and 3 females. Multiple depressions in the treated skin were observed during necropsy of one of the same males, of 2 other males, and of one other female. A dark red focus was also observed on the lung of one male. No other abnormalities were observed during necropsy of all males and 4 females, and no abnormalities were observed during necropsy of one female.

Applicant's summary and conclusion

Interpretation of results:
other: Irritating but otherwise practically non-toxic
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
SY-83 is not systemically toxic up to 2000 mg/kg dermal doses. It is irritating to skin.
Executive summary:

The test article, SY-83, was evaluated for acute dermal toxicity at a dose level of 2 grams/kilogram of body weight. The test article was applied to the skin (clipped free of hair and abraded) of 5 males and 5 females for 24 hours of exposure. This study was designed to comply with the procedures described in the EPA/OPP Guidelines, 1982.

All animals survived the 14-day duration of the study and gained body weight.

No abnormal clinical signs were observed during the study.

Severe erythema and severe edema were observed at the test sites of all animals after removal on day 1. Erythema decreased in severity for 3 animals on days 12 or 14, and was not observed for one female on day 14. Edema decreased in severity for 8 animals as early as day 2, and was not observed for one female on day 12 and for one male on day 14. Other dermal reactions observed at test sites included: blanching - all animals on day l and as late as day 6; necrosis - all animals on days l and 2 and as late as day 11 (4 females); eschar formation - all animals on days 2 to 11, and for 7 animals to day 14; eschar along abrasion lines only - one female on days 7 to 11; eschar peeled off - 3 animals on days 12 or 14; atonia - 8 animals from days 3 or 4 to day 14; desquamation - all animals from days 10 or 11 to day 14; fissures - 5 animals as early as day 5 to as late as day 14; and denuded areas along abrasion lines - one female on day 14. No other dermal reactions were observed during the study.

Necropsy of 3 males and 3 femalas on day 14 revealed brown, crusted discolorations of the treated skin. Multiple depressions in the treated skin were observed during necropsy of one of the same males and of 3 other animals (2 males and one female), and a dark red focus was also observed during necropsy of one other male. No other abnormalities were observed during necropsy of all males and 4 females, and no abnormalities were observed during necropsy of one female.