Ceraphyl 55

Specific investigations: other studies

Administrative data

Endpoint:

specific investigations: other studies

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

no guideline followed

GLP compliance:

yes (incl. QA statement)

Type of method:

in vivo

Endpoint addressed:

skin irritation / corrosion

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): Ceraphyl 55
- Supplied by: International Specialty Products Inc.
- Physical state:clear liquid
- Lot/batch No.: A7281
- Storage condition of test material: room temperature
- Sample preparation: the test article was used as received and mixed with a mixture of acetone/olive oil to appropriate concentrations.

Test animals

Species:

mouse

Strain:

Balb/c

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Boyertown, PA
- Received on: 04/06/2004 and 04/20/2004
- Date of birth: 2-15-2004 and 2-24/2004
- Weight at study initiation: 17-23 g
- Housing: 1/cage- suspended wire cages
- Diet (e.g. ad libitum): fresh PMI Rodent Chow (Diet 5001)
- Water (e.g. ad libitum): freely available
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Photoperiod (hrs dark / hrs light): 12 hr light/ 12 hr dark

Administration / exposure

Route of administration:

dermal

Vehicle:

unchanged (no vehicle)

Details on exposure:

TEST SITE
- Area of exposure: 2 cmx2 cm
- % coverage: 100%
- Type of wrap if used: no wrap used
- Time intervals for shavings or clipplings: the area was clipped free of hair once, before the test.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washing done with distilled water
- Time after start of exposure: 24 hr

TEST MATERIAL
- Total dose: 5000 mg/kg
- Dose used (if solution): 25 ul

Duration of treatment / exposure:

0-23 days (depending on the application side)

Doses / concentrations

Remarks:

Doses / Concentrations:
25 ul
Basis:
other: contact

No. of animals per sex per dose:

General test:
2 groups - 5 animal each

Control animals:

no

Examinations

Examinations:

Dermal observation, using the Draize Dermal Scoring Code below, were performed at the following intervals:
Group 1:
- dilution: 100%
- animals: 1-5
- ears (day): 0-3
- trunk (day): 0-3

Dermal observation, using the Draize Dermal Scoring Code below, were performed at the following intervals:
Group 2:
- dilution: 100%
- animals: 6-10
- ears (day): 0-3
- trunk (day): 0-3

Ear measuraments: ear thickness was measured to 0.01 mm using a thickness gauge at the following intervals:
Group 1: Day 0-3
Group 2: Day 0-3

Type and Frequency of Observation
- in vivo: All animals were observed at 1, 2 and 4 hr post dose and once daily for signs of pharmacologic or toxicologic effects. Animals were examined twice daily for mortality. Body weights were recorded pre-test, weekly, at death and at termination in the survivors.

-post mortem: Animals in a critical conditions and not expected to survive untill the next observation interval, were sacrificed using CO2. At study termination all survivors were sacrificed in the same manner. All animals were examined for gross pathology including auricular lymph nodes.

Results and discussion

Details on results:

Group 1: erythema scores ranged from 0 to 1 on both ears and trunk. No edema was noted. Four of five animals died within 72 hr of the 5000 mg/kg application. Pre-death physical signs included lethargy, ataxia, dyspnoea, tremors, flaccid muscle tone were recorded. Necropsy revealed abnormalities of the liver, gastrointestinal tract, emaciation and wetness of anogenital area (one animal). The auricular lymph nodes appeared normal.

Group 2: erythema and edema were absent on both ears and trunk. Three of five animals were sacrificed because the critical conditions (72 hr of the 5000 mg/kg application). Pre-death physical signs included lethargy, ataxia, dyspnoea, tremors, flaccid muscle tone were recorded. Necropsy revealed abnormalities of the liver, gastrointestinal tract, emaciation and wetness of anogenital area (one animal). The auricular lymph nodes appeared normal.

Group 3: erythema and edema were absent on both ears and trunk through day 9 and 10/11, respectively. No abnormal physical signs were recorded through day 8. Two animals experienced lethargy, wetness of the anogenital area. One animal died on day 10, the second was sacrificed due to the critical conditions.
Necropsy in those two animals showed abnormalities in the gastrointestinal tract and wetness of the anogenital area. The auricular lymph nodes appear larger than normal.

Group 4: erythema and edema were absent on both ears and trunk on days 0, 1, 2, 3, 4, 14 and 15. Signed of very well defined erythema was found on days 16, 17, 18. Edema was absent to very slight on days 16, 17, and 18. The trunk area showed dermal scores on days 16, 17, 18, absent on days 23,24,25.
No abnormal physical signs were recorded through day 15. One animal experienced lethargy, wetness of the anogenital area and on day 17 was sacrificed due to the critical conditions. Necropsy of the moribund animal showed wetness of the anogenital area. The auricular lymph nodes appear larger than normal. Alopecia at the base of the ears was notices in all the survived animals

Group 5: erythema and edema were absent on both ears and trunk on days 0, 1, 2, 3, 4, 14 and 15 and 16. Dermal scores were absent on days 23, 24, 25.
No abnormal physical signs were reordered during the study and necropsy resulted normal.

Group 6: erythema and edema of both ears were absent on day 23, 24, 25. No abnormal physical signs were recorded during the study and necropsy resulted normal.

Group 7 (control): No erythema or edema was noted. No abnormal physical signs were recorded during the study and necropsy resulted normal

Applicant's summary and conclusion

Conclusions:

Prolonged dermal exposure of mice ears to 75% of Ceraphyl 55 caused no abnormal physical signs and necropsy resulted normal.

Executive summary:

The study was conducted to determine the potential toxicity of Ceraphyl 55 when applied dermally to the dorsal and trunk area and the irritation potential for irritation when administered to the ear. Thirty-five female Balb/C Mice were assigned to seven groups corresponding to 6 different concentrations and the control. The results of G (Group) 1 (100%) showed erythema scores ranged from 0 to 1 on both ears and trunk. No edema was noted. However, four of five animals died within 72 hr of the 5000 mg/kg application. Pre-death physical signs included lethargy, ataxia, dyspnoea, tremors, flaccid muscle tone were recorded. Necropsy revealed abnormalities of the liver, gastrointestinal tract, emaciation and wetness of anogenital area (one animal). The auricular lymph nodes appeared normal. In G2 (100%) erythema and edema were absent on both ears and trunk. Three of five animals were sacrificed because the critical conditions (72 hr of the 5000 mg/kg application). Pre-death physical signs included lethargy, ataxia, dyspnoea, tremors, flaccid muscle tone were recorded. Necropsy revealed abnormalities of the liver, gastrointestinal tract, emaciation and wetness of anogenital area (one animal). The auricular lymph nodes appeared normal. In G3 (75%) erythema and edema were absent on both ears and trunk through day 9 and 10/11, respectively. No abnormal physical signs were recorded through day 8. Two animals experienced lethargy, wetness of the anogenital area. One animal died on day 10, the second was sacrificed due to the critical conditions. Necropsy in those two animals showed abnormalities in the gastrointestinal tract and wetness of the anogenital area. The auricular lymph nodes appear larger than normal. Regarding G4 (75%), erythema and edema were absent on both ears and trunk on days 0, 1, 2, 3, 4, 14 and 15. Signed of very well defined erythema was found on days 16, 17, 18. Edema was absent to very slight on days 16, 17, and 18. The trunk area showed dermal scores on days 16, 17, 18, absent on days 23, 24, 25. No abnormal physical signs were recorded through day 15. One animal experienced lethargy, wetness of the anogenital area and on day 17 was sacrificed due to the critical conditions. Necropsy of the moribund animal showed wetness of the anogenital area. The auricular lymph nodes appear larger than normal. Alopecia at the base of the ears was notices in all the survived animals. In G5 (50%) erythema and edema were absent on both ears and trunk on days 0, 1, 2, 3, 4, 14 and 15 and 16. Dermal scores were absent on days 23, 24, 25. No abnormal physical signs were recorded during the study and necropsy resulted normal. In G6 (50%) erythema and edema of both ears were absent on day 23, 24, 25. No abnormal physical signs were recorded during the study and necropsy resulted normal. Finally, the G7 (control) showed no erythema or edema. No abnormal physical signs were recorded during the study and necropsy resulted normal.