Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From November 28 to December 20, 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test conducted following internationally accepted testing guidelines and performed according to the GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Specie & strain: Albino rabbit; New Zealand White.
- Justification of Species: the rabbit is a representative species preferred by various regulatory agencies for use in an acute dermal testing.
- Source: Ray Nichols Rabbitry; Lumberton, TX
- Age at study initiation: 80 days.
- Weight at study initiation: males: 2.300-2.700 kg; females: 2.025-2.525 kg.
- Housing: one per cage.
- Cage type: suspended, wire bottom, stainless steel.
- Diet: PMI Feeds, Inc.TM Lab Rabbit Diet #5321, in measured amounts.
- Water: municipal water supply analyzed by TNRCC Water Utilities Division; tap water, available ad libitum (automatic system).
- Quarantine period: 5 days.

ENVIRONMENTAL CONDITIONS
Set to maintain
- Temperature: 20 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: 10-12 air change/hour.
- Photoperiod: 12 hours light/dark cycle.

IN-LIFE DATES
Animlas born in September 09, 2001. They were received by the laboratory at November 28 and were treated with the test substance on December 06. The in-life portion of the study was termined on December 20, 2001.

No contaminants were expected to have been present in the feed or water which would have interfered with or affected the results of the study.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Remarks:
deionised
Details on dermal exposure:
TEST SITE and APPLICATION of TS
- Preparation: each animal was prepared on the day prior to treatment by clipping the dorsal surface of the trunk free of hair. Care was taken to avoid abrading the skin. Only those animals with exposure area free of pre-existing skin irritation or defects were used for the study.
- Test substance application: the test substance was applied evenly to each exposure area in a thin, uniform layer.
- % coverage: expose not less than 10 %.
- Type of wrap if used: the area of application was covered with 4 ply, 8 x 4 in. surgical gauze patch and secured with non-irritating adhesive tape. The trunk of each animal was then wrapped with orthopaedic stockinet which was secured in place with non-irritating adhesive tape to prevent possible ingestion of the test substance.

REMOVAL OF TEST SUBSTANCE
- Washing: washed with room temperature tap water and a clean cloth.
- Time after start of exposure: after 24 hours.

VEHICLE
- Amount(s) applied: each dose was moistened with sufficient amount of deionised water (0.96 ml/g of test substance).
Duration of exposure:
24 hours
Doses:
5050 mg/kg
No. of animals per sex per dose:
5 males and 5 females (nulliparous and non-pregnant)
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for mortality and clinical/behavioural signs of toxicity were made at least three times on the day of dosing (Day 0) and at least once daily thereafter for 14 days. Individual body weights were recorded just prior to dosing and on Days 7 and 14.
- Necropsy of survivors performed: yes; on Day 14 after dosing, animals were euthanized by an intracardiac injection of Fatal Plus®. All study animals were subjected to gross necropsy and all abnormalities were recorded. After necropsy, the animal carcasses were discarded.
- Other examinations performed: observations for evidence of dermal irritation were made at approximately 60 minutes after removal of wrappings, and on Days 4, 7, 11 and 14.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 050 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality during the study. The estimated acute dermal LD50, as indicated by the data, was determined to be greater than 5050 mg/kg body weight.
Clinical signs:
Prominent in-life observations included decreased defecation and soft faeces in both sexes, on the day of dosing and Day 12.
Body weight:
Body weight gain was unaffected by the administration of the test substance.
Gross pathology:
The gross necropsy conducted at termination of the study revealed no observable abnormalities, except for pale kidneys in two males.
Other findings:
DERMAL IRRITATION
Irritation included very slight erythema through Day 4, very slight oedema an Day 1, and desquamation an Days 7 and 11; test substance residue was also observed.

Any other information on results incl. tables

Pharmacologic and/or toxicological signs

Reaction and severity Time after treatment
Hours Days
1.0 2.0 4.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
MALES
Soft faeces 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Decreased defecation 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 0 0
FEMALES
Decreased defecation 1 0 0 0 0 0 0 0 0 0 0 0 0 0 3 0 0
Soft faeces 0 0 2 0 0 0 0 0 0 0 0 0 0 0 0 0 0

Signs of dermal irritation

Animal Day 1 Day 4 Day 7 Day 11 Day 14
Er Oed Other Er Oed Other Er Oed Other Er Oed Other Er Oed Other
Male 1 0 T 0 0 T 0 0 - 0 0 - 0 0 -
Male 1 0 T 1 0 T 0 0 - 0 0 - 0 0 -
Male 1 1 T 0 0 T 0 0 - 0 0 - 0 0 -
Male 1 1 T 0 0 T 0 0 D, T 0 0 D, T 0 0 T
Male 1 0 T 0 0 T 0 0 D, T 0 0 - 0 0 -
Female 1 0 T 0 0 T 0 0 - 0 0 - 0 0 -
Female 1 0 T 0 0 T 0 0 T 0 0 - 0 0 -
Female 1 1 T 0 0 T 0 - 0 0 - 0 -
Female 1 0 T 1 0 T 0 0 D, T 0 0 D, T 0 0 -
Female 1 0 T 0 0 T 0 0 T 0 0 D, T 0 0 -

Er = Erythema; 0 = None; 1 = Very slight; 2 = Well-defined; 3 = Moderate; 4 = Severe

Oed = Oedema; 0 = None; 1 = Very slight; 2 = Slight; 3 = Moderate; 4 = Severe

D = Desquamation; T = Test substance residue

Note: A dash (-) is used if no other irritation is observed

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information according to the CLP Regulation Criteria used for interpretation of results: EU
Conclusions:
LD50 is greater than 5050 mg/kg in males and females.
Executive summary:

The test substance was evaluated for its dermal toxicity potential and relative skin irritancy when a single dose moistened with 0.96 ml of deionised water/g test substance, at a level of 5050 mg/kg, was applied to the intact skin of albino rabbits.

No mortality occurred during the study. Clinical signs included decreased defecation and soft faeces on Days 0 and 12 of the study. Signs of dermal irritation included erythema, oedema and desquamation. There was no effect on body weight gain during the study. The gross necropsy conducted at termination of the study revealed no observable abnormalities, except for pale kidneys in two animals.

Conclusion

The estimated LD50 was determined to be greater than 5050 mg/kg