Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985-09-05 to 1985-09-30
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study to Guideline but insufficient information included in the report

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar 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:
- Physical state: amber liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Inc., Boyertown, PA USA
- Age at study initiation: Not specified
- Weight at study initiation: 2.0 - 3.0 kg
- Fasting period before study: No
- Housing: In accordance with Guidance: DHEW No. 80-23
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitm
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 60 - 75°F
- Humidity (%): 55±25%
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From: 1985-09-05 To: 1985-09-19

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: 10% of body surface
- Type of wrap if used: Large porous gauze patch wrapped with impervious material

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.0 g/kg

Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 per sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Frequently on first day of dosing and twice per day (morning and afternoon) on week days, once on weekends and holidays. Weights recorded on day of dosing, weekly thereafter and prior to sacrifice.
- Necropsy of survivors performed: yes/no
- Other examinations performed: clinical signs, body weight, gross necropsy

Results and discussion

Preliminary study:
Not performed
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was one mortality, one female died at the day 12 observation period.
Clinical signs:
Males:
Signs of necrosis and severe oedema were observed for 5/5 animals after unwrapping at 24 hours. Eschar was noted in 3/5 animals at 48 hours and for 2/5 animals at 72 hours. The eschar began to peel at 7 days in 3/5 animals, at 8 days in 1/5 animals and at 9 days in 1/5 animals. Other than the above observations, all other animals appeared normal throughout the 14 day observation period.
Females:
Signs of necrosis and severe oedema were obsserved for 5/5 animals after unwrapping at 24 hours. Eschar was noted for 5/5 animals by 48 hours which began to peel in 4/5 animals at 8 days and in 1/5 animals at 10 days. No adverse syptoms (except loss of bodyweight) preceded the death of one animal on day 12. Other than the above observations, the remaining 4/5 animals appeared normal throughout the observation period.
Body weight:
Males: A loss of bodyweight was noted for 1/5 animals at 7 and 14 days
Females: Loss of bodyweight at 7 days in animal that died. Loss of bodyweight noted for 2/5 animals at 7 days and for 1/5 of remaining animals at 14 days.
Gross pathology:
Males:
No gross abnormalities were noted for the animals necropsied at the conclusion of the 14 day observation period.
Females:
Diarrhea, signs of dehydration and no formal fecal material in the lower gastrointestinal tract were noted for the animal found dead at 12 days. No gross abnormalities were noted for the animals necropsied at the conclusion of the 14 day observation period.
Other findings:
No measurable residual test material left on animals after the 24 hour contact period.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test article, when administered as received to male and female New Zealand White rabbits, had an acute dermal LD50 of greater than 2000 mg/kg bodyweight. In accordance with EU CLP Regulation (EC) No. 1272/2008, classification of this substance is not required for acute dermal toxicity.
Executive summary:

Test Guidance

Acute dermal toxicity was performed in a similar manner to a method described in EPA OPP 81 -2

Method and Material

A single dose of 2 g/kg undiluted test material was applied to the shaved backs of ten New Zealand White rabbits (5 males and 5 females). The test material was covered with an occlusive dressing for a period of 24 hours. At the end of the exposure period, the treated area was wiped to remove any residual test material. The animals were observed for deaths or overt signs of toxicity daily for 14 days. The sites were also examined for evidence of primary irritation daily for 14 days. Individual bodyweights were recorded prior to application of the test material at the start of the study and on days 7 and 14. At the end of the observation period all animals were euthanized and subjected to gross necropsy.

Results

There was one mortality, one female died at the day 12 observation period.

Males: Signs of necrosis and severe oedema were observed for 5/5 animals after unwrapping at 24 hours. Eschar was noted in 3/5 animals at 48 hours and for 2/5 animals at 72 hours. The eschar began to peel at 7 days in 3/5 animals, at 8 days in 1/5 animals and at 9 days in 1/5 animals. Other than the above observations, all other animals appeared normal throughout the 14 day observation period. A loss of bodyweight was noted for 1/5 animals at 7 and 14 days. No gross abnormalities were noted for the animals necropsied at the conclusion of the 14 day observation period.

Females: Signs of necrosis and severe oedema were obsserved for 5/5 animals after unwrapping at 24 hours. Eschar was noted for 5/5 animals by 48 hours which began to peel in 4/5 animals at 8 days and in 1/5 animals at 10 days. No adverse syptoms (except loss of bodyweight) preceded the death of one animal on day 12. Other than the above observations, the remaining 4/5 animals appeared normal throughout the observation period. There was a loss of bodyweight at 7 days in the animal that died. Loss of bodyweight was noted for 2/5 animals at 7 days and for 1/5 of remaining animals at 14 days. Diarrhea, signs of dehydration and no formal fecal material in the lower gastrointestinal tract were noted for the animal found dead at 12 days. No gross abnormalities were noted for the animals necropsied at the conclusion of the 14 day observation period.

The dermal LD50 of the test material in male and female rabbits has been determined to be greater than 2000 mg/kg bw.

Conclusion

In accordance with EU CLP Regulation (EC) No. 1272/2008, classification of this substance is not required for acute dermal toxicity.