Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 January 1984 - 21 February 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP-like (QA signature), guideline study with limited details on individual animals

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: US 16 CFR 1500.4 Federal Hazardous Substances Act
Deviations:
no
GLP compliance:
yes
Remarks:
GLP-like (QA signature)
Test type:
standard acute method
Limit test:
yes

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
- Source: Ace Animals, Inc., Boyertown, PA, USA
- Age at study initiation: No data available
- Weight at study initiation: 2.3-3.0 kg
- Fasting period before study:
- Housing: The animals were individually housed and maintained in accordance with standards set forth in the Guide for the Care and Use of Laboratory Animals (DHEW publication No. 80-23)
- Diet: Wayne 15 % Rabbit Ration was provided ad libitum
- Water: tap water was available ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 60-75
- Humidity (%): 40-45
- Air changes (per hr): controlled environment, but no air change information provided
- Photoperiod: 12 h light/dark cycle

IN-LIFE DATES: From: To: 1/26/84-2/9/84

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back, abraided and intact skin
- % coverage: approximately 10 % of total body surface area.
- Type of wrap if used: gauze patch covered with an impervious material.

REMOVAL OF TEST SUBSTANCE
- Washing: excess material was removed by wiping but not washing.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: correct amount to give a dose of 2000 mg/kg bw (not specified in the report)
- Concentration (if solution): the test material was used undiluted as supplied
- Constant volume or concentration used: yes
- For solids, paste formed: Not applicable

VEHICLE
- Amount(s) applied: Not applicable
- Concentration (if solution): Not applicable
- Lot/batch no.: Not applicable
- Purity: Not applicable
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed daily for deaths or overt signs of toxicity. Individual bodyweights were recorded prior to application of the test material and Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: gross necropsies were performed on all animals after sacrifice at the conclusion of the 14 day observation period.
Statistics:
No data available

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: Number of animals: 5; Number of deaths: 0
Female: Number of animals: 5; Number of deaths: 0
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
Male: no effects on bodyweight noted
Female: a loss of bodyweight was noted for 1/5 animals at 14 days
Gross pathology:
Male: No gross abnormalities were noted
Female: no formed fecal material and spongy kidneys were noted for the animal that exhibited a loss in bodyweight. No gross abnormalities were noted for the remaining four animals
Other findings:
- Other observations: dermal reactions

Male/female: mild to moderate erythema was observed after unwrapping at 24 hours. By 4 days all animals exhibited eschar which persisted through day 14 of the study.

Any other information on results incl. tables

Table 1: Summary of mortality and bodyweight data

 

Males

Females

Intact

Abraded

Abraded

Intact

Mortality after 14 days

0

0

0

0

Average

bodyweights (kg)

Initial

2.87

2.73

2.70

2.73

7thday

2.89

2.82

2.82

2.66

Final

2.92

3.01

2.86

3.05

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
Executive summary:

Test Guidance

Acute dermal toxicity was performed to a method described in US 16 CFR 1500.4 Federal Hazardous Substances Act

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 skin of five animals (2 males and 3 females) was abraded prior to dosing. 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 were no deaths or clinical signs of toxicity during the study. A loss of bodyweight was noted for one female at 14 days, all other animals showed expected gains. Mild to moderate erythema was observed in all animals after the 24 hour exposure and by day 4 of the observation period all animals exhibited eschar which persisted through day 14 of the study. Gross pathological examination showed no formed fecal material and spongy kidneys in the female that lost weight. No abnormalities were noted in the other animals. 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.