Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Date: September 24, 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Conducted in accordance with the regulations for Good Laboratory Practices as described by the FDA (21 CFR Part 58) and FDRL Standard Operating Procedures.
GLP compliance:
yes
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
additive
Test material form:
liquid
Details on test material:
FDRL Test Article ID: 81-0558
Sponsor Test Article ID: TA-54M75; tert-amyl peroxypivalate 75% in odorless mineral spirit
Specific details on test material used for the study:
FDRL Test Article ID: 81-0558
Sponsor Test Article ID: TA-54M75; tert-amyl peroxypivalate 75% in odorless mineral spirit

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
Five male and 5 female adult New Zealand White rabbits, weighing between 2.0 and 4.0 kg, were purchased from H.A.R.E. - Rabbits for Research, Hewitt, N.J. for use in this-study. H.A.R.E. - Rabbits is a USDA approved supplier.
All animals were acclimated a minimum of 5 days. During this acclimation period, the rabbits were examined with respect to their general health to assure their suitability as test animals. The rabbits were housed individually
in wire mesh bottom cages. NIH Animal Feed A (certified) and water were provided ad libitum. Animals were identified by use of ear tags and cage cards.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The back and flanks of each rabbit were clipped free of fur with electrical clippers not more than 24 hours before study initiation. The clipped area constituted approximately 30 percent of the total body surface.
On the day of testing and just prior to the application of the test article, abrasion of the skin was performed on the exposure sites of 3 males and 2 female rabbits. The skin of the remaining 2 male and 3 female rabbits was left intact. Abrasions were made with the point of a 22 gauge disposable hypodermic needle. The abrasions were minor incisions through the stratum corneurn that were not sufficiently deep enough to disturb the derma or to produce bleeding.
The test article was administered under an occlusive binder at a level of 2.0 g/kg. The occlusive binder consisted of a layer of plastic wrap, a protective cloth and stockinette binder, all securely held in place with masking tape. The occlusive binder is applied to maintain contact and minimize evaporation of the applied test article.
If the test article was solid, it was moistened with physiological saline, (1 ml saline per 1 g of test article) before dermal application. Liquid test articles are administered as received.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
no
Details on study design:
After an exposure period of 24 hours the occlusive binders were-removed. The exposure sites were then gently wiped with clean gauze to remove as much nonabsorbed test article as possible. Observations for mortality, local reactions, and toxicological findings were recorded for a total of 14 days. Body weights were recorded on the initial day of testing, day 8 and at study termination or day of death.
Only those animals that died during the progress of the study were subjected to a gross necropsy.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat.
95% CL:
>= 0 - <= 40
Mortality:
1 in 10 rabbits (10% mortality)

Any other information on results incl. tables

Table 1 Dosing schedule

Animal Number and Sex

Body Weight (g) at Day

Dosage level

g/kg

Dose

ml (Total)

1

8

15

WAD

001m

2.46kg

2.52kg

2.58kg

 

2.00 g/kg

5.29

002m

2.38kg

2.50kg

2.40kg

 

2.00 g/kg

5.12

003m

2.74kg

2.49kg

2.57kg

 

2.00 g/kg

5.89

004m

2.72kg

2.73kg

2.86kg

 

2.00 g/kg

5.85

005m

2.87kg

2.93kg

3.10kg

 

2.00 g/kg

6.17

006f

2.86kg

2.34kg

2.60kg

 

2.00 g/kg

6.15

007f

2.14kg

2.21kg

2.50kg

 

2.00 g/kg

4.60

008f

2.52kg

2.35kg

2.68kg

 

2.00 g/kg

5.42

009f

2.60kg

2.61kg

-

2.26kg

2.00 g/kg

5.59

010f

3.05kg

2.95kg

2.98kg

 

2.00 g/kg

6.56

WAD = weight after death

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The dermal LD50 is greater than 2000 mg/kg. Since one death is observed at 2000 mg/kg this warrants classification in category 5 according to GHS criteria (table 3.1.1 note g-ii).
Executive summary:

Results:

Dose level

g/kg

No. Rabbits Dosed

No. of Death on Study Day

Cumulative Mortality

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

2.0

10

0

0

0

0

0

0

0

0

0

0

0

0

0

1

0

1/10

Percent mortality = 10%

95% Confidence Interval = 0-40%

The above data indicate that the dermal LD50 is greater than 2.0 g/kg.