Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995-10-5 to 1996-01-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
The relative humidity (38-79%) exceeded the range specified in the protocol (40-70%). The p.m. mortality check was inadvertently not documented on study day 10 (10/29/95).
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: paste
Details on test material:
- State of aggregation: paste
- Density: 1.03 g/mL
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source: Geneseo, NY
- Lot/batch No.of test material: 8968525407
- Expiration Date: March 10, 1996

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Below 100˚F
- Solubility of the test substance: Slight

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: No prior treatment. The test article was administered as received from the Sponsor.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
Sprague - Dawley Crl : CD BR VAF / Plus rats were used
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Portage, Michigan
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: Young adult
- Weight at study initiation: Males: 285-305 g, females: 240-257 g
- Housing: Animals were housed individually in suspended stainless steel cages. Housing and care was based on the standards recommended by the Guide for the Care and Use of Laboratory Animals.
- Diet (e.g. ad libitum): ad libitum, Purina Certified Rodent Chow #5002
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 61 - 73 ˚F
- Humidity (%): 38-79
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- % coverage: 10
- Type of wrap if used: plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, residual test item was removed using gauze moistened with distilled water
- Time after start of exposure: 24 h

TEST MATERIAL
- Constant volume or concentration used: yes
Duration of exposure:
approx. 24 h
Doses:
2000 mg / kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Clinical observations: Test animals were observed for clinical abnormalities two times on study day 0 (postdose) and daily thereafter (days 1-14). A mortality check was performed twice daily, in the morning and afternoon. Dermal observations were made following patch removal on study day 1 and daily thereafter days (2 - 14).
- Frequency of weighing: Individual body weights were obtained prior to dosing on day 0, on days 7 and 14 and at the time of death for any animal dying on study (except those that die on day 0)
- Necropsy of survivors performed: yes
Statistics:
The LD50 value was estimated as follows:
< 50% mortality: LD50 was estimated as greater than the administered dose.
= 50% mortality: LD50 was estimated as equal to the administered dose.
> 50% mortality: L050 was estimated as less than the administered dose.

Body weight means and standard deviations were calculated separately for males and females for each limit level administered.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
One animal was found dead on Day 2.
Clinical signs:
Most notable clinical abnormalities observed during the study included urine stain and dark material around the facial area, observed within the first three days of the study. For the animal that died, the clinical observations included decreased activity, wobbly gait, apparent hypothermia, urine stain, rough haircoat and dark material around the facial area. Dermal irritation was noted at the site of test article application for all animals.
Body weight:
Body weight loss was noted for three female rats during the study day 0-7 interval and one female rat during the study day 7-14 interval. Body weight gain was noted for all other surviving animals during the test period.
Gross pathology:
For the animals that died, the most notable necropsy findings observed dark red mandibular lymph nodes, reddened mucosa in the stomach and congested meningeal vessels in the brain. No gross internal findings were observed at necropsy on day 14 for the surviving animals.

Any other information on results incl. tables

Table 1: Mortality during the limit test for the test item

Dose (mg/kg bw)

No. Dead / No. Dosed

 

Males

Females

Combined

2000

0 / 5

1 / 5

1 / 10

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In this study, the acute dermal LD50 of OO-tert-butyl monoperoxymaleate (25%) was estimated to be greater than 2000 mg/kg in the rat.
Executive summary:

In an acute dermal toxicity study, similar to OECD 402, groups of young adult male and female Sprague – Dawley rats (5/sex) were dermally exposed to OO-tert-butyl monoperoxymaleate (25%) for 24 hours to 10% of body surface area at a dose of  2000 mg/kg bw.  Animals then were observed for 14 days. Under the conditions of this test, the acute dermal LD50 of OO-tert-butyl monoperoxymaleate (25%) was estimated to be greater than 2000 mg/kg in the rat. 

Most notable clinical abnormalities observed during the study included urine stain and dark material around the facial area, observed within the first three days of the study. For the animal that died, the clinical observations included decreased activity, wobbly gait, apparent hypothermia, urine stain, rough haircoat and dark material around the facial area. Dermal irritation was noted at the site of test article application for all animals.

Body weight loss was noted for three female rats during the study day 0-7 interval and one female rat during the study day 7-14 interval. Body weight gain was noted for all other surviving animals during the test period.

For the animals that died, the most notable necropsy findings observed dark red mandibular lymph nodes, reddened mucosa in the stomach and congested meningeal vessels in the brain. No gross internal findings were observed at necropsy on the last day.