Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 1996-06-04 to 1996-09-19
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
OECD Guidelines for the Testing of Chemicals, Section 4, Health Effects, Subsection 401, February 24, 1987.
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
The EEC Guidelines Part B: Methods for the Determination of Toxicity, No. L 383 A/110, B.1, December 29, 1992.
Deviations:
no
Qualifier:
according to
Guideline:
EPA OTS 798.1175 (Acute Oral Toxicity)
Version / remarks:
Toxic Substances Control Act Test Guidelines, 40 CFR Part 798, Subpart B, Section 798.1175, July 1, 1992.
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
Lot No.: 0998603612
Purity: 59.6 %

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl:CD®BR VAF/Plus®
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Portage, Michigan, USA
- Females nulliparous and non-pregnant: yes
- Housing: individually in suspended stainless steel cages
- Weight at study initiation: males: 212 - 242 g; females: 216 - 241 g
- Age at study initiation: young adults
- Fasting period before study: overnight
- Diet: PMI Certified Rodent Chow #5002 (Purina Mills, Inc.) was provided ad libitum to the animals throughout the study (except during fasting).
- Water: Municipal tap water treated by reverse osmosis was available ad libitum throughout the study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 21 °C (60 - 70 °F)
- Humidity (%): 52 - 71
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Single oral dose application. The test item was applied in its initial form.
Doses:
2000, 3500 and 5000 mg/kg
No. of animals per sex per dose:
5 females and 5 males per dose
Control animals:
no
Details on study design:
Oral application on day 0. Post-dose observational period - 14 days.
Statistics:
The LD50 and 95% confidence intervals were calculated separately for males, females and the combined sexes using a computer adaption of the method of Litchfield and Wilcoxon.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
3 256.8 mg/kg bw
Based on:
test mat.
95% CL:
>= 2 537.8 - <= 4 179.4
Sex:
female
Dose descriptor:
LD50
Effect level:
2 645.8 mg/kg bw
Based on:
test mat.
95% CL:
>= 2 279.5 - <= 3 070.8
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 099.8 mg/kg bw
Based on:
test mat.
95% CL:
>= 2 707.6 - <= 3 548.9
Mortality:
Four males and five females died in both the 3500 and 5000 mg/kg dose groups. All mortality occurred by study day 6.
Clinical signs:
The most notable clinical abnormalities observed during the study in both the animals that died and those that survived included decreased activity, breathing abnormalities, decreased to no defecation, piloerection, hunched posture, rough haircoat, dehydration, dark material around facial area, low food consumption, lacrimation, and feces small in size. Fecal/urine stain and distended abdomen were noted only in the surviving animals. Additional clinical abnormalities noted in the animals that died only included prostration, apparent hypothermia, extremities pale in color, cyanosis, wobbly gait and eyelids partially closed. Salivation was also noted on day 0 only in both the animals that survived and those that died and was probably related to the irritant nature of the test article.
Body weight:
Body weight loss was noted in one 2000 mg/kg female during the day 0 to 7 body weight interval. Body weight gain was noted for all other surviving animals during the test period.
Gross pathology:
The most notable gross internal findings were observed in the animals that died and included abnormal contents, discoloration and thickened mucosa in the digestive tract, reddened thymus, abnormal and discolored contents in the trachea, abnormal contents in the urinary bladder, discolored lungs, livers and pancreas and congested meningeal vessels in the brain. No significant gross internal findings were observed at necropsy on study day 14, however single incidences of dilated pelvis of the kidney, gray raised area(s) on the spleen, thickened stomach mucosa and adhesion on the abdominal cavity were noted.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this test, the acute oral LD50 of the test item in the male rat was determined to be 3257 mg/kg. If the rat were female, the oral LD50 was determined to be 2646 mg/kg. In the sexes combined, the oral LD50 was determined to be 3100 mg/kg.
Executive summary:

The single-dose oral toxicity of Succinic Acid Peroxide was evaluated in Sprague-Dawley rats. An LD50 study was performed in which three groups of five male and five female rats received a single oral administration of the test article at graded dosage levels. Following dosing, the LD50 study rats were observed daily and weighed weekly. A gross necropsy examination was performed on all LD50 study animals at the time of death or scheduled euthanasia (day 14). Mortality occurred during the LD50 study in dose levels 3500 and 5000 mg/kg - 4 males and 5 females died ind each dose group. All mortality occurred by study day 6.

The most notable clinical abnormalities observed during the study in both the animals that died and those that survived included decreased activity, breathing abnormalities, decreased to no defecation, piloerection, hunched posture, rough haircoat, dehydration, dark material around facial area, low food consumption, lacrimation, and feces small in size. Fecal/urine stain and distended abdomen were noted only in the surviving animals. Additional clinical abnormalities noted in the animals that died only included prostration, apparent hypothermia, extremities pale in color, cyanosis, wobbly gait and eyelids partially closed. Salivation was also noted on day 0 only in both the animals that survived and those that died and was probably related to the irritant nature of the test article. Body weight loss was noted in one 2000 mg/kg female during the day 0 to 7 body weight interval. Body weight gain was noted for all other surviving animals during the test period. The most notable gross internal findings were observed in the animals that died and included abnormal contents, discoloration and thickened mucosa in the digestive tract, reddened thymus, abnormal and discolored contents in the trachea, abnormal contents in the urinary bladder, discolored lungs, livers and pancreas and congested meningeal vessels in the brain. No significant gross internal findings were observed at necropsy on study day 14, however single incidences of dilated pelvis of the kidney, gray raised area(s) on the spleen, thickened stomach mucosa and adhesion on the abdominal cavity were noted.

Under the conditions of this test, the acute oral LD50 of Succinic Acid Peroxide in the male rat was determined to be 3257 mg/kg. If the female rat, the dermal LD50 was determined to be 2646 mg/kg. In the sexes combined, the dermal LD50 was determined to be 3100 mg/kg.