Registration Dossier

Administrative data

Description of key information

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.

The acute dermal LD50 of the test item was estimated to be greater than 2000 mg/kg in the rat.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
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
Specific details on test material used for the study:
Lot No.: 0998603612
Purity: 59.6 %
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
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.
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.
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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
3 100 mg/kg bw
Quality of whole database:
1 study report, GLP conformity, performed according to OECD, EEC and EPA Guidelines.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 1996-06-04 to 1996-09-20
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
EPA OTS 798.1100 (Acute Dermal Toxicity)
Version / remarks:
Toxic Substances Control Act Test Guidelines, 40 CFR Part 798, Subpart B, Section 798.1100, July 1, 1992.
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
OECD Guidelines for the Testing of Chemicals, Section 4, Health Effects, Subsection 402, February 24, 1987.
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
The EEC Guidelines Part B: Methods for the Determination of Toxicity, No. L 383 A/121, B.3, December 29, 1992.
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
Lot No.: 0998603612
Purity: 59.6 %
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
- Age at study initiation: young adults
- Weight at study initiation: males: 264 - 351 g; females: 221 - 243 g
- Housing: individually in suspended stainless steel cages
- Diet: PMI Certified Rodent Chow #5002 (Purina Mills, Inc.) was provided ad libitum to the animals throughout the study.
- Water: Municipal tap water treated by reverse osmosis was available ad libitum throughout the study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 - 20.5 °C (59 - 69 °F)
- Humidity (%): 52 - 80
- Air changes (per hr): 10- 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: the dorsal trunk area of the animals, the fur was shaved and the area was clipped
- % coverage: ≥ 10% of the animal's body surface area (BSA)
- Type of wrap: an appropriately sized 4 ply porous gauze dressing, a plastic wrap and an elastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test article was removed using gauze moistened with distilled water followed by dry gauze.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 4 mL/kg
- Concentration: 2000 mg/kg
Duration of exposure:
24 h exposure, 14 days observation after exposure
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights were obtained for the limit test animals prior to dosing on day 0 and on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed:
= clinical signs: Limit test animals were observed for clinical abnormalities a minimum of two times on study day 0 (postdose) and daily thereafter (days 1-14). A general health/mortality check was performed twice daily.
= dermal observations: Limit test animals were examined for erythema and edema following patch removal on study day 1 and daily thereafter (days 2-14) according to the Macroscopic Dermal Grading System based on Draize. The dermal test sites were reclipped as necessary to allow clear visualization of the skin.
Statistics:
Data from the limit test were analyzed and an LD50 value 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: LD50 was estimated as less than the administered dose.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the limit test.
Clinical signs:
The most notable clinical abnormalities observed during the study included dark material around facial area, and urine stain. Dermal irritation was noted at the site of test article application.
Body weight:
Body weight gain was noted for all animals during the test period.
Gross pathology:
No significant gross internal findings were observed at necropsy on study day 14.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this test, the acute dermal LD50 of the test item was estimated to be greater than 2000 mg/kg in the rat.
Executive summary:

The single-dose dermal toxicity of the test item was evaluated on Sprague-Dawley rats. A limit test was performed in which one group of five male and five female rats received a single dermal administration of the test item at a dose of 2000 mg/kg body weight. Following dosing, the rats were observed daily and weighed weekly. A gross necropsy examination was performed on all limit test animals at the time of death or scheduled euthanasia (day 14).

No mortality occurred during the limit test. The most notable clinical abnormalities observed during the study included dark material around facial area, and urine stain. Dermal irritation was noted at the site of test article application. Body weight gain was noted for all animals during the test period. No significant gross internal findings were observed at necropsy on study day 14.

Under the conditions of this test, the acute dermal LD50 of the test item was estimated to be greater than 2000 mg/kg in the rat.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
1 study report, GLP conformity, performed according to OECD, EEC and EPA Guidelines.

Additional information

Acute oral

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.

Acute dermal

The single-dose dermal toxicity of the test item was evaluated on Sprague-Dawley rats. A limit test was performed in which one group of five male and five female rats received a single dermal administration of the test item at a dose of 2000 mg/kg body weight. Following dosing, the rats were observed daily and weighed weekly. A gross necropsy examination was performed on all limit test animals at the time of death or scheduled euthanasia (day 14).

No mortality occurred during the limit test. The most notable clinical abnormalities observed during the study included dark material around facial area, and urine stain. Dermal irritation was noted at the site of test article application. Body weight gain was noted for all animals during the test period. No significant gross internal findings were observed at necropsy on study day 14.

Under the conditions of this test, the acute dermal LD50 of the test item was estimated to be greater than 2000 mg/kg in the rat.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. The LD50 was greater than 2000 mg/kg bw in both oral and dermal exposure studies. As a result the substance is not considered to be classified for acute oral and dermal toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.