Dipropyl peroxydicarbonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

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

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dipropyl peroxydicarbonate

EC Number:

240-211-7

EC Name:

Dipropyl peroxydicarbonate

Cas Number:

16066-38-9

Molecular formula:

C8H14O6

IUPAC Name:

1-({[(propoxycarbonyl)peroxy]carbonyl}oxy)propane

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Portage, Michigan
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: no data
- Weight at study initiation: males 215-234 g, females 207-235 g
- Fasting period before study: overnight
- Housing: individually in suspended stainless steel cages
- Diet: PMI Certified Rodent Chow #5002 (Purina Mills, lnc.) was provided ad libitum
- Water: Municipal tap water treated by reverse osmosis was available ad libitum
- Acclimation period: >= 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 61-71°F
- Humidity: 56-74%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2000, 3500 and 4500 mg/kg (1.82, 3.18 and 4.09 ml/kg)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Clinical Observations
LD50 study animals were observed for clinical abnormalities two times on study day 0 (postdose) and daily thereafter (days 1-14). A general health/mortality check was performed twice daily (in the morning and in the afternoon).
- Body Weights
lndividual body weights were obtained for the LD50 study animals prior to fasting (day -1), prior to dosing on day 0 and for all surviving animals on days 7 and 14. Animals found dead after day 0 were also weighed.
- Gross Necropsy
All LD50 study animals which died spontaneously during the study or were euthanized by carbon dioxide inhalation at study termination (day 14) were necropsied. Body cavities (cranial, thoracic, abdominal and pelvic) were opened and examined. No tissues were retained.

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 levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 158 mg/kg bw

Based on:

test mat.

95% CL:

2 670.6 - 3 734.8

Mortality:

See table.

Clinical signs:

The most notable clinical abnormalities observed during the study included decreased activity, salivation, soft mucoid stools, dark material around facial area, decreased/no defecation, diarrhea, gelatinous material on litter, fecal/urine stain, rough haircoat, wobbly gait, breathing abnormalities, piloerection, prostration, hunched posture, eyelids partially closed, and apparent hypothermia. The majority of these observations were noted in bath the animals that died and those surviving to study termination. ln the 2000 mg/kg and 3500 mg/kg dose groups, most of the notable observations were generally noted during the first 3-4 days following dosing with the exception of fecal/urine stain which were noted through days 8-9. The clinical observations in the surviving 4500 mg/kg male were generally noted through study day 10.

Body weight:

Body weight gain was noted for all suriving animals during the test period.

Gross pathology:

The most notable gross internal findings observed in the animals that died included abnormal content in the digestive tract and abdominal cavity, perforated stomach, reddened mucosa in the stomach and small intestine, firm and rubbery stomach, white foci on the liver, discoloration on internal viscera, and mottled liver. The most notable gross internal findings which were observed in the animals that survived included abnormal content and thickened mucosa in the stomach.

Any other information on results incl. tables

SUMMARY OF MORTALITY

			Study Day
Sex	Dose Level (mg/kg)	No. of Animals	0	1	2	3	4	5	6	7	8	9	10	11	12	13	14	Mortality
Male	2000	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	015
	3500	5	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2/5
	4500	5	4	0	0	0	0	0	0	0	0	0	0	0	0	0	0	4/5
Female	2000	5	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1/5
	3500	5	2	0	0		0	0	0	0	0	0	0	0	0	0	0	3/5
	4500	5	4	1														5/5

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Under the conditions of this test, the acute oral LD50 of Lupersol 221 in the sexes combined was determined to be 3158 mg/kg.

Executive summary:

The single-dose oral toxicity of Lupersol 221 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 as follows:

 

Dose Level (mg/kg)	No. Dead/No. Dosed
	Males	Females	Combined
2000	015	1/5	1/10
3500	2/5	315	5/10
4500	415	515	9/10

All mortality occurred by study day 3. The most notable clinical abnormalities observed during the study included decreased activity, salivation, soft/mucoid stools, dark material around facial area, decreased/no defecation, diarrhea, gelatinous material on litter, fecal/urine stain, rough haircoat, wobbly gait, breathing abnormalities, piloerection, prostration, hunched posture, eyelids partially closed, and apparent hypothermia. The majority of these observations were noted in bath the animals that died and those surviving to study termination. ln the 2000 mg/kg and 3500 mg/kg dose groups, most of the notable observations were generally noted during the first 3-4 days following dosing with the exception of fecal/urine stain which were noted through days 8-9. The clinical observations in the surviving 4500 mg/kg male were generally noted through study day 10. Body weight gain was noted for all surviving animals during the test period. The most notable gross internal findings observed in the animals that died included abnormal content in the digestive tract and abdominal cavity, perforated stomach, reddened mucosa in the stomach and small intestine, firm and rubbery stomach, white foci on the liver, discoloration on internal viscera, and mottled liver. The most notable gross internal findings which were observed in the animals that survived included abnormal content and thickened mucosa in the stomach.

Under the conditions of this test, the acute oral LD50 of Lupersol 221 in the sexes combined was determined to be 3158 mg/kg.