Diisopropylbenzene hydroperoxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The test is comparable to a guideline study, even if there is no certificat of analysis.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Diisopropylbenzene hydroperoxide

EC Number:

247-988-1

EC Name:

Diisopropylbenzene hydroperoxide

Cas Number:

26762-93-6

Molecular formula:

C12H18O2

IUPAC Name:

reaction mass of 1-(3-isopropylphenyl)-1-methylethyl hydroperoxide and 1-(4-isopropylphenyl)-1-methylethyl hydroperoxide

Test material form:

liquid

Test animals

Species:

rat

Strain:

other: HSD/Win: Wu (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH
- Age at study initiation: no data
- Weight at study initiation: male: 151 to 174 g, female: 128 to 147 g
- Fasting period before study:
- Housing: conventionnal, separated by sex
- Diet (e.g. ad libitum): ad libitum until 16 h before application, 3 h after application, food ad libitum
- Water (e.g. ad libitum):yes
- Acclimation period:at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30-70%
- Air changes (per hr): 15 times/h
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 01/08 to 18/08/1994

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.06 cm3 test substance/kg bodyweight

Doses:

2000 mg/Kg bodyweight corresponding to 2.06 cm3/kg body weight

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 and weighing:
reseach of clinical symptoms: post administration: 1/2 h, 1h, 2h, 3h,4h, 5h and 6h, and every days the wo weeks after
bodyweigth measurement on day 0, 7 and 14
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:

no death

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks:

DIHP

Effect levels 2

Sex:

male/female

Dose descriptor:

LD0

Effect level:

1 624 mg/kg bw

Based on:

act. ingr.

Remarks:

diisopropylbenzene hydroperoxide

Mortality:

no mortality observed over the test duration

Clinical signs:

other: see table 2. The oral administration of a 2000 mg/kg bw dose of the test substance resulted in clearly toxic effects in the Wistar rats. Some symptoms, like squatting posture gave indications of pain for the animals. The animals were free of symptoms af

Gross pathology:

see table 3
The autopsy at the end of the test revealed however that the corrosive properties of the substance caused an ulceration of the stomach mucous membrane, which resulted in the adhesion of the stomach with the abdomen organs.

Any other information on results incl. tables

Table 1: Lethality and body weight development (Body weight and Limit test)

Male

Dosis (mg/kg body weight)	Animal	Application date	Bodyweight (g)			Mortality
			0	7	14	Time  after treatment	Body weight (g)
2000	1	02/08/1994	153	214	251	-	-
	2	02/08/1994	160	195	235	-	-
	3	04/08/1994	174	210	243	-	-
	4	04/08/1994	169	205	225	-	-
	5	04/08/1994	151	188	222	-	-

 

Female

Dosis (mg/kg body weight)	Animal	Application date	Bodyweight (g)			Mortality
			0	7	14	Time  after treatment	Body weight (g)
2000	1	02/08/1994	133	159	174	-	-
	2	02/08/1994	137	169	188	-	-
	3	04/08/1994	132	161	173	-	-
	4	04/08/1994	147	172	190	-	-
	5	04/08/1994	128	159	166	-	-

 

Table 2: Symptoms. Individuals data

Male (2000 mg/kg bw)

Symptoms	Hours after treatment (h)
	1/2	1	2	3	4	5	6	24	48	72	96
No symptoms	5								2	2	5
Abnormal gait		5	5	5
Squatting posture		5	5	5
Sudation					1	1	1
Motility increase								2
Motility decrease		5	5	5
Stagger		5	5	1	1	1	1
Breath sounds								1	1
Ruffled fur			5	5	5	5	5	5	3
Diarrhea								1	1
Body weight increase inhibition								2

 

Female (2000 mg/kg bw)

Symptoms	Hours after treatment (h)
	1/2	1	2	3	4	5	6	24	48	72	96
No symptoms	5								2	2	5
Abnormal gait		5	5	5		2	2
Squatting posture		5	5	5	2	4	3	1	1	1
Sudation				5	2	2	2
Motility increase								2	2	2
Motility decrease			5	5
Stagger		5	5	5	4	4	3
Ruffled fur			5	5	5	5	5	5	3	3
Hypothermia			5	5	4	4	3
Diarrhea					1	1	1	2	1	2
Body weight increase inhibition								4
Uncontrolled moves				5	2	2	2

Table 3: Observations after end of the observation period

Male (2000 mg/kg bw)

Total count	Autopsy
3 (3,4,5)	Adhesion of the liver with stomach
4 (1,3,4,5)	Adhesion of the stomach with the spleen, cartilaginous-like thickening of the gastric mucous membrane
3 (3,4,5)	Adhesion of the stomach with the peritoneum
1 (2)	cartilaginous-like thickening of the gastric mucous membrane

 

Female (2000 mg/kg bw)

Total count	Autopsy
3 (1,2,3)	Adhesion of the liver with stomach
3 (1,2,3)	Adhesion of the stomach with the spleen
5 (1,2,3,4,5)	cartilaginous-like thickening of the gastric mucous membrane
2(1,2)	Adhesion of the stomach with the peritoneum
1(3)	Adhesion of the stomach with the diaphragm
4(1,3,4,5)	Small intestine reddened

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Diisopropylbenzolhydroperoxid is not classified according to the Annex VI to the Directive 67/548/CEE and the CLP Regulation (1272/2008).

Executive summary:

DIHP, 81.2% Diisopropylbenzene hydroperoxide in diisoproylbenzene, was tested for acute oral toxicity according to OECD 401 guideline and in compliance with GLP. In a pretest, 2 males and 2 females were treated with 2000 mg/kg body weight by gavage. The results of that stage gave a basis for the final test dose. As there were no deaths, 3 additional individuals of each sex were tested at the same dose as the two of the pretest in order to get a validated Limit test with as little killed animals as possible. Examinations for mortality, clinical signs and body weight gain were performed during the 14-day observation period. All surviving animals were necropsied at the end of the observation period. Some symptoms, like squatting posture gave indications of pain for the animals. The autopsy at the end of the test revealed however that the corrosive properties of the substance caused an ulceration of the stomach mucous membrane, which resulted in the adhesion of the stomach with the abdomen organs. No mortality was observed throughout the study.

The acute oral LD0 of DIHP was found greater than 2000 mg/kg bw (1624 mg/kg bw as diisopropylbenzene hydroperoxide).