Bis(4-methylbenzoyl)peroxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Single treatment followed by an observation period of 15 days (September 3, 1991 to September 17, 1991)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: A reliability rating of K2 was assigned due to the following minor deficiencies: lack of inclusion of CAS number and the Certificate of Analysis of the test material.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Bis(4-methylbenzoyl)peroxide

EC Number:

407-950-9

EC Name:

Bis(4-methylbenzoyl)peroxide

Cas Number:

895-85-2

Molecular formula:

C16H14O4

IUPAC Name:

4-methylbenzoyl 4-methylbenzene-1-carboperoxoate

Test material form:

other: The test article was described as "Water damped powder 72% PMBP", the formulation was not clearly stated in the report. The formulation could have been a suspension or paste.

Details on test material:

- Name of test material (as cited in study report): Di-(4-Methylbenzoyl)-peroxid (INTEROX-PMBP)
- Physical state: solid, white
- Analytical purity: water damped powder 72% PMBP
- Purity test date: Not provided
- Batch No.: IR 240001
- Expiration date of the batch: Stable, November, 1991
- Stability under test conditions: Stable for at least 48 hours
- Storage condition of test material: In the original container; protected from light at room temperature (approx. 20 degrees C)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRl, Biological Research laboratories Ltd. Wolferstrasse 4, CH-4414 Fullinsdorf
- Age at study initiation: males: 8 weeks; females: 10 weeks
- Weight at study initiation: males: 189 - 212 g; females: 175 - 182 g
- Fasting period before study: yes, overnight, but had access to water

- Housing:
Groups of five in Makrolon type-3 cages (size: 22 x 37.5 x 15 cm) with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz).

Diet: Pelleted standard Kliba 343, Batches 85/91 and 86/91 rat maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst) available ad libitum. Results of analysis for contaminants are included in this report (see appendix).

Water: Community tap water from Fullinsdorf, available ad libitum. Results of bacteriological, chemical and contaminant analyses are included in this report.

- Acclimation period: August 27, 1991 to September 2, 1991

ENVIRONMENTAL CONDITIONS: Room No.: 103; standard Laboratory Conditions.
Air-conditioned with 10-15 air changes per hour, and continuously monitored environment with a temperature of 22 +/- 3 degrees centigrade
Relative Humidity between 40-70%.
Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light (approx. 100 Lux) / 12 hours dark, music during the light period.

IN-LIFE DATES: From: To: August 27, 1991 to September 17, 1991.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE: Polyethylene glycol. The lot/batch no. and purity were not mentioned.

MAXIMUM DOSE VOLUME APPLIED: Application Volume/ kg body weight: 10 ml at 2000 mg/kg

Semiocclusive

The animals received a single dose of the test article on a mg/kg body weight base by oral gavage after being fasted overnight (access to water was not interrupted). Food was again presented approximately 3 hours after dosing.

DOSAGE PREPARATION (if unusual): The test article was placed into a glass beaker on a tared Mettler PM 480 balance, and the vehicle, (Polyethylene glycol, PEG 400) was added. A weight by volume dilution was prepared using a homogenizer. Homogeneity of the test article in the vehicle was maintained during treatment using a magnetic stirrer. The preparation was made immediately prior to dosing.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

Rationale: The oral administration was used because this is one possible route of human exposure during manufacture, handling and use of the test article.

OBSERVATIONS

Mortality / Viability: Four times during test day 1, and daily during days 2 - 15.

Body Weights Test days 1 (pre-administration), 8 and 15.

Clinical Signs
Each animal was examined for changes in appearance and behaviour four times during day 1, and daily during days 2-15. All abnormalities were recorded. The animals were checked for the clinical signs listed below. Positive findings are indicated under Appendix B.

GENERAL BEHAVIOUR
Aggressiveness, vocalization, restlessness / excitation, nervousness, fear / sedation, somnolence, sleep and coma.

RESPIRATION
Apnea, dyspnea, and rales.

EYE
Chromodacryorrhea, exophthalmos, miosis, mydriasis, whitish discharge, lid adhesion, lacrimation, and negative corneal reflex.

NOSE
Rhinorrhea, epistaxis

MOTILITY
Akinesia, Ataxia, dropped head, hyperkinesia, hypokinesia, paralysis (flaccid), paralysis (spastic), paddling movements, stiff gait and rolling movements.

BODY POSTURE
ventral body position, lateral-abdominal position and hunched posture.

MOTOR SUSCEPTIBILITY
spasms, tonic muscle spasms, clonic muscle spasms, opisthotonus, saltatory spasms, trismus, tremor, muscle-twitching, and muscle-twitching generalized

SKIN
erythema, edema, and necrosis

VARIOUS
loss of weight, emaciation, diarrhea, ruffled fur, salivation, pallor, or cyanosis

DATA' COMPILATION
The following data were recorded on-line: mortality/viability, clinical signs, body weights, macroscopical findings.

Pathology
Necropsies were performed by experienced prosectors. All animals were necropsied. All animals were euthanized by intraperitoneal injection of sodium pentobarbitone.

Statistics:

The LOGIT-Model could not be applied to the observed rates of death. The toxicity was estimated without use of a statistical model.

Results and discussion

Preliminary study:

None reported.

Effect levels

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test article Di-(4-Methylbenzoyl)-peroxid (INTEROX-PMBP) was administered to rats of both sexes by oral gavage, at a single dose of 2000 mg/kg. The following death rate was observed: 0 % at 2000 mg/kg. The LOGIT-Model could not be applied to these data.

The acute oral toxicity of Di-(4-Methylbenzoyl)-peroxid (INTEROX-PMBP) in rats of both sexes, observed over a period of 15 days, was estimated to be greater than 2000 mg/kg.

Clinical signs:

other: The following clinical signs were observed: 2000 mg/kg: males/females - no systemic clinical signs noted (9); males - sedated (1). ( ) = number of positive animals. Local clinical effects: General erythema in 3 out of 5 males, and 4 out of 5 females was

Gross pathology:

The following macroscopical organ findings were observed: 2000 mg/kg: males/females - sacrificed - no macroscopical organ findings noted (10).

( ) = number of positive animals

Any other information on results incl. tables

The original study report has individual animal data tables: Appendix A (mortality), Appendix B (clinical signs), Appendix C (Body weights), and Appendix D (macroscopical findings). These agree with the findings already reported above. Additionally, Appendix E contained water and feed analyses as required.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral toxicity of Di-(4-Methylbenzoyl)-peroxid (INTEROX-PMBP) in rats of both sexes, observed over a period of 15 days, was estimated to be greater than 2000 mg/kg.

Executive summary:

The purpose of this acute oral study was to assess the toxicological profile of Di-(4 -Methylbenzoyl)-peroxid (INTEROX-PMBP)

when administered orally by a single dose followed by an observation period of 15 days. The test article Di-(4-Methylbenzoyl)-peroxid (INTEROX-PMBP) was administered to 8 -10 week old rats [(HanIbm: WIST (SPF)] of both sexes (five each) by oral gavage, at 2000 mg/kg, prepared in PEG 400. This GLP study by N. Hoff, 1991 was done according to OECD 401 and EU B.1 guidelines.

A reliability rating of K2 was given due to minor deficiencies: lack of inclusion of CAS number and the Certificate of Analysis of the test material.

The death rate was: 0 % at 2000 mg/kg. The LOGIT-Model could not be applied to these data.

 

The following clinical signs were observed: 2000 mg/kg: males/females - no clinical signs noted (9); males - sedated(1). The body weight gain of the animals was not affected by the test article treatment throughout the entire study period. All dosed males/females with 2000 mg/kg were sacrificed and macroscopic organ findings were not noted in any animal.

 

Conclusion: The acute oral toxicity of Di-(4-Methylbenzoyl)-peroxid (INTEROX-PMBP) in rats of both sexes, observed over a period of 15 days, was estimated to be greater than 2000 mg/kg.