1-[4-(1,1-dimethylethyl)phenyl]-3-(4-methoxyphenyl)propane-1,3-dione

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Comparable to guideline study with acceptable restrictions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

limit dose of 16000 mg/kg bw

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-[4-(1,1-dimethylethyl)phenyl]-3-(4-methoxyphenyl)propane-1,3-dione

EC Number:

274-581-6

EC Name:

1-[4-(1,1-dimethylethyl)phenyl]-3-(4-methoxyphenyl)propane-1,3-dione

Cas Number:

70356-09-1

Molecular formula:

C20H22O3

IUPAC Name:

1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione

Test material form:

solid

Details on test material:

- Name of test material : BMDBM
- Substance type: light yellowish powder
- Physical state: solid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: W. Gassner, Sulzfeld, Germany
- Weight at study initiation: 90 - 115 g
- Fasting period before study: 16 h
- Housing: 5 animals per Makrolon Type III cage with autoclaved sawdust as bedding
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1 °C
- Humidity (%): 55 ± 5 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 4 % w/v aqueous gum arabic solution

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 40 % w/v as suspension
- Amount of vehicle: 40 mL/kg bw

Doses:

limit dose of 16000 mg/kg bw

No. of animals per sex per dose:

10 males and 10 females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: frequently on the day of dosing and daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology (5 males and 5 females of the treated group and all organs with abnormal macroscopic appearance)

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 16 000 mg/kg bw

Remarks on result:

other: all animals survived at this dose

Mortality:

There were no mortalities in either the treated or control group.

Clinical signs:

other: Signs of reaction to treatment, observed shortly after dosing included pitoerection (only in control animals) and abnormal body carriage (hunched posture). These signs were accompanied by slight lethargy immediately after dosing in male rats only.

Body weight:

other body weight observations

Remarks:

Body weight gains in all treated rats were comparable with those of the control animals throughout the two week observation period.

Gross pathology:

Autopsy findings for rats killed at termination were considered to be normal.

Other findings:

HISTOPATHOLOGY:
The marked loss of sperm as well as the accumulation of cellular debris in the epididymal tubules of the 5 males examined and the slight vacuolation of hepatocytes (3 male and 2 female animals) may be attributable to treatment with butyl methoxydibenzoylmethane (BMDBM). The testes of all examined animals appeared normal.
Hemosiderin deposits occur commonly in the spleen of rats whereas hemopoiesis in the same organ occurs at a time of stress. Furthermore, the spleen is a hemopoietic organ in the embryo and up some weeks after birth. So indications of spleen hemopoiesis could also be remains of animal development. Unfortunately, no data of control animals were provided for comparison, so that attributing these findings uniquely to BMDBM treatment is not justified. Peribronchial lymphoid hyperplasia and focal interstitial pneumonitis are stages of evolution of chronic murine pneumonia. Small round infiltrates in the liver and focal interstitial nephritis may be considered as a bacterial infection.
Mitotic cells in kidneys, liver, stomach, duodenum, pancreas, adrenals, and epididymis are signs of growing organs.

Any other information on results incl. tables

Table 2: Acute toxicity signs as reaction to treatment with BMDBM

Day	Control Males	Control Females	16000 mg/kg bw Males	16000 mg/kg bw Females
1	15A	15A	15A / 21A / 1A	15B / 21A
	15A	15A	15A	15B
	15A	15A	15A	15B
2	15A	15A	15A	15B
3	15A	15A	15A	15B
4	N	N	N	15A
5	N	N	N	N
6-14	N	N	N	N

Signs of toxicity coding: 1. Lethargy, 15. Piloerection, 21. Hunched posture

Degree of reaction: A = slight, B = Moderate, C = Severe, N = No abnormalities detected

 

Table 3: Body weight gains of rates dosed once with BMDBM

Group	Sex	Bodyweight [g]^a)			Bodyweight gain [g]
		Day 1	Day 8	Day 15
Control	Male	108	167	214	106
	Female	99	152	178	79
16000 mg/kg bw	Male	106	166	218	112
	Female	101	151	175	74

^a)Average of 10 animals per group per sex

 

Table 4: Autopsy findings after acute oral toxicity study with BMDBM

Group	Sex	Organs examined	Autopsy findings
Control	Male	As listed in table 1	Within normal limits
	Female	As listed in table 1	Within normal limits
16000 mg/kg bw	Male	As listed in table 1	Within normal limits
	Female	As listed in table 1	Within normal limits

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

After oral administration of 16000 mg/kg bw of BMDBM as suspension in 4 % gum arabic in water w/v to male and female rats, no mortality was observed.

Executive summary:

Oral application of a suspension containing 16000 mg/kg bw by gavage to male and female rats resulted in no mortality within 14 days of post-observation. Also vehicle-treated animals showed no mortality. Both groups exhibited clinical signs in the first 4 days after treatment of which the most abundant was piloerection; the animals treated with BMDBM but not the controls showed signs of lethargy and hunched posture. Body weights and gross necropsy were in normal limits in all animals. Histopathological changes were observed mainly in the epididymes and spleen of treated animals, but no causal connection could be developed as animals suffered from a bacterial infection and pneumonia.

Taken together, the test item BMDBM has a LD50 (rat, oral) of >16000 mg/kg bw and therefore does not need to be classified under GHS and CLP.