Boronic acid, (4-ethylphenyl)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-10-16 to 2007-08-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2020

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(4-ethylphenyl)boronic acid

EC Number:

613-145-5

Cas Number:

63139-21-9

Molecular formula:

C8 H11 B O2

IUPAC Name:

(4-ethylphenyl)boronic acid

Test material form:

solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann, 33178 Borchen
- Age at study initiation: 6 to 8 weeks
- Weight at study initiation: The mean initial body weight at the start of the study was 164 g (range from 156 to 175 g).
- Fasting period before study: Diet was withheld from 17 hours before until up to 4 hours after treatment.
- Housing: Separately in type III Makrolon cages, Conventional softwood granulate was used as the bedding.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 7 days before dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 22
- Humidity (%): 47 to 60
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

Methocel K4M Premium solution

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 15 g/L and 100 g/L
- Amount of vehicle: 20 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 20 mL of 100 g/L test item

CLASS METHOD
- Rationale for the selection of the starting dose: Limit dose

Doses:

2000 mg/kg bw and 300 mg/kg bw

No. of animals per sex per dose:

300 mg/kg bw: 3 males and 3 females
2000 mg/kg bw: 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The behavior and general condition of all rats were monitored for at least 6 hours after administration and then checked daily. All animals were weighed before treatment and on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part.
- Necropsy of survivors performed: Yes

Statistics:

The body weight data were recorded with the PC-program "AKUDAT". The statistical evaluations of the body weight were carried out with the PC-program "TOX 511 A", developed by the Institute of Toxicology of Merck KGaA, Darmstadt. The body weight development of each rat and group was determined. The group mean value was calculated for each measurement.

Results and discussion

Preliminary study:

Males treated with 2000 mg/kg bw. Signs of toxicity were seen immediately up to 6 hours after oral administration (locomotor disturbance, dyspnea).

Effect levels

Key result

Sex:

female

Dose descriptor:

approximate LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

not specified

Mortality:

300 mg/kg bw: 0/3 males and 0/3 females;
2000 mg/kg bw: 3/3 females

Clinical signs:

other: In rats treated with 2000 mg/kg, clinical signs were seen immediately up to 3 hours after oral administration. They consisted of salivation, abdominal position, locomotor disturbance, and dyspnea. Signs of toxicity were seen in the rats treated with 300 m

Gross pathology:

Gross pathology of two animals treated with 2000 mg/kg revealed in the stomach gas and fluid content. Histology examination revealed no corresponding changes. In all other animals that died or were sacrificed as planned, no macroscopic changes were detected.

Any other information on results incl. tables

Table 1: Mortality

 

Dose mg/kg bw	Dead/ treated animals
	Males	Females
300	0/3	0/3
2000	-	3/3

 

Table 2: Clinical findings (summary) for 300 mg/kg bw in male rats

Symptoms of intoxication at time after treatment	Minutes		Hours						Day
	1-15	15-60	1-2	2-3	3-4	4-5	5-6	6-24	2	3	4	5	6	7	8	9	10	11	12	13	14	15
Sex: Male, Dose: 300 mg/kg bw
Number of animals observed	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3
Abdominal position	/	1	1	1	1	1
Locomotor disturbance	2	3	3	3	3	3	3
Dyspnea	2	2	1	1	1	1
No abnormal symptoms	1							3	3	3	3	3	3	3	3	3	3	3	3	3	3	3
Sex: Male, Dose: 2000 mg/kg bw
Number of animals observed	/	/	/	/	/	/	/	/	/	/	/	/	/	/	/	/	/	/	/	/	/	/

 

Table 3: Clinical findings (summary) for 300 mg/kg bw and 2000 mg/kg bw in female rats

Symptoms of intoxication at time after treatment	Minutes		Hours						Day
	1-15	15-60	1-2	2-3	3-4	4-5	5-6	6-24	2	3	4	5	6	7	8	9	10	11	12	13	14	15
Sex: Female, Dose: 300 mg/kg bw
Number of animals observed	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3
No abnormal symptoms	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3
Sex: Female, Dose: 2000 mg/kg bw
Number of animals observed	3	3	1	1
Salivation	3	3	1
Abdominal position	3	3	1	1
Locomotor disturbance	3
Dyspnea	3	3	1	1

 

Table 4: Body weights in grams (300 mg/kg bw, males and females)

			Day
Dose	Sex	Animal No	1	2	4	6	8	11	13	15
300 mg/kg bw	Male	1	164	187	204	219	236	258	270	280
	Male	2	175	207	220	239	256	278	294	305
	Male	3	156	172	192	203	218	234	242	250
	Female	4	163	179	179	187	188	197	198	203
	Female	5	163	180	183	194	196	208	214	218
	Female	6	162	178	178	185	181	198	201	203

 

Table 5: Body weights in grams (2000 mg/kg bw, females)

			Day
Dose	Sex	Animal No	1	2	4	6	8	11	13	15
2000 mg/kg bw	Female	7	160
	Female	8	161
	Female	9	170

 

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

According to the results of this study with the test item, the LD50 value is expected to be between 300 - 2000 mg/kg.

Executive summary:

The test material was tested for acute toxicity in rats after single oral administration of 300 and 2000 mg/kg body weight. The test material was suspended with aqueous Methocel® K4M Premium solution as vehicle.This study was performed according to the "Acute toxic class method" (ATC) as described in the OECD Guideline 423. The rats treated with 300 mg/kg bw survived until the end of the observation period, whereas all rats treated with 2000 mg/kg bw died within 45 minutes and 3 hours after dosing. Signs of toxicity were seen in the rats treated with 300 mg/kg bw immediately up to 6 hours after oral administration. They consisted of locomotor disturbance, dyspnea and one female rat showed temporarily abdominal position. The body weight development of the rats was inconspicuous. In rats treated with 2000 mg/kg bw, clinical signs such as salivation, abdominal position, locomotor disturbance and dyspnea were seen immediately after oral administration. Gross pathology of two animals treated with 2000 mg/kg bw revealed gas and fluid content in the stomach. Histology examination revealed no corresponding changes. In all other animals that died or were sacrificed as planned no macroscopic changes were detected.