Boronic acid, (4-ethylphenyl)-

Endpoint summary

Description of key information

Based on the results of an acute oral toxicity study according to OECD guideline 423, the LD50 value of the test item is expected between 300 - 2000 mg/kg bw. Based in GHS criteria, the test item is classified for acute oral toxicity, category 4. Based on the result of a acute dermal toxicity study according to OECD guideline, the test item can be considered to have no acute toxic potential to skin. The LD50 value was higher than 2000 mg/kg bw after dermal application to rats (reference 7.2.1-1 and 7.2.3-1).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

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

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

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.

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).

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.

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

 

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

300 mg/kg bw

Quality of whole database:

Guideline study under GLP conditions.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006-10-16 to 2006-12-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Age at study initiation: Approx. 7 to 11 weeks
- Weight at study initiation: Range from 214 to 244 g (mean: 230 g)
- Housing: Separately in type IE Makrolon cages with a shelter and softwood granulate as bedding.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 22
- Humidity (%): 48 to 66
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: Day 0 To: Day 14

Type of coverage:

semiocclusive

Vehicle:

paraffin oil

Details on dermal exposure:

TEST SITE
- Area of exposure: 6 x 6 cm
- Type of wrap: Gauze patch + self-adhesive fabric

REMOVAL OF TEST SUBSTANCE
- Washing: The remaining test material was wiped off.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 3.52 g test item preparation/kg bw
- Concentration: 569 g/L
- Constant volume or concentration used: Yes

VEHICLE
- Lot/batch No: K32250274 333

Duration of exposure:

24 hours

Doses:

- 2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 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
- Other examinations performed: All animals were subjected to a gross pathological investigation.

Statistics:

Not performed

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

All rats survived the observation period.

Clinical signs:

other: No signs of toxicity were detected in the 5 male and 5 female rats after dermal treatment with 2000 mg/kg of the test item.

Gross pathology:

At necropsy, no organ alterations were seen.

Table 1: Individual body weights in grams

			Day
Dose	Sex	Animal No	1	2	4	6	8	11	13	15
2000 mg/kg bw	male	1	244	236	248	259	273	291	296	312
	male	2	220	206	217	224	234	246	249	256
	male	3	233	231	244	260	269	285	295	303
	male	4	240	238	247	256	270	285	292	302
	male	5	243	235	251	264	275	292	300	311
	female	6	220	218	226	226	233	235	233	241
	female	7	227	208	226	221	229	232	234	236
	female	8	235	220	221	235	226	236	236	242
	female	9	224	224	230	233	238	242	232	239
	female	10	214	204	210	217	218	218	227	224
	male	N	5	5	5	5	5	5	5	5
		Mean	236	229	241	253	264	280	286	297
		Gain (%)	****	-3	2	7	12	19	21	26
	female	N	5	5	5	5	5	5	5	5
		Mean	224	215	223	226	229	233	232	236
		Gain (%)	****	-4	-1	1	2	4	4	6

 

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the result of this study, the test item can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg bw after dermal application to rats.

Executive summary:

The test material was tested for acute toxicity in 5 male and 5 female rats after dermal administration of 2000 mg/kg body weight. Directly before administration, the test material was moistened with liquid paraffin, spread on the shaven skin in an area of 6 x 6 cm, and covered with a gauze patch. This was kept in place by a self-adhesive fabric. The time of exposure was 24 hours. Then the gauze and adhesive fabric were removed and any remaining test material was wiped off carefully. No signs of toxicity were detected in the rats (5 males and 5 females) after treatment with 2000 mg/kg bw. There were no deaths during the course of the study. The body weight development was inconspicuous. The gross pathological examination revealed no organ alterations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Guideline study under GLP conditions

Additional information

Acute oral toxicity, key study

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.

 

Acute dermal toxicity study, key study

The test material was tested for acute toxicity in 5 male and 5 female rats after dermal administration of 2000 mg/kg body weight. Directly before administration, the test material was moistened with liquid paraffin, spread on the shaven skin in an area of 6 x 6 cm, and covered with a gauze patch. This was kept in place by a self-adhesive fabric. The time of exposure was 24 hours. Then the gauze and adhesive fabric were removed and any remaining test material was wiped off carefully. No signs of toxicity were detected in the rats (5 males and 5 females) after treatment with 2000 mg/kg bw. There were no deaths during the course of the study. The body weight development was inconspicuous. The gross pathological examination revealed no organ alterations.

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Thus, the test item is considered to be classified for acute oral toxicity (category 4) but not for acute dermal toxicity under Regulation (EC) No 1272/2008, as amended for fifteenth time in Regulation (EU) No 2020/217.