Isobutylbenzene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 2017 - November 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Certificate produced by "Landesanstalt für Umwelt, Messungen und Naturschutz Baden-Württemberg"

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Isobutylbenzene

EC Number:

208-706-2

EC Name:

Isobutylbenzene

Cas Number:

538-93-2

Molecular formula:

C10H14

IUPAC Name:

(2-methylpropyl)benzene

Test material form:

liquid

Details on test material:

- batch no.: EXP-18/11/346
- State of aggregation: liquid
- Log KOW: 3.94 (calculated); 4.8 at 23°C and pH 6.0 (measured)
- Molecular weight: 134.22 g/mol

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: BASF; Batch identification: EXP-18/11/346
- Expiration date of the lot/batch: October 2020

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: The stability of the test item under storage conditions over the study period was guaranteed.

FORM AS APPLIED IN THE TEST: undiluted

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: 188 g (mean); animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: single
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days before administration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: October 24, 2017 To: November 21, 2017

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.4 mL/kg body weight

time of day of administration: in the morning

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter; morbidity and mortality was checked at least once daily
- Frequency of weighing: shortly before administration (day 0), weekly thereafter and on the last day of observation
- Necropsy of survivors performed: yes, on the last day of the observation period

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality was observed

Mortality:

not observed

Clinical signs:

1st test group:
- poor general state in 3/3 animals from day 1 to day 2
- piloerection in 3/3 animals from day 1 to day 2
- dyspneoa, cowering position and apathy in 2/3 animals on day 1
- exsiccosis in 2/3 animals from day 1 to day 2 or on day 1
- exophthalmos and staggering 1/3 animals on day 1

2nd test group:
- impaired up to poor general state in 3/3 animals from day 1 to day 3
- piloerection in 3/3 animals from day 1 to day 2 or 3
- cowering position in 3/3 animals on day 1
- non defecation, exsiccosis, apathy in 2/3 animals on day 1
- reduced defecation in 1/3 animals on day 1

Body weight:

1st test group:
- stagnated or slightly decreased body weight in 2/3 animals during the 1st week (progression to normal weight gain during 2nd week)
- stagnated body weight in 1/3 animals during 2nd week

2nd test group: no effects observed

Gross pathology:

no effects observed

Any other information on results incl. tables

Table 1: Mortality

Mortality
Dose (mg/kg bw):	2000	2000
Sex:	female	female
Administration:	1	2
No. of animals:	3	3
Mortality (animals):	No mortality	No mortality

Table 2: Individual body weight changes

Individual body weight changes
Dose (mg/kg bw):	2000					2000
Administration:	1					2
Animal No.:	R	R	R	Mean weight	Standard- deviation	R	R	R	Mean weight	Standard- deviation
	645	646	647			671	672	673
Body weight at study day (g):
0	191	195	203	196.3	6.11	181	179	179	179.7	1.15
7	-	-	-	-	-	196	203	199	199.3	3.51
8*	196	199	195	196.7	2.08	-	-	-	-	-
14	199	207	206	204.0	4.36	204	211	210	208.3	3.79

 *Due to a public holiday the body weight determination in the first test group was performed on study day 8.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose of Isobutylbenzene after oral administration was found to be greater than 2000 mg/kg bw in rats.

Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class Method, a dose of 2000 mg/kg bw of the undiluted test substance was administered by gavage to two test groups of three fasted Wistar rats each (6 females).

The following test substance-related clinical observations were recorded, clinical signs occurred within the first 3 days after administration:

2000 mg/kg (first test group):

• No mortality occurred
• Impaired general state in all animals
• Poor general state in one animal
• Dyspnoea in two animals
• Piloerection in all animals
• Exsiccosis in two animals
• Exophthalmos in one animal
• Cowering position in two animals
• Staggering in one animal
• Apathy in two animals

2000 mg/kg (second test group):

• No mortality occurred
• Impaired general state in all animals
• Poor general state in two animals
• Piloerection in all animals
• Exsiccosis in two animals
• Cowering position in all animals
• Apathy in two animals
• Reduced defecation in one animal
• Non defecation in two animals

The body weight of two animals in the first 2000 mg/kg bw test group stagnated or slightly decreased during the first week, but these animals gained weight in a normal range during the second week. The body weight of the third animal increased normally during the first week, but stagnated during the second week.

The body weight of the animals in the second 2000 mg/kg bw test group increased within the normal range throughout the study period. There were no macroscopic pathological findings in any animal sacrificed at the end of the observation period (6 females).

The acute oral LD50 was calculated to be LD50, oral, rat > 2000 mg/kg bw