4-tert-butyltoluene

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data are given.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Toxicological studies on p-tertiary-butyltoluene.

Author:

Hine CH et al.

Year:

1954

Bibliographic source:

AMA Arch Ind Hyg Occup Med 9: 227-244.

Reference 2

Reference Type:

review article or handbook

Title:

p-tert-Butyoltoluol.

Author:

Greim H

Year:

1998

Bibliographic source:

Toxikologisch-arbeitsmedizinische Begründungen von MAK-Werten. Edited by Greim H. Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe der Deutschen Forschungsgemeinschaft (DFG), 26. Lieferung. Wiley-VCH-Verlagsgesellschaft, Weinheim.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

no data

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-tert-butyltoluene

EC Number:

202-675-9

EC Name:

4-tert-butyltoluene

Cas Number:

98-51-1

Molecular formula:

C11H16

IUPAC Name:

1-tert-butyl-4-methylbenzene

Details on test material:

- Name of test material (as cited in study report): p-tertiary-butyltoluene
- Physical state: liquid with distinct odour
- Analytical purity: no data
No further data

Test animals

Species:

rat

Strain:

Long-Evans

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
female Long-Evans rats
- Weight at study initiation: 110-156 g
- Fasting period before study: yes, 8 h prior to treatment
No further data.

ENVIRONMENTAL CONDITIONS: no data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Animals were exposed either in a 165 liter chamber to a constant flow of 14.6 liters per minute (about five air changes per hour) or in a chamber of about 200 liters capacity to an air flow of 21.2 liters per minute (six air changes per hour). A constant-metering device delivered TBT liquid in measured amounts to the evaporator, where it vaporized in the air entering the chamber. The air in the chamber was allowed to equilibrate to, theoretically, 95 to 99% of the desired concentration.

TEST ATMOSPHERE
Vapour samples were collected occasionally as a check on the nominal chamber concentration. Evacuated glass bulbs were used in procuring the samples. The bulb was attached to the sampling port, and air from the chamber was drawn through by suction at the rate of 3 liters per minute for five minutes. Five milliliters of isooctane was added to the bulb, which was then shaken for 10 minutes. The quantity of absorbed TBT was determined by ultraviolet spectrophotometry, as described in the section on Industrial Health Aspects (Section III).
No further data.

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

26 weeks

Frequency of treatment:

1, 2, 4, 7 hours/day on 5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
ca. 0.15, 0.3 mg/l (25-30, 50-60 ppm)
Basis:
nominal conc.

No. of animals per sex per dose:

groups of 10 females

Control animals:

yes, concurrent no treatment

Results and discussion

Results of examinations

Details on results:

CLINICAL SIGNS AND MORTALITY
The majority of exposed animals did not display any evidence of substance-related damage or abnormal behaviour. One of three high dose rats exposed for 7 h/d died after the 42nd exposure; the remaining two rats displayed injury at the front and hind limbs. During the study, clinical symptoms were limited to slight irritation of the eyes and slightly elevated respiratory rate.

BODY WEIGHT AND WEIGHT GAIN
no data

CLINICAL LABORATORY INVESTIGATIONS
A depression of erythropoiesis was observed. Hemoglobin, erythrocyte count and leukocyte count was decreased in high dose animals after 5 weeks of exposure. However, significant changes of these parameters were also observed in control animals at the beginning and end of the exposure period. Therefore, the authors did not consider the depression of erythropoiesis to be substance-related. No statistically significant changes in blood parameters were noted after 26 weeks of exposure, with exception of significantly decreased leukocyte counts observed in high dose rats treated for 2, 4, or 7 h/d.

ORGAN WEIGHTS
A time- and dose-related increase in relative liver and kidney weights was observed.

GROSS PATHOLOGY
no data

HISTOPATHOLOGY
Chronic encephalomeningitis was observed in both low and high dose rats exposed for 4 and 7 h. Slight fatty degeneration of the liver was noted in individual high dose rats.

No further data.

Effect levels

1

Dose descriptor:

NOAEC

Effect level:

< 0.15 mg/L air

Sex:

female

Basis for effect level:

other: According to a reviewer (Greim, 1998 = MAK-Begründung), a NOEL could not be established, based on adverse findings observed at both dose levels.

Remarks on result:

not determinable

Remarks:

no NOAEC identified

2

Dose descriptor:

LOAEC

Effect level:

0.15 mg/L air

Sex:

female

Basis for effect level:

other: According to a reviewer (Greim, 1998 = MAK-Begründung), a NOEL could not be established, based on adverse findings observed at both dose levels.

Target system / organ toxicity

Critical effects observed:

not specified