Solvent naphtha (petroleum), heavy arom.

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, non-guideline human population study, published in peer-reviewed literature, some limitations in design but otherwise acceptable for interpretation

Data source

Reference

Reference Type:

publication

Title:

Toluene exposure below 50 ppm and cognitive function: a follow-up study with four repeated measurements in rotogravure printing plants.

Author:

Seeber A, Schaper M, Zupanic M, Blaskewicz M, Demes P, Kiesswetter E and van Thriel C

Year:

2004

Bibliographic source:

Int Arch Occup Environ Health, 77, 1-9

Materials and methods

Study type:

longitudinal study

Endpoint addressed:

neurotoxicity

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Employees from 14 magazine rotary printing plants were classified into groups of "high" (printing area) vs "low" (end-processing) and "short" vs "long" exposure. Psychological performance tasks (attention [symbol digit substitution, switching attention, simple reaction], memory [digit span forward and backwards, immediate and delayed reproduction of pictures], and psychomotor functions [steadiness, line tracing, aiming, tapping, peg board]) were measured 4 times over 5 years in the same subjects.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Toluene

EC Number:

203-625-9

EC Name:

Toluene

Cas Number:

108-88-3

Molecular formula:

C7H8

IUPAC Name:

toluene

Details on test material:

Name of test material (as cited in study report): Toluene

Method

Type of population:

occupational

Ethical approval:

confirmed and informed consent free of coercion received

Details on study design:

Neurobehavioural and sensory function changes as a consequence of toluene exposure were assessed in employees from 14 magazine rotary printing plants were investigated. Psychological performance tasks, memory, and psychomotor functions were measured 4 times over 5 years in the same subjects.
SAMPLE SIZE: 192-333
METHOD OF DATA COLLECTION
- Type: Interview, questionnaire and computer-administered tests

STUDY PERIOD: 1996-2001

SETTING: Employees from 14 magazine rotary printing plants

STUDY POPULATION
- Total population: 333
- Total number of subjects participating in study: 192-333
- Sex/age/race: Sex not reported / mean 37.5 ± 9.3 years / race not reported
- Total number of subjects at end of study: 192

Exposure assessment:

measured

Details on exposure:

TYPE OF EXPOSURE: inhalation

EXPOSURE CONCENTRATION: Current exposure 26 ppm in High-exposure group, 3ppm low-exposure group. LWAE 45 ppm High-exposure group, 9 ppm low-exposure group

TYPE OF EXPOSURE MEASUREMENT: Individual air sampling in the employees' breathing zone during a working day

EXPOSURE LEVELS and EXPOSURE PERIOD: See Table 2 (for sub-groups with repeated measurements, n=192)

DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES: See Table 2

Statistical methods:

Non-transformed original data were used to derive stepwise regression analyses and repeated-measures analyses of covariance. Log-transformed data lead to no changes in the tendencies of the results (e.g. simple reaction time). All calculations were performed using SPSS and SAS.

Results and discussion

Results:

NOAEC for neurobehavioural effects is 26 ppm (98 mg/m3).
There was no evidence that long-term occupational exposure of toluene at concentrations below 50 ppm (188 mg/m3) had any effect on psychological performance. LOAEC for neurobehavioural effects was considered to be above 59 +/- 13 ppm (222 mg/m3).

Any other information on results incl. tables

Co-variables included in analyses (age, level of education, carbohydrate-deficient transferrin as an alcohol marker, and trait anxiety as personality characteristic) had no major exposure impacts. LWAE or current exposure measures were not significantly affected byrepeated-measures analyses of covariance. The main cause of variability were age and education although, carbohydrate-deficient transferrin and trait anxiety had some impacts on the test results.

Applicant's summary and conclusion

Conclusions:

There was no evidence that long-term occupational exposure of toluene at concentrations below 50 ppm had any effect on psychological performance.

Executive summary:

Employees (total of 192) from 14 magazine rotary printing plants were classified into groups of "high" (printing area) vs "low" (end-processing) and "short" vs "long" exposure. Attention (symbol digit substitution, switching attention, simple reaction), memory (digit span forward and backwards, immediate and delayed reproduction of pictures), and psychomotor functions (steadiness, line tracing, aiming, tapping, peg board) were measured as dependent variables.

There was no evidence that long-term exposure to toluene at 26 ppm for 21 years had any effects on cognitive function. Evidence for psychological performance effects due to long-term toluene exposure below 50 ppm could not be proved. The human NOAEC from this study was 26 ppm (98 mg/m3).