Registration Dossier

Toxicological information

Sensitisation data (human)

Currently viewing:

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
other: Review
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The WHO document reviews the toxicity and effects of exposure to cyclic anhydrides including trimellitic anhydride.

Data source

Reference
Reference Type:
publication
Title:
CYCLIC ACID ANHYDRIDES: HUMAN HEALTH ASPECTS
Author:
WHO
Year:
2009
Bibliographic source:
Concise International Chemical Assessment Document 75

Materials and methods

Type of sensitisation studied:
respiratory
Study type:
other: literature review
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
The WHO document reviews the toxicity and effects of exposure to cyclic anhydrides including trimellitic anhydride.
GLP compliance:
no
Remarks:
: not applicable (literature review)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Cyclic anhydrides, including trimellitic anhydride

Method

Type of population:
occupational
Ethical approval:
not specified
Route of administration:
inhalation

Results and discussion

Any other information on results incl. tables

The WHO CICADS document reviews the published data on the respiratory sensitisation of TMA; the conclusions are detailed below.

In one study, Letz et al (1987) examined all nine workers at a barrel manufacturing plant who were exposed to trimellitic anhydride breathing zone concentrations of 1700–3600 μg/m3. Four workers had trimellitic anhydride–induced irritant effects. Three had symptoms and IgG levels consistent with late-type respiratory syndrome, one had specific IgE against trimellitic anhydride, and one worker was asymptomatic.

No trimellitic anhydride–related disease was found over a 2-year period among 11 factory workers preparing epoxy resin coating material. The trimellitic anhydride exposure level was less than 180 μg/m3 (McGrath et al, 1984).

Zeiss et al (1990) conducted a 12-year (1976–1987) clinical and immunological study of 196 workers in the trimellitic anhydride manufacturing industry. The workers were administered a questionnaire and tests for total trimellitic anhydride antibodies and trimellitic anhydride–specific IgE. IgE-mediated immediate-type asthma or rhinitis was found in 21 workers and late-type asthma in 10 workers. A total of 113 workers had only irritant symptoms, and 46 were asymptomatic. No data were available on exposure, but there was an annual decline in the number of sensitized workers due to improvements in the workplace. The same authors (Zeiss et al, 1992) conducted a cross-sectional study of 474 workers in the same factory as in the earlier study. Five exposure groups were assigned by an industrial hygienist on the basis of job history and the results of personal monitoring. Trimellitic anhydride–specific IgE antibodies were found only in the high exposure group (0.54–6500 μg/m3, geometric mean = 170 μg/m3). Sensitisation and illnesses due to trimellitic anhydride were concentrated in the three highest exposure groups (170 μg/m3 [geometric mean]; 87 μg/m3 [geometric mean]; and 0.44–0.55 μg/m3). Current or former smoking, but not age, sex, or date of hire, was found to be associated with total antibody levels (P = 0.01).

One year after 29 sensitised workers were moved to low-exposure jobs, their symptoms and pulmonary functions had improved and their specific antibody levels had decreased (Grammer et al, 1993).

Barker et al (1998) examined 63 workers exposed to trimellitic anhydride. The prevalence of sensitisation and work-related symptoms increased with increasing exposure. The odds ratios for positive skin prick tests for workers exposed to 10–40 μg/m3 and >40 μg/m3 compared with workers exposed to 1<0 μg/m3 were 10.0 and 20.7, respectively. The odds ratios of work-related respiratory symptoms in those exposed to 10–40 μg/m3 and >40 μg/m3 were 5.9 and 7.4, respectively. There was no increase in prevalence of sensitization or symptoms with smoking or atopy.

Applicant's summary and conclusion

Conclusions:
The WHO document concludes that sensitisation and work-related respiratory symptoms have been reported at trimellitic anhydride (TMA) concentrations as low as 10–40 μg/m3.
Executive summary:

The WHO document reviews the human data on respiratory sensitisation and concludes that sensitisation and work-related respiratory symptoms have been reported at trimellitic anhydride (TMA) concentrations as low as 10–40 μg/m3.