Benzene-1,2,4-tricarboxylic acid 1,2-anhydride, oligomeric reaction products with ethane- l,2-diol

Health surveillance data

Administrative data

Endpoint:

health surveillance data

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This is a synopsis of observational studies by various authors, compiled by an expert scientific body (OECD HPV Programme SIDS Review Committee) which drew conclusions on the impact of occupational exposures to the test substance.

Data source

Reference

Reference Type:

review article or handbook

Title:

SIDS Initial Assessment Report for the 15th SIAM, Trimellitic Anhydride & Trimellitic Acid, CAS No. 552-30-7; 528-44-9

Author:

OECD HPV Programme

Year:

2002

Bibliographic source:

http://www.inchem.org/documents/sids/sids/TLANA.pdf

Report date:

2002

Materials and methods

Study type:

other: Combined health records, exposure monitoring, etc.

Endpoint addressed:

other: respiratory irritation, respiratory sensitisation, immune response

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Human exposure experience as reviewed in health records, exposure monitoring data, etc.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Benzene-1,2,4-tricarboxylic acid 1,2-anhydride

EC Number:

209-008-0

EC Name:

Benzene-1,2,4-tricarboxylic acid 1,2-anhydride

Cas Number:

552-30-7

Molecular formula:

C9H4O5

IUPAC Name:

1,3-dioxo-1,3-dihydro-2-benzofuran-5-carboxylic acid

Constituent 2

Reference substance name:

trimellitic anhydride

IUPAC Name:

trimellitic anhydride

Test material form:

not specified

Details on test material:

No data provided in the summaries

Method

Type of population:

occupational

Ethical approval:

not specified

Details on study design:

Generally retrospective reviews of exposure data and outcomes

Results and discussion

Results:

After occupational exposure to trimellitic anhydride, workers exhibited respiratory symptoms of coughing, wheezing, asthma, rhinitis, congestion, generalized ache and sometimes illness.

Any other information on results incl. tables

The following are synopses of various studies of occupational outcomes to trimellitic anhydride exposure:.

(a)    

Results:   Highest arithmetic mean TMA exposures of 19.3 ug/m3 were found in a resin factory (approximately half the eight-hour TWA OES of 40 ug/m3). Remarks: A retrospective cohort study was carried out in four factories (three alkyd resin factories and one cushioned flooring factory) to investigate the nature of exposure-response relationships for sensitization to TMA and other anhydrides. Arithmetic mean exposure levels to TMA were below their respective OES’s in the resin factories. Relatively high full-shift exposures to TMA occurred in the cushioned floor facility, although no high peak exposures were detected. Reference:  vanTongeren et al. 1995.

(b) Results: Seven employees had positive IgE antibody levels against TM-human serum albumin, one of these employees had rhinitis, and another possibly had TMA asthma/rhinitis. Positive IgG antibody levels against TM-HSA was reported in fourteen employees (although only three had titers high enough to cause disease).Remarks: This was an eleven year study of employees exposed to TMA that included periodic serum antibody studies and health questionnaires. Industrial hygiene data from the plant in 1989 reported exposures ranging from <0.003 mg/m3 to 0.77 mg/m3. Respirators with a protection factor of 100 were worn routinely in areas where TMA was used. Reference:  Grammer et al., 1991.

(c) Results:  Personal  monitoring  data  results  included  geometric  means for different exposure classes:  1:  0.17 mg/m3; 2:  0.087 mg/m3;3:  <0.00055 mg/m3; 4: <0.00041 mg/m3; 5:<0.00053 mg/m3. Nearly 7% of the employees had a TMA immunologic syndrome, 31.6% displayed an irritant response, and the remaining employees (61.6%) had no symptoms. Remarks:     Employees of a large chemical manufacturing complex were (n=474)  were studied to relate TMA exposure to serologic and clinical outcomes. All employees were assigned to a TMA exposure class from 1 (highest) to 5 (lowest). Reference:  Zeiss et al., 1992.

 (d) Results: Mean personal monitoring data results were presented by an exposure class: 1 (0.13 mg/m3); 2 (0.036 mg/m3); 3 (0.002 mg/m3); 4(0.00051 mg/m3); and 5 (<0.00053 mg/m3). Of the 28 employees that were assigned to exposure class 1, 29%developed disease (related to IgG or IgE titer).  In exposure class 2, 4% of the employees developed disease, 5% of the employees in class3 developed disease,and no employees developed disease in exposure classes 4 and 5. Remarks:  A three-year study of 286 employees of a TMA manufacturing facility was performed. Employees were assigned exposure classifications ranging from 1 (highest) to 5 (lowest), and immunological response was related to exposure. Reference:  Grammer et al., 1999

(e) Results:   Mean full-shift TMA exposure in four facilities ranged from  0.5 -19.3 ug/m-3  Remarks: Workers exposed to TMA were studied to determine the relation between exposure to TMA (and other acid anhydrides, AA) and the risk of developing skin prick test responses to AA-HSA. Reference: Barker et al., 1998.

(f) Results: This study investigated nine workers who were exposed to a paint powder that contained TMA at a 55 -gallon drum manufacturing plant. Environmental monitoring showed airborne TMA levels to be over 100 times the OHSA PEL of 0.04 mg/m3. Remarks:   One employee exhibited obvious illness and two of the workers had definite evidence of TMA-related pulmonary dysfunction and immunologic response. Three workers showed IgG antibody against TM-HSA significantly higher than control serum. One worker showed IgE antibody against TM-HSA. Reference:  Letz et al., 1987

 (g) Results: Forty-six employees exposed to TMA were investigated using periodic serum antibody studies and questionnaires. Remarks:   Seven employees had positive IgE antibody against trimellitic-human serum albumin (TM-HSA), one had TMA rhinitis,and another potentially had TMA asthma/rhinitis. Positive IgG antibody against TM-HSA was observed in fourteen employees, although only three had titers high enouth to causedisease (none of them had symptoms associated with late respiratory systemic syndrome (LRSS) or pulmonary disease anemia (PDA)). TMA exposure concentrations for two different job categories ranged from <0.001 -2.1 mg/m3 and 0.005 -0.32mg/m3 over a 14 -year period. Reference:  Grammer, et al., 1992

(h) Results:  Average airborne TMA dust concentrations ranged from 0.006 -2.1 mg/m3 for three different job categories.   Five workers had antibody against TM-HSA, of these, three were diagnosed with the LRSS and one with TMA-induced allergic rhinitis. After local exhaust ventilation had been improved, average airborne dust concentrations decreased to approximately 0.01 mg/m3 and the symptomatic improvement as noted in the individuals with the LRSS. Remarks:   Eighteen workers exposed to TMA powder were evaluated.Annual clinical evaluations and serum radioimmunoassays for total antibody binding and specific IgE binding to TM-HSA were performed. Reference: Bernstein et al., 1983.

(i) Results:  A total of 119 subjects exposed to TMA for at least one year were identified from a previous cross-sectional study. These individuals were studied for the next five years to determine if they would develop an immunologic respiratory disease due to TMA exposure. In 1990, 16 individuals showed IgE against TMA conjugated to human serum albumin. Of these, three had immediate asthma and six developed asthma during the five-year follow-up. Of those without IgE against TM-HSA, none had immediate asthma in 1990 and only 1 out of 102 developed asthma after five years. Of those with IgG against TM-HSA (44), six had immunologic respiratory disease in 1990 and two more developed it in the following 5 years.Remarks: Development of antibody (both IgE and IgG) against TM-HSA is predictive of subjects who have or will develop immunlogically mediated respiratory disease based on TMA exposure.The authors also concluded that the absence of antibody is a potent negative predictor. Reference:  Grammer et al., 1998.              

(k) Results: Workers (n=196 individuals) involved in the manufacture of TMA were studied for 12 years.   Seventeen workers had IgE-mediated asthma/rhinitis with a positive prick test to TM-HSA (with IgE antibody of 0.8 -57 ng TM-HSA bound/ml). Seven individuals had a late respiratory systemic syndrome (LRSS) and four workers had both syndromes. Three workers had late onset asthma, one had marked arthralgia and myalgia occurring hours after exposure to TMA.Remarks: The authors reported a reduction in the number of workers exhibiting an immunologic syndrome during 1982 -1987 in spite of the increased TMA production. This finding paralleled environmental control and worker education efforts. Reference:  Zeiss et al., 1990.

Applicant's summary and conclusion

Conclusions:

In retrospective observational studies of occupational exposure to trimellitic anhydride, adverse health effects were found in a portion of workers. It was observed that workers who had measurable levels of antibodies to TMA-serum albumin adducts exhibited a higher incidence/severity of respiratory symptoms of exposure (coughing, wheezing, asthma, rhinitis, congestion, generalized ache and illness). Increased environmental and personal protective equipment decreases incidence and severity of symptoms. This study is informative for evaluation of the toxicity of members of the cyclic acid anhydride category.