4-chloroformylphthalic anhydride

Sensitisation data (human)

Administrative data

Endpoint:

sensitisation data (humans)

Remarks:

review by WHO

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

sensitisation data (humans)

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

The document of the read-across justification is attached below

Reason / purpose for cross-reference:

read-across source

Specific details on test material used for the study:

Trimellitic anhydride-chloride (TMAC)

Conclusions:

The WHO concluded that cyclic acid anhydrides including Trimetillic anhydride can cause sensitization in Humans after direct contact with the skin and the mucous membranes or after exposure by inhalation.

Materials and methods

Study type:

case report

Principles of method if other than guideline:

The Concise International Chemical Assessment Document (CICAD) 1 on cyclic acid anhydrides was prepared by Sciences International, Inc. and is based on a review prepared by the Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals and the Dutch Expert Committee on Occupational Standards (Keskinen, 2004). To address literature citations not included in this review, a comprehensive literature search of several online databases was conducted in June 2006. Information on the source document and its peer review is presented in Appendix 2 of the attached document.
This CICAD was considered and approved as an international assessment at a Final Review Board meeting held in Helsinki, Finland, on 26–29 March 2007.

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-2-benzofuran-5-carboxylic acid

Specific details on test material used for the study:

Cyclic anhydrides, including Trimellitic anhydride (CAS 552-30-7)

Results and discussion

Results of examinations:

Extract from the WHO report:
Trimellitic anhydride:
"Letz et al. (1987) examined all nine workers at a barrel manufacturing plant who were exposed to tri-mellitic 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 prepar-ing 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.
In 1988–1989, Zeiss et al. (1992) conducted a cross-sectional study of 474 workers in the same factory as in his earlier (1990) study. Five exposure groups were assigned by an industrial hygienist on the basis of job history and the results of personal monitoring. Tri-mellitic anhydride–specific IgE antibodies were found only in the high exposure group (0.54–6500 μg/m3, geometric mean = 170 μg/m3). Sensitizations 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 sensi-tized 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 sensitization 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 com-pared with workers exposed to <10 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."......
"Allergic asthma is a well documented disease of cyclic acid anhydride exposure in workers. Allergic asthma is often preceded by rhinoconjunctivitis. IgE-mediated sensitization has been verified in exposed workers using skin prick tests with conjugates of the cyclic acid anhydrides and human serum albumin. Bronchial hyperresponsiveness has been correlated with specific sensitization (Barker et al., 2000)."

Applicant's summary and conclusion

Conclusions:

The WHO concluded that cyclic acid anhydrides including Trimetillic anhydride can cause sensitization in Humans after direct contact with the skin and the mucous membranes or after exposure by inhalation.

Executive summary:

The Concise International Chemical Assessment Document (CICAD) 1 on cyclic acid anhydrides was prepared by Sciences International, Inc. and is based on a review prepared by the Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals and the Dutch Expert Committee on Occupational Standards (Keskinen, 2004). To address literature citations not included in this review, a comprehensive literature search of several online databases was conducted in June 2006. This CICAD was considered and approved as an international assessment at a Final Review Board meeting held in Helsinki, Finland, on 26–29 March 2007.

WHO cocluded that cyclic acid anhydrides including Trimetillic anhydridec an cause sensitization in Humans after direct contact with the skin and the mucous membranes or after exposure by inhalation. Irritation is caused by the corresponding dicarboxylic acid that is formed when cyclic acid anhydrides interact with water. The most common aller-gic diseases are rhinoconjunctivitis and asthma, both immediate-type IgE-mediated allergies.