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Toxicological information

Direct observations: clinical cases, poisoning incidents and other

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Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
other: injury case study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
1949
Report date:
1949

Materials and methods

Study type:
poisoning incident
Endpoint addressed:
eye irritation
respiratory irritation
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
The report presents seven case studies of eye and respiratory injuries due to occupational exposure to maleic anhydride.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Maleic anhydride
EC Number:
203-571-6
EC Name:
Maleic anhydride
Cas Number:
108-31-6
Molecular formula:
C4H2O3
IUPAC Name:
2,5-dihydrofuran-2,5-dione
Details on test material:
no data

Method

Type of population:
occupational
Subjects:
- Number of subjects exposed: 7
- Sex: male
Ethical approval:
confirmed, but no further information available
Route of exposure:
inhalation
ocular
Reason of exposure:
unintentional, occupational
Details on exposure:
At the time of incident, liquid maleic anhydride is being drummed in a small room. The men performing this work are continuously exposed to the vapors of maleic anbydride. When the drum-filling procedure is being carried out, the liquid maleic anhydride enters the drum through a nozzle. The drums are cold and the material relatively hot (60°C), and as the initial portion of the liquid maleic anhydride flows into the drum, a small cloud of vapor arises into the air through the opening of the drum. Immediately above the bung is a vacuum air stream which circulates through an air washer. Some of the vapor arising from the bung is not trapped in this air stream and consequently contaminates the small room were this drum-filling procedure is carried out with increasing intensity during a work shift.

Results and discussion

Clinical signs:
Burning eyes, wheezing and coughing.
Reddened conjunctiva, eyelids evidenced blepharitis with reddening and edema.
The mucous membranes of the nose and throat were mildly reddened and a thin profuse watery discharge from the nose.
On further examination, this individual also presented the typical symptoms of an asthma-like attack of his lower respiratory tract.

Any other information on results incl. tables

Worker #1, white, male, age 42, was drumming: maleic anhydride for 8 h over night. During this time he wore a gas mask with an organic vapour and acid gas type canister which is recommended for one hour's service. He did not wear vapour proof goggles as eye protection. At the end of the work shift he complained to the shift superintendent, that his eyes burned. At that time the superintendent irrigated the worker's eyes with saline solution and instilled sterile mineral oil. The worker left the plant and slept for a few hours at home.

He returned to his regular work the same morning and visited the plant dispensary, complaining of burning eyes, wheezing and coughing. At this time the duty nurse irrigated his eyes for a period of ten minutes and found that on staining with fluorescin, each eye took faint greenish stain on the cornea. She referred the worker to the plant physician because of his chest complaints.

The worker stated that in addition to his eyes burning that he had started coughing and wheezing while he had been drumming. After arriving home he noticed constriction of his chest and had coryza with the symptoms of a hayfever-like attack of his eyes and upper respiratory tract. His conjunctiva were reddened, his eyelids evidenced blepharitis with reddening and edema. The mucous membranes of his nose and throat were mildly reddened and he had a thin profuse watery discharge from his nose. On further examination, this individual also presented the typical symptoms of an asthma-like attack of his lower respiratory tract. On auscultation he presented sibilant and sonorous rales all over his chest in all lobes on expiration only. On inspiration the breath sounds were clear and physiological. He further stated that a doctor who had examined him 11 years before had told him that he had a 'touch of asthma' at that time. At this first examination the patient had a blood pressure of 118/70, a pulse count of 92 per minute, and a urine specimen was normal. He was sent to a hospital on the same day for a CBC, a urinalysis, and a chest X-ray. The CBC was normal except for an elevation of his WBC of 16,000 with 70% segmented neutrophils. His urinalysis was normal. The chest X-ray reading was as follows: Chest reveals a great number of small discrete calcified tubercles throughout both lung fields. This appearance is generally ascribed as a hoaled aspergillus infection. The appearance is essentially normal otherwise. Upon his return to work, the worker was started on oxygen inhalations under positive pressure for Intervals of one-half hour each.

On the next day, the worker was still coughing and wheezing and complaining of mild intermittent constriction of his chest anteriorly. Examination of the chest by auscultation revealed sibilant and sonorous rales over all the chest on inspiration and expiration. Oxygen therapy was continued as before.

On the next day he still had rales but not as pronounced as on the previous exminations. He was sent to a Laboratory for a CBC, which was reported as normal except for a WBC of 12,650 and segmented neutrophile count of 63%. At this time his eosinophile count was 4.

The worker continued to improve and received oxygen inhalations daily until the eight day after the incident, when he was discharged as cured. No rales were heard at this time but he still had mild coughing attacks occasionally. A total of 8 days from time of exposure was required for breath sounds to be considered physiological in this case.

 

Worker #2, a white, male, age 33, was assisting worker #1 on his work shift drumming maleic anhydride. He wore no respiratory protection, but did wear rubber splash goggles that were not vapor proof. At the end of the work shift he also had his eyes irrigated by the shift superintendent, after which he went to his home. He was seen on overnext day in the afternoon after having been requested by the duty nurse to come to the dispensary for examination. His eyes were negative to fluorescin staining and he did not present hayfever-like symptoms of his upper respiratory tract, except for a mild coryza which he mistook for a common cold. He was complaining, however, of wheezing and occasional coughing episodes: Auscultation of his chest revealed sibilant and sonorous rales over all the chest on inspiration and expiration. He denied any previous attacks of asthma, hayfever or other allergic manifestations. He was started on oxygen inhalations under positive pressure for 30 minutes daily. On the the next day, a stereoscopic X-ray of his chest was reported as: "'There is no pathology visualized in the heart or lungs. A CBC was essentially negative with a WB C of 8,500 and a neutrophil count of 71. A urinalysis was negative.

This man was examined daily and evidenced rales until day 5 , when his breath sounds were clean and essentially physiological. He was discharged as cured. Mild coughing occasionally was still occurring.

Five other workers were exposed the MA while working in the MA unit, in some cases for weeks. After excessive vapour exposure, the men revealed comparable symptoms in alleviated strength during examinations. If done at all, medical treatment consists of oxygen therapy. In one case, CBC was performed with again increased WBC and segmented neutrophils.

Worker#3, a pipefitter, was working on the second floor of the Catalyst warehouse building and was exposed to the vapors of maleic anhydride over a period of three weeks while working on the molding machine. On November 9 the vapor was excessive, as a spill occurred while repairing a line. On November 10, he requested to be examined because of coughing and wheezing. Examination revealed nothing remarkable except sibilant rales of his lower lobes only at the height of inspiration. He was started on Mercodol cough syrup, 1 teaspoonful every 3 hours, and oxygen inhalations for 30 minutes, BID.

On November 11, auscultation of his chest revealed squeaking, bubbling rales in all lobes at the height of inspiration. A Chest X-ray performed at this time revealed no pathology and a CBC was essentially normal, with a WEC of 9700 and a segmented neutrophil count of 58%. This man was examined and received oxygen therapy daily. During this 11-day period the squeaky musical rales heard at the height of inspiration persisted and gradually faded out by November 21, when his breath sounds became physiological. He was discharged as cured on that date.

Worker#4, a pipefitter working with -waugh was seen in the dispensary on November 9, complaining of coughing and wheezing. He had faint sibilant rales over all his chest on expiration only. He was started on oxygen inhalations, B.I.D. No laboratory work was performed on this patient and he was discharged on November 21 as cured since his chest was negative. He still complained of mild coughing attacks intermittently.

Worker#5, a Shipping Department employee working regularly on the maleic anhydride molding machine, was called in for an examination which was essentially negative. He stated that he regularly wore a gas mask when the maleic anhydride vapours started to irritate his eyes, nose and throat.

Worker#6, a Shipping Department employee, had been working on November 7, setting up drums and capping the full drums of maleic anhydride. Seventeen drums were filled by this man and the man he was assisting (Case VII). Examination of this man was negative, but he was complaining of photophobia and an excessive secretion of tears. Since eye staining was negative, he was issued dark glasses and given no other treatment. Rogers had been wearing a canister gas mask While working at this job.

Worker#7,a Shipping Department employee, had been filling 17 drums of maleic anhydride on November 7. Examination was negative.Healso wore a canister type gas mask during the drumming operations.

Applicant's summary and conclusion

Conclusions:
In conclusion, based on these case studies a correlation between report findings and maleic anhydride as causing agent is comprehensible.
Executive summary:

The report presents seven case studies of eye and respiratory injuries due to occupational exposure to maleic anhydride. Two workers, who filled 84 drums during one continuous period of 8 hours received respiratory injuries which resulted in asthma-like chest findings. Two fitters were also subjected to relatively high concentrations of maleic anhydride vapors. These exposures were due to vapors escaping from spills resulting from maintenance work being performed on the maleic anhydride molding machine. These men had similar asthma-like chest findings but were much less severe. These fitters came to the dispensary voluntarily for examination because of their annoying symptom. The three other case studies did not indicate any manifestations or symptoms relative to a maleic anhydride except mild conjunctivitis and blepharitis, which is to be expected from very low concentrations.