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Exposure related observations in humans: other data

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Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
other: human case
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Entry adopted from the OECD SIAR on sulfur dioxide without modification.Old study meets generally accepted scientific principles, sufficiently documented; comparison of adequate groups of exposed and unexposed subjects, exposure and reference group adjusted for a range of parameters; groups well characterised except for details on smoking habits; differentiated analysis of effects during initial exposure with development of tolerance, during customary exposure and occasional severe exposure; study acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
On the effects of prolonged exposure to sulfur dioxide.
Author:
Kehoe, R.A. et al.
Year:
1932
Bibliographic source:
J. Ind. Hyg. 14: 159-173

Materials and methods

Endpoint addressed:
skin irritation / corrosion
repeated dose toxicity: inhalation
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Study reports exposure- related observations in humans.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no data

Method

Ethical approval:
not specified
Details on study design:
In 1932 workers from an electric refrigerator plant which used sulphur dioxide as refrigerant were examined for irritatory and health effects and compared to 100 subjects occupied in the same plant without exposure to sulphur dioxide.
Exposure assessment:
measured
Details on exposure:
TYPE OF EXPOSURE: SO2 in air

TYPE OF EXPOSURE MEASUREMENT:
- Measurement: a system of air analysis was established in 1927, before 1927 analyses at irregular intervals, methods not specified
INVESTIGATIONS
- Questionnaire: (1) length and nature of exposure to sulphur dioxide, (2) exposure to possible other occupational hazards, (3) symptoms of initial period of exposure, duration of period of acclimatisation, (4) symptoms arising from usual minimum exposure, influence of exposure on common colds (5) symptoms arising from heavy intolerable periodic exposure as irritation and symptoms of eye, nose and throat, chest pain, aggravation of usual symptoms, haemoptysis or epistaxis, hacking cough at night or in morning, polydipsia, polyuria, weakness, appetite and digestion, headaches and nervous system symptoms, constipation and diarrhoea, (6) residual symptoms as altered susceptibility to other chemical or physical irritants, alteration in sense of taste or smell, permanent injury of any type
- Physical examination
- Hematology: erythrocytes, leukocytes, haemoglobin, polymorphonuclear leukocytes, lymphocytes
- Urine analysis: acidity and alkality, no further details
- X-ray examination of the chest: classified into 4 subgroups - (1) average normal chests, (2) chests slightly suspicious for the existence of pathologic development, (3) chests suspicious of active or healed disease, (4) definite chest pathology
- Carbon dioxide content in alveolar space and blood plasma carbon dioxide combining capacity (not further specified)

EXPOSURE LEVELS:
- Charging department: average concentration about 20 ppm, range 10-40 ppm, on single occasions up to 70 ppm in winter; an effective ventilation system was established in 1927; prior to 1927: analyses at irregular intervals showed average concentrations from 80-100 ppm
- Storage and distribution department: average concentration about 30 ppm, range 15-55 ppm
- Repair department: especially in the repair department and less frequent in the charging and storage and distribution department escape of sulphur dioxide causes a brief but unendurable exposure from which the operators find it necessary to escape


EXPOSURE PERIOD:
STUDY POPULATION
- 74% had 2-4.9 years of exposure; mean years in plant: 4.0 +- 0.13, mean years in industry: 8.0 +- 0.35
- Co-exposure: no exposure to paints, lacquers and metallic dusts (similar to reference population)
REFERENCE POPULATION
- mean years in plant: 4.5 +- 0.17, mean years in industry: 12.3 +- 0.65


DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES:
STUDY POPULATION
- Number: 100 males
- Age: 37.0 +- 0.7 years
- Working history: From the workmen handling sulphur dioxide, 100 subjects were selected on the basis of severity and duration of exposure, most of these subjects worked in the sulphur dioxide storage and distribution department, the refrigerating unit charging department, and the repair department.
REFERENCE POPULATION
- Number: 100 males
- Age: 35.7 +- 0.55 years
- Working history: Employed as workers in the assembling department, tool room, punch press room, carpentry shop and shipping department without exposure to sulfur dioxide, paints, lacquers and metallic dusts.

Results and discussion

Results:
EXAMINATION OF ACCLIMATIZATION:
80% of all exposed subjects developed tolerance without experiencing notable intensity of initial symptoms mean length of time necessary for acclimatisation was estimated to 2.84 months with a standard deviation of 2 months based on the individual questionnaires
TOXICOLOGICAL ENDPOINTS:
- Haematology: lymphocyte count significantly increased in exposed group, polymorphonuclear leukocytes significantly increased in control group; findings without clinical relevance
- Urine analysis: acidity to methyl red E 87%, C 47%; alkality to methyl red E 10%, C 53%, P0.000001
- Physical examination: significant increases of incidences of the following findings (E=exposed, C=control group) pharyngitis: slight - E 32%, C 22%, P=0.0009; chronic - E 38%, C 9%, P0.000001; slight and chronic - E 70%, C 31%, P0.000001tonsilitis - slight and chronic: E 34%, C 12%, P=0.00018 abnormal reflexes (no further information): E 31%, C 15%, P=0.007
- X-ray findings: no significant differences between exposed and control group
SYMPTOMS (from questionnaires):
- Initial symptoms (before acclimatization): irritation of upper respiratory tract, coughing, epistaxis, constriction in the chest, haemoptysis; severity is a function of individual variation of the subjects, no correlation with frequency of severe exposure
- Symptoms associated with minimum exposure: all exposed subjects showed some symptomatic evidence of a chronic type of low grade irritation of the upper respiratory tract; initial symptoms appeared in a much milder form, additional symptoms were hacking cough, morning cough, nasal irritation and discharge, prolongation of common colds, and expectoration; no association with the frequency of severe exposures but with individual variation
- Colds: incidence of colds not sensibly different - E 88%, C 81%; however, 2-3 times increases of total man weeks of colds - E 1,141, C 462, average duration of colds E 13, C 5.7 weeks, number of workers having colds all winter E 40%, C13%; no association between prolongation of colds and frequency of severe exposure
- Symptoms associated with irregular severe exposure: intensified form of symptoms associated with minimum exposure - coughing and sneezing, conjunctival irritation, soreness of throat and larynx; less frequent were thirst, weakness, transitory chest pains, loss of appetite for succeeding meal, polyuria, chest pain of a more or less prolonged type
- Significantly increased symptoms in comparison to control group: alteration in sense of smell - E 14%, C 0%, P=0.0001; increase in sensitivity to other irritants - E 14%, C 0%, P=0.0001; shortness of breath on exertion - E 42%, C 19%, P=0005; positive correlation with frequency of severe exposure P=0.0082 increase in fatigability in employment - E 27%, C9%, P=0.0009; positive correlation with frequency of severe exposure P=0.0047 alteration in sense of taste - E 10%, C 0%, P=0.0009

Applicant's summary and conclusion

Conclusions:
A group of 100 workers exposed to average concentrations of about 20-30 ppm sulfur dioxide was compared to unexposed workers in 1932. Local irritations of the respiratory tract as indicated by nasopharyngitis, alterations in sense of smell and taste and increased sensitivity to other irritants were found. Initial symptoms were tolerated by 80% of the exposed subjects within an acclimatization period of about 2-3 months. Abnormal urinary acidity, a tendency to increased fatigue, of shortness of breath on exertion, and of abnormal reflexes pointed to systemic effects of sulfur dioxide. There was no demonstrable association between frequency of heavy exposure (up to 70 ppm) and frequency or severity of initial symptoms or symptoms arising from customary exposure. In contrast increased fatigability and shortness of breath on exertion demonstrated a positive correlation to frequency of heavy exposure. The incidence of colds was not significantly different between the 2 groups, whereas the duration was extended in sulfur dioxide-exposed subjects. X-ray findings gave no evidence of inflammatory or pathological changes in the lungs of exposed workers.