Reaction mass of copper oxide and manganese dioxide

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

experimental study

Adequacy of study:

key 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 1

Reference Type:

publication

Title:

Assessment of the permissible exposure level to manganese in workers exposed to manganese dioxide dust

Author:

Roels, H.A.; Ghyselen, P.; Buchet, J.P.; Ceulemans, E.; Lauwerys, R.R.

Year:

1992

Bibliographic source:

British Journal of Industrial Medicine, 49, 25-34

Reference 2

Reference Type:

publication

Title:

Toxicological Profile for Manganese.

Author:

ATSDR, Agency for Toxic Substances and Disease Registry

Year:

2012

Bibliographic source:

U.S. Department of Health and Human Services; Public Health Service; https://www.atsdr.cdc.gov/toxprofiles/tp151.pdf

Reference 3

Reference Type:

review article or handbook

Title:

Manganese and its inorganic com pounds [German MAK Value Documentation]

Author:

Hartwig, A.

Year:

2011

Bibliographic source:

Gesundheitsschädliche Arbeitsstoffe, Toxikologisch-arbeitsmedizinische Begründungen von MAK-Werten, Loseblattsammlung, 50. Lfg; online - http://onlinelibrary.wiley.com/book/10.1002/3527600418/topics

Materials and methods

Study type:

cross sectional study

Endpoint addressed:

repeated dose toxicity: inhalation

Test guideline

Qualifier:

according to guideline

Guideline:

other: cross sectional study

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Manganese dioxide

EC Number:

215-202-6

EC Name:

Manganese dioxide

Cas Number:

1313-13-9

Molecular formula:

MnO2

IUPAC Name:

Manganese dioxide

Test material form:

solid

Method

Type of population:

occupational

Ethical approval:

other: only volunteers participated

Details on study design:

STUDY POPULATION:
occupational cohort involving 92 male workers in a dry alkaline battery plant. They and the 101 age-and area-matched controls (with no industrial exposure to manganese) were observed for performance on a battery of neurobehavioral tests.

details on matching: age matched control workers not exposed to neurotoxic chemicals or lung irritants was recruited in a polymer processing factory. Because both plants are located in the same area, have the same occupational physician, and apply similar hiring criteria, an efficient matching between the Mn and control groups was achieved with regard to socioeconomic state (salary, education), general environment (place of residence), and workshift and workload characteristics.

METHOD OF DATA COLLECTION
- Type:
a) Questionnaire - respiratory sysmptoms, neurovegetative complaints
b) Clinical tests - biological parameters, neurobehavioural test battery

Confounding: Potential confounding factors related to hobby activities or previous employment, personal habits (smoking, coffee, and alcohol consumption), and medical history were controlled by questionnaire and interview. At the time of the survey, all the participants were in good health. To be included in the final database, participants should never have been occupationally exposed to mercury, lead, cadmium, solvents, or hazards interfering with lung function. At the time of the examination the concentrations of lead (PbB) and zinc protoporphyrin (ZPP) in blood and of cadmium (CdU) and mercury (HgU) in urine had to be in the normal range-namely, PbB < 35 ug/100 ml, ZPP < 2-5 pg/g Hb, CdU < 2 ug/g creatinine, and HgU < 10 ig/g creatinine

- The clinical examination was carried out in the medical departments of the plants. At a rate of about eight subjects each shift, the morning and afternoon shift workers were examined on a Tuesday and a Wednesday between 8.30 am and
6.00 pm, and the night shift workers on a Thursday between 10.00 pm and 2.30 am. The workers first took a shower, put on their civil clothes before starting the examination, and were asked to refrain from smoking for at least one hour before showering.
The survey was conducted by two trained persons who took care of the same part of the examinations throughout the whole study period and who respected the following sequence: physical examination, blood and urine sampling for biological analyses,
control of questionnaire, and performance of spirometric and neurofunctional tests.


HEALTH EFFECTS STUDIED
neuropsychological and respiratory symptoms, lung ventilatory parameters, neurofunctional performances (visual reaction time, eye-hand coordination, hand steadiness, audioverbal short term memory), and several biological parameters (calcium, iron, luteinising hormone (LH), follicle stimulating hormone (FSH), and prolactin concentrations in serum, blood counts, manganese (Mn) concentration in blood and in urine)

Exposure assessment:

measured

Remarks:

personal sampling of total and respirable dust

Details on exposure:

TYPE OF EXPOSURE: MnO2 dust

TYPE OF EXPOSURE MEASUREMENT: Personal sampling
Mn concentration in "total" and "respirable" dust was determined in the breathing zone of the workers with the use of a Casella cyclone elutriator/filter head (type 13043/1) equipped with an integral pulsation smoother connected to a battery operated Casella pump (type 13051/2) (Casella Ltd, London). A cellulose ester filter (Millipore filter type AAWPO3700) was placed in the filter cassette to collect the "respirable" fraction (Johannesburg's curve), whereas the grit pot was equipped with a plastic cup to collect the "non-respirable" fraction (total = respirable fraction + non-respirable fraction). Air was sampled at a mean flow rate of 1.85 (SD 0.44) 1/min. The air sampling exceeded 4-5 hours in 80% of the measurements and was carried out during a period representative of each worker's usual activities. The Mn contents of the respirable and non-respirable fractions were determined by flame atomic absorption spectrometry (Perkin-Elmer, Model 305)

EXPOSURE PERIOD: Manganese workers were exposed for an average (geometric mean) of 5.3 years (range: 0.2–17.7 years)

POSTEXPOSURE PERIOD: not specified

Statistical methods:

Statistical analyses were by SAS procedures.'2 Variables with a skewed distribution were logarithmically transformed to approximate the normal distribution. The Pearson correlation coefficient (r) and regression
equation or Spearman rank correlation coefficient (r) were calculated to assess the association between variables. The association between lifetime integrated exposure to airborne respirable or total Mn dust andthe probability of abnormal neurofunctional
outcomes were analysed using the logistic regression model, ln = p/(1-p) = beta 0 + beta1x1, where x1 was either log LIRD or log LITD. beta 1 was expressed in terms of odds ratio (OR) for subjects with characteristics x1 and x1*, and its 95% confidence interval (95% CI) was also calculated. A p value <=0.05 was considered as the criterion of statistical significance.

Results and discussion

Results:

EXPOSURE
- Average concentrations: workers were exposed to a respirable dust concentration of 215 μg manganese/m³ (range 21-1317 µg Mn/m³) and a total dust concentration of 948 μg manganese/m³ (range 46-10840 µg Mn/m³).
The authors noted that plant exposure conditions had not changed considerably in the last 15 years, suggesting that past exposures were consistent with those measured at the time of the study.

FINDINGS
- Performance in measured neurobehavioral tests, especially on measures of simple reaction time, eye-hand coordination, and hand steadiness, was significantly worse in manganese-exposed workers than in the comparison group. For these tests, the prevalences ofabnormal results were related to the lifetime integrated exposure to total and respirable Mn dust.
- The geometric means oftheMn concentrations in blood (MnB) and in urine (MnU) were significantly higher in the Mn exposed group
than in the control group (MnB 0.81 vs 0.68 µg/100 ml; MnU 0.84 vs 0.09 µg/g creatinine). On an individual basis, MnU and MnB were not related to various external exposure parameters (duration of exposure, current exposure, or lifetime integrated exposure to
airborne Mn). On a group basis, a statistically significant association was found betweenMnU and current Mn concentrations in air.
- no differences: between the exposed and the control workers was found with regard to the other biological measurements (calcium, LH, FSH, and prolactin in serum). Although the erythropoietic parameters and serum iron concentration were in the normal range for both groups, there was a statistically significant trend towards lower values in the Mn exposed workers. The prevalences of reported neuropsychological and respiratory symptoms, the lung function parameters, and the audioverbal short term memory scores did not differ between the control and exposed groups.

STATISTICAL RESULTS
- Other: most critical endpoint
BMCL 10 = 142 µg Mn/m³ for for abnormal eye-hand coordination scores in workers exposed to manganese

Applicant's summary and conclusion

Conclusions:

Within this cross sectional study, which investigated an occupational cohort of male workers from a dry alkaline battery exposed to MnO2 dust and their unexposed age-and area-matched controls, a statistically significant differences in results of neurobehavioral tests, particularly in simple reaction time, eye-hand coordination, and hand steadiness, was noted. The reference value derived based on the most critical endpoint was the BMCL10 estimate from the logistic model of 142 μg Mn/m3.

Executive summary:

In this cross sectional study a occupational cohort involving 92 male workers in a dry alkaline battery plant (exposure to dust containing MnO2) and the 101 age-and area-matched controls (with no industrial exposure to manganese) were investigated for performance on a battery of neurobehavioral tests as well as for some biological parameters. The selection of study participants as well as the matching of controls was reasonable and both populations were well matched for age, height, weight, work schedule, coffee and alcohol consumption and smoking.

Exposure assessment was done by personal sampling and the average (geometric mean) exposure duration was 5.3 years (range: 0.2–17.7 years) and the average exposure concentration was 215 μg manganese/m³ of respirable dust and of 948 μg manganese/m³ for toal dust.

Manganese-exposed workers performed significantly worse than the controls on the neurobehavioral tests, with particular differences in simple reaction time, eye-hand coordination, and hand steadiness.

Additional data not published (individual exposure levels and whether the individual had an abnormal performance in the neurobehavioral tests (scores below the 5th percentile score of the control group)) was provided by the study authors Dr. Harry Roels to a US agency (ATSDR - Agency for Toxic Substances and Disease Registry), which then calculated a benchmark dose based on the most sensitive endpoint among the end points showing statistically significantly elevated incidences of abnormal scores, i.e. percent precision score in the eye-hand coordination test.

Average exposure concentration for each worker was calculated by dividing the individual lifetime integrated respirable concentration (LIRD; calculated by Dr. Roels from occupational histories and measurements of workplace air manganese concentrations) by the individual’s total number of years working in the factory. Individuals were grouped into six exposed groups and the control group, and the average of the range in each group was used in benchmark dose (BMD) modeling of the incidence data for number of workers with abnormal percent precision eye-hand coordination scores.

The agency identified the BMCL₁₀estimates from the logistic model as the best fitting model by the AIC measure and the respective BMCL₁₀is 142 μg Mn/m³.