Calcium cyanamide

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

other: review

Adequacy of study:

key study

Study period:

2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

MAK value documentation

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

sensitisation data (humans)

Type of information:

other: review

Adequacy of study:

key study

Study period:

2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

MAK value documentation

Type of sensitisation studied:

respiratory

skin

Study type:

survey

Qualifier:

no guideline followed

Principles of method if other than guideline:

Exposure of humans in calcium cyanamide production plant.

GLP compliance:

not specified

Specific details on test material used for the study:

Different test substances in the review taken into consideration

Type of population:

occupational

Ethical approval:

not applicable

Subjects:

- Number of subjects exposed: 65 workers in health study 1 and 62 workers in health study 2
- age: In health study 1, workers were between 33 and 65 years of age; for health study 2, the age of the workers is not stated.
- Other: The total duration of employment in the calcium cyanamide production plant was between 5 and 41 years in health study 1.

Clinical history:

No data on clinical history are provided in the review.

Controls:

No data

Route of administration:

other: inhalation and dermal exposure was investigated

Details on study design:

SKIN SENSITIZATION
- Finn chamber test (health study 2): A standard test plaster was soaked with 0.1 mL of 0.5% aqueous solution of calcium cyanamide and was applied to the skin of the workers for 24 hours. The skin was examined after 24.5, 48 and 72 hours. Control test sites were treated at distilled water. Workers were divided in two groups: persons of group 1 were mainly engaged in direct production and persons of group 2 had various workplaces. Both groups participated in extensive medical check-ups.


RESPIRATORY SENSITIZATION
- Health study 1: The health status of the workers was established by means of extensive physical and clinicochemical examinations. Workers were divided in three groups for the examination: calcium cyanamide workplace concentration > 2.5 mg/m3 (n = 18), 1 - 2.5 mg/m3 (n = 24) and < 1 mg/m3 (n = 23)

Results of examinations:

Health study 1:
The study did not provide evidence of adverse effects on health or disorders caused by calcium cyanamide in relation to exposure (workplace concentration between 0.23 and 8.36 mg/m3). Nor was a decrease in glutathione level in whole blood detected. Among 22 workers who had ingested alcohol 1 to 7 hours after work, there was a moderate alcohol intolerance reaction in 6 cases and a weak intolerance reaction in 7 cases. No relation was found between the effect of calcium cyanamide or the specific group and the intensity of the reaction.

Health study 2:
Exposure of the plant workers (group 1) was estimated via contamination of the hands (determination of cyanamide in the hand washing water) and persons of group 2 (various workplaces) were examined for excretion of acetylcyanamide in urine. The plant workers revealed more or less pronounced contamination of their hands (0.2 - 139.7 mg cyanamide per 2 hands). From this, absorption of cyanamide can be concluded. The acetylcyanamide concentrations found in the urine of the persons of group 2 were between a few milligrams and the detection limit. There were no differences in health status of either group, nor were there any contact allergies detected in the Finn chamber test.

no remarks

Conclusions:

Except for alcohol intolerance no adverse effects on health were observed among workers in a calcium cyanamide production plant. The current MAK value of 1mg/m3 (established in 1979) is not changed. No evidence for sensitization is provided in the human health studies. Therefore, calcium cyanamide is not designated with "Sa" or "Sh".

Executive summary:

Two health studies are summarized in the MAK value documentation on calcium cyanamide.

In the first study, the health status of 65 workers of a calcium cyanamide production plant who were between 33 and 65 years old and had been working in the plant between 5 and 41 years, was determined by extensive physical and clinicochemical examination. The analytically determined calcium cyanamide workplace concentration was 0.23 - 8.36 mg/m3 and the cohort was divided in three groups according to the workplace concentration: > 2.5 mg/m3 (group 1), 1 - 2.5 mg/m3 (group 2) and < 1 mg/m3 (group 3). The study did not provide evidence of adverse effects on health or disorders caused by calcium cyanamide in relation to exposure, nor was a decrease in glutathione level in whole blood detected. Among 22 workers who had ingested alcohol 1 to 7 hours after work, there was a moderate alcohol intolerance reaction in 6 cases and a weak intolerance reaction in 7 cases. No relation was found between the effect of calcium cyanamide or the specific group and the intensity of the reaction.

In the second occupational health study, two cohorts from a calcium cyanamide production plant were examined. The persons of group 1 were mainly engaged in direct production and persons of group 2 had various workplaces. Both groups participated in extensive medical check-ups. One point of focus was the question of allergic properties of cyanamide, which was examined by Finn chamber test. Exposure of the plant workers was estimated via contamination of the hands (determination of cyanamide in the hand washing water) and persons of group 2 (various workplaces) were examined for excretion of acetylcyanamide in urine. The plant workers revealed more or less pronounced contamination of their hands (0.2 - 139.7 mg cyanamide per 2 hands). From this, absorption of cyanamide can be concluded. The acetylcyanamide concentrations found in the urine of the persons of group 2 were between a few milligrams and the detection limit. There were no differences in health status of either group, nor were there any contact allergies detected in the Finn chamber test.

In both studies, neither respiratory sensitization nor skin sensitizing properties of calcium cyanamide were detected. Consequently, human evidence support, that Kalkstickstoff has not to be classified with regard to respiratory sensitisation.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

2007

Reference 2

Reference Type:

publication

Title:

Felduntersuchung von Personen mit langjähriger Exposition gegenüber Kalkstickstoff (Field study of workers with long-term exposure to calcium cyanamide)

Author:

Schiele R. et al.

Year:

1981

Bibliographic source:

Zentralbl Bakteriol Parasitenk Infektionskr Hyg, Abt 1, Orig, Reihe B 173: 13–28

Materials and methods

Study type:

cohort study (retrospective)

Endpoint addressed:

repeated dose toxicity: inhalation

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: Occupational health study with 65 workers who were exposed to calcium cyanamide
- Short description of test conditions: Exposure of 65 workers of a calcium cyanamide (nitrolime) production plant were investigated in an occupational health study. Workplace concentrations of calcium cyanamide were analytically determined, and the cohort of workers were divided and assessed in groups based on the calcium cyanamide workplace concentrations.
- Parameters analysed / observed: The health status of the workers was established by means of a detailed questionnaire on anamnesis and via extensive physical and clinicochemical examinations.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Calcium cyanamide

EC Number:

205-861-8

EC Name:

Calcium cyanamide

Cas Number:

156-62-7

Molecular formula:

CN2.Ca

IUPAC Name:

calcium cyanoazanediide

impurity 1

Reference substance name:

Calcium oxide

EC Number:

215-138-9

EC Name:

Calcium oxide

Cas Number:

1305-78-8

Molecular formula:

CaO

IUPAC Name:

oxocalcium

impurity 2

Reference substance name:

Carbon

EC Number:

231-153-3

EC Name:

Carbon

Cas Number:

7440-44-0

Molecular formula:

C

IUPAC Name:

carbon

impurity 3

Reference substance name:

Hematite (Fe2O3)

EC Number:

215-275-4

EC Name:

Hematite (Fe2O3)

Cas Number:

1317-60-8

Molecular formula:

Fe2O3

IUPAC Name:

diiron oxide

impurity 4

Reference substance name:

Urea

EC Number:

200-315-5

EC Name:

Urea

Cas Number:

57-13-6

Molecular formula:

CH4N2O

IUPAC Name:

urea

impurity 5

Reference substance name:

Silicon dioxide

EC Number:

231-545-4

EC Name:

Silicon dioxide

Cas Number:

7631-86-9

Molecular formula:

O2Si

IUPAC Name:

dioxosilane

impurity 6

Reference substance name:

Trisilicon tetranitride

EC Number:

234-796-8

EC Name:

Trisilicon tetranitride

Cas Number:

12033-89-5

Molecular formula:

N4Si3

IUPAC Name:

trisilicon tetranitride

impurity 7

Reference substance name:

Calcium dihydroxide

EC Number:

215-137-3

EC Name:

Calcium dihydroxide

Cas Number:

1305-62-0

Molecular formula:

CaH2O2

IUPAC Name:

calcium dihydroxide

impurity 8

Reference substance name:

Aluminium oxide

EC Number:

215-691-6

EC Name:

Aluminium oxide

Cas Number:

1344-28-1

Molecular formula:

Al2O3

IUPAC Name:

aluminium oxide

impurity 9

Reference substance name:

Cyanoguanidine

EC Number:

207-312-8

EC Name:

Cyanoguanidine

Cas Number:

461-58-5

Molecular formula:

C2H4N4

IUPAC Name:

2-cyanoguanidine

impurity 10

Reference substance name:

Calcium acetylide

EC Number:

200-848-3

EC Name:

Calcium acetylide

Cas Number:

75-20-7

Molecular formula:

C2Ca

IUPAC Name:

calcium ethynediide

impurity 11

Reference substance name:

unknown

IUPAC Name:

unknown

Test material form:

solid: particulate/powder

Details on test material:

Kalkstickstoff (calcium cyanamide, technical grade)

Specific details on test material used for the study:

- Name of the test material in the study: calcium cyanamide (nitrolime)
- Nitrolime consists of 60% calcium cyanamide, 15% calcium oxide, 10% free carbon and of calcium salts, silicates and aluminium, iron and magnesium oxides.

Method

Type of population:

occupational

Ethical approval:

not specified

Details on study design:

- Sixty-five workers of a calcium cyanamide (nitrolime) production plant (nitrolime consists of 60% calcium cyanamide, 15% calcium oxide, 10% free carbon and of calcium salts, silicates and aluminium, iron and magnesium oxides), who were between 33 and 65 years old (average of 47 years), were investigated in an occupational health study.
- The total duration of employment in the plant was between 5 and 41 years (average of 19 years).
- The analytically determined workplace concentrations of calcium cyanamide were in a range between 0.23 and 8.36 mg/m³.
- The cohort was divided into 3 groups for the examinations: calcium cyanamide workplace concentrations above 2.5 mg/m³ (n = 18), 1 to 2.5 mg/m³ (n = 24) and below 1 mg/m³ (n = 23).
- The health status of the workers was established by means of a detailed questionnaire on anamnesis and via extensive physical and clinicochemical examinations (e.g. measurement of glutathione level).

Exposure assessment:

measured

Remarks:

analytically determined workplace concentrations

Details on exposure:

TYPE OF EXPOSURE: Inhalation

TYPE OF EXPOSURE MEASUREMENT: Area air sampling / Personal sampling / Exposure pads / Biomonitoring (urine) / Biomonitoring blood / other: not specified

EXPOSURE LEVELS: Range between 0.23 and 8.36 mg/m³

EXPOSURE PERIOD: 7.5 hours per shift; total duration of employment: between 5 and 41 years (average 19 years)

POSTEXPOSURE PERIOD: not specified

DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES: The cohort was divided into 3 groups for the examinations: calcium cyanamide workplace concentrations above 2.5 mg/m³ (n = 18), 1 to 2.5 mg/m³ (n = 24) and below 1 mg/m³ (n = 23).

Statistical methods:

Not specified

Results and discussion

Results:

The study did not provide evidence of adverse effects on health or disorders caused by calcium cyanamide in relation to exposure. There was also no decrease of the glutathione level in whole blood detected. Among 22 workers from all 3 groups who had ingested alcohol 1 to 7 hours after work, there was a moderate alcohol intolerance reaction in 6 cases and a weak alcohol intolerance reaction in 7 cases. No relation was found between the effect of calcium cyanamide or the specific group and the intensity of the reaction.

Applicant's summary and conclusion

Conclusions:

In this study, no adverse effects on health were observed among 65 workers in a calcium cyanamide production plant (workplace concentration range of 0.23 to 8.36 mg/m³). Weak to moderate alcohol intolerance is considered to be the main effect of calcium cyanamide of this study. The current MAK value for calcium cyanamide of 1 mg/m³ (established in 1979) remains unchanged.

Executive summary:

In an occupational health study, summarised in the MAK value documentation on calcium cyanamide (2007), 65 workers of a calcium cyanamide (nitrolime) production plant (nitrolime consists of 60% calcium cyanamide, 15% calcium oxide, 10% free carbon and of calcium salts, silicates and aluminium, iron and magnesium oxides), who were between 33 and 65 years old (average of 47 years), were investigated in an occupational health study. All persons worked in a continuous alternating shift system with a shift of 7.5 hours. The total duration of employment in the plant was between 5 and 41 years (average of 19 years). The analytically determined workplace concentrations of calcium cyanamide were in a range between 0.23 and 8.36 mg/m³. The cohort was divided into 3 groups for the examinations: calcium cyanamide workplace concentrations above 2.5 mg/m³ (n = 18), 1 to 2.5 mg/m³ (n = 24) and below 1 mg/m³ (n = 23). The health status of the workers was established by means of a detailed questionnaire on anamnesis and via extensive physical and clinicochemical examinations.

The study did not provide evidence of adverse effects on health or disorders caused by calcium cyanamide in relation to exposure. There was also no decrease of the glutathione level in whole blood detected. Among 22 workers from all 3 groups who had ingested alcohol 1 to 7 hours after work, there was a moderate alcohol intolerance reaction in 6 cases and a weak alcohol intolerance reaction in 7 cases. No relation was found between the effect of calcium cyanamide or the specific group and the intensity of the reaction. The observed alcohol intolerance is considered to be the main effect of calcium cyanamide.

In this MAK value documentation, the current MAK value for calcium cyanamide of 1 mg/m³ has been published.