Calcium cyanamide

Endpoint summary

Description of key information

CALCIUM CYANAMIDE: Several studies are available for the human exposure of calcium cyanamide.

Sixty-five people who had been working in a calcium cyanamide production plant between 5 and 41 years with calcium cyanamide workplace concentration of 0.23 -8.36 mg/m3 did not show evidence of adverse effects on health or disorders caused by calcium cyanamide in relation to exposure (MAK, 2007). Moderate alcohol intolerance was seen in 6 cases and a weak intolerance was seen in 7 cases out of the 22 workers who ingested alcohol 1 to 7 hours after work.

 

Neither respiratory sensitisation nor skin sensitising properties were detected in calcium cyanamide workers. For example, a separate occupational health study examined the allergic potential of calcium cyanamide in two groups of workers at a calcium cyanamide production plant: plant workers engaged in direct production of calcium cyanamide and workers of various workplaces (MAK, 2007). Exposure of the plant workers was 0.2 – 139.7 mg cyanamide per 2 hands as measured in hand-washing water, and absorption of cyanamide can be concluded. In the workers of various workplaces, the acetylcyanamide concentrations in the urine were between a few milligrams and the detection limit. No health status differences seen between the groups, and neither group had contact allergies detected in the Finn chamber test.

 

In a study from Mertschenk et al. (1993), blood samples of 21 exposed and 9 non-exposed male volunteers were examined for follicle-stimulating hormone (FSH), luteinising hormone (LH), testosterone and several thyroid hormones such as total triiodothyronine (TT3), total tetraiodothyronine (TT4), thyroxine-binding globulin (TBG) and thyrotropin (TSH). The concentration of acetylcyanamide was determined in the urine of the volunteers exposed to obtain information about the extent of their exposure to calcium cyanamide. In this study, the concentrations determined after work were clearly higher (calculated mean cyanamide level: 2.14 mg/L after work versus 0.75 mg/L before work). All hormone levels determined were in the normal range, and there was no significant difference between exposed and non-exposed persons.

 

Peachey et al. (1998) investigated patients with alcoholism, which were randomly assigned to a 56-day treatment with calcium carbimide (50 mg tablet taken orally twice per day) or a placebo taken orally twice per day and routine laboratory tests included liver function tests (GGT, alkaline phosphatase) and several parameters of thyroid function (thyroid stimulating hormone (TSH), total serum triiodothyronine (T3RIA), triiodothyronine uptake (T3U), thyroxine (T4) and thyroid function index (TFI, as T4 X T3U) and TFI thyroid stimulating hormone) were assessed. There was no evidence of hepatoxicity, behavioral or thyroid toxicity.

 

In an efficacy study from Brunner Orne et al. (1962) 3 alcoholics patients were orally exposed to 50 mg citrated calcium carbamide very day for 6 months. The health status of patients was established via clinic-chemical examinations (e.g. blood pressure). Thyroid functions were also examined via Protein-Bound Iodine (PBI) tests.

 

The study did not provide evidence of adverse effects on health or disorders caused by exposure to citrated calcium carbimide. There were no significant changes in Protein-Bound Iodine (PBI) tests (assessed using the Modified Barker Method) and no clinical observations of hypothyroidism among the 53 patients.

 

In a worker study from Mertschenk et al. (1991) approximately 30 workers employed in the calcium cyanamide production units and associated area of SKW Trostberg AG were investigated in an occupational health study. In this study, adverse effects on health were not observed among workers in the calcium cyanamide production units and associated area of SKW Trostberg AG. Furthermore, no case of confirmed or suspected allergy to cyanamide was found.

 

It can be concluded that the main observed effect of calcium cyanamide in humans is the disturbance of alcohol metabolism. No other adverse effects on health were observed in workers of a calcium cyanamide production plant. Thus, the MAK value for calcium cyanamide of 1 mg/m³ as published in the MAK documentation of 1979 has not changed based on the available studies.

 

CYANAMIDE: Multiple case studies (Bujan, 1994) report allergic contact dermatitis suspected to be due to exposure during administration of cyanamide formulations used to treat alcoholism (Colme). A 35-year-old nurse reported a 3-month long period with erythematovesicular dermatitis and severe oedema that limited the movement of her fingers in addition to erythematoviolaceous lesions with haemorrhagic blisters and slight erythema on the right hand. A 32-year-old assistant with a history of dyshidrotic eczema reported 5 days with erythemato-edematous lesions and isolated bullae on the hands. A 54-year-old assistant reported eczema of fingers, face, dorsa of hands, and bullous lesions on her fingers which recurred 4 times in 1.5 years. For all three cases, lesions healed when the case subject was away from work and treated with topical corticosteroids. In another case (De Corres, 1982), a woman with history of atopy and previous nickel contact dermatitis reported vesicular dermatitis for 2 months, which likely coincided with her administration of cyanamide solution (Colme) for 4 months. Patch test showed positive reactions (++) to nickel sulphate and 1% and 10% Colme. After 4 weeks with no contact to Colme, the patient had no symptoms except for a slight increase of greyish coloured pigmentation. Also, in another case (Conde, 1981), a 32-year-old man handling medicines in the form of capsules, pills, and solutions in a psychiatric ward reported erythematosquamous dermatitis that did not respond to topical applications and antihistamines. During patch testing he had a positive (+++) reaction to 10% and 50% 6 g/mL cyanamide in sorbic acid, sodium acetate and water (Colme) and positive reactions to 0.1, 0.5, 1, and 5 % cyanamide in water. Removing contact with cyanamide (Colme) the dermatitis resolved these symptoms. In a chemistry lab (Calnan, 1970), 2 workers developed dermatitis while working with paraformaldehyde, nitrogen and carbodiimide (cyanamide) in DMSO. Patch tests with 0.01, 1.0, and 5.0 % carbodiimide were positive; six controls also showed a toxic reaction to the 5.0 % dilution. One subject was re-tested and was sensitised to the 0.01 % dilution of carbodiimide.

 

Multiple cases of contact dermatitis and sensitisation are reported with cyanamide exposure. However, due to the different findings in human sensitisation studies, it is not possible to conclude that cyanamide is a suitable read-across partner for calcium cyanamide.