Hydrogen cyanide

Specific investigations: other studies

Administrative data

Endpoint:

specific investigations: other studies

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Experimental data was reviewed by the ECETOC Task Force, author of the JACC Report No. 53, “Cyanides of Hydrogen, Sodium and Potassium, and Acetone Cyanohydrin (CAS No. 74-90-8, 143-33-9, 151-50-8 and 75-86-5)”, 2007. The report is a weight of evidence approach to an extensive body of literature, much of which was undertaken prior to development of guidelines. The report was peer reviewed by the scientific non-governmental organization (NGO), which judged the data to be reliable with restrictions.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

The blood cyanates in the treatment of hypertension

Author:

Barker MH

Year:

1936

Bibliographic source:

JAMA 106: 762-767

Reference 2

Reference Type:

publication

Title:

Further experiences with thiocyanates

Author:

Barker MH, Lindberg HA, Wald MH

Year:

1941

Bibliographic source:

JAMA 117: 1591-1594

Materials and methods

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

Potassium thiocyanate

EC Number:

206-370-1

EC Name:

Potassium thiocyanate

Cas Number:

333-20-0

IUPAC Name:

potassium thiocyanate

Test animals

Species:

human

Sex:

male/female

Results and discussion

Details on results:

Information on possible adverse effects of thiocyanate in humans can be derived from human experience with the former use of sodium or potassum thiocyanate as an antihypertensive drug. Barker (1936) descibed his experience with thiocyanate therapy for hypertension of 45 patients that received thiocyanate therapy for 1 to 4 years. A larger follow-up study of 246 patients, treated for 4-10 years, was subsequently published Barker et al (1941). Oral doses of 300 mg/d usually led to blood levels of 50 to 100 mg SCN-/l, but in some cases higher or lower levels were obtained. When blood levels were maintained between 80 and 120 mg/l, most of the side effects could be avoided. In the first group, 3 patients and in the second group, 20 patients were identified who had indication of hypothyroidism. In the publications, the corresponding blood thiocyanate levels were not given. The rental function and the iodine status of the patients were not controlled. The authors reported that a reduction of the thiocyanate dose to 65 to 130 mg SCN ion/dl led to a recovery within 2 weeks.

Any other information on results incl. tables

The level of thiocyanate that is tolerated by humans is 65 -130 mg SCN ion per deciliter, suggestive of a human NOEL of about 20 to 40 mg SCN ion/l blood.

Applicant's summary and conclusion

Conclusions:

Information on possible adverse effects of thiocyanate in humans can be derived from human experience with the former use of sodium or potassiu thiocyanate as an antihypertensive drug. Barker (1936) described his experience with thiocyanate therapy for hypertension of 45 patients that received thiocyanate therapy for 1 to 4 years. A larger follow-up study of 246 patients, treated for 4-10 years, was subsequently published Barker et al (1941). Oral doses of 300 mg/d usually led to blood levels of 50 to 100 mg SCN/l, but in some cases higher or lower levels were obtained. When blood levels were maintained between 80 and 120 mg/l, most of the side effects could be avoided. In the first group, 3 patients and in the second group, 20 patients were identified who had indications of hypothyroidism. In the publications, the corresponding blood thiocyanate levels were not given. The renal function and the iodine status of the patients were not controlled. The authors reported that a reduction of the thiocyanate dose to 65 to 130 mg SCN/d led to a recovery within 2 weeks. This would be suggestive of a human NOEL of about 20 to 40 mg SCN ion/l blood.