Registration Dossier

Administrative data

Endpoint:
dermal absorption
Type of information:
other: review article or handbook
Adequacy of study:
key study
Study period:
1932-2007
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

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
Unnamed
Year:
2007
Reference Type:
secondary source
Title:
Two mathematical skin permeation models for vapours. In Brain KR, James VJ, Walter KA. Prediction of percutaneous penetration.
Author:
Wilschut A, tenBerge WF
Year:
1996
Bibliographic source:
PPP conference, Cardiff, UK

Materials and methods

Principles of method if other than guideline:
Various methods used in peer-reviewed studies were evaluated by the ECETOC Task Force and found to be valid.

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Absorption in different matrices:
Cyanide is soluble in water, and the critical factor in cyanide permeation from aqueous solutions of NaCN through human skin in vitro is the pH of the solution. At a pH of 9.11 (approximate pKa) about 50% is present as undissociated HCN. The ratio of HCN and CN ion at a selected pH follows from the Henderson-Hasselbach equation. HCN permeates 30 times faster than CN anion. Cyanide is also able to be absorbed through the skin from gaseous sources. Using an overall permeation coefficient (Kp skin-air-air) for HCN is 6.25 cm/h, it has been calculated that the ratio of absorption by skin compared to lung for HCN is 0.18 or 18%.
Percutaneous absorption
Remarks on result:
other: Overall permeation coefficient for HCN is 6.25 cm/h.

Any other information on results incl. tables

Total dermal CN permeation rate, expressed in mg/cm²/h, = (3.5 × 10–4 × CN ion + 10–2 × HCN) × Kskin-water [HCN]. HCN, CN ion and CN total are expressed in mg/ml. Aqueous permeation coefficient: Kskin-water [HCN] = 0.01 cm/h.

For dermal absorption from the air  (Partition coefficient water-air):

Kwater-air= (R x T x Sb)/Mw x Vp.

 

Where R = gas constant 8.314 Nm/mol/°K

T = temperature in °K

Sb = water solubility in mg/l

Mw = molecular weight (mass)

Vp = vapour pressure in Pascal (= N/m²)

 

 

Permeation coefficient skin-air: Kpsk-air= Kpsk-water× Kwater(cm/h).

Permeation coefficient stagnant air layer: Kpair= Dair/∂ (cm2/h)

Where ∂ = 3 cm (stagnant air layer, simulating barrier of clothing) (Lotens and Wammes, 1993)

Mw = 76

Dair= 360× √76/Mw         (diffusivity in air, cm2/h)

A case report illustrates the potential toxicity of HCN via the dermal route (Drinker, 1932). Three male workers equipped with respiratory protection (filter masks) felt symptoms of dizziness, weakness and strongly increased heartbeat, after exposure to 22,000 mg HCN/m3 (19,600 ppm) for about 9 minutes. This simple scenario allows for calculation of the absorption of HCN through the skin, as follows: The LC01 at 10 minutes for humans has been estimated to be 211 mg/m3 (188 ppm). During normal activities workers inhale 1.25 m3/h, or 0.21 m3/10 min. Assuming a retention of HCN of 50% in the lungs (Landahl and Hermann 1950), the dose of HCN absorbed after 10 minutes exposure to 211 mg/m3 is estimated to be about 22 mg. This can be assumed to be the amount of HCN that the workers reported by Drinker (1932) had absorbed through the skin when symptoms of HCN poisoning became evident after 9 minutes. Without respiratory protection, the workers (inhaling 0.19 m3/9 min at 22,000 HCN mg/m3 and assuming a lung retention of 50%) would have retained 2,090 mg HCN. Based on this calculation, the amount of HCN absorbed through the human skin (within 9 minutes) was as low as 1.3% of the respiratory absorption at a given concentration in air. This is more than one order of magnitude lower than the percentage of 18% estimated from Dugard (1987), and may be due to some lag time before HCN permeates the skin fully. The example shows that respiratory protection alone does not protect workers exposed to high concentrations of HCN. This is borne out by industrial experience.

Applicant's summary and conclusion

Conclusions:
Cyanide is able to be absorbed through the skin from aqueous solutions or from gaseous sources. The permeation of cyanide from aqueous solutions of NaCN through human skin in vitro was strongly influenced by the pH of the solution. At a pH of 9.11 (= pKa) about 50% is present as undissociated HCN. The ratio of HCN and CN ion at a selected pH follows from the Henderson-Hasselbach equation. HCN appeared to permeate 30 times faster than CN ion. The overall skin permeation coefficient (Kp skin-air-air) for HCN was determined to be 6.25 cm/h. Using this, it has been calculated that the ratio of absorption by skin compared to lung for HCN is 0.18 or 18%.