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Description of key information

For that endpoint, one reliable study to assess the repeated dose toxicity on hydrogen cyanide on rats was available.

Based on the similarity of chemical structures of zinc cyanide and hydrogen cyanide, the study results on hydrogen cyanide can be extrapolated to zinc cyanide.

Hydrogen cyanide has a NOAEL of 100 ppm, which can be converted into a NOAEL of 10.8 mg/kg/day for the cyanide.

When extrapolated to zinc cyanide, the NOAEL of zinc cyanide becomes 24.3 mg/kg/day.

These calculations are supported by the Integrated Risk Information System (IRIS).

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1955
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
Weanling male and female albino rats of the Carworth Farms strain were used. The rats were individually housed in wire-mesh cages elevated above the drop- pings, with water and the appropriate diets available at all tlmes. The food was fumigated with hydrogen cyanide.The control and two experimental groups of 10 males and 10 females were initiated on the 2-year feeding study. One experimental group was placed on a 100 p.p.m. feeding level, and the other received a diet containing 300 p.p.m. of hydrogen cyanide. The food of the test rats was prepared fresh every 2 days for the 2-year period and analyzed for its initial hydrogen cyanide content.
The parameters analysed in this study are :
- mortality, tumor development, body weight, level of cyanide and thiocyanate in blood.
- weight of liver, kidneys, spleen, brain, heart, adrenals, and ovaries of each animal
- histopathology of heart, lung, liver, spleen, stomach, small and large intestines, kidney, adrenal, thyroid, uterus and ovary, and the cerebrum and cerebellum of the brain.
GLP compliance:
not specified
Species:
rat
Strain:
not specified
Sex:
male/female
Route of administration:
oral: feed
Vehicle:
not specified
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
2 years
Frequency of treatment:
every 2 days
Dose / conc.:
0 ppm
Remarks:
control
Dose / conc.:
100 ppm
Dose / conc.:
300 ppm
No. of animals per sex per dose:
10 animals per sex per dose
Control animals:
yes, concurrent no treatment
Positive control:
No positive control
Statistics:
No statistical analysis were done
Clinical signs:
not examined
Mortality:
mortality observed, non-treatment-related
Description (incidence):
A comparison of survival data of the control animals with the experimental ones indicates a random distribution of mortality. During the first 75 weeks of feeding the total mortality of each group of 20 rats was as follows: three in the control group, two at the 100 p.p.m. level, and two at the 300 p.p.m. level. In the ensuing 29 weeks of feeding, deaths became more frequent and a final analysis of survival data shows that seven control animals had died as compared with eight in the 100 p.p.m. group and five in the 300 p.p.m. group. The higher incidence in the latter months of the study is probably due to the increasing age of the rats.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
The growth curves are almost identical for the three groups of males throughout the 104-week feeding period. The females, however, showed considerable variation. The controls of this group exhibited an abnormal rise after 91 weeks of feeding, accompanied by 2 deaths. The 100 p.p.m. females reached an abnormal peak at 78 weeks; this peak was due to tumor development in 1 rat which died after 78 weeks, with a terminal weight of 759 grams. The dashed line is the curve for the entire 100 p.p.m. group; the dotted line from the 52nd week to the 91st week represents the group exclusive of this tumored rat. The sudden decline after 1.5 years of feeding appeared to be due to rapid loss of weight, particularly by two rats, but there were also a general senility and weight loss in this group. The 300 p.p.m. level appeared to be of normal nature, reaching a peak at the end of 78 weeks of feeding and declining slowly as the rats approached the 104th week.
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
The liver, kidneys, spleen, brain, heart, adrenals, and testes or ovaries of each animal were weighed, and the ratios of organ weight to body weight appeared to be within normal limits.
Gross pathological findings:
effects observed, non-treatment-related
Description (incidence and severity):
During the 2 years of feading no gross signs of cyanide toxicity were observed. In the latter stages of the study a number of the rats were unthrifty in appearance, with alopecia, emaciation, tumors, and sores on their bodies. Gross findings which were frequently encountered were: pale, granular and thickened livers, congestion of the medulla of the kidney, abnormally small spleens, enlarged adrenals, atrophied, encysted, and inflamed genital organs, and enlarged, hemorrhagic pituitaries. Many nodes and tumors were found throughout the viscera.
Neuropathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Key result
Dose descriptor:
NOAEL
Effect level:
100 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
Critical effects observed:
no
Conclusions:
In a study conducted for a 2-year period, food containing 100 and 300 p.p.m. of hydrogen cyanide produced no noticeable signs of cyanide toxicity. Therefore, the concentration of 100 ppm of hydrogen cyanide is used as NOAEL. By extrapolation of the results, the cyanide NOAEL level is therefore 10,8 mg/kg/day. This NOAEL is supported by the Integrated Risk Information System (IRIS).
Endpoint:
chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
hydrogen cyanide
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Zinc cyanide and Hydrogen cyanide have similar chemical structures. They share the cyanide group.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source substance is Hydrogen cyanide.
The target substance is Zinc cyanide.

3. ANALOGUE APPROACH JUSTIFICATION
Based on the similarity of chemical structures between zinc cyanide and hydrogen cyanide, the analogue read across approach is justified. Therefore, the study results on hydrogen cyanide can be extrapolated to zinc cyanide .
Reason / purpose for cross-reference:
read-across source
Key result
Dose descriptor:
NOAEL
Effect level:
100 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
Critical effects observed:
no
Conclusions:
Based on the similarity of chemical structures of zinc cyanide and hydrogen cyanide, the study results on hydrogen cyanide can be extrapolated to zinc cyanide.
Hydrogen cyanide has a NOAEL of 100 ppm, which can be converted into a NOAEL of 10.8 mg/kg/day for the cyanide.
When extrapolated to zinc cyanide, the NOAEL of zinc cyanide becomes 24.3 mg/kg/day.
These calculations are supported by the Integrated Risk Information System (IRIS).
Executive summary:

For that endpoint, one reliable study to assess the repeated dose toxicity on hydrogen cyanide on rats was available.

Based on the similarity of chemical structures of zinc cyanide and hydrogen cyanide, the study results on hydrogen cyanide can be extrapolated to zinc cyanide.

Hydrogen cyanide has a NOAEL of 100 ppm, which can be converted into a NOAEL of 10.8 mg/kg/day for the cyanide.

When extrapolated to zinc cyanide, the NOAEL of zinc cyanide becomes 24.3 mg/kg/day.

These calculations are supported by the Integrated Risk Information System (IRIS).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
24.3 mg/kg bw/day
Study duration:
chronic
Species:
rat

Additional information

Justification for classification or non-classification