Zinc cyanide

Repeated dose toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1955

Report date:

1955

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

formonitrile

Cas Number:

74-90-8

Molecular formula:

HCN

IUPAC Name:

formonitrile

Test material form:

aerosol dispenser: not specified

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Administration / exposure

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

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 ppm

Remarks:

control

Doses / concentrations 2

Dose / conc.:

100 ppm

Doses / concentrations 3

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

Examinations

Statistics:

No statistical analysis were done

Results and discussion

Results of examinations

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

Effect levels

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

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

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).