Aminoiminomethanesulphinic acid

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: No details on methods published

Data source

Reference

Reference Type:

publication

Title:

Toxicologic characteristics of thiourea and its dioxide

Author:

Zhislin LE, Ovetskaia NM

Year:

1972

Bibliographic source:

Gig Tr Prof Zabol. 1972, Jun; 16(6) 51-52 (russ.) (Gigiena truda i professional'nye zabolevaniia] Toxline citation: http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~d3hGJg:3

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Author's own methods

Principles of method if other than guideline:

Chronic inhalation exposure of white rats (more than 100 animals, including 40 controls were used in the experiment) to thiourea (TU) dust and tiourea dioxide (TUD) was carried out for 1, 3 and 9 months at a concentration of dust in the chambers amounting to 47,2 ± 2,1 and 48,9 ± 2,8 mg/m3 respectively.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Aminoiminomethanesulphinic acid

EC Number:

217-157-8

EC Name:

Aminoiminomethanesulphinic acid

Cas Number:

1758-73-2

Molecular formula:

CH4N2O2S

IUPAC Name:

aminoiminomethanesulphinic acid

Test material form:

solid

Test animals

Species:

rat

Sex:

not specified

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

not specified

Details on inhalation exposure:

Chronic inhalation exposure of white rats (more than 100 animals, including 40 controls were used in the experiment) to thiourea (TU) dust and thiourea dioxide (TUD) was carried out for 1, 3 and 9 months at a concentration of dust in the chambers amounting to 47,2 ± 2,1 and 48,9 ± 2,8 mg/m3 respectively.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

1 month, 3 month, 9 month

Frequency of treatment:

continously

Doses / concentrations

Remarks:

Doses / Concentrations:
48.9 +- 2,8 mg/m³
Basis:
no data

No. of animals per sex per dose:

Female + male: 60

Control animals:

not specified

Examinations

Observations and examinations performed and frequency:

The body weight, blood levels of red blood cells and hemoglobin (using hematoscope), leukocytes (counting in the Goryaev chamber) resistance of erythrocytes in 0.4 and 0.5% sodium chloride solutions (by comparing the number of red blood cells in hypo- and isotonic solutions) was determined in 7 animals of each group, the excitability of the nervous system was studied using the method by M.L. Rylova and S.V. Speranski. Oxygen consumption was tested using the advanced installation proposed by I.I. Shvaiko and N.V. Verzhikovskaya.

Other examinations:

At the end of the exposure functional status of the thyroid gland of the rats was studied by means of specially designed installation in relation to the accumulation of iodine131 in the thyroid gland in 2, 4, 6, 24, 48 and 72 hours after its subcutaneous injection in a dose of 0.4-0.6 mcc.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

There was no significant effect of the test substances on the functional state of some organs and systems.

Mortality:

no mortality observed

Description (incidence):

There was no significant effect of the test substances on the functional state of some organs and systems.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

In the chronic experiment with exposure to TUD dust from the third month the weight gain of the animals dropped, compared to the effects of TU and control.

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

effects observed, treatment-related

Description (incidence and severity):

reticular tissue proliferation

Haematological findings:

no effects observed

Description (incidence and severity):

No changes to red blood cells and white blood cell count, erythrocyte resistance to hypotonic solutions.

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

Hemoglobin in blood of TUD exposed animals to TUD was somewhat higher (at different times 14,6 ± 0,80 / 16, 2 ± 0,79 mg%) in comparison with the control (13,8 ± 0,74 / 15, 0 ± 0,38 mg%), under the influence of TU reduced to 12,5 ± 0,20 / 14,1 ± 0.08 mg%.

Urinalysis findings:

not specified

Behaviour (functional findings):

no effects observed

Description (incidence and severity):

The excitability of the nervous system has not changed much during the exposure.

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

In lungs the catarrhal-desquamative bronchiolitis, foci of chronic non-specific interstitial pneumonia, edema were observed as well as the areas of atelectasis emphysema. In parenchymal organs, granular and fatty degeneration, and other effects on organs.

Histopathological findings: neoplastic:

not specified

Details on results:

In the chronic experiment with exposure to TUD dust from the third month the weight gain of the animals dropped, compared to the effects of TU and control. There was no significant effect of the test substances on the functional state of some organs and systems; red blood cells and white blood cell count, erythrocyte resistance to hypotonic solutions, WBC, and consumption of oxygen and the excitability of the nervous system have not
changed much during the exposure. Hemoglobin in the blood of the animals exposed to TUD was somewhat higher (at different times 14,6 ± 0,80 / 16, 2 ± 0,79 mg%) in comparison with the control (13,8 ± 0,74 / 15, 0 ± 0,38 mg%), under the influence of TU it was reduced to 12,5 ± 0,20 +14,1 ± 0,08 mg%.

A decrease in the functional activity of the thyroid gland was found to be more prominent when exposed to TU: delay and decrease in the accumulation of iodine-131 in the thyroid gland, more intense release of radioactive iodine in the urine. The zobogenny (goitrogenic) effect of TU is clearly visible – the relative weight of the thyroid gland in this group reaches at different times 16,3 ± 2,35 / 9, 1 ± 2,12 mg/100 g compared to 10,7 ± 1,62 /13,3 ± 0,87 mg/100 g (TUD) and 8,8 ±1,06 mg/100 g (control). In experimental animals increased lung weights, to 1,07 ± 0,09 g/100g during exposure of TU and 1,2 ± 0,21 and even 1,75 ± 0,19 g/100g (in the dead animals) during effect of TUD (control 0,77 ± 0,45 g/100 g).

Effect levels

Dose descriptor:

NOAEL

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Histologically, the animals of experimental groups at different times of the exposure showed circulatory disorders. In the lungs, the catarrhal-desquamative bronchiolitis, foci of chronic non-specific interstitial pneumonia, edema were observed as well as the areas of atelectasis emphysema. In parenchymal organs, granular and fatty degeneration was detected. In the spleen, hyperplasia of lymphoid follicles with moderate myeloid metaplasia, focal proliferation of reticular tissue was observed. In the thyroid gland there was excessive overgrowth of the stroma, foci of destruction with limited areas of functional activity (under the influence of TUD, the pronounced desquamation of follicular epithelium was observed).

Applicant's summary and conclusion

Conclusions:

In chronic inhalation exposure of white rats with TU and TUD aerosols, the possibility of adverse effects on the body is established, so it is necessary to take measures not to let these substances in the body of the workers in a production environment (de-dusting activities, work in respirators, etc.).

Executive summary:

Chronic inhalation of thiourea dioxide (formamidine sulfinic acid) dust of 48.9 mg/m³ concentration up to 9 month in white rats revealed organ effects: loss of organ weight, bronchiolitis, interstitnal pneunomia, edema, emphysema in the lungs, granular and fatty degeneration of parynchymal organs, hyplasia of lymphoid follicles in the spleen, proliferation of reticular tissue, excessive overgrow of the stroma and foci of destruction with dequamation of follicular epithelium of the thyroid glands.