Ammonium thiocyanate

Carcinogenicity

Description of key information

Thiocyanates are not genotoxic, and although thiocyanate is able to induce hyperplasia (goitre), it is not known whether humans are susceptible, as are rodents, to the development of thyroid cancer from thyroid-pituitary disruption. 

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

no data

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Very limited reporting. Single dose level. The study was not performed according to OECD guidline or under GLP.

Qualifier:

no guideline followed

GLP compliance:

no

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Frederik cancer research facility
- Age at study initiation: 8 weeks
- Weight at study initiation: no data
- Fasting period before study: not applicable
- Housing: 4 to a cage
- Diet (e.g. ad libitum): Purine Autoclavable Laboratory chow, ad libitum.
- Water (e.g. ad libitum): each cage of rats was given 80 ml of a solution of sodium thiocyanate or of sodium nitrite + sodium thiocyante each day for 5 days of each week. On the remaining 2 days the rats were given acidified (to ph 2.5) tap water ad libitum to allow them to make up any water definciency they had incurred.
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data

Route of administration:

oral: drinking water

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
no data

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

The life span of the rats, over 2 years.

Frequency of treatment:

Each cage of rats was given 80 ml of a solution of sodium thiocyanate or of sodium nitrite + sodium thiocyante each day for 5 days of each week. On the remaining 2 days the rats were given acidified (to ph 2.5) tap water ad libitum to allow them to make up any water definciency they had incurred.

Post exposure period:

No post exposure period.

Remarks:

Doses / Concentrations:
0.32%
Basis:
nominal in water
approximately 250 mg/kg bw

No. of animals per sex per dose:

20

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: based on earlier experiments
- Rationale for animal assignment (if not random): no data
- Rationale for selecting satellite groups: not applicable
- Post-exposure recovery period in satellite groups: not applicable
- Section schedule rationale (if not random): no data

Observations and examinations performed and frequency:

no data

Sacrifice and pathology:

All of the treated animals were allowed to die naturally, or killed when moribund, expet for survivors which were sacrificed at week 130. Each animals was necropsied, all lesions and major organs and tissues were fixed in formalin, embedded in papaffin, sectioned and stained with hematoxylin and eosin for histologic examination.

Other examinations:

None

Statistics:

No data

Relevance of carcinogenic effects / potential:

Due to the limitations of the study, no conclusion on the carcinogenic activity and/or promotor activity of the thiocyanate can be drawn.

Treatment with sodium thiocyante did not affect the treated rats noticably, mortality was not increased. There is no indication in the results of this study that sodium thiocyanate, alone or mixed with sodium nitrite is carcinogenic.

Conclusions:

Treatment with sodium thiocyante did not affect the treated rats noticably, mortality was not increased. There is no indication in the results of this study that sodium thiocyanate, alone or mixed with sodium nitrite is carcinogenic. However due to the limitations of the study, no conclusion on the carcinogenic activity and/or promotor activity of the thiocyanate can be drawn.

Executive summary:

Chronic toxicity tests of sodium thiocyanate with sodium nitrite in F344 rats. Lijinsky W, Kovatch RM Toxicol Ind Health 1989 Jan 5:1 25-9.

Abstract: Sodium thiocyanate, a common environmental chemical, was found to increase the incidence of liver tumors in a group of rats treated with 0.08% in drinking water. To test the possibility that thiocyanate was catalyzing the formation of carcinogenic nitrosamines from amines and nitrite in the food, a group of 20 male and 20 female rats was given a higher dose of sodium thiocyanate (0.32%) together with sodium nitrite (0.2%) in drinking water. Similar groups of rats were given 0.32% sodium thiocyanate or 0.2% sodium nitrite in drinking water or were untreated. All treatments lasted most of the lifetime of the rats, at least 2 years. There was no difference between the groups, treated or untreated, in survival, or in the incidence of any tumor that could be related to the treatment. The results indicate that sodium thiocyanate is without carcinogenic activity in rats, alone or combined with sodium nitrite.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Study duration:

chronic

Species:

rat

Quality of whole database:

Due to the limitations of the study, no conclusion on the carcinogenic activity and/or promotor activity of the thiocyanate can be drawn.

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thiocyanates are not genotoxic, and although thiocyanate is able to induce hyperplasia (goitre), it is not known whether humans are susceptible, as are rodents, to the development of thyroid cancer from thyroid-pituitary disruption. Available data is not sufficient to justify classification.

Additional information

A chronic study (Lijinsky W, Kovatch RM Toxicol Ind Health 1989 Jan 5:1 25-9) in rats supplied with 0.32% thiocyanate together with sodium nitrite (0.2%) in their drinking water for at least for 2 years, showed no effects in survival, or in the incidence of any tumor that could be related to the treatment. Due to limited reporting, a low validity was assigned to this report.

 

Thiocyanates are naturally occurring substances with ubiquitous presence in living nature. Many studies evaluated the background thiocyanate levels in serum of man showing levels between 23 to 50 µmol/L to up to 100 µmol/L in case of smokers.Tsuge (2000) reported background serum concentrations of thiocyanate of 33.5 ± 25.4 µM for non-smokers and 111.2 ± 92.1 µM smokers, and after diner levels up to 160 µM (equivalent to 12 mg NH4SCN/L!) in serum were seen (Eminedoki, 1994).Thiocyanates are not genotoxic, and although thiocyanate is able to induce hyperplasia (goitre), it is not known whether humans are susceptible, as are rodents, to the development of thyroid cancer from thyroid-pituitary disruption. In any case, it appears that humans are less sensitive to the carcinogenic effects than are rodents. Therefore, a further carcinogenicity study in rodents is not justified.

Justification for selection of carcinogenicity via oral route endpoint:
Only carcinogenicity study identified.