Guanidinium thiocyanate

Endpoint summary

Description of key information

In an acute oral toxicity study according to OECD guideline 401 with Guanidine Thiocyanate in Sprague Dawley rats, three groups of five fasted female animals were given a single oral dose of test material, in distilled water at dose levels of 354, 500 and 707 mg/kg bodyweight. A further group of five fasted males was similarly treated, at a dose level of 354 mg/kg bodyweight, to confirm that this sex was not markedly more sensitive to the test material. The surviving animals were observed for fourteen days after the day of dosing. All animals were subjected to gross pathological examination.

 

Oral LD₅₀ Females = 593 mg/kg bw (95% C.I. 431 - 816)

Oral LD₀ Males = 354 mg/kg bw

 

Deaths were noted during the day of dosing at 500 and 707 mg/kg bw. Clinical observations noted were ataxia, clonic convulsions, pallor of the extremities, hunched posture, lethargy, piloerection, ptosis, decreased respiratory rate, gasping, laboured and noisy respiration, increased salivation, staining around the mouth and snout and splayed or tiptoe gait. Surviving animals recovered one to three days after dosing except for male animals treated with 354 mg/kg which appeared normal throughout the study.

Surviving animals showed expected gain in bodyweight during the study.

 

Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver, dark kidneys and haemorrhagic gastric mucosa. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-03-04 to 1998-03-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd
- Age at sudy initation: 8 -12 weeks
- Weight at study initiation: Males: 201 to 212g; Females 201 to 225g
- Fasting period before study: Overnight
- Housing: In groups of up to five by sex in solid-floor polypropylene cages

- Diet (e.g. ad libitum): Rat and Mouse Expanded Diet No. 1, (Special Diets Services Limited, Witham, Essex UK), ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23 °C
- Humidity (%): 50 - 60 %
- Air changes (per hr): 15/ hr
- Photoperiod (hrs dark / hrs light): twelve hour continuous light/dark cycle

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
-Concentration in vehicle: 35.4 mg/mL; 50 mg/mgl; 70.7 mg/mL
Amount of vehicle: 10 mL/kg

Doses:

females: 354 mg/kg bw, 500 mg/kg bw, 707 mg/kg bw
males: 354 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administation: 14 days
- Frequency of observations and weighing: 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days
- Necropsy of suvivors performed: Yes
- Other examinations performed: bodyweight, clinical signs

Statistics:

Probit Analysis, the LD50 and 95 % confidence limits were calculated for females only.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

593 mg/kg bw

Based on:

test mat.

95% CL:

431 - 816

Key result

Sex:

male

Dose descriptor:

LD0

Effect level:

354 mg/kg bw

Based on:

test mat.

Mortality:

0/5 males died 1 day after the administration (354 mg/kg bw)
0/5 females died 1 day after the administration (354 mg/kg bw)
3/5 females died 1 day after the administration (500 mg/kg bw)
3/5 females died 1 day after the administration (707 mg/kg bw)

Clinical signs:

other: Clinical observations noted were ataxia, clonic convulsions, pallor of the extremities, hunched posture, lethargy, piloerection, ptosis, decreased respiratory rate, gasping, laboured and noisy respiration, increased salivation, staining around the mouth a

Gross pathology:

Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver, dark kidneys and haemorrhagic gastric mucosa. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 value for Guanidine Thiocyanate was determined to be 593 mg/kg bw (95 % confidence interval 431 - 816 mg/kg bw in female animals.
Male animals were considered not to be markedly more sensitive to the test material than female animals.

Executive summary:

In an acute oral toxicity study according to OECD guideline 401 with Guanidine Thiocyanate in Sprague Dawley rats, three groups of five fasted female animals were given a single oral dose of test material, in distilled water at dose levels of 354, 500 and 707 mg/kg bodyweight. A further group of five fasted males was similarly treated, at a dose level of 354 mg/kg bodyweight, to confirm that this sex was not markedly more sensitive to the test material. The surviving animals were observed for fourteen days after the day of dosing. All animals were subjected to gross pathological examination.

 

Oral LD₅₀ Females = 593 mg/kg bw (95% C.I. 431 - 816)

Oral LD₀Males = 354 mg/kg bw

 

Deaths were noted during the day of dosing at 500 and 707 mg/kg bw. Clinical observations noted were ataxia, clonic convulsions, pallor of the extremities, hunched posture, lethargy, piloerection, ptosis, decreased respiratory rate, gasping, laboured and noisy respiration, increased salivation, staining around the mouth and snout and splayed or tiptoe gait. Surviving animals recovered one to three days after dosing except for male animals treated with 354 mg/kg which appeared normal throughout the study.

Surviving animals showed expected gain in bodyweight during the study.

 

Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver, dark kidneys and haemorrhagic gastric mucosa. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

354 mg/kg bw

Quality of whole database:

Data from a GLP compliant guideline study with reliability 1.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the oral LD50 value of 593 mg/kg bw in female rats and the LD0 value of 354 mg/kg bw for acute oral toxicity Cat. 4 is required according to CLP (EU-GHS) Regulation (EC) No 1272/2008 for Guanidine Thiocyanate, which is consistent to legal binding C&L for acute toxicity Cat. 4 all routes.