Registration Dossier

Administrative data

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:
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 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:
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.
Male animals treated with 354 mg/kg appeared normal throughout the study.
Body weight:
All surviving animals gained weight in both weeks p.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
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

Additional information

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.