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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1984-01-19 to 1984-02-14
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to national (US) guideline, comparable to OECD guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: EPA TS-792 Acute exposure, oral toxicity. Health effects test guidelines, EPA, August 1982; EPA 560/6-82-001
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Guanidine hydrochloride

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Bantin Kingman, Fremont, CA
- Weight at study initiation: 150 – 255 g
- Fasting period before study: yes, over night
- Housing: individually
- Diet (e.g. ad libitum): Certified Purina Rodent Chow Diet 5062, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 11 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.2°C to 25°C
- Humidity (%): 40 to 53%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): 0.74-1.02 mL/animal in males, 0.59-0.74 mL/animal in females
- Justification for choice of vehicle: test substance is soluble in water
Doses:
0, 278, 360, 464, 600, 775 mg/kg bw (expressed as active ingredient Guanidine), corresponding to 0, 453.14, 756.32, 978, 1263.25 mg/kg bw Guanidine hydrochloride
No. of animals per sex per dose:
9 in treated groups; 5 in vehicle control and cage control
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs, mortality: after 2 and 4 h, daily thereafter
Body weight: twice weekly
- Necropsy of survivors performed: yes; completet gross necropsy
- Other examinations performed: histopathology of CNS for animals with neurological symptoms
Statistics:
Probit analysis

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
556.5 mg/kg bw
Based on:
other: Guanidine
95% CL:
492.3 - 630.9
Sex:
female
Dose descriptor:
LD50
Effect level:
474.6 mg/kg bw
Based on:
other: Guanidine
95% CL:
402 - 562.7
Sex:
male
Dose descriptor:
LD50
Effect level:
907.1 mg/kg bw
Based on:
test mat.
Remarks:
Guanidine hydrochloride
95% CL:
802.45 - 1 028.4
Sex:
female
Dose descriptor:
LD50
Effect level:
773.6 mg/kg bw
Based on:
test mat.
Remarks:
Guanidine hydrochloride
95% CL:
655.3 - 917.2
Mortality:
- vehicle control: 0/5 males, 0/5 females died
- cage control: 0/5 males, 0/5 females died
- 278 mg/kg bw: 0/9 males, 0/8 females died
- 360 mg/kg bw: 0/9 males, 2/8 females died
- 464 mg/kg bw: 2/9 males, 5/9 females died
- 600 mg/kg bw: 5/9 males, 4/7 females died
- 775 mg/kg bw: 9/9 males, 9/9 females died
(reduced total numbers are due to misdosing; those animals were removed from the study)
Clinical signs:
most frequent clinical signs:
- central nervous system-neuromuscular disturbances at all dose groups( 80 of 86 animals)
- increased startle reflex, hyperactivity, and disorientation up to 464 mg/kg bw, recovery within one week
- in the two higher dose groups (600 and 775 mg/kg bw), incressed startle reflex, hyperactivity (as indicated by random jumping, tremors and/or twitching), and depressed grasping and righting reflexes within 4 hours of dosing were observed; most animals in these dose groups died within 24 h

- gastrointestinal tract symptoms (hunched posture, increased salivation with some staining of the muzzle, and diarrhea) in 53/86 animals at all dose levels, but severity was dose-dependent


Body weight:
no significant effects
Gross pathology:
- no test compound-related lesions in the CNS (gross and light microscopic examination)
- the only test compound-related findings were in the gastrointestinal tract (black/serosanguinous material in the stomach, focal depression in the glandular mucosa of the stomach, black and diffuse red areas in the glandular mucosa of the stomach, black and tarry material in the intestine, black and tarry feces)
- in surviving animals no test compound-related gross lesions were reported; 2 male and 1 female rats had a unilateral dilated renal pelvis, which is considered incidential
Other findings:
- Histopathology:
Several rats exhibited central nervous system (CNS) signs. Some rats that exhibited CNS signs died and some others survived. The cerebrum, brainstem and cerebellum of 4 animals died were examined by light microscopy and no lesions were observed.

Any other information on results incl. tables

Sex       Endpoint       Effect level                                     95% CL

male       LD10       441.8 mg/kg bw (Guanidine base) 326.3 — 497.9

female       LD10       321.4 mg/kg bw (Guanidine base) 209.1 — 383.9

male       LD90       701.1 mg/kg bw (Guanidine base) 621.1 — 956

female       LD90       700.8 mg/kg bw (Guanidine base) 584.8 — 1089.9

Applicant's summary and conclusion

Interpretation of results:
other: Acute toxicity Category 4
Remarks:
Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
The oral LD50 for Guanidine hydrochloride in rats was 907.1 mg/kg bw (95% c.i. 802.45 - 1028.4) in males and 773.6 mg/kg bw (95% c.i 655.3 - 917.2) in females. Thus, Guanidine hydrochloride has to be classified for Acute oral toxicity, Category 4.
Executive summary:

In an acute oral toxicity study similar to OECD guideline 401, groups of fasted Sprague-Dawley rats (9/sex) were given a single oral dose of Guanidine hydrochloride (>98% purity, 61.8% base equivalent Guanidine) in water at doses of 0, 278, 360, 464, 600 and 775 mg/kg bw (expressed as Guanidine base), corresponding to 0, 453.14, 756.32, 978, 1263.25 mg/kg bw Guanidine hydrochloride and observed for 14 days.

No mortality occurred in the lowest dose group. 0/9 males, 2/8 females in the 360 mg/kg bw dose group died; 2/9 males, 5/9 females in the 464 mg/kg bw dose group; 5/9 males, 4/7 females in the 600 mg/kg bw dose group and 9/9 males, 9/9 females in the 775 mg/kg bw dose group. Reduced total numbers are due to misdosing; those animals were removed from the study.

Clinical signs were observed in the CNS (increased startle reflex, hyperactivity, and disorientation) and in the gastro-intestinal tract (hunched posture, increased salivation with some staining of the muzzle, and diarrhea) in all dose groups. However, there were no microscopic findings in cerebrum, brainstem and cerebellum of animals with CNS symptoms.

Gross pathology revealed black/serosanguinous material in the stomach, focal depression in the glandular mucosa of the stomach, black and diffuse red areas in the glandular mucosa of the stomach, black and tarry material in the intestine, black and tarry feces.

In the surviving animals no test compound-related gross lesions were reported.

Several rats exhibited central nervous system (CNS) signs. Some rats that exhibited CNS signs died and some others survived. The cerebrum, brainstem and cerebellum of 4 animals died were examined by light microscopy and no lesions were observed.

Oral LD50 Males = 556.5 mg Guanidine/kg bw (95% C.I. 492.3 - 630.9 mg/kg bw)

Oral LD50 Females = 474.6 mg Guanidine/kg bw (95% C.I. 402 - 562.7 mg/kg bw)

corresponding to:

Oral LD50 males = 907.1 mg/kg bw (95% c.i. 802.45 - 1028.4) Guanidine hydrochloride

Oral LD50 females = 773.6 mg/kg bw (95% c.i 655.3 - 917.2) Guanidine hydrochloride

Thus, Based on these data, Guanidine hydrochloride has to be classified for Acute toxicity, Category 4.