Guanidinium chloride

Acute Toxicity: oral

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:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: EPA TS-792 Acute exposure, oral toxicity. Health effects test guidelines, EPA, August 1982; EPA 560/6-82-001

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system 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 levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

556.5 mg/kg bw

Based on:

other: Guanidine

95% CL:

492.3 - 630.9

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

474.6 mg/kg bw

Based on:

other: Guanidine

95% CL:

402 - 562.7

Effect levels 3

Key result

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

Effect levels 4

Key result

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:

other: 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 gr

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:

Category 4 based on GHS criteria

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.