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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
4 May - 1 June 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (not performed according to GLP).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1,1,3,3-tetramethylguanidine
EC Number:
201-302-7
EC Name:
1,1,3,3-tetramethylguanidine
Cas Number:
80-70-6
Molecular formula:
C5H13N3
IUPAC Name:
N,N,N',N'-tetramethylguanidine
Details on test material:
- Name of test material (as cited in section 1): 1,1,3,3-Tetramethylguanidine

Test animals

Species:
rat
Strain:
other: Crl:(WI)BR strain
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate, Kent, UK
- Age at study initiation (LD50 study): between 6 and 10 weeks
- Weight at study initiation (LD50 study): 133 - 160 g (males), 131-159 g (females)
- Fasting period before study: yes, overnight fasting before the study
- Housing: in groups of 4 by sex (screening study) or in groups of 5 by sex and dose group (LD 50 study) in solid floor polypropylene cages
- Diet: SQC Rat and Mouse Maintenance Diet No. 1, modified, expanded (Special Diets Services Ltd., Stepfield, Witham, Essex, UK), ad libitum
- Water: mains water, ad libitum
- Acclimation period (LD50 study): 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22
- Humidity (%): 42 - 59
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle:
- Screening study: 5, 25, 125 and 500 mg/mL
- LD50 study: 40, 56.6, 80 and 113.1 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:
- Screening study: 50, 250, 1250 and 5000 mg/kg bw
- LD50 study: 400, 566, 800 and 1131 mg/kg bw
No. of animals per sex per dose:
- Screening study: 1 male and 1 female animal
- LD50 study: 5 male and 5 female animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
All animals were observed for overt signs of toxicity or behavioural change at 1/4, 1, 2 and 4 hours after treatment and subsequently once daily for 14 days. All gross or visible toxic or pharmacological effects were recorded. Individual body weights were recorded on the day before treatment (day-1), on the day of treatment, 7 and 14 days after treatment and at death.
- Necropsy of survivors performed: All animals dying during the working day and sick animals at the end of the study were subjected to gross necropsy. No tissues were retained. Animals surviving until the end of the study were sacrificed by exposure to high levels of carbon dioxide.

Screening study:
The animals were observed for mortality only. Frequent observations were made during 48 hours after treatment. Individual body weights were recorded on the day of treatment to allow the calculation of individual treatment volumes. No necropsies were performed in this study. The animals were killed after 48 hours.
Statistics:
The acute oral median lethal dose (LD50) and 95% fiducial limits for combined male and female groups were calculated using a probit analysis (Finney D.J. (1964), Statistical Method for Biological Assay, 2nd Edition, London, Charles Griffin). Separate LD50 values and 95% fiducial limits were calculated for male and female animals.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
835 mg/kg bw
Based on:
test mat.
95% CL:
738 - 944
Sex:
male
Dose descriptor:
LD50
Effect level:
794 mg/kg bw
Based on:
test mat.
95% CL:
725 - 869
Sex:
female
Dose descriptor:
LD50
Effect level:
895 mg/kg bw
Based on:
test mat.
95% CL:
738 - 1 086
Mortality:
One male treated with 800 mg/kg bw was found dead 1 hour after treatment. One male treated with 800 mg/kg bw and one female treated with 1131 mg/kg bw were found dead 4 hours after treatment. All other deaths with 2 exceptions were noted 24 or 48 hours after treatment. Two females treated with 800 mg/kg bw were found dead 7 and 12 days after treatment, respectively.
See also Table 1 under "any other information on results".
Clinical signs:
other: Animals treated with 400 mg/kg bw appeared normal throughout the study period. Only male animals treated with 566 mg/kg bw showed overt signs of toxicity. These signs, most pronounced during the day of dosing were lethargy, red staining around nose and m
Gross pathology:
The major pathological findings noted at necropsy were associated with the stomach, gastrointestinal tract and lungs. Data on the irritancy of the test article and the extreme alkalinity of the test article formulations suggest a severe irritant or corrosive effect on the intestinal linings and tissues with the delayed deaths being possibly due to resultant peritonitis.

Any other information on results incl. tables

Table 1. Acute oral toxicity.

 

Dose

[mg/kg bw]

Mortality

Clinical signs

 

N*

N*

Males

400

0/5

0/5

566

0/5

5/5

800

3/5

5/5

1131

5/5

5/5

Females

400

0/5

0/5

566

0/5

0/5

800

2/5

5/5

1131

4/5

5/5

*N = Number of animals / number of animals used

 

Table 2. Screening study.

Dose

[mg/kg bw]

Mortality

 

N*

Males

 

50

0/1

250

0/1

1250

1/1

5000

1/1

Females

 

50

0/1

250

1/1

1250

1/1

5000

1/1

* N = Number of animals / number of animals used

The mortalities indicated a LD50 in the range 250 - 1250 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: Acute Oral 4, H302
Executive summary:

The study was performed in year 1982 according to the standard acute Method.

This study was undertaken to determine the oral median lethal dose (LD50) of test article LZ 754 in Wistar rats.

The LD50 was calculated using a probit method. The calculated value for male and female rats is 835 mg/kg bw.

Therefore, the test item is classified as Acute Tox Oral 4, H302 according to Regulation (EC) 1272/2008.