Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 Jan-11 Feb 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Deviations:
no
Principles of method if other than guideline:
- Principle of test: Test doses were determined based on an initial "viability test" conducted at 5000 mg/kg bw. Doses administered via gavage were 1200, 300, and 75 mg/kg bw, based on initial fasted body weights to groups of four young male rats per dose level, which were then observed for mortality and clinical signs of toxicity daily for up to 7 days following administration.
- Short description of test conditions: Standard acute oral toxicity testing under controlled laboratory conditions, at three dose levels, with necropsy 7 days after administration. Dead animals were necropsied as soon as possible to try to ascertain the cause of death.
- Parameters analysed / observed: Body weights, food consumption, water consumption, clinical observations of toxicity and mortality.
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: CRJ-F344
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Labouratories Japan, Inc.
- Age at study initiation: 6-wk
- Weight at study initiation: 105.5 ± 5.17 g
- Fasting period before study: from 16 h before dosing to 6 h after administration
- Housing: individually in five-modular stainless steel cages with barrier system
- Diet: solid feed NMF, Oriental Yeast Co., Ltd., autoclave sterilized, ad libitum
- Water: tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 55 ± 5
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 28 Jan 1982 To: 11 Feb 1982

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 7.5, 30 and 120 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw

Dose range-finding study:
- Rationale for the selection of the doses: A "viability test" was conducted at 5000 mg/kg bw
Doses:
75, 300 and 1200 mg/kg bw
No. of animals per sex per dose:
4 males/dose
Control animals:
other: one control group was tested for all 9 test compounds
Details on study design:
- Duration of observation period following administration: 7 days after dosing
- Frequency of observations and weighing: Observations for clinical signs of toxicity and mortality were conducted on the day of dosing immediately after dosing, 1, 2, 4, 6 and 8 h post-dose, and at the same time each morning on days 1 to 7 after dosing. Food consumption and water consumption were measured on Days 1, 2, 3, 5 and 7 after dosing. Body weights were measured on the day of dosing (fasted, prior to administration), and 1, 2, 3, 5 and 7 days after dosing.
- Necropsy of survivors performed: yes
Statistics:
Means with SD were calculated for body weights, food consumption and water consumption.

Results and discussion

Preliminary study:
A viability test was conducted on 9 test articles via oral administration of 5000 mg/kg bw using rats, prior to conduct of this LD50 study.
Effect levels
Key result
Dose descriptor:
LD50
Effect level:
> 75 - < 300 mg/kg bw
Mortality:
75 mg/kg bw: 0/4 males died
300 mg/kg be: 3/4 males died
1200 mg/kg bw: 3/4 males died
Clinical signs:
75 mg/kg bw: piloerection in 4/4 males (2-6 h post-dose)
300 mg/kg bw: piloerection and lacrimation in 4/4 males (2 h post-dose); convulsion, cyanosis, respiratory depression, and death in 2/4 males (day of dose); cyanosis, piloerection and lacrimation in 1/4 males (4-8 h post-dose) then piloerection, hunched posture and hypothermia (Day 1 and 2 post-dose) followed by death (Day 3 post-dose).
1200 mg/kg bw: lacrimation in 4/4 males (30 minutes post-dose); lacrimation, piloerection and salivation in 4/4 males (2 h post-dose); convulsions and respiratory paralysis followed by death in 1/4 males (day of dosing); in addition to the previous clinical signs, hunched posture in 2/4 males (4 h post-dose) followed by prostrate position (8 h post-dose) and death (Day 1 post-dose).
Body weight:
75 mg/kg bw: similar body weight gain to control group throughout the study
300 mg/kg bw: body weight loss after dosing until Day 2 post-dose, and then a gain in body weight throughout the study, but lower overall than control group, indicating no complete recovery of body weight.
1200 mg/kg bw: body weight loss after dosing until Day 2 post-dose, and then a gain in body weight throughout the study, but lower than control group, indicating no complete recovery of body weight.
Gross pathology:
At the necropsies of the animals found dead during the study period, atrophy of the stomach and exfoliation of gastric mucosa were noted. During the necropsies conducted at termination of the study, no abnormalities were found.
Other findings:
Food consumption
75 mg/kg bw: similar trend with control group
300 and 1200 mg/kg bw: decreased food consumption throughout the study compared to control group

Water consumption
75 mg/kg bw: similar trend with control group
300 and 1200 mg/kg bw: decreased water consumption through Day 2 post-dose, then recovering to the control group level throughout the remainder of the study

Any other information on results incl. tables

 Mortality and Clinical Signs for CD-3 Acute Oral Toxicity Study in Rats

Dose

[mg/kg bw]

Mortality

Clinical Signs

Na

Na

Males

0

0/4

0/4

75

0/4

4/4

300

3/4

4/4

1200

3/4

4/4

aNumber of animals dosed

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS Category 3 (H301) according to Regulation (EC) No 1272/2008
Conclusions:
The test substance CD-3 when administered at a dose level of 75 mg/kg bw produced no deaths in 4 dosed animals, however at a dose level of 300 mg/kg bw, 3 of 4 dosed animals died.
Therefore, in this study an LD50 value greater than 75 mg/kg bw but smaller than 300 mg/kg bw was found for CD-3, giving a Acute Tox. Hazard Category 3 classification.