Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
method of administration unclearly defined: using a metal
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Specific details on test material used for the study:
Lot: V-156
Expected purity: 75%
Appearance: light yellow highly viscous liquefied substance

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Shizuoka Agricultural Cooperative Association for Laboratory Animals.
- Age at study initiation: 4 weeks upon arrival
- Weight at study initiation: 99 ± 3.3g (male) and 83 ± 2.5g (female)
- Fasting period before study: One night prior to the test. Feeding was resumed three hours after administration.
- Housing: Ten animals were housed in a cage
- Diet: ample food
- Water: ample water
- Acclimation period: Tamed under breeding circumstances for one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 2.0 C
- Humidity (%): 45 to 85

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
1.170 mL/ kg and 0.988 mL/ kg of undiluted substance for male and female animals, respectively.
Doses:
Males: 0.392, 0.485, 0.606, 0.714, 0.825, 0.918 and 1.170 mL/ kg bw
Females: 0.349, 0.471, 0.588, 0.741, 0.864 and 0.988 mL/ kg bw
No. of animals per sex per dose:
10
Control animals:
yes
Remarks:
no administration
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weight was recorded at 0, 1, 3, 5, 8, 11 and 14 days after exposure.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight are recorded.
Statistics:
LD50 values are calculated according to the Probit method.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
630 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Corresponding to a dose level of 0.55 mL/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
730 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Corresponding to a dose level of 0.63 mL/kg bw
Mortality:
1/10, 5/10, 3/10, 5/10, 6/10, 9/10 and 10/10 males died in observation period after exposure period to 0.392, 0.485, 0.606, 0.714, 0.825, 0.918 and 1.170 mL/ kg bw, respectively.
0/10, 5/10, 7/10, 6/10, 8/10 and 10/10 females died in the observation period after exposure period to 0.349, 0.471, 5.88, 0.741, 0.864 and 0.988 mL/ kg bw, respectively.

The mortalities occurred on day 4 to 8 of the 14-day observation period. No deaths occurred in the control group.
Clinical signs:
No toxic symptoms were noted for 2 days after administration, but severe diarrhoea, reddish brown vomit or lacrimation, decline of spontaneous movement and
blephroptosis were suddenly observed on and after the third day after administration in the order of the dosage . These symptoms continued until around the last
day of the test. Rats succumbing during observation exhibited ataxia and oppression in breathing before death.
Body weight:
Bodyweight and weight gain were significantly reduced in male and female animals during the 14 day observation period. Between day 1 and 5 after exposure, a dose-dependent decrease in bodyweight was observed compared to day 0. Between day 5 and 14 the bodyweights increased, with the absolute body weight being lower on each timepoint, in a dose dependent manner, compared to the control animals.
Gross pathology:
As to rats that died during the test, ulceration or necrosis was observed in the stomach and intestinal canal. Such symptoms in the stomach were particularly pronounced. No remarkable change was observed in other organs. As to rats that lived for 14 days, the accretion of the stomach (mainly anteriorly) with thoracie peritoneum was observed in the male group with a tendency to increasing accretion at higher doses. No extreme change was observed in the female group.

Any other information on results incl. tables

Calculation of LD50 value according to Probit method.

Male: 0.63 mL/kg (0.53-0.73 mL/kg, p=0.05) = 730 mg/kg (610-840 mg/kg, p= 0.05)

Female: 0.55 mL/kg (0.45-0.64 mL/kg, p=0.05) = 630 mg/kg (520- 730 mg/kg, p=0.05)

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute oral toxicity test showed a LD50 of 630 and 730 mg/kg bw for female and male rats, respectively.
Executive summary:

A pre-guideline study, similar to OECD guideline 401, was performed to identify the acute oral toxicity of the test substance. Although the details on administration are not very clearly described, it is clear that the substance was administered by gavage. In this study 10 conventional Wistar rats were used per sex and per dose group, which were observed for 14 days post administration. In the males, administration of 0.392, 0.485, 0.606, 0.714, 0.825, 0.918 and 1.170 mL/ kg bw resulted in mortality in 1/10, 5/10, 3/10, 5/10, 6/10, 9/10 and 10/10 of the animals, respectively. For females exposed to 0.349, 0.471, 5.88, 0.741, 0.864 and 0.988 mL/ kg bw mortality was observed in 0/10, 5/10, 7/10, 6/10, 8/10 and 10/10 of the animals, respectively. No mortality was observed in the control (untreated) group. The Probit method was used to calculate the LD50 values, which were determined to be 630 mg/kg bw (0.55 mL/kg bw) for females and 730 mg/kg bw (0.63 mL/kg bw) for males.

Clinical signs were noted from day 2 till the end of the observation period and included severe diarrhoea, reddish brown vomit or lacrimation, decline of spontaneous movement and blephroptosis. Rats succumbing during observation exhibited ataxia and oppression in breathing before death. Bodyweight was reduced in a dose dependent manner between day 1 and 5 if compared to the bodyweight at day 0. During the whole observation period, the absolute bodyweight of the treated animals was lower compared to the controls. Necropsy revealed ulceration or necrosis in the stomach and intestinal canal of the rats that died during the observation period. In these rats no remarkable change was observed in other organs. As to rats that lived for 14 days, the accretion of the stomach (mainly anteriorly) with thoracie peritoneum was observed in the male group with a tendency to increasing accretion at higher doses. No extreme change was observed in the female group. Based on the LD50 values obtained, the substance is considered to be acutely harmful Category 4.