Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guideline
Qualifier:
according 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

Test animals

Species:
rat
Strain:
other: Crj:CD(SD)IGS
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Japan Co. (Yokoyama, Kanagawa Prefecture).
- Age at study initiation: 6 weeks of age
- Weight at study initiation: 167-187g (males), 128-144g (females)
- Fasting period before study: yes, 16 hours prior to administration.
- Housing: 202 barrier system cages
- Diet (e.g. ad libitum): solid food MF (oriental Yeast Co., Tokyo), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23+/-3°C
- Humidity (%): 55+/-20%
- Air changes (per hr): 20
- Photoperiod (hrs dark / hrs light): 12/12 (150-300 lux, lighted at 7am, darkened at 7 pm).

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The administration dose was 0.5mL per 100g of body weight, and the administration dose was calculated individually based on the measured body weight. A stomach probe was used between 10:00 and 11:00 for forced oral administration into thee stomach of animals who had fasted for 16 hours prior to administration of DPG.
DGP was dissolved in corn oil and prepared at the time of use.
Doses:
0, 50, 65, 85, 110 and 143 mg/kg
No. of animals per sex per dose:
5 rats/sexe/dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations : Observations on toxic symptoms and mortalities were performed at one hour intervals until six hours after administration, and then twice a day, in the morning and afternoon, until the 14th day.
- Frequency of weighing: The body weights were measured immediately before administration, and then again on the 7th and 14th days after administration.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology
Statistics:
The LD50 values and the 95% confidence interval were calculated from the mortality rate 14 days after administration, using the Probit method.

Results and discussion

Preliminary study:
The results from the preliminary tests conducted prior to this study (Doses: 10, 50, 100, 250 and 500 mg/kg; vehicle: corn oil, administration weight: 0.5mL/100g bw) included 3 cases of mortality among 3 males at 100 mg/kg and higher, and 2 of 3 cases in the 100 and 500 mg/kg groups, as well as 3 of 3 cases in the 250 mg/kg group. Five doses from 50 to 143 mg/kg were established for this particular study (ratio 1:3), and a solvent control group was set for both sexes.
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
111 mg/kg bw
95% CL:
> 86 - < 161
Sex:
female
Dose descriptor:
LD50
Effect level:
107 mg/kg bw
95% CL:
> 78 - < 177
Mortality:
The mortality rate for the 0, 50, 65, 85, 110 and 143 mg/kg groups 0, 0, 0, 0, 40 and 60% respectively for the males and 0, 0, 0, 0, 40 and 60% respectively for the females. Most of the deaths were confirmed during 1 and 3 hours after administration.
Clinical signs:
All animals of both sexes in the test substance administration groups exhibited a reduction in spontaneous motor activity, lying laterally and staggered gait immediately after administration. Most of the mortalities exhibited the aforementioned symptoms between one and three hours after administration with some of the animals in the low dose group exhibiting tremors approximately 4 hours after administration. Additionally, other findings included one case each of salivation and closed eyelids in live animals in the 110 mg/kg group of females. These symptoms all disappeared within 2 days after administration.
Nothing abnormal was noted in either of the sexes in the solvent control group.
Body weight:
None increase of bodyweight was observed in any group.
Gross pathology:
Nothing abnormal was noted for any of the animals during pathological necropsy of mortalities during the test period as well as after completion of the period of observation.
Other findings:
no

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
With a LD50 of 107-111 mg/kg (females/males), DPG was classified in the Category 3 in accordance to the Guidance on the Application of the CLP Criteria (2008).
Executive summary:

An acute oral toxicity study of 1.3 -diphenylguanidine was conduted using Crj:CD(SD)IGS rats with five males and five females in each group.

DPG was suspended in corn oil, and single forced oral administration of 50 -143 mg/kg was conducted on both sexes. A solvent control group was established, with administration of only corn oil. The observation period was 14 days, and then observations were made on the mortality, toxicity and period of onset, changes in weight, and pathological examinations were also concluded.

The LD50 value was 111 mg/kg for males and 107 mg/kg for females.