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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
June 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Relatively well reported study according to guideline/standard; however there is some doubt on BW data.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of test compound: PDTN
Appearance: white crystalline solid
Chemical name: Acetonitrile,2,2',2'',2'''-(1,3-propanediyldinitrilo)tetrakis-
Batch no: JNN98038
Composition: PDTN 99.2±1.0% m/m; water 0.5±0.1% m/m
Storage: at room temperature in the dark
Expiry date: 1 June 2000

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: ca. 7 weeks
- Weight at study initiation: 182-228 g (males); 170-206 g (females)
- Fasting period before study: overnight prior to dosing until ca. 3-4 h after dosing
- Housing: 3 per sex in polycarbonate cages
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): ca. 21 (no exact data reported)
- Humidity (%): ca. 50 (no exact data reported)
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 2 To: 18 June 1998

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: based on a pre-test.
- Lot/batch no. (if required): no info
- Purity: no info
- Specific gravity: 1.127 g/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION (if unusual): immediately prior to dosing. Adjustment made for specific gravity of vehicle. Homogeneity was accomplished to a visually acceptable level.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: limit concentration of 2000 mg/kg bw
The study was started with males, females were dosed 2 days later
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: frequently on the day of dosing; once/twice daily; BW weekly
- Necropsy of survivors performed: yes
Statistics:
Not required.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: 1/3 females died
Mortality:
One female was found dead on day 3 (day 1 is day of dosing).
Clinical signs:
Lethargy, hunched posture, piloerection, diarrhoea and red staining of the snout were noted among the animals between days 1
and 3. Salivation was observed in two males immediately after treatment. This finding is commonly seen after treatment by oral
gavage and is considered not toxicologically significant.
Body weight:
The body weight gain shown by the surviving animals over the study period was considered by the author to be similar to that
expected of untreated animals of the same age and strain. However, a BW gain of 88 g in the first week and another BW gain of 42 g (in total 130 g) for one male rat is not expected for male rats of this strain and age.
Gross pathology:
Macroscopic post mortern examination of the animal that died revealed a hemorrhagic content of the urinary bladder. No
abnormalities were found in the surviving animals.
Other findings:
Not reported.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Because of 1/6 deaths at 2000 mg/kg bw, the anticpated LD50 may be between 2000-5000 mg/kg bw. As such, classification in
Category V according to OECD-GHS is warranted.
Executive summary:

Assessment of acute oral toxicity with PDTN in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in EC Commission Directive 96/54/EC, Part B.1 tris and OECD No.423. PDTN was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly

determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice 14 days after dosing. One female was found dead on day 3 (day 1 is day of dosing). Lethargy, hunched posture, piloerection, diarrhoea and red staining of the snout were noted among the animals between days 1 and 3. The body weight gain shown by the surviving animals over the study period was stated to be normal. However, a BW gain of 88 g in one week for one of the males is not expected.

Macroscopic post mortem examination of the animal that died revealed a hemorrhagic content of the urinary bladder. No abnormalities were found in the surviving animals. The oral LD50 of PDTN in Wistar rats was established as exceeding 2000 mg/kg body weight. Based on these results and according to the OECD-GHS criteria for classification, PDTN requires classification in Category 5.