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Administrative data

Endpoint:
acute toxicity: dermal
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 the reported age of the animals in relation to their 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 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
male rats were in excess of the range of 200-300 g
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Principles of method if other than guideline:
An occlusive dressing was used. This is considered acceptable, but a semi-occlusive dressing is preferred (according to the
guidelines).
GLP compliance:
yes
Test type:
standard acute 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: it was stated that rats were ca. 9 weeks old; however with the indicated BW at study start (see below)
rats of this strain and age, especially males, should have been ca. 12-13 weeks old.
- Weight at study initiation: 327-357 g (males); 204-239 g (females)
- Fasting period before study: not required for a dermal study
- Housing: individually 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): 21 (no exact data reported)
- Humidity (%): 50 (no exact data reported)
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 3 To: 17 June 1998

Administration / exposure

Type of coverage:
occlusive
Vehicle:
polyethylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: ca. 10% of total body surface (viz. ca. 25 cm2 for males and ca. 18 cm2 for females)
- % coverage: 5x7 (25 cm2) of skin was clipped
- Type of wrap if used: The test substance was held in contact with the skin with a dressing, consisting of a nonwoven swab
(Dispomed L), successively covered with aluminium foil and Coban flexible bandage. A piece of Micropore tape was additionally
used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after 24 h dressings were removed and residual test substance was removed using a tissue moistened with
tap water

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg bw
- Concentration (if solution): 200 mg/mL
- Constant volume or concentration used: constant concentration
- For solids, paste formed: no the test material was dissolved/suspended in polyethylene glycol. Homogeneity was accomplished to a visually acceptable level

VEHICLE
- Amount(s) applied (volume or weight with unit): 10 mL/kg bw
- Specific gravity: 1.127 g/mL (adjusment was made for the specific gravity of the vehicle.
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
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 thereafter; 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
Mortality:
None.
Clinical signs:
Red staining of the neck was noted in one female between days 3 and 7. Scabs or scales were seen in the treated skin-area of
two other females between days 3 and 6.
Body weight:
The changes noted in body weight gain in males and females were stated to be within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
However, it should be noted that there was slight BW gain in males and hardly no weight gain in females during the 2-week period.
If animals indeed would have been ca. 9 weeks at the start of the study, the slight BW gain in males or absence of BW gain in
females would point at a toxicological relevant effect. However, based on the reported BW weights at the start of the study it is
more likely that animals of this strain (Wistar) were much older and were, therefore, out of their growing phase.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
Not reported

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Although the LD50 is in excess of 2000 mg/kg bw it is not known what effects will be obtained at higher levels. Therefore,
classification in Category V is warranted according to OECD-GHS.
Executive summary:

Assessment of acute dermal toxicity with PDTN in the rat.

The study was carried out based on the guidelines described in: EC Comm Directive 92/691EEC, Part B.3 and OECD No.402. PDTN was administered to five Wistar rats of each sex by dermal occlusive application at 2000 mglkg body weight for 24 hours. Animals were subjected to daily

observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15; day 1 is day of dosing). No mortality occurred. Red staining of the neck was noted in one female between days 3 and 7. Scabs or scales were seen in the treated skin-area of two other females between days 3 and 6. Body weight gain during the observation period was slight in male rats and almost absent in female rats. If animals indeed would have been ca. 9 weeks at the start of the study, the slight BW gain in males or absence of BW gain in

females would point at a toxicological relevant effect. However, based on the reported BW weights at the start of the study it is more likely that animals of this strain (Wistar) were much older and were, therefore, out of their growing phase.

No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value 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 V, as toxicity at (much) higher levels was not tested.