2-Isobutyryl-3,N-diphenylacrylamide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-11-28 to 1990-12-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: study was conducted according to GLP guidelines as described by the FDA (21 CFR Part 58) and standard operating procedures

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 402 not explecitely mentioned but similar

GLP compliance:

yes

Test type:

other:

Limit test:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Name of test material (as cited in study report): 89-0292 and PD 132,408

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Inc. Boyertown, PA
- Weight at study initiation: 1.94-2.48 kg
- Fasting period before study: no
- Housing: stainless stell cage
- Diet: Food and water ad libitum
- Acclimation period: >5 days before study initiation

ENVIRONMENTAL CONDITIONS
All housing and care conformed to the standard established in the "Guide for the care and use of laboratory animal" DEHW Publication No. (NIH) 85-23

Administration / exposure

Type of coverage:

occlusive

Vehicle:

physiological saline

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- Type of wrap if used: plastic


REMOVAL OF TEST SUBSTANCE
- Washing (if done): sites were wiped gently with clean gauze
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bodyweight


VEHICLE
- Amount applied to the control group: 2000 mg/kg

Duration of exposure:

24 h

Doses:

2000 mg/kg (Limit test) for each sex

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: hourly for six hours after the treatment; twice daily thereafter
- Weighing on day: 0, 1, 3, 7, 11, 14
- Necropsy of survivors performed: gross necropsy. The external body surface and orifices, major visceral organs, body cavities and the carcass were examined

Statistics:

Analysis of variance for the weight differences

Results and discussion

Preliminary study:

limit test

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

Signs of toxicity related to dose levels:
Anorexia, diarrhea, a gel like substance in the waste tray, nasal discharge and soft stools were noted in both groups during the observation period. The observations were considered incidential and unrelated to dose administration.

Body weight:

Two test and three control animals lost weight from study initiation to termination. No compound related statistical significance (analysis of variance) was noted when the test group was compared to the control group.

Gross pathology:

No treatment related changes in the organs.

Other findings:

Erythema and edema were found immediatly after binder removal in both treated and control animals with various severity but subsided within 24h hours

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the acute dermal LD50 of PD 132,408 is considered to be greater than 2000 mg/kg bodyweight.

Executive summary:

All animals in both the test and the control groups survived to study termination following dose administration. Two test and three control animals lost weight from study initiation to termination. Under the conditions of this study, the acute dermal LD50 of PD 132,408 is considered to be greater than 2000 mg/kg bodyweight.