Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 April 1996 - 25 April 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: done under GLP and OECD method

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes
Test type:
standard acute method

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
424-660-8
EC Name:
-
Cas Number:
224631-15-6
Molecular formula:
Hill formula: C18H26N4O5S CAS formula: C18H26N4O5S
IUPAC Name:
(S)-2,5-dioxopyrrolidin-1-yl 2-(3-((2-isopropylthiazol-4-yl)methyl)-3-methylureido)-3-methylbutanoate
Details on test material:
Abbott-133816

Test animals

Species:
rat
Strain:
other: Crl:CD®(SD)BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Inc. Portage Michigan
- Age at study initiation: approx 5 weeks
- Weight at study initiation: 120 to 140g
- Housing: Individual stainless steel hanging cages
- Diet :Certified Rodent Chow, ad libitum
- Water: ad libitum
- Acclimation period: min 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 71° to 74°
- Photoperiod (hrs dark / hrs light): 12hrs/12hrs

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
corn oil
Details on dermal exposure:
TEST SITE
- Area of exposure: approx 10% of total body area

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The semi-occlusive dressing and gauze were removed and the treated area of the skin was rinsed with warm water to remove any residual test material. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2g/kg BW

VEHICLE
- Amount(s) applied (volume or weight with unit): Sufficient corn oil to make a paste
Duration of exposure:
24 hr
Doses:
2g/kgbw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
All rats observed frequently on day of treatment and daily for 13 days for total of 14 days. The daily observations included signs of toxicity in addition to lethality and irritation at the exposure site.
All animals weighed prior to dosing and weekly thereafter.
Necropsy of survivors performed: yes, 2 weeks after treatment.

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2,000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2,000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Body weight:
No apparent treatment related effects on body weight were observed.
Gross pathology:
No gross morphological changes were observed in rats that were euthanized and necropsied at the end of the two week observation period.
Other findings:
No signs of toxicity were observed.
Moderate erythema was noted in one female rat on day 1.

Applicant's summary and conclusion

Conclusions:
The acute dermal median lethal dose (LD50) of Abbott-133816 in rats was demonstrated to be >2,000 mg/kg bodyweight