Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 March 1999 - 22 June 1999
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:
1999
Report Date:
1999

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Abbott-164220

Test animals

Species:
rat
Strain:
other: Hsd:Sprague Dawley®SD®
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague Dawley Inc, Inianapolis, Indiana
- Age at study initiation: 7 - 9 weeks
- Weight at study initiation: 190 to 220g
- Housing: Individual stainless steel hanging cages
- Diet :Certified Rodent Chow, ad libitum
- Water: ad libitum
- Acclimation period: min 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 66° to 71°
- Photoperiod (hrs dark / hrs light): 12hrs/12hrs

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
sufficient sterile water for injection to make a thick paste.
Details on dermal exposure:
TEST SITE
- Hair clipped from the lumbar dorsal region on day before treatment. 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: 24hr

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


VEHICLE
- Amount applied: Sufficient sterile water for injection to make a thick 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: 1
Female: 2,000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
One male rat died on day 1.
Red discharge from the nose and mouth was observed in female rats in this study. I addition, red coloured urine, decreased activity, rough coat, red discharge (eyes) and diarrhoea were observed in male rats and urine stained abdomen in several female rats.
All signs observed were confined to the day of treatment or the day following treatment.
Body weight:
Decreased body weight gain in two females and body weight loss in two additional females were observed during week one.
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:
Analyticfal tests conducted on the test material at the end of the study indicated that the test materrial remained stable during the treatment period.

Applicant's summary and conclusion

Conclusions:
The acute dermal median lethal dose (LD50) of Abbott-164220 in rats was demonstrated to be greater than the limit dose, 2000 mg/kg bodyweight