Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was performed according to OECD 402 guideline and in compliance with the GLP Regulations. No significant deviations can be observed from the study guidelines, which could have an impact on the performed study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
purity no reported
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 6398-21-1
- Physical state: clear, colorless liquid
- Analytical purity: responsibility of the Sponsor
- Lot/batch No.: 90-013
- Stability under test conditions: no apparent change in the physical characteristics of the test article during administration
- Storage condition of test material: no data
- Other: gravity: 1.06g/ml; pH=12 (litmus paper)

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hare-Marland, Hewitt, New Jersey
- Age at study initiation: young adult
- Weight at study initiation: 2.119-2.764 kg
- Housing:Rabbits were housed individually in cages sized in accordance with the "Guide for the Care and Use of Laboratory Animals" of the Institute of Laboratory Animal Resources, National Research Council
- Diet (e.g. ad libitum): Purina Rabbit Ration H.F., ad libitum,
- Water (e.g. ad libitum):fresh tap water, ad libitum
- Acclimation period: min. 5d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C±3°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12h dark/12h light


IN-LIFE DATES: From: To:

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of trunk (clipped free of fur)
- Type of wrap if used: rubber dam and an elastic bandage


REMOVAL OF TEST SUBSTANCE: no data


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3000 mg/kg
- Constant volume or concentration used: YES


Duration of exposure:
24h
Doses:
3000 mg/kg
No. of animals per sex per dose:
10 (5 ♀ and 5♂)
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:observation:daily through 14d/Body weight: d0, d7 and d14
- Necropsy of survivors performed: YES
- Other examinations performed: clinical signs, body weight
Statistics:
Not applicable.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
3 000 mg/kg bw
Mortality:
No mortality observed during study.
Clinical signs:
Days 1 and 2: 10/10 animals:decreased activity, bnormal stance& gait. Days 3 up to 14 no signs in all observed animals.
Day 1: 1/10 animal:diarrhea. Days 3 up to 14 no signs in all observed animals.
Day 2: 10/10 animals poor grooming. Days 3 up to 14 no signs in all observed animals.
Days 1 &2 10/10 animals and Day 4 3/10 animals: dyspnea. Days 5 up to 14 no signs in all observed animals.
-necrosis and sloughing of the skin at application site/a clear, mucous and discharge and yellow discoloration of fur surrounding application site
Body weight:
Observation
d0-d7: both ♂ and ♀: body weight decreases (mean male bw: 2417 - 2384g; mean female bw: 2493 - 2457g)
d7-d14: both ♂ and ♀ : body weight increase (mean male bw: 2384 - 2555g; mean female bw: 2457 - 2615g)
Gross pathology:
Terminal necropsy of the animals revealed severe irritation and/or yellow discoloration of the underlying muscle tissue at the application site, necrotic or discolored yellow fascia at the application site, mottled lungs and pale kidneys.
Other findings:
no other data

Applicant's summary and conclusion

Conclusions:
Based upon the observations made in the Acute Exposure Dermal Toxicity study in rabbits, the estimated dermal LD50 for 6398-21-1 was determined to be greater than 3000mg/kg.