Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From March 06 to May 09, 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study performed similarly to OECD Guideline 402 with minor deviation: no data on test substance purity
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
no data on purity
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
no data on purity
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Desiccant L-10
- Source: Pennwalt Corporation, USA
- Physical state: Light blue, clear liquid
- Date of receipt: January 4, 1985
- Lot/batch No.: 8158
- Storage condition of test material: Room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hazleton-Dutchland, Inc., Denver, USA
- Age at study initiation: Young adults (at least 8 weeks old)
- Weight at study initiation: Males: 2.2-2.8 kg; females: 2.2-2.7 kg
- Housing: Individually housed in suspended, stainless steel cages
- Diet (e.g. ad libitum): Lab Rabbit Chow HF (Purina #5326), ad libitum
- Water (e.g. ad libitum): Municipal water supply (Elizabethtown Water Co.), ad libitum
- Acclimation period: 22, 23 or 24 days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 60-70 °F
- Humidity (%): 30-70%
- Photoperiod (hours dark / hours light): 12 hours dark / 12 hours light

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Trunk (dorsal surface)
- % coverage: At least 10% of the body surface area
- Type of wrap if used: Test material was placed directly onto a strip (4” x 12”) of 8-ply gauze; applied on the clipped skin of the animal and then wrapped with an impervious plastic sleeve.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test sites were not washed but wiped free of excess test material
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1, 0.21, 0.41, 0.82 and 1.6 mL/kg bw
Duration of exposure:
24 hours
Doses:
200, 400, 800, 1600 and 3200 mg/kg bw
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed twice daily for viability; clinical signs were observed at 1, 2 and 4 hours after dosing and daily thereafter for 14 days; weighed pre-test, at the time of clipping and on Day 7 and 14 or at death
- Necropsy of survivors performed: Yes; surviving animals were killed on Day 14 by an intravenous overdose of sodium pentobarbital and examined grossly
Statistics:
LD50 was estimated using probit analysis (Miller LC and Tainter ML, 1944).

Results and discussion

Preliminary study:
Not applicable
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 750 mg/kg bw
Based on:
test mat.
95% CL:
944 - 2 556
Sex:
female
Dose descriptor:
LD50
Effect level:
2 300 mg/kg bw
Based on:
test mat.
Remarks on result:
other: CL cannot be calculated due to distribution of mortality
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat.
95% CL:
1 583 - 2 417
Mortality:
- At 200, 400 and 800 mg/kg bw: No deaths
- At 1600 mg/kg bw: 2/5 males died within 2 days
- At 3200 mg/kg bw: All males and females died within 2 days
Clinical signs:
- 9/10 animals in 3200 mg/kg bw group which died within 24 hours were hypoactive four hours post-dosing; one animal which died on Day 2 exhibited hypoactivity, irregular breathing, nasal discharge and decreased food consumption prior to death.
- No antemortem abnormalities were noted in the animal in 1600 mg/kg bw group which died within 24 hours; animal which died on Day 2 exhibited decreased food consumption.
- Decreased food consumption, occasional occurrences of soft or mucoidal stool and other isolated abnormalities were observed in the surviving animals. One male in 800 mg/kg bw, which exhibited large weight loss, exhibited ataxia, hypoactivity, mucoidal stool and emaciation. Most surviving animals were free of abnormalities at study termination.
- Dermal effects including necrosis, generally followed by eschar formation and exfoliation, were seen at the dose site in single animals in the 200 and 400 mg/kg bw group, some animals in the 800 mg/kg bw group and several animals in the 1600 mg/kg bw group.
Body weight:
- Most animals exhibited minimal weight changes (± 0.2 kg) over the study period except one male at 800 mg/kg bw (48% weight loss).
- Some dose-relationship was evident, with most animals in the 200 and 400 mg/kg bw groups showing slight gains and several animals in the 800 and 1600 mg/kg bw group showing slight losses.
Gross pathology:
- Necropsy of the dead animals revealed dermal lesions and abnormalities in the lungs and gastrointestinal tract associated with postmortem autolytic changes, antemortem stress and/or normal physiologic variation.
- Necropsy of the surviving animals revealed no abnormalities.
Other findings:
None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the acute dermal LD50 for Desiccant L-10 was calculated to be 2000 (1583-2417) mg/kg bw in rabbits therefore it is classified as ‘R21 Harmful in contact with skin’ according to the Annex VI of the Directive 67/548/EEC and ‘Category 4’ according to the CLP Regulation (EC) No. 1272/2008.
Executive summary:

In an acute dermal toxicity study performed similarly to OECD guideline 402 and in compliance with GLP, groups of New Zealand White rabbits (5/sex/dose) received a single dermal dose of Desiccant L-10 at 200, 400, 800, 1600 and 3200 mg/kg bw on clipped area of the trunk representing at least 10% of the total body surface area. The application was occluded and exposure was for 24 hours. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all macroscopically necropsied after death or sacrifice.

 

Mortalities were 0, 20 and 100% at 200-800, 1600 and 3200 mg/kg bw, respectively. All animals exhibited minimal weight changes (± 0.2 mg/kg bw) except one male at 800 mg/kg bw (48% weight loss). Severe abnormalities (hypoactivity, irregular breathing, nasal discharge and decreased food consumption) were observed in animals which died within 2 days. Clinical signs noted in surviving animals were decreased food consumption, occasional occurrences of soft or mucoidal stool and other isolated abnormalities. Most surviving animals were free of abnormalities at study termination. Necropsy of the dead animals revealed dermal lesions and abnormalities in the lungs and gastrointestinal tract associated with postmortem autolytic changes, antemortem stress and/or normal physiologic variation. Necropsy of the surviving animals revealed no abnormalities. The acute dermal LD50 for males and females were determined to be 1750 (944-2556) and 2300 mg/kg bw, respectively. The combined dermal LD50 was calculated to be 2000 (1583-2417) mg/kg bw.

 

Dermal reactions noted in several animals were necrosis followed by eschar formation and exfoliation.

 

Under the test conditions, the acute dermal LD50 for Desiccant L-10 was calculated to be 2000 (1583-2417) mg/kg bw in rabbits therefore it is classified as ‘R21 Harmful in contact with skin’ according to the Annex VI of the Directive 67/548/EEC and ‘Category 4’ according to the CLP Regulation (EC) No. 1272 /2008.

This study is acceptable and satisifes the guideline requirement for an acute dermal toxicity study (OECD 402).