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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: non-GLP study equivalent to OECD guideline 402

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1-propoxypropan-2-ol
EC Number:
216-372-4
EC Name:
1-propoxypropan-2-ol
Cas Number:
1569-01-3
Molecular formula:
C6H14O2
IUPAC Name:
1-propoxypropan-2-ol
Details on test material:
Name of test material (as cited in study report): PROPASOL Solvent P
- Physical state: clear, non-viscous liquid
- Lot/batch No.: #3251; S-066890

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.0 - 3.0 kg
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped intact skin of the trunk
- Type of wrap if used: Test material was retained under impervious sheeting. Vetrap Bandaging Tape was wrapped over the impervious sheeting.

REMOVAL OF TEST SUBSTANCE
After the contact period (24 hours) excess fluid was removed to diminish ingestion.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.0, 4.0, 8.0 ml/kg
- Concentration (if solution): pure (liquid) substance
- Constant volume or concentration used: doses are varied by adjusting the volume of the test material
Duration of exposure:
24 hours
Doses:
2.0, 4.0, 8.0 ml/kg
The relative density of Propasol Solvent P is 0.88 g/ml.
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals weights were recorded at 0 days (before dose), 7 days and 14 days (just prior to sacrifice)
- Necropsy of survivors performed: at death or sacrifice each animal was subjected to gross pathologic evaluation
Statistics:
LD50's and the estimated LD50 slopes are calculated by the moving average method and are based on a 14-day observation period.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
4.29 mL/kg bw
95% CL:
2.9 - 6.34
Sex:
female
Dose descriptor:
LD50
Effect level:
4.92 mL/kg bw
95% CL:
3.58 - 6.78
Sex:
male
Dose descriptor:
LD50
Effect level:
3 775 mg/kg bw
95% CL:
2 552 - 5 579
Sex:
female
Dose descriptor:
LD50
Effect level:
4 330 mg/kg bw
95% CL:
3 150 - 5 966
Mortality:
8.0 ml/kg (males): 5/5
4.0 ml/kg (males): 2/5
2.0 ml/kg (males): 0/5

8.0 ml/kg (females): 5/5
4.0 ml/kg (females): 1/5
2.0 ml/kg (females): 0/5
Clinical signs:
8.0 ml/kg (males): erythema, edema, necrosis at death; ecchymosis on 2 at death; comatose appearance within 15 min; dilated pupils in 2 at death; death of 4 at 2.5-3.5 hours
4.0 ml/kg (males): erythema, edema at 1 day; ecchymosis on 2 at 1 to 7 days; necrosis, desquamation, scabs, fissuring (on 1), ulceration (on 1) at days 7 to 14; comatose appearance within 20 min; unsteady gait in 1 at 1 day; prostration, lacrimation in 1 at 1 day; survivors recovered at 1 day
2.0 ml/kg (males): erythema at 1 day; edema, necrosis at 1 to 7 days; desquamation at 7 to 14 days; scabs on 2 at 7 to 14 days; alopecia, ulceration (on 1) at 14 days; comatose appearance within 30 min; recovery within 1 day

8.0 ml/kg (females): erythema, edema, necrosis at death; ecchymosis on 1 at death; dilated pupils, comatose appearance within 15 min; death at 1 to 3 hours
4.0 ml/kg (females): erythema, edema, ecchymosis (on 2) at 1 day; necrosis at 1 to 14 days; fissuring on 2 at 7 days; desquamation, scabs at 7 to 14 days; ulceration, alopecia in 2 at 14 days; comatose appearance within 20 min; dilated pupils in 1 at 20 min; sluggishness, unsteady gait in 2 at 1 day; survivors recovered at 2 days
2.0 ml/kg (females): erythema, edema at 1 day; necrosis at 1 to 7 days; fissuring on 2 at 7 days; scabs, desquamation at 7 to 14 days; alopecia on 2 at 14 days; comatose appearance within 30 min; recovery within 1 day
Body weight:
All surviving animals showed body weight gain over the 14 day observation period.
Gross pathology:
8.0 ml/kg (males): tracheas red
4.0 ml/kg (males): in victims: lungs mottled, dark red; tracheas red; in survivors: nothing remarkable
2.0 ml/kg (males): nothing remarkable

8.0 ml/kg (females): lungs dark red; trachea of 1 red
4.0 ml/kg (females): in victim: lungs and trachea red; in survivors: nothing remarkable
2.0 ml/kg (females): lungs of 2 mottled light and dark pink

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
PROPASOL Solvent P was moderately toxic following single dermal application. According to EU criteria no classification for acute dermal toxicity is required based on the LD50 > 2000 mg/l.
Executive summary:

Three groups of 5 male and 5 female New Zealand White rabbits, weighing between 2.0 and 3.0 kg, were subjected to 24 hours of contact with 8.0, 4.0 or 2.0 ml/kg of PROPASOL Solvent P which was retained under impervious sheeting on the clipped, intact skin of the trunk. As necessary for larger doses, gauze was wrapped around the trunk over the sample to prevent leakage. Vetrap Bandaging Tape was wrapped over the impervious sheeting and the animal was returend to its cage for the contact period. Doses were varied by adjusting the volume of the test material. After the contact period, excess fluid is removed to diminish ingestion. Observations for skin reaction were made at one hour, 7 days and 14 days after the contact period.

The LD50 for male rabbits was 4.29 ml/kg. The LD50 for females was 4.92 ml/kg. Local dermal effects included erythema, edema, ecchymosis, necrosis, desquamation, fissuring, ulceration, scabs and alopecia. A rapid comatose appearance, followed by dilated pupils, unsteady gait, sluggishness and prostration were among the signs of toxicity observed. Time to death ranged from one hour to 2 days. Survivors recovered at one to 2 days. Gross pathologic findings included red lungs and red tracheas.

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