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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: - followed recognized toxicology testing procedures - GLP compliant - study results copied without further assessment from the SIDS dossier

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
other: Consistent with NAS Publication 1138 dtd 1977); Thompson-Weil Moving Average Method (1947) and Litchfield/Wilcoxon
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): 1,2,3-Trichloropropane
- Substance type: short-chain chlorinated hydrocarbon
- Physical state: clear colorless liquid
- Analytical purity: 98.25%
- Impurities (identity and concentrations): light ends of 0.66% and heavy ends 1.09%
- Composition of test material, percentage of components: not reported
- Purity test date: not reported
- Lot/batch No.: not reported
- Expiration date of the lot/batch: not reported
- Stability under test conditions: not reported
- Storage condition of test material: not reported

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: not reported
- Age at study initiation: not reported in SIDS dossier
- Weight at study initiation: 2 - 3 Kg
- Fasting period before study: not reported in SIDS dossier
- Housing: 1 per cage
- Diet (e.g. ad libitum): not reported in SIDS dossier
- Water (e.g. ad libitum): not reported in SIDS dossier
- Acclimation period: not reported in SIDS dossier


ENVIRONMENTAL CONDITIONS
- not reported in SIDS dossier

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: backs were shaved and one half of the test animals were further prepared by abrading their backs (deep enough to penetrate the stratum corneum but not to the derma).
- % coverage: not reported in SIDS dossier
- Type of wrap if used: The area was wrapped with gauze and occluded with clear polyethylene film.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): backs were gently wiped with a moist towel
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.18, 0.32, 0.56, 0.78, 1.00, 1.80, and 3.20 mL/Kg bw (equivalent to: 253, 450, 788, 1097, 1406, 2530 and 4500 mg/Kg bw)
- Concentration (if solution): undiluted
- Constant volume or concentration used: no



VEHICLE
- no vehicle used
Duration of exposure:
24 h
Doses:
males: 0.18, 0.32, 0.56, 0.78, 1.00, 1.80, and 3.20 mL/Kg bw (equivalent to: 253, 450, 788, 1097, 1406, 2530 and 4500 mg/Kg bw)
females: 0.32, 0.56, 0.78, 1.00, 1.80, and 3.20 mL/Kg bw (equivalent to: 450, 788, 1097, 1406, 2530 and 4500 mg/Kg bw)
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation: at 24 hours, and twice daily for 14 days; weighing: at day 0, 7 and 14, or at the time of discovery of death
- Necropsy of survivors performed: yes
Statistics:
Thompson-Weil Moving Average Method (1947) and Litchfield/Wilcoxon

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
523 mg/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
390 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
765 mg/kg bw
Mortality:
Mortality was observed at all dose levels; all males died at 0.56 ml/kg or higher, and all females at 1.0 ml/kg.
Clinical signs:
The most prevalent cageside in-life observations included: activity decrease, ataxia and nasal discharge. As dose increased the following additional signs were observed: few feces, no urination, hematuria, swollen testes/urethra, iritis, cyanosis and death.
Body weight:
no details reported in the SIDS dossier
Gross pathology:
Gross necropsy observations included: discolored internal organs (kidney, lungs, urinary bladder, liver, intestines); organs distended with blood; mottled organs (kidney, liver); swollen testes; fluid in abdominal cavity and pronounced serosal blood vessels on intestines.

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute dermal toxicity of 1,2,3-trichloropropane was tested using a recognized scientific procedure and followed recognized GLP procedures.
The following threshold values were determined:
LD50 (dermal, rabbit, male) = 390 mg/Kg bw
LD50 (dermal, rabbit, female) = 765 mg/Kg bw
LD50 (dermal, rabbit, combined) = 523 mg/Kg bw
Executive summary:

In the present study (Shell Development Company, 1980) male and female New Zealand White rabbits were treated once with undiluted 1,2,3 -trichloropropane dermaly under occlusive conditions for 24 h and analysed for mortality, body weight development and clinical signs following generally the OECD TG 403 in compliance with GLP.

The following threshold values were determined:

LD50 (dermal, rabbit, male) = 390 mg/Kg bw

LD50 (dermal, rabbit, female) = 765 mg/Kg bw

LD50 (dermal, rabbit, combined) = 523 mg/Kg bw

Based on this results 1,2,3 -trichloropropane is classified as Category III (Toxic in contact with skin (dermal)) according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU.

Six male and 6 female New Zealand White rabbits were divided equally into 7 dosage groups (except the lowest dose which had no females; 0.18, 0.32, 0.56, 0.78, 1.00, 1.80, and 3.20 mL/Kg bw (equivalent to: 253, 450, 788, 1097, 1406, 2530 and 4500 mg/Kg bw)). Their backs were shaved and one half of the test animals were further prepared by abrading their backs (deep enough to penetrate the stratum corneum but not to the derma). The area was wrapped with gauze and occluded with clear polyethylene film for 24 hours. After 24 hours the bandages were removed, and the backs were gently wiped with a moist towel. Animals were observed at 24 hours, and twice daily for 14 days. Body weights measured at day 0, 7 and 14, or at the time of discovery of death. A gross necropsy was performed on each animal.

The authors reported that severe dermal lesions were not present on any animal at any time during the study. The most prevalent cageside in-life observations included: activity decrease, ataxia and nasal discharge. As dose increased the following additional signs were observed: few feces, no urination, hematuria, swollen testes/urethra, iritis, cyanosis and death. Gross necropsy observations included: discolored internal organs (kidney, lungs, urinary bladder, liver, intestines); organs distended with blood; mottled organs (kidney, liver); swollen testes; fluid in abdominal cavity and pronounced serosal blood vessels on intestines. Mortality was observed at all dose levels; all males died at 0.56 ml/kg or higher, and all females at 1.0 ml/kg. The dermal LD50 in male rabbits was 0.277 ml/kg (390 mg/kg); the dermal LD50 in females was 0.544 ml/kg (765 mg/kg), slope of 2.52; and combined it was 0.372 ml/kg (523 mg/kg), slope of 1.61