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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:
02/1996 - 11/1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study on supporting substance (with limited range, C8-C12) conducted in compliance with GLP; acceptable, well-documented study report which meets basic scientific principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OTS 798.1100 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Kerosine (Fischer-Tropsch), limited-range, C8-12 - branched and linear
IUPAC Name:
Kerosine (Fischer-Tropsch), limited-range, C8-12 - branched and linear
Details on test material:
- Substance type: Organic
- Physical state: Liquid
- Analytical purity: 100%
- Impurities (identity and concentrations): Information not available
- Expiration date of the lot/batch: Information not available
- Stability under test conditions: Stable under normal temperature and pressure
- Storage condition of test material: Under cool conditions (approximately 4°C)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: male animals were approximately 7 - 8 weeks, the females approximately 10 - 11 weeks old
- Weight at study initiation: 208 - 240 g for males and 212 - 232 g for females
- Fasting period before study: none
- Housing: stainless steel grid cages (RS Biotech, England); on completion of dosing, the animals were accommodated in individual
cages (North Kent Plastic Cages Limited, England)
- Diet (e.g. ad libitum): ad libitum [pelleted rodent diet (RM1 (E) SQC, from Special Diets Services Limited, Witham, Essex, England]
- Water (e.g. ad libitum): ad libitum (tap water)
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23.5
- Humidity (%): 46-52
- Air changes (per hr): at least 10 complete air changes per hour without recirculation
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: approximately December 1995 (female)/ January 1996 (male) To: 07 March 1996

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: body surface area
- % coverage: 5 cm x 5 cm area (approximately 10% of the body surface area)
- Type of wrap if used: 5 cm x 5 cm gauze patch, occluded with aluminium foil; the foil was kept in place and protected by a pad of cotton wool and a bandage of waterproof plaster and tape (Blenderm and Sleek, Community Care Products, 3M Health Care, Loughborough, England and TJ Smith and Nephew Medicals Limited, Kingston-upon-Hull, England)


REMOVAL OF TEST SUBSTANCE
- Washing (if done): the dermal site was gently wiped with wet disposable tissues to remove residual test material
- Time after start of exposure: 24 hours after administration


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): not available - quantity of dose was determined for each animal according to its bodyweight
- Constant volume used: no


VEHICLE
none
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 male and 5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- observations: three separate recordings of signs were made during the first hour after administration and two further recordings during the
remainder of Day 1; from Day 2 onwards, the animals were inspected twice daily and recordings of systemic and local signs were made once daily
- weighing: on days 1, 8 and 15
- Necropsy of survivors performed: yes
Statistics:
none

Results and discussion

Preliminary study:
A preliminary study was carried out using one male and one female rat given 'Kerosine (Fischer-Tropsch), limited-range, C8-12 - branched and linear' at a dosage of 2000 mg/kg. There was no death; no other data for this preliminary study is reported.
On the basis of this result, the main study was carried out using one group of five male and five female rats given 'Kerosine (Fischer-Tropsch), limited-range, C8-12 - branched and linear' at the maximum practicable dosage of 2000 mg/kg (Regulatory Limit test). Since no rat died as a result of treatment the low toxicity of 'Kerosine (Fischer-Tropsch), limited-range, C8-12 - branched and linear' was demonstrated and no further groups of animals were employed.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no death
Clinical signs:
other: no local or systemic sign of reaction to treatment
Gross pathology:
necropsy revealed no significant macroscopic lesion
Other findings:
none

Any other information on results incl. tables

1) Bodyweights (Dosage 2000 mg/kg bw):

Bodyweight [g]
Male-1 Male-2 Male-3 Male-4 Male-5
Day -1 227 226 208 240 239
Day 1 232 238 214 246 248
Day 8 259 278 227 285 281
Day 15 296 331 264 337 323
Increment 69 105 56 97 84
Mean of Increment         82

Bodyweight [g]
Female-1 Female-2 Female-3 Female-4 Female-5
Day -1 232 217 212 221 231
Day 1 237 221 215 225 234
Day 8 252 238 244 235 244
Day 15 265 253 237 255 280
Increment 33 36 25 34 49
Mean of Increment         35

2) Necropsy observations (Dosage 2000 mg/kg bw):

Animal and sex Died or Sacrificed Time of death Necropsy observations
Male-1  Sacrificed Day 15 External
Application site: No significant lesion
Other: No significant lesion
Internal
No significant lesion
Male-2 Sacrificed Day 15
Male-3 Sacrificed Day 15
Male-4 Sacrificed Day 15
Male-5 Sacrificed Day 15
Female-1 Sacrificed Day 15 External
Application site: No significant lesion
Other: No significant lesion
Internal
No significant lesion
Female-2 Sacrificed Day 15
Female-3 Sacrificed Day 15
Female-4 Sacrificed Day 15
Female-5 Sacrificed Day 15

3) Systemic and local signs (Dosage 2000 mg/kg bw):

Number of animals showing signs+
Male Female
No abnormality detected 5 5
Total number of survivors 5 5

+ Five animals in each sex-group

4) Mortality (Dosage 2000 mg/kg bw):

Mortality
Male Female Combined
Dosage 2000 mg/kg bw 0/5 0/5 0/10

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
There was no death and no local or systemic sign of reaction to treatment. All animals achieved anticipated bodyweight gains and necropsy revealed
no significant macroscopic lesion. Under the conditions of this study, the acute dermal median lethal dosage (LD50) of the supporting substance 'Kerosine (Fischer-Tropsch), limited-range, C8-12 - branched and linear' was greater than 2000 mg/kg. According to Annex VI of Council Directive 67/548/EEC (and Regulation EC 1272/2008) 'Kerosine (Fischer-Tropsch), limited-range, C8-12 - branched and linear' is unclassified with regards to acute dermal toxicity; hence, 'Kerosine (Fischer-Tropsch), full range, C8-16-branched and linear' should also not be classified.
Executive summary:

According to EU-Method B.3 the acute dermal toxicity of an analogue with limited range 'Kerosine (Fischer-Tropsch), limited-range, C8 -12 - branched and linear' was investigated in a group of five male and five female CD rats. The test material was applied to the closely-clipped dorsum of each animal at a dosage of 2000 mg/kg bodyweight, and was covered by an occlusive dressing for 24 hours.

Mortality, systemic and local signs of reaction to treatment were recorded during a subsequent 14-day period of observation. The animals were killed on the following day and subjected to necropsy.

There was no death and no local or systemic sign of reaction to treatment. All animals achieved anticipated bodyweight gains and necropsy revealed no significant macroscopic lesion. Under the conditions of this study, the acute dermal median lethal dosage (LD50) of the test material was greater than 2000 mg/kg bw. Finally, the LD50 of 'Kerosine (Fischer-Tropsch), full range, C8 -16 - branched and linear` should be also greater than 2000 mg/kg bw.

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