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Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Hypothesis for the analogue approach:
The hypothesis for the analogue approach is that the test substance GTL Base Oil Distillates (C18-C50 branched, cyclic and linear hydrocarbons – Distillates / 848301-69-9 / 482-220-0) is produced in the same Fischer-Tropsch process as the test substance GTL Gasoil which is the starting material from which the registration substance is produced by fractional distillation. The source substances contain constituents of the target substance, Hydrocarbons, C18-C24, iso-alkanes, <2% aromatics (GS310), although they cover a wider carbon number distribution. The substances therefore have qualitatively similar properties (RAAF Scenario 2 applies).
2. Source and target chemical(s)
The source substance GTL Base Oil Distillates (Distillates (Fischer-Tropsch), heavy, C18-50 - branched, cyclic and linear) is composed of linear, branched and cyclic hydrocarbons of chain length C18-C50.
The source substance GTL Gasoil (C8-C26) (C8-C26 branched and linear hydrocarbons – Distillates) is composed of linear, branched and cyclic hydrocarbons of chain length C8-C26.
The target substance, Hydrocarbons, C18-C24, iso-alkanes, <2% aromatics (GS310), is composed of linear, branched and cyclic hydrocarbons of chain length C18-24.
3. Analogue approach justification
The constituents of the source and target substances are all hydrocarbons. Identical constituents have identical toxicity profiles. There is no evidence of toxicity in the studies on the source substance, and no evidence of toxicity in studies on hydrocarbons with shorter carbon chain length and a narrower range of carbon number, therefore there is no evidence for mixture effects or for increased toxicity with increased concentration.
The source substance GTL Gasoil (C8-C26) has low dermal penetration with the increasing carbon chain length contained in the constituents. The constituents of the target substance, Hydrocarbons, C18-C24, isoalkanes, <2% aromatics (GS310) have carbon numbers predominantly ≥ C18, these carbon chain lengths indicate that most of the applied material will remain in the stratum corneum with negligible systemic exposure. It is concluded that because of the low penetration of the alkanes contained in GS310, it will be of low acute dermal toxicity and its effects will be lower or similar (but not greater) than those observed with GTL Gasoil. See the document attached to the target study record for more detailed discussion of read-across of toxicity data between the two substances. See the document attached to the target study record for more detailed discussion of read across of toxicity data between the two substances.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan laboratories, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: minimum 200 g
- Fasting period before study:
- Housing: solid floor polypropylene cages, furnished with woodflakes
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: not defined
- % coverage: ca. 10%
- Type of wrap if used: surgical gauze, semi-occluded with a piece of self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was wiped with cotton wool, moistened with arachis oil BP
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.62 mL/kg
- Concentration (if solution): undiluted
- Constant volume or concentration used: yes



Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5/sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed for deaths and overt signs of toxicity at 0.5, 1, 2, and 4 hours after dosing. Individual body weights were recorded prior to application of the test item on day 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: The test sites were examined for evidence of primary irritation and scored. The appearance of any macroscopic abnormalities were recorded at necropsy, no tissues were retained.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
All animals showed expected gains in body weight.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Very slight erythema and crust formation and/or small superficial scattered scabs were noted at the test sites of four females. There were no signs of dermal irritation noted at the test sites of the remaining animals.
Interpretation of results:
GHS criteria not met
Conclusions:
An LD50 value of >2000 mg/kg bw is reported in a reliable study conducted according to an OECD test guideline and in compliance with GLP.
Executive summary:

The acute dermal toxicity study is a reliable test performed with Distillates (Fischer-Tropsch), C8-26 – branched and linear, in accordance with OECD 402 and in compliance with GLP. 2000 mg/kg bw of test substance was applied to five male and five female Wistar rats for a twenty-four hour exposure period under semiocclusive conditions. The animals were observed for deaths or overt signs of toxicity, and the test sites were observed for primary irritation for fourteen days before sacrifice and necroscopy. No deaths occurred and no signs of overt toxicity were observed. There were no abnormalities noted at necroscopy. Very slight erythema and crust formation and/or small superficial scattered scabs were noted at the test sites of four females. There were no signs of dermal irritation noted at the test sites of the remaining animals.

Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2014-01-08 to 2014-01-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar: (RccHan; WIST)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories Ltd, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 200 g
- Fasting period before study:
- Housing: housed individually during the exposure period; in groups of 5 by sex for the rest of the study period; housed in polypropylene cages
- Diet: 2014C Teklad Global Rodents diet, ad libitum
- Water: drinking water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks
- % coverage: 10 % of the total body surface area
- Type of wrap if used: surgical gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-hout exposure period the area was wiped with cotton wool moistened with arachis oil BP
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume or concentration used: yes; 2.48 mL/kg


Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were examined at 30 min, 1, 2, and 4 hours post-application, and every day for the 14 day study period. Body weights were recorded prior to the treatment and at days 7 and 14.
- Necropsy of survivors performed: yes; at the end of the study the animals were killed by cervical dislocation; external examination and opening of the abdominal and thoracic cavities were performed at necropsy
- Other examinations performed: behavioural and clinical observations, gross lesions, body weight changes, mortality and any other toxicological effects were noted during the 14 day study period. The test sites were examined for evidence of primary irritation and scored.
Statistics:
No statistics were used in the study.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities occured.
Clinical signs:
No signs of systemic toxicity were observed.
Body weight:
All females showed no body loss or gain in body weight during the first week and expected gain in body weight in the second week. The males showed expected gain in body weight during the 14 day study period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Slight desquamation was observed in 3 females on days 4, 5 and 6 of the 14-day study period.
Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Based on the available information from the key acute dermal toxicity study for GTL Base Oil Distillates (Distillates (Fischer-Tropsch), heavy, C18-50-branched, cyclic and linear), an LD50 value was concluded to be > 2000 mg/kg bw. The study was conducted according to OECD TG 402, and in compliance with GLP.
Executive summary:

An acute dermal toxicity study for GTL Base Oil Distillates (Distillates (Fischer-Tropsch), heavy, C18-50-branched, cyclic and linear)

was performed to assess the acute dermal toxicity in rat.

A single dose of 2000 mg/kg bw of undiluted test material was applied onto the skin of 5 male and 5 female rats. The test item was held in contact with the skin under semi-occluded dressing for 24 hours. Observations for clinical signs of toxicity were performed at 30 min, 1, 2, and 4 hours post-application and every day for the 14 day study period. Body weights were recorded prior to the treatment and at days 7 and 14. At the end of the study the tested animals were killed by cervical dislocation. External examination and opening of the abdominal and thoracic cavities were performed at necropsy. Behavioural and clinical observations, gross lesions, body weight changes, mortality and any other toxicological effects were noted during the 14 day study period. The test sites were examined for evidence of primary irritation and scored.

No mortalities occured at during the 14 -day study period. There were no signs of systemic toxicity. All females showed no body loss or gain in body weight during the first week and expected gain in body weight in the second week. The males showed expected gain in body weight during the 14 day study period. No abnormalities were noted at necropsy.

The LD50 value for GTL Base Oil Distillates (Distillates (Fischer-Tropsch), heavy, C18-50-branched, cyclic and linear)

was concluded to be > 2000 mg/kg bw. The study was conducted according to OECD TG 402, and in compliance with GLP.

Data source

Materials and methods

Test material

Constituent 1
Chemical structure
Reference substance name:
Hydrocarbons, C18-C24, iso-alkanes <2% aromatics
EC Number:
940-734-7
Molecular formula:
C18H38, C19H40, C20H42, C21H44, C22H46, C23H48, C24H50
IUPAC Name:
Hydrocarbons, C18-C24, iso-alkanes <2% aromatics

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw

Applicant's summary and conclusion