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Administrative data

Description of key information

Oral LD50 (rat) > 5000 mg/Kg bw

Inhalation LC50 (rat) >5000 mg/m³

Dermal LD50 (rabbit) > 3.16 mL/Kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From November 14, 1994 To January 5, 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to or similar to OECD guideline 401: GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
acute toxic class method
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Taconic Farms
- Age at study initiation: Approximately 10-11 weeks
- Weight at study initiation: 195 to 282 grams
- Housing: 5 per cage
- Diet (e.g. ad libitum): ad libitum, Purina Rodent Chow
- Water (e.g. ad libitum):ad libitum
- Acclimation period:21days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): maintained range 20-24.4
- Humidity (%): maintained range 40-70
- Photoperiod (hrs dark / hrs light): 12hrs dark / 12 hrs light
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Undiluted test material was administered by a single oral intubation via syringe and a No. 13 ball tipped feeding needle.
Doses:
5000mg/kg
No. of animals per sex per dose:
10 animals per dose (5 male; 5 female)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were made as to the nature, onset, severity, and duration of toxicological signs at 1, 2, 4, and 6 hours after dosing, and once per day thereafter for a total of 14 Days. Body weights were recorded on the day prior to dosing (pretest), the day of dosing (Day 0), on Day 7, and on Day 14, and at death for those which succumbed.
- Necropsy of survivors performed: yes
Statistics:
The means and standard deviations of the body weights and body weight changes, by sex and group were calculated .
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
5000 mg/kg: 0 males; 0 females
Clinical signs:
Ano-genital staining, observed at the 6 hour interval, was the only remarkable clinical in-life observation.
Body weight:
All surviving animals displayed increases in body weight over their Day 0 values.
Gross pathology:
All animals were free of abnormalities at postmortem examination.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 for MRD-83-205 is >5000 mg/kg. Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

MRD-83-205 was administered via oral intubation to 5 male and 5 female rats at a dose of 5000 mg/kg to assess acute oral toxicity.  Animals were observed daily for 14 days post dosing.  No overt signs of toxicity were apparent.  All animals survived to study termination. All animals were free of abnormalities at postmortem examination.  All surviving animals displayed increases in body weight over their day 0 values.  The acute oral LD50 for MRD-83-205 is >5000 mg/kg. Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable well-documented study report which meets basic scientific principles: non-GLP
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
only one dose tested
GLP compliance:
yes
Test type:
fixed dose procedure
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Sex: Males (5); Females (5)
- Weight at study initiation: Males (190-195 g), Females (194-205 g)
- Housing: individual
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
A single dose of MRD-77-10 (15 g/kg) was administered by oral gavage.
Doses:
15 g/kg
No. of animals per sex per dose:
Male (5), Female (5)
Control animals:
no
Details on study design:
The acute oral toxicity of MRD-77-10 was investigated in a group of 5 male and 5 female rats. Each animal received a single oral dose of 15 g/kg administered by oral gavage. The condition of all animals was observed over a 14 day period following dosing.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 15 000 mg/kg bw
Mortality:
No mortality was observed in any of the animals treated with 15 g/kg MRD-77-10.
Clinical signs:
Hair loss of the urogenital region was noted in 4 males/5 females. Kidneys appeared darker then normal in 2 males and 3 females, but no pathology was noted. All animals gained weight through out the observational period.
Body weight:
All surviving animals showed an increase in body weight over their initial values at the end of the observation period.
Gross pathology:
Kidneys appeared darker then normal in 2 males and 3 females, but no pathology was noted.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The LD50 for MRD-77-10 following oral gavage was >15 g/kg . Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

The acute toxicity of MRD-77-10 was evaluated in rats via oral gavage at a dose of 15 g/kg bw. Observations were made as to the nature, onset, severity, and duration of toxicological signs once per day for a total of 14 days. All animals survived the entire observational period and displayed a low incidence of clinical symptoms.  The LD50 for MRD-77-10 following oral gavage was >15 g/kg. Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Four key read across studies available from structural analogues.

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000/07/17-2000/07/31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to or similar to guideline study OECD 403: GLP.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Inc.
- Age at study initiation: 9-10 weels
- Weight at study initiation: Males: 299-325 g; Females: 221-244g
- Fasting period before study:
- Housing: single housed
- Diet (e.g. ad libitum): PMI Feeds
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 64-72
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
The animals were individually housed within a 150-liter stainless steel and acrylic whole body inhalation exposure chamber. The chamber operated under slight negative pressure to the room, at an airflow of approximately 30 liters per minute. The exposure period was 4 hours, plus time for equilibration (theoretical T99 = 23 minutes). Chamber airflow, temperature, and relative humidity were monitored continuously throughout the exposure and recorded approximately every 30 minutes.

The concentration of solvent in the test atmosphere was monitored continuously during the exposure by means of a high temperature total hydrocarbon analyzer. The instrument was calibrated using a gravimetric procedure.

Test Atmosphere Generation: The test material was volatilized at 160 deg C. The resulting vapors were drawn into the exposure chamber by the supply air moving countercurrent to the liquid flow.

Exposure Concentrations: Nominal concentrations were determined by subtracting the weight of the syringe from the weight of the syringe plus test material. Analytical concentrations were determined through the use of a calibrated infrared monitor. Chamber concentrations were recorded every 30 minutes. Uniformity of the test atmosphere was conducted by sampling the concentration of the four corners of the exposure chamber.

Analytical verification of test atmosphere concentrations:
yes
Remarks:
4951 mg/m3; maximum attainable vapor
Duration of exposure:
4 h
Concentrations:
4951 mg/m3 (analytical); 5250 mg/m3 (nominal); maximum attainable vapor
No. of animals per sex per dose:
5 males; 5 females
Control animals:
no
Details on study design:
Experimental Evaluation
The animal population as a whole was observed for mortality and obvious signs of toxicity at approximately 1 5-minute intervals during the first hour of exposure and once each hour thereafter throughout the exposure. Detailed individual animal observations were recorded pre-exposure, post-exposure upon removal from the chamber, and once daily for 14 days post-exposure. Body weights were recorded prior to exposure (Day 0), and on Days 7 and 14 post-exposure.

Termination
After the Day 14 observations, all surviving animals were sacrificed by exsanguination from the abdominal aorta while under sodium pentobarbital anesthesia (administered intraperitoneal). A gross necropsy which included an examination of the external surface of the body, the cranial, thoracic, abdominal cavities and their contents, and complete examination of the respiratory tract (primarily the external surfaces) was performed on all animals.
Statistics:
Statistical analyses included the calculations of means and standard deviations for body weight and body weight change by sex (Snedecor and Cochran, 1989).
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4 951 mg/m³ air (analytical)
Exp. duration:
4 h
Remarks on result:
other: maximum attainable vapor concentration
Mortality:
All rats survived to the end of the experimental observation.
Clinical signs:
other:
Body weight:
No effects noted
Gross pathology:
All animals were free of any pathological symptoms at their postmortem examination.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The LC50 for acute inhalation exposure to MRD-00-586 vapor is greater than the highest obtainable vapor concentration (4951 mg/m3). Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

MRD-00-586 was administered via individual inhalation chambers for four hours to ten rats at the maximum attainable vapor concentration of 4951 mg/m3 for four hours to assess acute inhalation toxicity. There were no mortality or gross pathological alterations noted in any of the animals.  Based on the conditions of this study, the LC50 for acute inhalation exposure to MRD-00-586 vapor is greater than the highest obtainable vapor concentration (4951 mg/m3).  Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1980/09/24 - 1980/10/08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to or similar to guideline study OECD 403. GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Albino; COX-SD
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Sex: 5 males; 5 females
- Weight at study initiation: 220 - 299 g
- Housing: individually
- Diet (e.g. ad libitum): Purina Rodent Lab Chow, ad libitum
- Water (e.g. ad libitum): ad libitum
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Undiluted C10-C12 n-Paraffins was introduced into the chamber as a mist, by means of a DeVilbiss Nebulizer, at a delivery flow concentration of approximately 5.6 milligrams per liter of air at a total flow rate of ten liters per minute for a period of four hours (plus a 26-minute equilibration period*). NOTE: Prior to test exposure, exploratory runs were made with the inhalation equipment to establish a dose-setting relation of the equipment and the test compound.

*prior to the actual four-hour exposure, the test compound was introduced into the chamber for twenty-six minutes at the above flow rate in order that the test atmospheric concentration could reach theoretical equilibration (approximately 99%). The animals were within the inhalation chamber during the equilibration period.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Remarks on duration:
plus 26 minute equilibration period
Concentrations:
5.6 mg/L
No. of animals per sex per dose:
5 males; 5 females
Control animals:
no
Details on study design:
Ten albino rats (five males and five females, COX-SD strain), weighing 220 to 299 grams, were used to evaluate the acute (single exposure) inhalation toxicity produced by the test compound, C10-C12 n-Paraffins when introduced in the form of a mist into a 57 liter capacity glass chamber containing the animals. Throughout the study, the animals were individually housed in metal, wire-bottomed cages elevated above the droppings. Each animal was examined before testing and only those animals from the supply on hand without observable defects were used. The animals were not fasted prior to exposure to inhalation of the test compound.

Undiluted C10-C12 n-Paraffins was introduced into the chamber as a mist, by means of a DeVilbiss Nebulizer, at a delivery flow concentration of approximately 5.6 milligrams per liter of air at a total flow rate of ten liters per minute for a period of four hours (plus a 26-minute equilibration period*). NOTE: Prior to test exposure, exploratory runs were made with the inhalation equipment to establish a dose-setting relation of the equipment and the test compound.

*prior to the actual four-hour exposure, the test compound was introduced into the chamber for twenty-six minutes at the above flow rate in order that the test atmospheric concentration could reach theoretical equilibration (approximately 99%). The animals were within the inhalation chamber during the equilibration period.

The animals were observed frequently for gross effects during the exposure. Upon removal from the chamber, the animals were cleaned with lukewarm tap water to remove any test compound having accumulated on their coats and were dried with towels. After drying, the animals were weighed and placed in their individual cages. Feed consisting of Purina Rodent Laboratory Chow (pelletized) and tap water were freely available at all times.

The animals were observed for gross effects at regular intervals during the remainder of the day of exposure and once daily thereafter for fourteen days. Body weights were recorded at seven and fourteen days post—exposure. Following the fourteen—day observation period, all surviving animals were sacrificed and necropsied.
Statistics:
no details
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 600 mg/m³ air (nominal)
Remarks on result:
other: All animals survived
Mortality:
No mortality noted.
Clinical signs:
other:
Body weight:
Body weight records of the animals showed constant weights except for two animals at seven days post-exposure (+/- 3 grams); the remaining animals at seven days, and all animals at fourteen days, post-exposure showed gains within expected limits.
Other findings:
Necropsy of the animals was performed at the termination of the study (fourteen days). Three animals had severe congestion of the lungs (approximately 30 to 50%); the findings for the other seven animals were unremarkable.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The LC50 for acute inhalation exposure to the test material (aerosol) is >5.6mg/L. Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

Ten albino rats (five males and five females, COX-SD strain), weighing 220 to 299 grams, were exposed by the route of inhalation for four hours to undiluted C10-C12 n-paraffins in the form of a mist, at a delivery flow concentration of approximately 5.6 mg/L of test compound. All of the animals survived the exposure and the fourteen-day observation period which followed.

 

The LC50 for acute inhalation exposure to the test material (aerosol) is >5.6mg/L. Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations. 

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable well-documented study report which meets basic scientific principles: non-GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Shell Toxicology Laboratory, Breeding Unit.
- Age at study initiation: 10-13 weeks
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Five rats of each sex, age 10 to 13 weeks, were housed in a tubular glass chamber, and exposed for 4 hours to test atmospheres generated dynamically, by the near saturation of air supplied to the test chamber. The animals were observed over the subsequent 14 days. Food and water were available to the animals at all times except for the 4 hour exposure period.

The concentration of solvent in the test atmosphere was monitored continuously during the exposure by means of a high temperature total hydrocarbon analyzer. The instrument was calibrated using a gravimetric procedure.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
9.3 mg/l (near saturation)
Duration of exposure:
4 h
Concentrations:
9.3 mg/l (near saturation)
Details on study design:
Five rats of each sex
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 9 300 mg/m³ air
Exp. duration:
4 h
Remarks on result:
other: conc. near saturation
Mortality:
All rats survived to the end of the experimental observation.
Clinical signs:
other:
Body weight:
No effects noted
Gross pathology:
All animals were free of any pathological symptoms
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The LC50 for acute inhalation exposure to Shellsol TD vapor is greater than the highest obtainable vapor concentration (9.3 mg/L). Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

Shellsol TD was administered via individual inhalation chambers for four hours to ten Sprague-Dawley rats at the maximum attainable vapor concentration of 9.3 mg/L for four hours to assess acute inhalation toxicity. There was no mortality and no gross pathological alterations noted in any of the animals.  Based on the conditions of this study, the LC50 for acute inhalation exposure to Shellsol TD vapor is greater than the highest obtainable vapor concentration (9.3 mg/L).  Classification as an acute inhalation toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 000 mg/m³
Quality of whole database:
Six key or weight of evidence studies available from structural analogues.

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July - September 1961
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13
Reason / purpose for cross-reference:
read-across: supporting information
Principles of method if other than guideline:
Standard acute method, applying 4 different doses to the clipped, intact abdominal skin
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
other: albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.4 - 2.3 kg
- Housing: Throughout the observation period, the rabbits were housed individually in metal cages elevated above the droppings. Purina Rabbit Pellets and water were freely available at all times.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: abdominal skin
- Type of wrap if used: dental daming binder; wrapped with gauze and adhesive tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): with sponge and warm water
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
100, 316, 1000, 3160 µL/kg bw
No. of animals per sex per dose:
4
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days (daily)
- Frequency of observations and weighing: 0, 1, 4, 24 hours
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3.16 mL/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 200 - 2 500 mg/kg bw
Remarks on result:
other: Recalculated values based on the LD50 of 3.16 mL/kg bw; the range of LD50 is due to the range of density 0.71 -0.78 g/cm3.
Mortality:
No deaths at any dosage level.
Clinical signs:
Apart from 3 rabbits (2 of the 100 µL/kg dose group and one of the 3160 µL/kg dose group) which showed diarrhea for 2 to 4 days during the observation period, all animals seemed normal in appearance and behaviour throughout the study.
Body weight:
The final body weight of 2 of the animals which exhibited diarrhea showed a decrease from the initial body weight, while the remaining animals showed a normal body weight gain.
Gross pathology:
At autopsy, the 3 rabbits which showed diarrhea for 2 to 4 days during the observation period, exhibited pathological findings. One animals of the 100 µL/kg dose group showed paleness of the cortical portion of the kidneys. The other animals from the 100 µL/kg dose group showed an excessive amount of clear fluid in the peritoneal cavity and congested, pitted, tough kidneys. The rabbit of the high dose group showed inflammation of the intestines.
Other findings:
Dermal effects: Following removal of the binders at the end of the exposure period, the abdomens and binders were dry. At this time, the exposed skin areas of the animals showed a slight degree of erythema. Within an additional one to three days, the erythema had completely subsided in all animals. The low level animals showed no other signs of irritation during the reminder of the observation period. The high level animals showed slight or moderate desquamation during the final few days of the first week and during most of the second week. At termination, however, the exposed skin of the surviving animals was completely free of signs of irritation.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: other: CLP
Conclusions:
There is no need for classification.
Executive summary:

There is no need for classification.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July - September 1961
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions.
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13
Reason / purpose for cross-reference:
read-across: supporting information
Principles of method if other than guideline:
Standard acute method, applying 4 different doses to the clipped, intact abdominal skin
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
other: albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 1.4 - 2.3 kg
- Housing: Throughout the observation period, the rabbits were housed individually in metal cages elevated above the droppings. Purina Rabbit Pellets and water were freely available at all times.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: abdominal skin
- Type of wrap if used: dental daming binder; wrapped with gauze and adhesive tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): with sponge and warm water
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
100, 316, 1000, 3160 µL/kg bw
No. of animals per sex per dose:
4
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days (daily)
- Frequency of observations and weighing: 0, 1, 4, 24 hours
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3.16 mL/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 200 - 2 500 mg/kg bw
Remarks on result:
other: Recalculated values based on the LD50 of 3.16 mL/kg bw; the range of LD50 is due to the range of density 0.71 -0.78 g/cm3.
Mortality:
There were three deaths, one at each at the 100, 1000, and 3160 µL/kg bw levels. These deaths were apparently the result of a severe intestinal infection. Blood samples were collected by cardiac puncture. All samples were frozen
Clinical signs:
100 µL/kg dose: 2 animals normal in appearance and behaviour; One animal normal until 11th day, at which time this animal showed diarrhea and on day 14 depression, labored respiration, diarrhea
316 µL/kg dose: all animals showed normal behaviour
1000 µL/kg dose: 3 animals showing normal behaviour
3160 µL/kg dose: 3 animals showing normal behaviour
Body weight:
100 µL/kg dose: 2 animals showing typical weight gain, 1 animal weight loss after day 11 after exposure, 1 animal died on day 12
316 µL/kg dose: all animals showed normal body weight gain
1000 µL/kg dose: 3 animals showing typical weight gain, 1 animal dead on day 10
3160 µL/kg dose: 3 animals showing typical weight gain, 1 one of the 3 showed a decrease in weight at termination on day14, 1 animal died on day 12
Gross pathology:
100 µL/kg dose: congestion of the kidneys, inflammation of the samll intestine, and a large amount of fluid in the gastrointestinal tract was found in one animal sacrificed
316 µL/kg dose: no pathology observed
1000 µL/kg dose: no pathology observed
3160 µL/kg dose: firm, elevated, blanched areas on the gallbladder, and extensive amount of fluid in the peritoneal cavity, and inflammation of the intestines
Other findings:
Dermal effects: Following removal of the binders at the end of the exposure period, the abdomens and binders were dry. At this time, the exposed skin areas of the animals showed a slight degree of erythema. Within an additional one to three days, the erythema had completely subsided in all animals. The low level animals showed no other signs of irritation during the reminder of the observation period. The high level animals showed slight or moderate desquamation during the final few days of the first week and during the second week. At termination, however, the exposed skin of the surviving animals was completely free of signs of irritation.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: other: CLP
Conclusions:
There is no need for classification.
Executive summary:

There is no need for classification.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Quality of whole database:
Two key read across studies available from structural analogues.

Additional information

There is no acute dermal toxicity data available for Hydrocarbons, C10-C12, isoalkanes, <2% aromatics. However, data is available for structural analogue, Hydrocarbons, C7-C9, isoalkanes. For acute oral and inhalation toxicity, substance specific as well as analogue data from Hydrocarbons, C11-C13, isoalkanes, < 2% aromatics, and isohexadecane is also presented. This data is read across to based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

Oral

Hydrocarbons, C10-C12, isoalkanes, <2% aromatics

In a key study (Exxonmobil Corp, 1995), the test material (Hydrocarbons, C10-C12, isoalkanes, <2% aromatics) was administered via oral intubation to 5 male and 5 female rats at a dose of 5000 mg/Kg to assess acute oral toxicity.  Animals were observed daily for 14 days post dosing. No overt signs of toxicity were apparent.  All animals survived to study termination. All animals were free of abnormalities at post-mortem examination. All surviving animals displayed increases in body weight over their day 0 values. The acute oral LD50was determined to be >5000 mg/Kg.

In another key study (Exxonmobil Corp, 1977), the acute toxicity of Hydrocarbons, C10-C12, isoalkanes, <2% aromatics was evaluated in rats via oral gavage at a dose of 15 g/Kg bw. Observations were made as to the nature, onset, severity, and duration of toxicological signs once per day for a total of 14 days. All animals survived the entire observational period and displayed a low incidence of clinical symptoms.  The LD50 following oral gavage was >15 g/Kg.

Isohexadecane

In a supporting study (INEOS, 1980), the toxicity of isohexadecane in Sprague-Dawley rats was tested by gavage of the undiluted liquid test substance as supplied. The animals were observed for 4 weeks after treatment. At the end of observation period, they were killed and a necropsy was performed. The test doses were 2.15, 4.64, 10.0, 21.15, 31.6 and 46.4 mL/Kg bw. Five males and five females were tested at the three lower doses while 10 rats of both sexes were treated at the three higher dose groups. No mortality was observed at any tested dose. Sublethal effects were noted such as oily secretion in the area of anus for tested dose from 4.64 mL/kg bw to 46.4 mL/kg bw. Moreover, 28% and 11% daily food intake decrease was recorded in females treated at 31.6 mL/kg bw on the first and the second day of observation, respectively. The same effects (32% and 49% food intake decreases) were observed at the 24 and 48-hour observation periods in females treated with the highest dose. Decrease of body weight intake was also observed on first observation day in treated females at 46.4 mL/kg bw, corresponding to 37 g/kg bw. No LD50was determined.

Inhalation

Hydrocarbons, C10-C12, isoalkanes, <2% aromatics

In a key study (Sasol, 1982), ten albino rats (five males and five females, COX-SD strain), weighing 220 to 299 grams, were exposed by the route of inhalation for four hours to undiluted C10-C12 n-paraffins in the form of a mist, at a delivery flow concentration of approximately 5.6 mg/L of test compound. All of the animals survived the exposure and the fourteen-day observation period which followed. The LC50 for acute inhalation exposure to the test material (aerosol) is >5.6mg/L.

In another key study (Shell, 1977), Hydrocarbons, C10 – C12, isoalkanes, < 2% aromatics was administered via individual inhalation chambers for four hours to ten Sprague-Dawley rats at the maximum attainable vapor concentration of 9.3 mg/L for four hours to assess acute inhalation toxicity. There was no mortality and no gross pathological alterations noted in any of the animals.  Based on the conditions of this study, the LC50 for acute inhalation exposure to Hydrocarbons, C10 – C12, isoalkanes, < 2% aromatics vapor is greater than the highest obtainable vapor concentration (9.3 mg/L).

In a supporting study (Exxon Chemical Company, 1998), the test material (Hydrocarbons, C10-C12, isoalkanes, <2% aromatics) was administered via individual whole-body inhalation chambers for four hours to two groups of ten Crl:CDBR rats at either an estimated aerosol concentration of 5247 mg/m3 or an analytical concentration of 5266 mg/m3 (5213 mg/m3 aerosol, 53 mg/m3 vapor). Animals were observed for fourteen days following exposure. No mortality was observed, and all animals that received the estimated aerosol concentration of 5247 mg/m3 were free of gross pathological abnormalities. In the second group (5266 mg/m3 aerosol), 4 males and 1 female exhibited red foci on the lungs, one male displayed dark red nasal turbinates, and 3 males and 1 female had alopecia and/or scabs on the dorsal surface, extremities, and/or head. Based on the conditions of this study, the LC50 for acute inhalation exposure to an aerosol atmosphere of Hydrocarbons, C10-C12, isoalkanes, <2% aromatics is greater than 5266 mg/m3.

In a second supporting study (Exxon Chemical Company, 1997), the test material (Hydrocarbons, C10-C12, isoalkanes, <2% aromatics) was administered via individual whole-body inhalation chambers for four hours to ten Crl:CDBR rats at a total chamber concentration of 5991 mg/m3 (5428 mg/m3 aerosol, 562 mg/m3 vapor). Animals were observed for fourteen days following exposure. There were no mortality or gross pathological alterations in the animals, with the exception of two animals that displayed scabs and one with a necrotic and truncated tail. Based on the conditions of the study, the LC50 for acute inhalation exposure to an aerosol atmosphere of Hydrocarbons, C10-C12, isoalkanes, <2% aromatics is greater than 5991 mg/m3.

Hydrocarbons, C11 – C13, isoalkanes, < 2% aromatics

In a key study (Exxonmobil Corp., 2005), the test material Hydrocarbons, C11 – C13, isoalkanes, < 2% aromatics was administered via individual inhalation chambers for four hours to ten rats at the maximum attainable vapor concentration of 4951 mg/m3for four hours to assess acute inhalation toxicity. There were no mortality or gross pathological alterations noted in any of the animals. Based on the conditions of this study, the LC50 for acute inhalation exposure to Hydrocarbons, C11 – C13, isoalkanes, < 2% aromatics vapor is greater than the highest obtainable vapor concentration (4951 mg/m3). 

Dermal

There is no data available for Hydrocarbons, C10-C12, isoalkanes, <2% aromatics. However, data is read across to structural analogue Hydrocarbons, C7-C9, isoalkanes, <2% aromatics. This data is read across to based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13. Dermal penetration decreases with increasing carbon range and therefore this read across represents a worst case scenario for the higher carbon number hydrocarbon solvents such as Hydrocarbons, C10-C12, isoalkanes, <2% aromatics.

Hydrocarbons C7-C9, isoalkanes, <2% aromatics

Two studies were performed in which hydrocarbons, C7-C9, isoalkanes, were applied to the clipped, intact abdominal skin of albino rabbits (4/sex/dose) at 100, 316, 1000, 3160 µL/kg bw for 24 h under occlusive conditions. In the first study, there were three deaths, one each at the 100, 1000, and 3160 µL/kg bw levels. These deaths were apparently the result of a severe intestinal infection. In the 100 µL/kg group one animal showed diarrhoea on day 11 and on day 14 depression, labored respiration and diarrhoea. In the same group, congestion of the kidneys, inflammation of the small intestine, and a large amount of fluid in the gastrointestinal tract was found in one animal at necropsy. At the 3160 µL/kg level, firm, elevated, blanched areas on the gallbladder, and extensive amount of fluid in the peritoneal cavity, and inflammation of the intestines were observed.

In the second study, no deaths at any dosage level occurred. Apart from 3 rabbits all other animals showed normal behaviour and appearance throughout the study. Two rabbits from the lowest dose treatment showed diarrhoea for two to four days and a decrease in body weight. At autopsy one showed paleness of the cortical portion of the kidneys, the other an excessive amount of clear fluid in the peritoneal cavity and congested, pitted, tough kidneys. One rabbit of the high dose group showed inflammation of the intestines.

In both studies the following dermal effects were noted: After removal of the binders at the end of the exposure period, the abdomens and binders were dry. At this time, the exposed skin areas of the animals showed a slight degree of erythema. Within an additional one to three days, the erythema had completely subsided in all animals. The low dose animals showed no other signs of irritation during the remainder of the observation period. The high dose animals showed slight or moderate desquamation during the final few days of the first week and during the second week. At termination, however, the exposed skin of the surviving animals was completely free of signs of irritation.

The LD50 value was greater than 3.16 mL/Kg bw in both studies (ExxonMobil Chemical, 1961c,d).

Justification for classification or non-classification

Based on available data, Hydrocarbons, C10-C12, isoalkanes, <2% aromatics are minimally toxic via ingestion where the LD50 is >5000 mg/Kg, via dermal exposure where the LD50 is >3.16 mL/Kg, and by inhalation where the LC50 > 5000 mg/m3.  These findings do not warrant classification under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

Hydrocarbons, C10-C12, isoalkanes, <2% aromatics are classified under EU CLP guidelines as a Category 1 aspiration hazard based on its physical and chemical properties (hydrocarbon fluid, viscosity ≤ 20.5 mm2/s).