Hydrocarbons, C13-C15, n-alkanes, isoalkanes, cyclics, < 2% aromatics

Endpoint summary

Description of key information

Oral LD₅₀ (rat) > 5000 mg/Kg bw

Inhalation LC₅₀ (rat) >4951 mg/m³

Dermal LD₅₀ (rabbit) > 2000 mg/Kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989/03/01-1989/03/15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to or similar to guideline study OECD 401: GLP .

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

only one dose tested

GLP compliance:

yes

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 France
- Sex: Males (5); Females (5)
- Weight at study initiation: 102-146 g
- Housing: individual
- Diet (e.g. ad libitum): Biosure LAD 1, ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 50%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

A single dose of P-D 20/26 (5g/kg) was administered by oral gavage.

Doses:

5 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 P-D 20/26 was investigated in a group of 5 male and 5 female rats. Each animal received a single oral dose of 5 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:

> 5 000 mg/kg bw

Mortality:

No mortality was observed in any of the animals treated with 5 g/kg P-D 20/26.

Clinical signs:

other: Pilo-erection was observed in all rats within five minutes of dosing and throughout the remainder of Day 1. There were no other clinical signs and recovery, as judged by external appearance and behavior, was complete by Day 2.

Gross pathology:

Terminal autopsy findings were normal.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 for P-D 20/26 following oral gavage was >5 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 P-D 20/26 was evaluated in rats via oral gavage at a dose of 5 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 animals displayed little or no abnormalities. The LD50 for P-D 20/26 following oral gavage was >5 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.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1977-06-16 to 1977-06-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to or similar to guideline study OECD 401: pre-GLP

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Housing: individually

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

15g/kg

No. of animals per sex per dose:

5 males and 5 females/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Days 0, 7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 15 000 mg/kg bw

Mortality:

No mortatlity

Clinical signs:

other: Diarrhea observed in multiple animals on day 1 and 1/10 animals on days 9 and 10; hair loss observed in animals on days 7-14

Gross pathology:

Kidneys darker than normal in 2 males and 3 females

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 following oral gavage of MRD 77-11 is greater than 15g/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 77 -11 was administered via oral gavage to ten albino Wistar rats (5 males and 5 females) at a dose of 15.0 g/kg to assess the acute oral toxicity.  Animals were observed for mortality and toxic effects immediately and 1, 2, 3, 4, and 6 hours after dosing and daily for 14 days.  Necropsies were performed on all rats.  No deaths were observed.  Hair loss in 9/10 animals and darkened kidneys in 5/10 animals were observed at necropsy.  The oral LD50 for MRD 77-11 was greater than 15.0 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.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1977-06-16 to 1977-06-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to or similar to guideline study OECD 401: pre-GLP

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Housing: individually
- Diet (e.g. ad libitum): ad libitum except for 18 hours prior to dosing
- Water (e.g. ad libitum):ad libitum

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

15g/kg

No. of animals per sex per dose:

5 males and 5 females/dose

Control animals:

no

Details on study design:

Rats were observed for mortality and toxic effects immediately and 1, 2, 4, and 6 hours after dosing and daily for 14 days. Necropsies were performed on all rats. Weights were recorded pretest and weekly

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 15 000 mg/kg bw

Mortality:

No mortatlity

Clinical signs:

other: During the first 24h after hyperactivity to noise, dilated pupils, and slight lethargy were observed. Chromorhinorrhea was observed in 4 males and 1 female on day 1 after exposure and alopecia in anogenital region was observed in all females on Day 14 aft

Gross pathology:

Red ovaries in 3/5 females; portions of uterus red in 2/5 females.

Other findings:

Slight alopecia in anogenital area in 9/10 animals

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 following oral gavage of MRD 77-12 is greater than 15g/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 77-12 was administered via oral gavage to ten albino Wistar rats (5 males and 5 females) at a dose of 15.0 g/kg to assess the acute oral toxicity.  Animals were observed for mortality and toxic effects immediately and 1, 2, 3, 4, and 6 hours after dosing and daily for 14 days.  Necropsies were performed on all rats.  No deaths or clinical signs of toxicity were observed.  Slight alopecia in the anogential area was observed in 9/10 animals and darkened ovaries in 3/5 female animals were observed at necropsy.  The oral LD50 for MRD 77-12 was greater than 15.0 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:

Three key and one supporting read across studies from structural analogues available for assessment.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

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.

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: 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.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report equivalent or similar to OECD guideline 403 : GLP.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Age at study initiation: 9-11 weeks
- Weight at study initiation: 245-325 g
- Housing:individually
- Diet (e.g. ad libitum): ad libitum during non-exposure, food withheld while in chamber
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-76
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Exposure apparatus: 150 liter stainless steel inhalation chamber
- Exposure chamber volume: 150 liter
- Temperature, humidity, pressure in air chamber: 75° F, 48%, slight negative pressure to the room


TEST ATMOSPHERE
- Brief description of analytical method used: calibrated infrared monitor
- Samples taken from breathing zone: no



CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

actual vapor concentration of6100 mg/m3

No. of animals per sex per dose:

10 animals/dose (5 males; 5 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Day 0, 7, and 14
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

>= 6 100 mg/m³ air (analytical)

Exp. duration:

4 h

Mortality:

None

Clinical signs:

other: other:

Body weight:

Body weight appeared normal throughout experiment. One female lost 2 grams during the Day 7-14 post-exposure observation period.

Gross pathology:

All animals appeared normal.

Other findings:

N/A

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LC50 for acute inhalation exposure to MRD-94-979 vapor is greater than 6100 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-94-979 was administered via individual inhalation chambers for four hours to ten Sprague-Dawley rats (5 males, 5 females) to an average actual vapor concentration of 6100 mg/m³ for four hours to assess acute inhalation toxicity. Animals were observed for fourteen days following exposure.  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-94-979 vapor is greater than 6100 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.

Reference 3

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1995-09-20 to 1995-10-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to or similar to guideline study OECD 403: GLP

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute 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., Kingston, New York USA
- Age at study initiation: Males, approximately 6 weeks; Females, approximately 7 weeks
- Weight at study initiation: Males, 155 to 168 grams; Females, 157 to 177 grams
- Fasting period before study: none
- Housing: Single housed during the study period. Suspended stainless steel and wire mesh.
- Diet (e.g. ad libitum): Certified Rodent Diet #5002, from PMI Feeds, Inc., Richmond, Indiana, ad libitum, during non-exposure periods. Food withheld while animals were in chamber.
- Water (e.g. ad libitum): Automatic watering system, ad libitum, during non-exposure periods. Water withheld while animals were in chamber.
- Acclimation period: 8 days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68-76 degrees F while in animal room; 71-74 degrees F while in exposure chamber
- Humidity (%): 40-70% relative humidity while in animal room; 82-95% relative humidity while in exposure chamber
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark


IN-LIFE DATES: From: 1995-09-21 To: 1995-10-05

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 150 liter stainless steel and acrylic whole-body inhalation exposure chamber.
- System of generating particulates/aerosols: The test atmosphere was generated using a Laskin nebulizer and a 3-neck round-bottom flask as a reservoir for the liquid test material. Compressed air was supplied to the nebulizer at approximately 4-5 psi back-pressure, producing a liquid droplet aerosol within the 3-neck flask. The aerosol was mixed with additional room air and then drawn into the exposure chamber.
- Method of particle size determination: Sierra Instruments Model 210 Cascade Impactor. Preweighed glass fiber filters were used to collect the aerosol on each stage. A bulk estimation technique was employed to characterize the particle size distribution of the test atmosphere. The change in weight of the filter for each stage was measured and the cumulative percent of the sample collected on each stage was calculated. This information plus the stage constants for the impactor were used to calculate the 15.9%, 50.0% and 84.1% particle sizes, the geometric standard deviation, and the estimated percent of the aerosol less than or equal to 1, 10, and 15 microns in size.
- Temperature, humidity, pressure in air chamber:

TEST ATMOSPHERE
- Brief description of analytical method used: Analytical chamber concentrations were determined during each hour of the exposure by drawing a known volume of the test atmosphere through a sample train consisting of a glass-fiber filter for collection of non-volatile aerosol and a charcoal sorbent tube for collection of volatile hydrocarbons (vapor).

Non-volatile aerosol concentrations were first determined gravimetrically by dividing filter weight gain by the sample volume. The filters and the charcoal tubes were then analyzed by GC/FID. Total hydrocarbons and individual hydrocarbons (full scan) were reported for both sample types. Total analytical chamber concentrations were reported as the sum of the gravimetric aerosol and total hydrocarbon vapor results.

PARTICLE SIZA DATA
-Mass median equivalent aerodynamic diameter (50% size): 3.4 microns
-Gravimetric standard deviation: 2.1
-Percent <= 15 microns: 98.0%
-Percent <= 10 microns: 93.3%
-Percent <= 1 micron: 4.6%

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gravimetrically (aerosol); GC/FID (vapor)

Duration of exposure:

4 h

Concentrations:

5991 mg/m3 (5428 mg/m3 aerosol, 562 mg/m3 vapor)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Approximately 15 minute intervals during the first hour of exposure and once each hour thereafter through the termination of exposure.
- Necropsy of survivors performed: yes

Statistics:

Means and standard deviations for body weight and body weight change by group and sex

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 991 mg/m³ air (analytical)

Exp. duration:

4 h

Remarks on result:

other: No mortalities.

Mortality:

No mortalities occurred.

Clinical signs:

other: other:

Body weight:

All animals displayed increases in body weight over their initial (Day 0) values.

Gross pathology:

All ten animals were free of internal macroscopic abnormalities at post-mortem examination.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LC50 for acute inhalation exposure (aerosol atmosphere) to MRD-95-289 is greater than 5991 mg/m3 (5428 mg/m3 aerosol, 562 mg/m3 vapor). This finding does not warrant classification of Isopar M as an acute inhalation toxicant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

To assess acute inhalation toxicity, MRD-95 -289 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 MRD-95 -289 is greater than 5991 mg/m³.

This finding does not warrant classification of MRD-95 -289 as an acute inhalation toxicant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the 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:

4 951 mg/m³ air

Quality of whole database:

Two key, one weight of evidence, and one supporting read across study from structural analogues available for assessment.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992/11/10-1992/11/24

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well-documented study report which meets basic scientific principles: GLP

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

; 1987 Guidelines

Deviations:

yes

Remarks:

occlusive dressing used

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products
-Sex: Male (3); Female (3)
- Age at study initiation: 12-13 weeks
- Weight at study initiation: Male: 2.01 to 2.21 kg; Female: 2.17 to 2.48 kg
- Housing: individually housed
- Diet (e.g. ad libitum): AgwayCertified Diet RCA Rabbit, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8-day acclimatization

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-70
- Humidity (%): 40 to 60
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

On the day prior to application the trunk of each animal was clipped free of hair. For each treated animal, 5000 mg/kg of MRD-92-405 was applied to the trunk beneath a gauze patch and secured by an occlusive wrap to prevent evaporation. The whole patch assembly was held in place with tape. The patches were left in position for approximately 24 hours. Residual test material was removed and animals were observed 1, 2.5, and 4 hours after dosing and once per day thereafter for a total of 14 days.

Duration of exposure:

24 hours

Doses:

5000 mg/kg: (3) males; (3) female

No. of animals per sex per dose:

Animals: (3) males; (3) female

Control animals:

no

Details on study design:

SCORING SYSTEM: Draize scale
- Dermal response observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Differences between treated and control group mean values for bodyweight gain were analysed by Student's t-test. Where individual variance ratios were significant (P <0.05 or less), Cochrans approximation was applied (Snedecor and Cochran, Statistical Methods, 6th Ed. Iowa State. 1973). Where zero variance was found in one or more groups, intergroup comparison was performed by the Wilcoxon Rank Sum Test.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

There were no animal deaths prior to study termination.

Clinical signs:

other: Well-defined erythema was noted upon removal of the test patches in all animals exposed to MRD-92-405, with edema noted in two animals. At Day 14, three animals were noted as having very slight erythema and only one animal was noted as having well-defined

Gross pathology:

One animal was free of macroscopic abnormalities. Five animals were observed with desquamation.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 of MRD-92-405 was > 5000 mg/kg. Classification as an acute dermal 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:

Three male and three female rabbits were exposed to MRD-92-405 for 24h via an occluded patch.  Dermal evaluations occurred at 24 hours post patch removal and once daily until the study termination at day 14. Exposure had no affect on viability; all animals survived the exposure.  The LD50 of MRD-92-405 was > 5000 mg/kg. Classification as an acute dermal 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.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989/01/27 - 1989/02/10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to or similar to guideline study OECD 402: GLP .

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute 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 France
-Sex: Male (5); Female (5)
- Weight at study initiation: 209 to 254 g
- Housing: individually housed
- Diet (e.g. ad libitum): Labsure LAD 1, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 71%
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

On the day prior to application the trunk of each animal was clipped free of hair. For each treated animal, 2000 mg/kg of P-D 20/26 was applied to the trunk beneath a gauze patch and secured by an occlusive wrap to prevent evaporation. The whole patch assembly was held in place with tape. The patches were left in position for approximately 24 hours. Residual test material was removed and animals were observed soon after dosing and twice per day thereafter for a total of 14 days.

Duration of exposure:

24 hours

Doses:

2000 mg/kg: (5) males; (5) female

No. of animals per sex per dose:

Animals: (5) males; (5) female

Control animals:

no

Details on study design:

SCORING SYSTEM: Draize scale
- Dermal response observations: daily
- Other examinations performed: clinical signs, body weight

Statistics:

Differences between treated and control group mean values for bodyweight gain were analysed by Student's t-test. Where individual variance ratios were significant (P <0.05 or less), Cochran's approximation was applied (Snedecor and Cochran, Statistical Methods, 6th Ed. Iowa State. 1973). Where zero variance was found in one or more groups, intergroup comparison was performed by the Wilcoxon Rank Sum Test.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no animal deaths prior to study termination.

Clinical signs:

other: Well-defined erythema accompanied by slight oedema was observed in all five males and one female after removal of the dressings. A small amount of test substance remained on the skin site in these animals. Slight erythema only was observed in the remainin

Gross pathology:

Terminal autopsy findings were normal.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 of P-D 20/26 was > 2000 mg/kg. Classification as an acute dermal 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:

Five male and five female rabbits were exposed to P-D 20/26 for 24h via an occluded patch.  Dermal evaluations occurred at 24 hours post patch removal and twice daily until the study termination at day 14. Exposure had no affect on viability; all animals survived the exposure.  The LD50 of P-D 20/26 was > 2000 mg/kg. Classification as an acute dermal 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.

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report equivalent or similar to OECD guideline : GLP

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton
- Age at study initiation: 19 weeks
- Weight at study initiation: 3.14-3.51
- Housing: individual
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 50 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-71
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12

Details on dermal exposure:

TEST SITE
- Area of exposure: shoulder region to lumbar region
- Type of wrap if used: gauze and plastic sleeve


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing, wiped with gauze
- Time after start of exposure: 24h

Duration of exposure:

The test material was applied to the skin at the appropriate dose, covered with a gauze patch, secured with tape, and covered with a plastic sleeve. After ca. 24h of exposure, the plastic sleeve, tape and gauze patch were removed. The skin was then wiped (but not washed) with gauze and water to remove any remaining test material.

Doses:

The test material was applied to the skin at the appropriate dose, covered with a gauze patch, secured with tape, and covered with a plastic sleeve. After ca. 24h of exposure, the plastic sleeve, tape and gauze patch were removed. The skin was then wiped (but not washed) with gauze and water to remove any remaining test material.

No. of animals per sex per dose:

6 animals/dose (3 males; 3 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:2, 4, 24 hours after dosing and daily for 14 days
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight

Statistics:

The means and standard deviations of the body weights were calculated.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 3 160 mg/kg bw

Mortality:

none

Clinical signs:

other: There was an overall low incidence of clinical in-life observations noted during the study. Observations included nasal discharge, dry rales, alopecia. Topical exposure elicited very slight to well defined erythema in all animals and very slight edema i

Gross pathology:

N/A

Other findings:

N/A

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 for MRD-83-349 is greater than 3160 mg/kg. Classification as an acute dermal 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 dermal toxicity of MRD-83-349 was evaluated in rabbits following topical occlusive exposure.  Test material was applied as a single dose of 3160 mg/kg to the clipped backs of 3 male and 3 female rabbits, covered with a gauze patch, and secured with non-irritating tape and a plastic sleeve.  The test material remained in contact with the skin for 24 hours.  Observations were made as to the nature, onset, severity, and duration of toxicological signs 2, 4, and 24 hours after dosing and once per day thereafter, for a total of 14 days.  Dermal responses were evaluated 24 hours after topical application and on Days 3, 7, 10, and 14 according to the Draize method of scoring.  Application of MRD-83-349 at a dose level of 3160 mg/kg showed no evidence of systemic toxicity under the conditions of this study and all animals survived to study termination.  There were no deaths or treatment-related clinical signs.  Topical exposure elicited very slight to well defined erythema in all animals and very slight edema in four animals.  Desquamation was noted in five animals during the study.  By Day 14, all animals were clear of erythema and edema.  Based on the results of this study, the dermal LD50 for MRD-83-349 is greater than 3160 mg/kg.  Classification as an acute dermal 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:

2 000 mg/kg bw

Quality of whole database:

Three key read across studies from structural analogues available for assessment.

Additional information

There is no acute oral, inhalation, or dermal toxicity data available for Hydrocarbons, C13-C15, n-alkanes, isoalkanes, cyclics, <2% aromatics. However, data is available for structural analogues, Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics; Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, <2% aromatics; Hydrocarbons, C11-C13, isoalkanes, <2% aromatics; Hydrocarbons, C11-14, n-alkanes, <2% aromatics; Hydrocarbons, C11-C14, isoalkanes, cyclics, <2% aromatics; Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, <2% aromatics; Hydrocarbons, C12-C16, isoalkanes, cyclics, <2% aromatics; and isohexadecane. This data is read across to Hydrocarbons, C13 -C15, n-alkanes, isoalkanes, cyclics, <2% aromatics 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-C13, n-alkanes, isoalkanes, cyclics, <2% aromatics

In a key study (ExxonMobil Corp., 1977), the test material (C10-C13, n-alkanes, isoalkanes, cyclics, <2% aromatics) was administered via oral gavage to ten albino Wistar rats (5 males and 5 females) at a dose of 15.0 g/kg to assess the acute oral toxicity.  Animals were observed for mortality and toxic effects immediately and 1, 2, 3, 4, and 6 hours after dosing and daily for 14 days.  Necropsies were performed on all rats.  No deaths were observed.  Hair loss in 9/10 animals and darkened kidneys in 5/10 animals were observed at necropsy.  The oral LD50 for Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, <2% aromatics was greater than 15.0 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).

Hydrocarbons, C11-C14, isoalkanes, cyclics, < 2% aromatics

In a key study (ExxonMobil, 1989), the acute toxicity of the test material (Hydrocarbons, C11-C14, isoalkanes, cyclics, < 2% aromatics) was evaluated in rats via oral gavage at a dose of 5 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 animals displayed little or no abnormalities. The LD50following oral gavage was determined to be >5 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).

 

Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, < 2% aromatics

In a key study (ExxonMobil, 1977), the test material (Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, < 2% aromatics) was administered via oral gavage to ten albino Wistar rats (5 males and 5 females) at a dose of 15.0 g/Kg to assess the acute oral toxicity. Animals were observed for mortality and toxic effects immediately and 1, 2, 3, 4, and 6 hours after dosing and daily for 14 days. Necropsies were performed on all rats. No deaths or clinical signs of toxicity were observed. Slight alopecia in the anogential area was observed in 9/10 animals and darkened ovaries in 3/5 female animals were observed at necropsy. The oral LD50 was greater than 15.0 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).

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, C9-C11, isoalkanes, cyclics, <2% aromatics

In a key study (ExxonMobil, 1995), the test material was administered via individual inhalation chambers for four hours to ten Sprague-Dawley rats (5 males, 5 females) to an average actual vapor concentration of 6100 mg/m³ for four hours to assess acute inhalation toxicity. Animals were observed for fourteen days following exposure. 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 the test material vapor is greater than 6100 mg/m³. 

 

Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, <2% aromatics

In a supporting study (Chevron, 1969), the saturated vapor of the test material (Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, <2% aromatics) was fed into a stainless steel and glass exposure chamber (volume‑85 cubic feet) at a rate of 8.5 cubic feet per minute for approximately 15 minutes prior to introduction of the test animals.  Exposure to the test material vapors at a calculated concentration of 11600 mg/m³(1806.5 ppm) lasted for six hours.  All four monkeys survived the exposure.  During the exposure period, all monkeys showed signs of retching and two monkeys vomited.  All animals rubbed their eyes and held their heads during the exposure period.  All four monkeys were certified healthy by a veterinarian at the end of 14 days of observation.

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

In a key study (ExxonMobil, 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 test material 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).

Hydrocarbons, C12-C16, isoalkanes, cyclics, < 2% aromatics

To assess acute inhalation toxicity, the test material (Hydrocarbons, C12-C16, isoalkanes, cyclics, < 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/m³aerosol, 562 mg/m³vapor). 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 the test material was greater than 5991 mg/m³.

 

This finding does not warrant classification of Hydrocarbons, C12-C16, isoalkanes, cyclics, < 2% aromatics as an acute inhalation toxicant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).

Dermal

Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics

In a key acute dermal toxicity study (ExxonMobil, 1984), the acute dermal toxicity of the test material was evaluated in rabbits following topical occlusive exposure. Test material was applied as a single dose of 3160 mg/Kg to the clipped backs of 3 male and 3 female rabbits, covered with a gauze patch, and secured with non-irritating tape and a plastic sleeve. The test material remained in contact with the skin for 24 hours. Observations were made as to the nature, onset, severity, and duration of toxicological signs 2, 4, and 24 hours after dosing and once per day thereafter, for a total of 14 days. Dermal responses were evaluated 24 hours after topical application and on Days 3, 7, 10, and 14 according to the Draize method of scoring. Application of the test material at a dose level of 3160 mg/Kg showed no evidence of systemic toxicity under the conditions of this study and all animals survived to study termination. There were no deaths or treatment-related clinical signs. Topical exposure elicited very slight to well defined erythema in all animals and very slight edema in four animals. Desquamation was noted in five animals during the study. By Day 14, all animals were clear of erythema and edema. Based on the results of this study, the dermal LD₅₀ for the test material was determined to be greater than 3160 mg/Kg. 

Hydrocarbons, C11-C14, n-alkanes, < 2% aromatics

In a key study (ExxonMobil, 1993), three male and three female rabbits were exposed to the test material (Hydrocarbons, C11-C14, n-alkanes, < 2% aromatics) for 24h via an occluded patch. Dermal evaluations occurred at 24 hours post patch removal and once daily until the study termination at day 14. Exposure had no affect on viability; all animals survived the exposure. The LD50 was determined to be >5000 mg/kg. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Hydrocarbons, C11-C14, isoalkanes, cyclics, < 2% aromatics

In another key study (Cepsa Quimica, 1989), five male and five female rabbits were exposed to the test material (Hydrocarbons, C11-C14, isoalkanes, cyclics, < 2% aromatics) for 24h via an occluded patch. Dermal evaluations occurred at 24 hours post patch removal and twice daily until the study termination at day 14. Exposure had no affect on viability; all animals survived the exposure. The LD50 was determined to be >2000 mg/Kg. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

Justification for classification or non-classification

Based on available read across data, Hydrocarbons, C13-C15, n-alkanes, isoalkanes, cyclics, <2% aromatics is minimally toxic via ingestion where the LD₅₀ is >5000 mg/Kg, via dermal exposure where the LD₅₀ is >2000 mg/Kg, and by inhalation where the LC₅₀ >4951 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, C13-C15, n-alkanes, isoalkanes, cyclics, <2% aromatics is 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).