Hydrocarbons, C9-C11, 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:

read-across from supporting substance (structural analogue or surrogate)

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.

Justification for type of information:

The justification for read across is provided 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 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:

other: Ano-genital staining, observed at the 6 hour interval, was the only remarkable clinical in-life observation.

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.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

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 .

Justification for type of information:

The justification for read across is provided 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 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 3

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1988/5/10 - 1988/5/24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to OECD test guideline 401. GLP.

Justification for type of information:

The justification for read across is provided as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

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: Kleintierfarm Madoerin AG
- Age at study initiation: 9 weeks
- Weight at study initiation: males: 179-197g, females: 162-180g
- Fasting period before study: 12-18h
- Housing: individually
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, batch 95/88 rat maintenance diet, ad libitum
- Water (e.g. ad libitum): community tap water from Itingen, ad libitum
- Acclimation period: at least one week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: undiluted, as delivered by sponsor
- Amount of vehicle (if gavage): 5000 mg/kg
- Justification: the oral administration was used, because this is one possible route of human exposure during manufacture, handling and use of the test article

Doses:

5000 mg per kg bodyweight

No. of animals per sex per dose:

5 males and 5 females (one dose)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: observations were made as to the nature, onset, severity, and duration of toxicological signs 4 times during day one, and once per day during day 2-15. Body weights were recorded on the test day prior to dosing and on Day 8 and Day 15, and at death for those which succumbed.
- Necropsy of survivors performed: yes

Statistics:

The LOGIT-model could not be applied to the observed rates of death. The toxicity was estimated without use of a statistical model.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortality

Clinical signs:

other: 5000 mg/kg: sedation, dyspnea, hunched posture, ruffled fur All animals had recovered until day 5 of the observation

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 the test material 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:

C9 -C11 cyclic aliphatics were administered via oral gavage to 5 male and 5 female rats at a dose of 5000 mg/kg to assess acute oral toxicity.  Animals were observed daily for 15 days post dosing.  At a dose of 5000 mg/kg, signs of toxicity were sedation, dyspnea, hunched posture and ruffled fur. All animals had recovered until day 5 of observation and 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 C9 -C11 cyclic aliphatics 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.

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

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

Justification for type of information:

The justification for read across is provided 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 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:

other: 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.

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.

Reference 5

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

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

Justification for type of information:

The justification for read across is provided 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 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 6

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

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

Justification for type of information:

The justification for read across is provided 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 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:

Six key 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:

read-across from supporting substance (structural analogue or surrogate)

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:

The justification for read across is provided 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: All rats appeared normal during the exposure and during the 14 day post-exposure period.

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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1999/09/29-1999/10/22

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

The justification for read across is provided 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)

Deviations:

yes

Remarks:

An 8hr exposure for 3 consecutive days, one day post-treatment observation

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: WAG/RijCrlBR

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deuschland, Sulzfeld, Germany
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 33-50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

Test atmosphere was generated by pumping liquid C9-C11 cyclic aliphatic into stainless steel tubing using peristaltic pumps. The tubing was led through a water bath at 74 deg C and the resulting vapour was transported with an air stream from a compressed air source and added to the main airflow system. The test atmospheres were analysed by two total carbon analysers.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

total carbon analysers

Duration of exposure:

8 h

Concentrations:

0 (air), 1 g/m3 (170ppm), 2.5 g/m3 (430ppm), 5 g/m3 (860ppm)

No. of animals per sex per dose:

8 animals per dose

Control animals:

yes

Details on study design:

Animals were exposed to the test atmosphere in modified H100 inhalation chambers Hazleton System Inc., USA). Each chamber was fitted with a manometer that allowed monitoring the slightly negative pressure inside. Three test groups (with one control) comprising of 8 rats each were exposed to Nappar 10 at different concentrations including: 0 (air), 1 g/m3 (170ppm), 2.5 g/m3 (430ppm), 5 g/m3 (860ppm). Animals were exposed to the test atmosphere 8hours/day for 3 consecutive days. All rats were checked for health and viability at least once daily. Body weight was recorded during randomization on days of testing.

Statistics:

All data were analyzed using the SAS statistical software package (v. 6.12). For each test measure, probability of p<= 0.05 were considered significant.

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 5 000 mg/m³ air (nominal)

Exp. duration:

8 h

Remarks on result:

other: no deaths noted after 3 consecutive days of exposure

Mortality:

All animals survived to the end of the study.

Clinical signs:

other: One animal (2.5 g/m3) and three animals (5.0 g/m3) were noted with bloody exudation around the nose and mouth after the third exposure.

Body weight:

No significant changes were noted after exposure.

Gross pathology:

N/A

Other findings:

N/A

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

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:

C9 -C11 cyclic aliphatics were administered via individual inhalation chambers for eight hours to eight Sprague-Dawley rats at vapor concentration of 0 (air), 1 g/m³ (170ppm), 2.5 g/m3 (430ppm), 5 g/m³ (860ppm) for three consecutive days. There was no mortality noted in any of the animals.  Based on the conditions of this study, the LC50 for acute inhalation exposure to C9 -C11 cyclic aliphatics vapor is greater than the highest obtainable vapor concentration (5 g/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:

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.

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: None

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 4

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

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.

Justification for type of information:

The justification for read across is provided 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)

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: During the exposure, all of the animals displayed one or more of the following gross signs of test compound induced adverse effects: Slight to pronounced hypoactivity (10/10), malaise (10/10), and proneness (4/10). Following removal from the chamber and t

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. 

Reference 5

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

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.

Justification for type of information:

The justification for read across is provided 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:

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: Rats exposed for 4 hours to a near saturated atmosphere of SHELLSOL TD (9.3 mg/l) were lethargic (males) or restless (females) during exposure but recovered within 5 minutes.

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:

> 4 951 mg/m³ air

Physical form:

inhalation: vapour

Quality of whole database:

One key substance specific and four key read across studies along with three supporting read across studies 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:

read-across from supporting substance (structural analogue or surrogate)

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

Justification for type of information:

The justification for read across is provided 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 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:

read-across from supporting substance (structural analogue or surrogate)

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 .

Justification for type of information:

The justification for read across is provided 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 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

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.

Key result

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:

One key substance specific and two key read across studies from structural analogues available for assessment.

Additional information

There is substance specific acute inhalation and dermal toxicity data available for Hydrocarbons, C9-C11 isoalkanes, cyclics, <2% aromatics. This data is supported by acute oral, inhalation, and dermal toxicity data available for structural analogues, Hydrocarbons, C9-C11, isoalkanes, <2% aromatics; Hydrocarbons, C9-C11, cyclics, <2% aromatics; Hydrocarbons, C10-C12, isoalkanes, <2% aromatics; Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, <2% aromatics; Hydrocarbons, C11-C13, isoalkanes, <2% aromatics; Hydrocarbons, C11-C14, n-alkanes, <2% aromatics; Hydrocarbons, C11-C14, isoalkanes, cyclics, <2% aromatics; and Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, <2% aromatics and presented in the dossier. This data is read across to Hydrocarbons, C9-C11 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, C9 -C11, cyclics, <2% aromatics

In a key acute oral toxicity study (ExxonMobil, 1988), the test material (C9-C11, cyclic aliphatics) was administered via oral gavage to 5 male and 5 female rats at a dose of 5000 mg/Kg. Animals were observed daily for 15 days post dosing. At a dose of 5000 mg/Kg, signs of toxicity were sedation, dyspnea, hunched posture and ruffled fur. All animals had recovered until day 5 of observation and 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 C9-C11 cyclic aliphatics was determined to be >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).

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

In a key acute oral toxicity study (ExxonMobil, 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. 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 Hydrocarbons, C10-C12, isoalkanes, <2% aromatics was determined to be >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).

 

In a second key acute oral toxicity study (ExxonMobil, 1977), the acute toxicity of the test material (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 for Hydrocarbons, C10-C12, isoalkanes, <2% aromatics 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).

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

In a key study (ExxonMobil, 1977), the test material 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 was greater than 15.0 g/Kg.

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

In a key study (ExxonMobil, 1989), the acute toxicity of the test material 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 of the test material following oral gavage was >5 g/Kg.

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

In a key study (ExxonMobil, 1977), the test material 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 the test material was greater than 15.0 g/Kg.

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/m³for 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, C9-C11, isoalkanes, <2% aromatics

In a key acute inhalation toxicity study (ExxonMobil, 2001), the test material (C9-C11, cyclic aliphatics) were administered via individual inhalation chambers for eight hours to eight Sprague-Dawley rats at vapor concentration of 0 (air), 1 g/m³ (170ppm), 2.5 g/m³ (430ppm), 5 g/m³ (860ppm) for three consecutive days. There was no mortality noted in any of the animals. Based on the conditions of this study, the LC₅₀ for acute inhalation exposure to C9-C11 cyclic aliphatics vapor is greater than the highest obtainable vapor concentration (5 g/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, 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) was determined to be >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).

 

In a second key study (Shell, 1977), the test material (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). 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).

 

In a supporting acute inhalation toxicity study (ExxonMobil, 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 was determined to be greater than 5266 mg/m³.

 

This finding does not warrant classification of Hydrocarbons, C10-C12, isoalkanes, <2% aromatics as an acute inhalation toxicant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).

 

In a second supporting acute inhalation toxicity study (ExxonMobil, 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 was determined to be greater than 5991 mg/m³.

 

This finding does not warrant classification of Hydrocarbons, C10-C12, isoalkanes, <2% aromatics as an acute inhalation toxicant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).

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

In a key acute inhalation toxicity 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/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 the test material was 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, C10-C13, n-alkanes, isoalkanes, cyclics, < 2% aromatics

In a supporting study (Chevron Philips Chemical Company, 1969), 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.

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 LD₅₀for 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 effect on viability; all animals survived the exposure. The LD₅₀was 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 a key acute dermal toxicity 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 effect on viability; all animals survived the exposure. The LD₅₀was 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 substance specific and read across data, Hydrocarbons, C9-C11, 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 is >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, C9-C11, 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).