Hydrocarbons, C9-C11, n-alkanes, isoalkanes,

Endpoint summary

Description of key information

Oral LD₅₀ (rat) > 5000 mg/Kg bw

Inhalation LC₅₀ (rat) >5000 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:

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:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 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:

experimental study

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:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

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 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 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 4

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

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 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 5

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1961

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (limited documentation).

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Study was performed before actual guideline was established. Limited documentation.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 101 - 132 g
- Fasting period before study: Food was withheld from the animals for a period of 3 to 4 hours prior to dosage.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.1, 1.0 or 10 % volume/volume solution in corn oil (Mazola)

Doses:

31.6; 100; 316; 1000; 3160; and 10,000 µL/kg body weight

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations (mortality and toxic effects): immediately after administration; at 1, 4 and 24 hours; and once daily thereafter for a total of 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: body weight, pathology (brain, liver, kidney), blood levels were collected by exsanguination

Statistics:

no data

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 10 mL/kg bw

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 7 100 - 7 800 mg/kg bw

Remarks on result:

other: recalculated values based on the LD50 of 10 mL/kg bw; the range is due to the range of density (0.71-0.78 g/cm3)

Mortality:

The test material produced no deaths at any dosage level tested.

Gross pathology:

There were no pathological findings in any animal at autopsy following sacrifice.

Other findings:

The animals at all dosage levels seemed normal in appearance and behaviour following intubation and daily during the 14 -day observation period.

The acute oral LD50 of MRD-61-33 for male albino rats is therefore greater than 10 mL/kg body weight corresponding to 7100 - 7800 mg/kg bw.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: other: CLP

Conclusions:

Under the conditions of this study the test substance, hydrocarbons, C7-C9, isoalkanes, does not need to be classified.

Executive summary:

Under the conditions of this study the test substance, hydrocarbons, C7-C9, isoalkanes, does not need to be classified.

Reference 6

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July - September 1961

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. Limited documentation.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Study was performed before actual guideline was established.

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 101 - 132 g
- Fasting period before study: Food was withheld from the animals for a period of 3 to 4 hours prior to dosage.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.1, 1.0 or 10 % volume/volume solution in corn oil (Mazola)

Doses:

31.6; 100; 316; 1000; 3160; and 10,000 µL/kg body weight

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations (mortality and toxic effects): immediately after administration; at 1, 4 and 24 hours; and once daily thereafter for a total of 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: body weight, pathology (brain, liver, kidney), blood levels were collected by exsanguination

Statistics:

no data

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 10 mL/kg bw

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 7 100 - 7 800 mg/kg bw

Remarks on result:

other: recalculated values based on the LD50 of 10 mL/kg bw; the range is due to the range of density (0.71-0.78 g/cm3)

Mortality:

The test material produced no deaths at any dosage level tested.

Gross pathology:

There were no pathological findings in any animal at autopsy following sacrifice.

Other findings:

The animals at all dosage levels seemed normal in appearance and behaviour following intubation and daily during the 14 -day observation period.

The acute oral LD50 of MRD-61-33 for male albino rats is therefore greater than 10 mL/kg bw corresponding to 7100 - 7800 mg/kg bw.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: other: CLP

Conclusions:

Under the conditions of this study the test substance, hydrocarbons, C7-C9, isoalkanes, does not need to be classified.

Executive summary:

Under the conditions of this study the test substance, C7-C9, isoalkanes, does not need not to be classified.

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 available from structural analogues.

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:

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:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

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: other:

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 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.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. Limited documentation.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories (males: Lakeview Facility, Lakeview, New Jersey; females: Kingston Facility, Stone Ridge, New York)
- Age at study initiation: probe study: 8-9 weeks
- Weight at study initiation: 237-363 g
- Housing: individually housed during and after exposure; stainless steel wire mesh
- Diet: non-certified, pelleted, rat and mouse ration (NIH-07), Zeigler Bros., Inc., Gardners, PA, USA; not contaminated; ad libitum during non-exposure periods
- Water: automatic watering system (Elizabethtown Water Company, NJ, USA); not contaminated; ad libitium during non-exposure periods
- Acclimation period: 22 days; paired by sex for one week, then individiually thereafter
- Other: Random allocation to groups via computer-generated random numbers, with assignment to groups so as to nearly equalise by sex the initial mean group body weights.
Animals were identified by ear tags and corresponding cage identification.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22.2 °C (68-72 degree Fahrenheit)
- Humidity (%): 33-67 %
- 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:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass inhalation chamber
- Exposure chamber volume: approximately 1000 L
- Method of holding animals in test chamber: individually housed
- Source and rate of air: 200 L per minute; equivalent to 12 air changes
- Temperature, humidity: 21.1-27.8°C (70-82 °Fahrenheit); 31-42 %

Dual generators were needed to volatilise the test material. The test material was pumped (Fluid Metering, Inc.) at a fixed rate into the top of each generator, so that it would run down along the internal spiral shelf of the generator. As it ran down in contact with the heated surface, the test material volatilised, and was swept into the dosing chamber by the chamber airflow.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Actual exposure concentrations were determined by spectrophotometry (Miran 1A Ambient Air Analyser).

Duration of exposure:

4 h

Concentrations:

21.25 mg/L nominal
21.00 mg/L actual

No. of animals per sex per dose:

6

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Detailed individual observations were performed again upon removal from the chamber following exposure, and once daily for 14 days post-exposure.
- Necropsy of survivors performed: yes - A gross necropsy was performed on each animal by a qualified prosector.
- Other examinations performed: Lungs (with trachea), liver, kidneys, and whole head were collected and preserved in 10 % neutral-buffered formalin (lungs perfused by a constant pressure device) for possible future histopathological evaluation.

Statistics:

Means and standard deviations of relevant animal and exposure data were calculated. In addition, group mean body weights were compared statistically by group and sex. A computerised statistical evaluation for equality of means (2 groups) was performed, using a 2 sample t-test. The computer performed a standard F-test to determine if the 2 groups had equal variance. If the variances were equal, testing was be based on the standard t-test. If the variances were not equal, the Smith-Satterthwaite Correction for unequal variances was used. The F-test for equal variances was conducted at the 1% level of significance. The t-test were conducted at the 5% and 1% level of significance.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 21 mg/L air (analytical)

Exp. duration:

4 h

Remarks on result:

other: 21 mg/L correspond to 4504 ppm.

Mortality:

no mortality

Clinical signs:

other: other:

Body weight:

Mean animal body weights for all males and females were unremarkable at all weighing intervals.

Gross pathology:

There were 7 control rats and 8 dosed rats without abnormalities at necropsy. Of the remainder, there was a greater incidence of focal lung discoloration in the controls than in the dosed rats, a comparable incidence of dilated renal pelvis, and one instance of a dosed rat having a broken upper incisor. None of these observations was considered to be related to treatment with the test substance.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: EU

Reference 4

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. Only 6 males tested per dose level, limited documentation on environmental conditions.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Study was performed before actual guideline was established.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: adult
- Weight at study initiation: mean weight range: 254 - 397 g
- Fasting period before study: no
- Housing: in groups
- Diet (e.g. ad libitum): ad libitum during pre-and postexposure period
- Water (e.g. ad libitum): ad libitum during pre-and postexposure period
- Acclimation period: yes, duration not reported

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic exposure chamber
- Exposure chamber volume: 20 liter
- Method of holding animals in test chamber: none
- System of generating particulates/aerosols: The compound was mixed with air and metered: room air was passed through the heated test substance in a fritted-disc glass gas washing bottle. Different chamber concentrations were obtained by: 1) dilution of the saturated main air stream with make-up air in varying ratios, or 2) elevating the generation temperature and thus increasing the vapour pressure to provide a supersaturated vapour. The test material vapour was generated at 75°F (23.9°C).
- Method of particle size determination: not applicable


TEST ATMOSPHERE
- Brief description of analytical method used: 1) Determination of the ratio of the net loss of material to the total air flow volume for the period of exposure; 2) Sampling with a Model 40 M.S.A. Combustible Gas Meter standardized against pentane. The latter method required the use of a correction for each reading due to a Lower Explosive Limit of 1.4 for pentane and of 1.0 for the test compound.
- Samples taken from breathing zone: no


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: not applicable, vapour

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Sampling with a Model 40 M.S.A. Combustible Gas Meter standardized against pentane

Duration of exposure:

4 h

Concentrations:

1850, 3100, 5750, 10000 ppm

No. of animals per sex per dose:

6 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, histopathology (not performed, but sections of lungs, liver, spleen, kidneys, adrenals and testes were prepared for possible future analysis)

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

4 240 ppm

Exp. duration:

4 h

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

17.3 - 22.2 mg/L air

Exp. duration:

4 h

Remarks on result:

other: Recalculated values based on the LC50 of 4240 ppm; the range of LC50 is due to unknown amounts of hydrocarbons in the test substance with chain lengths ranging from C7 to C9.

Mortality:

1850 ppm: 0/6
3100 ppm: 0/6
5750 ppm: 6/6
> 10000 ppm: 6/6

Clinical signs:

other: other:

Gross pathology:

The lungs of animals which died during exposure showed hemorrhagic areas with gray spots on the surfaces. Severe lung congestion was an isolated finding and lung consolidation was seen infrequently. In general, the livers and kidneys were congested in these animals, but all other organs appeared normal. Animals surviving the 14-day observation period revealed little of interest at autopsy. In a few instances, hemorrhagic areas were noted on the lung surfaces and an occasionally darkened liver or kidney was seen. All other organs appeared normal.

Vapour concentrations in the air in the range of 0.5 to 1.0 % are easily produced by the volatilization of the test substance at room temperature.

Interpretation of results:

other: Harmful

Remarks:

Criteria used for interpretation of results: expert judgment

Conclusions:

The LC50 value was calculated to be 4240 ppm, corresponding to 17300 -22200 mg/m³ (recalculated values based on the LC50 of 4240 ppm). The range of LC50 is due to unknown amounts of hydrocarbons in the test substance with chain lengths ranging from C7 to C9.

Due to the unknown composition of the test substance of hydrocarbons of varying chain length (C7-C9), there is the possibility of a recalculated LC50 below 20 mg/L. Therefore, the test substance should be classified as harmful if inhaled (Category 4) according to the criteria of the CLP.

Executive summary:

The LC₅₀ value was calculated to be 4240 ppm, corresponding to 17300 -22200 mg/m³ (recalculated values based on the LC50 of 4240 ppm). Ther ange of LC₅₀ is due to unknown amounts of hydrocarbons in the test substance with chain lengths ranging from C7 to C9.

Due to the unknown composition of the test substance of hydrocarbons of varying chain length (C7-C9), there is the possibility of a recalculated LC50 below 20 mg/L. Therefore, the test substance should be classified as harmful if inhaled (Category 4) according to the criteria of the CLP.

Reference 5

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. Only 6 males tested per dose level, limited documentation on environmental conditions.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Study was performed before actual guideline was established.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: adult
- Weight at study initiation: mean weight range: 272 - 318 g
- Fasting period before study: no
- Housing: in groups
- Diet (e.g. ad libitum): ad libitum during pre-and postexposure period
- Water (e.g. ad libitum): ad libitum during pre-and postexposure period
- Acclimation period: yes, duration not reported

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic exposure chamber
- Exposure chamber volume: 20 liter
- Method of holding animals in test chamber: none
- System of generating particulates/aerosols: The compound was mixed with air and metered: room air was passed through the heated test substance in a fritted-disc glass gas washing bottle. Different chamber concentrations were obtained by: 1) dilution of the saturated main air stream with make-up air in varying ratios, or 2) elevating the generation temperature and thus increasing the vapour pressure to provide a supersaturated vapour. The test material vapour was generated at 75°F (23.9°C).
- Method of particle size determination: not applicable


TEST ATMOSPHERE
- Brief description of analytical method used: 1) Determination of the ratio of the net loss of material to the total air flow volume for the period of exposure; 2) Sampling with a Model 40 M.S.A. Combustible Gas Meter standardized against pentane. The latter method required the use of a correction for each reading due to a Lower Explosive Limit of 1.4 for pentane and of 1.0 for the test compound.
- Samples taken from breathing zone: no


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: not applicable, vapour

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Sampling with a Model 40 M.S.A. Combustible Gas Meter standardized against pentane

Duration of exposure:

4 h

Concentrations:

1050, 2390, 4450, 7140 ppm

No. of animals per sex per dose:

6 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (histopathology was not performed, but sections of lungs, liver, spleen, kidneys, adrenals and testes were prepared for possible future analysis)

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

4 450 ppm

Exp. duration:

4 h

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

18.2 - 23.3 mg/L air (analytical)

Exp. duration:

4 h

Remarks on result:

other: Recalculated values based on the LC50 of 4450 ppm; the range of LC50 is due to unknown amounts of hydrocarbons in the test substance with chain lengths ranging from C7 to C9.

Mortality:

1050 ppm: 0/6
2390 ppm: 0/6
4450 ppm: 3/6
> 7140 ppm: 6/6

Clinical signs:

other: other:

Gross pathology:

The lungs of animals which died during exposure showed hemorrhagic areas with gray spots on the surfaces. Severe lung congestion was an isolated finding and lung consolidation was seen infrequently. In general, the livers and kidneys were congested in these animals, but all other organs appeared normal. Animals surviving the 14-day observation period revealed little of interest at autopsy. In a few instances, hemorrhagic areas were noted on the lung surfaces and an occasionally darkened liver or kidney was seen. All other organs appeared normal.

Vapour concentrations in the air of the order of 0.5 to 1.0 % are easily produced by the volatilization of the test substance at room temperature.

Interpretation of results:

other: harmful

Remarks:

Criteria used for interpretation of results: expert judgment

Conclusions:

The LC50 value was calculated to be 4450 ppm, corresponding to 18200 -23300 mg/m³ (recalculated values based on the LC50 of 4450 ppm). The range of LC50 is due to unknown amounts of hydrocarbons in the test substance with chain lengths ranging from C7 to C9.

Due to the unknown composition of the test substance of hydrocarbons of varying chain length (C7-C9), there is the possibility of a recalculated LC50 below 20 mg/L. Therefore, the test substance should be classified as harmful if inhaled (Category 4) according to the criteria of the CLP.

Executive summary:

The LC₅₀ value was calculated to be 4450 ppm, corresponding to 18200 -23300 mg/m³ (recalculated values based on the LC50 of 4450 ppm). The range of LC₅₀ is due to unknown amounts of hydrocarbons in the test substance with chain lengths ranging from C7 to C9.

Due to the unknown composition of the test substance of hydrocarbons of varying chain length (C7-C9), there is the possibility of a recalculated LC50 below 20 mg/L. Therefore, the test substance should be classified as harmful if inhaled (Category 4) according to the criteria of the CLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 000 mg/m³ air

Quality of whole database:

Two key and three wieght of evidence studies available from structural analogues.

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:

1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 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.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July - September 1961

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Principles of method if other than guideline:

Standard acute method, applying 4 different doses to the clipped, intact abdominal skin

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

other: albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 1.4 - 2.3 kg
- Housing: Throughout the observation period, the rabbits were housed individually in metal cages elevated above the droppings. Purina Rabbit Pellets and water were freely available at all times.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: abdominal skin
- Type of wrap if used: dental daming binder; wrapped with gauze and adhesive tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): with sponge and warm water
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

100, 316, 1000, 3160 µL/kg bw

No. of animals per sex per dose:

4

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days (daily)
- Frequency of observations and weighing: 0, 1, 4, 24 hours
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3.16 mL/kg bw

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 200 - 2 500 mg/kg bw

Remarks on result:

other: Recalculated values based on the LD50 of 3.16 mL/kg bw; the range of LD50 is due to the range of density 0.71 -0.78 g/cm3.

Mortality:

There were three deaths, one at each at the 100, 1000, and 3160 µL/kg bw levels. These deaths were apparently the result of a severe intestinal infection. Blood samples were collected by cardiac puncture. All samples were frozen

Clinical signs:

other: 100 µL/kg dose: 2 animals normal in appearance and behaviour; One animal normal until 11th day, at which time this animal showed diarrhea and on day 14 depression, labored respiration, diarrhea 316 µL/kg dose: all animals showed normal behaviour 1000 µL/k

Gross pathology:

100 µL/kg dose: congestion of the kidneys, inflammation of the samll intestine, and a large amount of fluid in the gastrointestinal tract was found in one animal sacrificed
316 µL/kg dose: no pathology observed
1000 µL/kg dose: no pathology observed
3160 µL/kg dose: firm, elevated, blanched areas on the gallbladder, and extensive amount of fluid in the peritoneal cavity, and inflammation of the intestines

Other findings:

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

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: other: CLP

Conclusions:

There is no need for classification.

Executive summary:

There is no need for classification.

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July - September 1961

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Principles of method if other than guideline:

Standard acute method, applying 4 different doses to the clipped, intact abdominal skin

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

other: albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 1.4 - 2.3 kg
- Housing: Throughout the observation period, the rabbits were housed individually in metal cages elevated above the droppings. Purina Rabbit Pellets and water were freely available at all times.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: abdominal skin
- Type of wrap if used: dental daming binder; wrapped with gauze and adhesive tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): with sponge and warm water
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

100, 316, 1000, 3160 µL/kg bw

No. of animals per sex per dose:

4

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days (daily)
- Frequency of observations and weighing: 0, 1, 4, 24 hours
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3.16 mL/kg bw

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 200 - 2 500 mg/kg bw

Remarks on result:

other: Recalculated values based on the LD50 of 3.16 mL/kg bw; the range of LD50 is due to the range of density 0.71 -0.78 g/cm3.

Mortality:

No deaths at any dosage level.

Clinical signs:

other: Apart from 3 rabbits (2 of the 100 µL/kg dose group and one of the 3160 µL/kg dose group) which showed diarrhea for 2 to 4 days during the observation period, all animals seemed normal in appearance and behaviour throughout the study.

Gross pathology:

At autopsy, the 3 rabbits which showed diarrhea for 2 to 4 days during the observation period, exhibited pathological findings. One animals of the 100 µL/kg dose group showed paleness of the cortical portion of the kidneys. The other animals from the 100 µL/kg dose group showed an excessive amount of clear fluid in the peritoneal cavity and congested, pitted, tough kidneys. The rabbit of the high dose group showed inflammation of the intestines.

Other findings:

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

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: other: CLP

Conclusions:

There is no need for classification.

Executive summary:

There is no need for classification.

Endpoint 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 available from structural analogues.

Additional information

There is no acute oral, inhalation, or dermal toxicity data available for Hydrocarbons, C9-C11, n-alkanes, isoalkanes, <2% aromatics. However, data is available for structural analogues, Hydrocarbons, C9-C11, isoalkanes, <2% aromatics; Hydrocarbons, C9-C11, cyclics, <2% aromatics;

Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics; Hydrocarbons, C10-C12, isoalkanes, <2% aromatics, Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, <2% aromatics; Hydrocarbons, C7-C9, isoalkanes, <2% aromatics, and isohexadecane. This data is read across to based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

Oral

Hydrocarbons, C7-C9, isoalkanes, <2% aromatics

The acute oral LD₅₀ value in rats was greater than 10 mL/Kg for hydrocarbons, C7-C9, isoalkanes in two studies performed according to a protocol similar to OECD 401. The test material produced no deaths at any dosage level tested (31.6-10000 µL/Kg body weight). There were no pathological findings in any animal at autopsy following sacrifice. The animals at all dosage levels seemed normal in appearance and behaviour throughout the study period (ExxonMobil Chemical, 1961a,b).

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

In a key acute toxicity study (ExxonMobil, 1988), 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).

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

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

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

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.

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, C7-C9, isoalkanes, <2% aromatics

Hydrocarbons, C7-C9, isoalkanes, have been tested in several studies for acute inhalation toxicity following both standard (similar to OECD 403) and non-standard protocols.

In one study, 6 rats (male and female) were exposed to a nominal concentration of 21500 mg/m³ (21000 mg/m³ actual concentration) in a whole body chamber for 4 h. Another group of 6 animals was sham-exposed to room air and served as control. No mortalities occurred throughout the duration of the study (14 days). After exposure 3 of 12 rats had dried red nasal discharge, 1 of 12 rats had slight salivation, and 1 of 12 rats had slight lacrimation. All abnormal signs in the dosed animals were cleared by day 2 post-exposure. One control rat exhibited dried red nasal discharge on days 10 and 11 post-exposure, but this sign was considered inconsequential to the study outcome. There were 7 control rats and 8 dosed rats without abnormalities at necropsy. Of the remainder, there was a greater incidence of focal lung discoloration in the controls than in the dosed rats, a comparable incidence of dilated renal pelvis, and one instance of a dosed rat having a broken upper incisor. None of theses observations was considered to be related to treatment with the test substance. The LC₅₀ was greater than 21000 mg/m³, corresponding to 4504 ppm (ExxonMobil Chemical, 1985).

In two earlier studies, rats (6 males) were exposed for 4 h to 1850, 3100, 5750 and 10000 ppm and 1050, 2390, 4450 and 7140 ppm, respectively. In the first study, mortalities occurred at 5750 ppm (6/6) and higher. Exposure to lethal concentrations induced a rapid and dramatic response. Repeated episodes of violent epileptiform convulsions, interspersed with periods of running and jumping. Death occured within 17 minutes for all rats tested at the highest concentration. The lungs of animals which died during exposure showed hemorrhagic areas with gray spots on the surfaces. Severe lung congestion was an isolated finding and lung consolidation was seen infrequently. In general, the livers and kidneys were congested in these animals, but all other organs appeared normal. Animals surviving the 14-day observation period revealed little of interest at autopsy. In a few instances, hemorrhagic areas were noted on the lung surfaces and an occasionally darkened liver or kidney was seen. All other organs appeared normal. The LC₅₀value was calculated to be 4240 ppm, corresponding to 17300 -22200 mg/m³. The range of LC₅₀ is due to unknown amounts of hydrocarbons in the test substance with chain lengths ranging from C7 to C9 (ExxonMobil Chemical, 1962).

In the second study, 3/6 and 6/6 animals died at 4450 and 7140 ppm, respectively. Animals exposed to lethal concentrations exhibited clonic convulsions, laboured respiration, ataxia, and prostration preterminally. At the highest concentration, all six rats died within 1 hour; animals which survived 4 hours of exposure to 4450 ppm had a bloody exudate around the eyes and nose at the end of the exposure period. The lungs of animals which died during exposure showed hemorrhagic areas with gray spots on the surfaces. Severe lung congestion was an isolated finding and lung consolidation was seen infrequently. In general, the livers and kidneys were congested in these animals, but all other organs appeared normal. Animals surviving the 14-day observation period revealed little of interest at autopsy. In a few instances, hemorrhagic areas were noted on the lung surfaces and an occasionally darkened liver or kidney was seen. All other organs appeared normal. The LC₅₀ value was 4450 ppm, corresponding to 18200 -23300 mg/m³. As mentioned above, the range of LC₅₀ is due to unknown amounts of hydrocarbons in the test substance with chain lengths ranging from C7 to C9 (ExxonMobil Chemical, 1962).

Two further studies were performed on guinea pigs and rats following non-guideline procedures. In each study, 5 animals were exposed to 9400 mg/m³ for 10 min every 30 min during 4 h, yielding a total of eight 10-min exposures. In both studies, none of the guinea pigs or rats exposed died during the exposures or during the 14-day observation period which followed. No pathological, histopathological or behavioural effects were observed throughout the study. The LC₅₀ value in both guinea pigs and rats was greater than 9400 mg/m³ (ExxonMobil Chemical, 1972).

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

In a key acute inhalation toxicity study (ExxonMobil, 2001), 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, 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. 

Dermal

Hydrocarbons, C7-C9, isoalkanes, <2% aromatics

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

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

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

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

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. 

Justification for classification or non-classification

Based on available read-across data, Hydrocarbons, C9-C11, n-alkanes, isoalkanes, <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 >5000 mg/m³. These findings do not warrant classification under Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

Hydrocarbons, C9-C11, n-alkanes, isoalkanes, <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).