Registration Dossier

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Administrative data

Description of key information

Oral LD50 (rat) > 5000 mg/Kg bw

Inhalation LC50 (rat) >6100 mg/m³

Dermal LD50 (rabbit) > 3160 mg/Kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From November 14, 1994 To January 5, 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to or similar to OECD guideline 401: GLP.
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.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989/03/01-1989/03/15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to or similar to guideline study OECD 401: GLP .
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)
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.

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.

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.

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
- 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 available from structural analogues.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
6 100 mg/m³ air
Quality of whole database:
One key study available from structural analogues.

Acute toxicity: via dermal route

Link to relevant study records
Reference
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 160 mg/kg bw
Quality of whole database:
One key read across study available from structural analogues.

Additional information

There are no acute oral, inhalation, or dermal toxicity data available for Hydrocarbons, C12-C15, n-alkanes, isoalkanes, <2% aromatics. However, data are available for structural analogues, Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics; Hydrocarbons, C10-C12, isoalkanes, <2% aromatics, Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, <2% aromatics; Hydrocarbons, C11-C14, isoalkanes, <2% aromatics, Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, <2% aromatics; and isohexadecane. These data are read across to Hydrocarbons, C12-C15, n-alkanes, isoalkanes, <2% aromatics based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

Oral

Hydrocarbons, C10-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.

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 (ExxonMonil, 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.

Isohexadecane

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

Inhalation

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

In a key study (ExxonMobil, 1995), the test material was administered via individual inhalation chambers for four hours to ten Sprague-Dawley rats (5 males, 5 females) to an average actual vapor concentration of 6100 mg/m3 for four hours to assess acute inhalation toxicity. Animals were observed for fourteen days following exposure. There were no mortality or gross pathological alterations noted in any of the animals. Based on the conditions of this study, the LC50 for acute inhalation exposure to the test material vapor is greater than 6100 mg/m3. 

Dermal

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

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

Justification for classification or non-classification

Based on available read-across data, Hydrocarbons, C12-C15, n-alkanes, isoalkanes, <2% aromatics is minimally toxic via ingestion where the LD50 is >5000 mg/Kg, via dermal exposure where the LD50 is >3160 mg/Kg, and by inhalation where the LC50 >6100 mg/m3. These findings do not warrant classification under Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP).

Hydrocarbons, C12-C15, n-alkanes, isoalkanes, <2% aromatics is classified under the EU CLP Regulation as a Category 1 aspiration hazard based on its physical and chemical properties (hydrocarbon fluid, viscosity ≤ 20.5 mm2/s).