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Administrative data

Description of key information

Acute Toxicity-Oral LD50 > 5000 mg/kg in rats (OECD TG 401)

Acute Toxicity-Inhalation LC50 > 6100 mg/m3 (OECD TG 403)

Acute Toxicity-Dermal LD50 > 3160 mg/kg in rabbits (OECD TG 402)

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:
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.
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:
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.
Body weight:
All surviving animals showed an increase in body weight over their initial values at the end of the observation period.
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:
1977-06-16 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
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 15 000 mg/kg bw
Mortality:
No mortatlity
Clinical signs:
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
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 15 000 mg/kg bw
Mortality:
No mortatlity
Clinical signs:
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 after exposure.
Gross pathology:
Red ovaries in 3/5 females; portions of uterus red in 2/5 females.
Other findings:
Slight alopecia in anogenital area in 9/10 animals
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The LD50 following oral gavage of MRD 77-12 is greater than 15g/kg. Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

MRD 77-12 was administered via oral gavage to ten albino Wistar rats (5 males and 5 females) at a dose of 15.0 g/kg to assess the acute oral toxicity.  Animals were observed for mortality and toxic effects immediately and 1, 2, 3, 4, and 6 hours after dosing and daily for 14 days.  Necropsies were performed on all rats.  No deaths or clinical signs of toxicity were observed.  Slight alopecia in the anogential area was observed in 9/10 animals and darkened ovaries in 3/5 female animals were observed at necropsy.  The oral LD50 for MRD 77-12 was greater than 15.0 g/kg. Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

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

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
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
Sex:
male/female
Dose descriptor:
LC50
Effect level:
>= 6 100 mg/m³ air (analytical)
Exp. duration:
4 h
Mortality:
None
Clinical signs:
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:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to or similar to guideline study OECD 403.
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:
8 hour exposure
GLP compliance:
not specified
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
Male Sprague-Dawley rats were obtained from Mollegaard A/S. The animals were acclimatized for 4 to 6 days prior to exposure at a temperature of 22 +/-1 oC, a humidity of 40-70% and a dark-light cycle of 12 hours. The same conditions were used during exposure. Food and water was given ad libitum, except during exposure. At exposure, the weights of animals were within the range of 200g +/- 20%.
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Exposure system. During exposure the animals were kept in conically shaped 0.7 m3 steel chambers with glass front door and walls. Dynamic exposure was performed by passing high oil- and dust- filtered air under pressure through 4 reservoirs of each containing 0.5 1 of the test alkane. At an air flow rate of 30-441 L/min, an outlet concentration equal to 95% of vapour saturation was achieved. The vapour generating system was located in a water bath with a temperature control unit allowing a range of temperature from 0 to 50. Saturation concentrations of alkanes at 2W were achieved by keeping a constant temperature in the bath of 21.6, slightly lower than the temperature in the inhalation chamber. At one occasion (n-nonane, 5280 ppm.) vapour was generated at 22.5°. Air from the vapour generating system was introduced at the top of the exposure chamber and drained from the chamber through a perforated bottom outlet.
Air was withdrawn from the inhalation chambers by a ventilation fan creating a negative pressure of 2-5 mm H20 on the inside of the chamber. During exposure the flow of air through the chambers (exposure and control) was 30-40 L/mm., corresponding approximately to 3 air changes per hour. With a maximum number of 18 animal in each chamber, the volume of animals represented about 0.5% of the total chamber volume. This is a small volume compared to the maximum limit of 5% recommended by WHO. With a volume ratio of 0.5%, 3 air changes per hour was sufficient in order to prevent significant concentrations of ammonia in the inhaled air. The presence of alkane aerosol in the inhalation chamber during exposure was investigated by a Royco mod. 225 particle monitor with an aerosol particle counter sensor mod. For n-tridecane (nC13) the number of aerosol particles in the air with a diameter greater than 0.3 pm was less than 460 per liter. Assuming a mean particle size of 0.7 um, the aerosol n-tridecane concentration in the air would be 1.24 x 10^-7 mg/L. The measured concentration of n-tridecane vapour at saturation was 0.38 mg/L (50 p.p.m.), giving a vapour/aerosol ratio of 3.04 x 10^6.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Concentration of alkanes in the inhalation chambers was monitored automatically every 15 min by on-line gas chromatography.
Duration of exposure:
8 h
Concentrations:
n-C9 (n-nonane): 5280, 4438, 3560, 2414 ppm
n-C10 (n-decane): 1369 ppm (saturation)
n-C11 (n-undecane): 442 ppm (saturation)
n-C12 (n-dodecane): 142 (saturation)
n-C13 (n-tridecane): 41 ppm (saturation)
No. of animals per sex per dose:
8 animals for each substance at each dose
Control animals:
yes
Details on study design:
The inhalation period was 8 hours at daytime during the light period for all alkanes followed by an observation period of 14 days. For each alkane a high level exposure was performed at its maximum concentration in the air at 20 deg C, i.e. saturated vapour. When this exposure proved lethal, additional exposures were performed in order to determine an exact LC50 value. During inhalation all animals were observed at 15 and 30 mm. intervals. For the first 8 hours after exposure all animals were observed at hourly, then at 2 hours’ intervals during daytime for 14 consecutive days. Groups of 8 animals were exposed for determination of alkane concentrations in blood and brain. Control groups of 4 animals were exposed simultaneously but only to air under otherwise identical conditions. Measurements were performed in 5 surviving animals from the exposed group and in 4 control animals. Groups of 10 animals were included in the pathological study. All were subjected to a complete necropsy which included examination of the external surface of the body, all orifices, and the cranial, thoracic and abdominal cavities and their contents according to the OECD procedures (OECD 1987). Animals dying during exposure to the saturated air concentration of alkanes at 20 deg C were immediately examined by autopsy, while animals surviving this concentration were killed and examined after the observation period of 14 days. A maximum of 5 exposed animals were investigated for each alkane except for the n-nonane exposure where all 10 animals were examined. The control group for each alkane exposure consisted of 3 rats, giving a total number of 15 control animals.

Determination of alkane concentration in biological material. Concentrations of alkanes were determined in blood and brain via head space gas chromatography immediately after the end of the 8 hour exposure period. Animals were removed from the chamber one by one for immediate decapitation and sample preparation. The preparation of samples was performed after a standardized time schedule with less than two mi between decapitation and isolation of blood and the brain samples from each animal. Immediately after decapitation 2 ml of blood was collected from each animal in heparinized (1,000 IU) glass tubes and rapidly transferred to 15 mln head space vials which were closed by a screw cap with a teflon-faced neoprene septum. After equilibrating the control, “exposed” and standard (0.5—1000 mg/L) samples at 60 for 1 hour during continuous agitation, a 0.1 ml head space sample was taken with a pre-warmed gas-tight syringe and injected onto the gas chromatograph. The gas chromatographic conditions were identical to the conditions described previously for the measurement of alkane concentrations in the inhaled air. After decapitation and blood collection the brain was excised, weighed, and homogenized in 4 volumes of 0.25 M sucrose at 4 in a Potter-Elvehjem homogenizer. Two ml of homogenate was transferred to head space vials and further treated as described above, loss of alkanes during the sampling procedures represented no significant analytical source of error as demonstrated in recovery studies with n-nonane, the most volatile of the test substances.

Determination of LC50. The LC50 value was determined by 8 hour exposure and an observation period of 14 days. Groups of 10 animals were exposed to 4 different concentrations of alkanes, the highest concentration produced close to a 100% mortality. The lowest concentration and two intermediate concentrations reported no cases of death.

Behavioural effects. In addition to general activity, acute effects as coordination difficulties, tremor, spasms and lethality were monitored.

Fixation procedures. For histological examinations the entire brain, both lungs, the liver, the heart and the kidneys were initially fixed for 12 hours in 10% formol ethanol containing 5% glacial acetic acid. Pieces of each organ were then transferred to 70% ethanol and processed for paraffin embedding. Sections were cut with the microtome knife. Sections from each organ were stained in batches with haematoxylin-eosin-saffron.

Light microscopic evaluation. After staining, the slides were given random numbers. Each slide was studied by a group of 4 pathologists working in pairs. One transverse section of the cerebrum, one sagittal section of the cerebellar vermis, one section of each lung and one section of the heart, the liver and the right kidney were evaluated for each animal.

Morphometry. Morphometry was carried out in order to quantify the loss of cerebellar Purkinje cells in the animals exposed to nonane.
Statistics:
For a detailed description of the morphometrical procedure, see Weibel (1979).
Weibel, E. K.: Stereological methods. Vol. I. Academic Press. London 1979.

Sex:
male
Dose descriptor:
other: NOAEC
Effect level:
2 414 ppm
Exp. duration:
8 h
Remarks on result:
other: for all materials tested (n-C9 to n-C13 alkanes)
Sex:
male
Dose descriptor:
LC50
Effect level:
4 467 ppm
Exp. duration:
8 h
Remarks on result:
other: n-nonane
Sex:
male
Dose descriptor:
LC50
Effect level:
> 1 369 ppm
Exp. duration:
8 h
Remarks on result:
other: n-decane; maximum attainable concnetration
Sex:
male
Dose descriptor:
LC50
Effect level:
> 442 ppm
Exp. duration:
8 h
Remarks on result:
other: n-undecane; maximum attainable concnetration
Sex:
male
Dose descriptor:
LC50
Effect level:
> 142 ppm
Exp. duration:
8 h
Remarks on result:
other: n-dodecane; maximum attainable concnetration
Sex:
male
Dose descriptor:
LC50
Effect level:
> 41 ppm
Exp. duration:
8 h
Remarks on result:
other: n-tridecane; maximum attainable concnetration
Mortality:
No deaths were noted for the maximum vapor concentration for the n-C10 to n-C13 alkanes tested. For n-nonane (n-C9) the following deaths were observed: 5280 ppm - 9/10; 4438 ppm - 4/10; 3560 ppm - 1/10; 2414 ppm - 0/10.
Clinical signs:
other:
Body weight:
There was a significant body weight increase in the 4438 ppm exposed animals. No other body weight changes were noted.
Gross pathology:
No significant differences in the weight of the heart, kidneys, liver, or brain were demonstrated between the groups. No morphological alterations were observed in heart or kidneys.
Other findings:
Microscopically, dilatation of the sinusoids was found in all four animals dying during exposure to n-nonane and three of these animals also showed definite though slight fatty changes of the liver cells. In animals surviving exposure to n-nonane and in animals exposed to other alkanes, and among the controls, no such changes were observed.

Lungs. The total weight of the lungs in two of the animals dying during exposure to n nonane was approximately twice the weight of the controls 2.86 g and 2.88 g, respectively. Among the other animals exposed to various other alkanes, no weight alterations were observed. Microscopically, three animals showed marked pulmonary edema. These animals died during exposure to n-nonane and in two of them the pulmonary weight was also increased. All animals exposed to 4438 ppm n-nonane showed a blue discoloration of the skin during exposure, giving the impression of peripheral cyanosis, and thus cardiopulmonary insufficiency.

Brain. No macroscopic abnormalities were recorded in any of the animals. No pathological changes were found in the large brain in any of the animals exposed to the series n-Cl0 to n-Cl3 or of their respective controls. In animals exposed to n-nonane (4438 ppm) and which died during exposure, pathological changes were absent. Among the six animals surviving for 14 days after exposure, one animal showed a few severely damaged neurons of the hippocampus. In the cerebellar cortex no alteration could be demonstrated among animals exposed to n-Cl0 to n-C13 or their controls or in animals dying acutely during exposure to n-nonane or their controls. However, in n-nonane (4438 ppm treated group) exposed animals surviving for 14 days after exposure, extensive changes were observed including rarification of Purkinje cells and in some instances also a high number of severely damaged neurons were observed. These changes apparently were not entirely random but seemed to some extent to be segmental. In areas showing massive loss of Purkinje cells there was no obvious glial reaction.

Morphometry of the cerebellum. The results demonstrate clearly a loss of Purkinje cells in the animals which survived exposure to 4438 ppm n-nonane. This is reflected by a reduced density of Purkinje cell profiles along the line which defines the Purkinje cell layer (N0). The reduced density of the visible transections is only in part explained by a reduction of the cell size, as there are also a significantly reduced number of Purkinje cells per unit area of Purkinje cell layer (Ns). The results also indicate a reduction of tissue volume in the other layers of the cerebellum as there was a decrease in cerebellar volume relative to the extent of the Purkinje cell layer. There was no clear-cut change of the volume distribution between the different layers. There was no detectable difference between the animals which died during exposure and the controls.


Table 1 Concentration of alkanes in rat blood and brain at the end of an 8 hour exposure period
  Exposure Conc. (ppm) Blood concentration (mg/L) Brain concentration (mg/kg) Blood/air ratio Blood/air ratio
n-C9 (n-nonane) 5280 238* 1136* 8.6 41.3
  4438 109 919 4.7 39.5
  3560 135 590 7.2 31.7
  2414 57 314 4.5 24.3
n-C10 (n-decane) 1369 (saturation) 542 239.7 6.8 29.9
n-C11 (n-undecane) 442 (saturation) 11.7 45.4 4.1 16
n-C12 (n-dodecane) 142 (saturation) 3.3 4.2 3.3 4.3
n-C13 (n-tridecane) 41 (saturation) 0.84 < 0.5 1.6 <1.6
           
*Concentration measured in one animal that died 0.5 hour before the end of the exposure period.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The LC50 after an 8 hour exposure for acute inhalation exposure to n-C10 to n-C13 alkane vapors is greater than the highest obtainable vapor concentration. The LC50 after an 8 hour exposure for n-C9 alkane vapors was determined to be 4467ppm. For n-C9 to n-C13 alkanes, 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:

Individual alkanes (n-C9 to n-C13) were administered via individual inhalation chambers to eight Sprague-Dawley rats at their respective maximum attainable vapor concentration (n-C9: 5280, 4438, 3560, 2414 ppm; n-C10: 1369 ppm; n-C11: 442 ppm, n-C12; 142 ppm; n-C13: 41 ppm) for eight hours to assess acute inhalation toxicity. There was no mortality and no gross pathological alterations noted in any of the animals treated with n-C10 to n-C13.  The LC50 after an 8 hour exposure for n-C9 alkane vapors was determined to be 4467 ppm.  The LC50 after an 8 hour exposure for acute inhalation exposure to n-C10 to n-C13 alkane vapors is greater than the highest obtainable vapor concentration. The LC50 after an 8 hour exposure for n-C9 alkane vapors was determined to be 4467 ppm. For n-C9 to n-C13 alkanes, 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
Quality of whole database:
Two key read across studies 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.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 3 160 mg/kg bw
Mortality:
none
Clinical signs:
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 in four animals. Desquamation was noted in five animals during the study. By Day 14, all animals were clear of erythema and edema
Body weight:
3/6 test animals gained weight during the 14 day test period.
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:
1 key read across study available from a structural analogue.

Additional information

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

Oral

  

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

In a key study (ExxonMobil Corp., 1977), the test material (Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, <2% aromatics) was administered via oral gavage to ten albino Wistar rats (5 males and 5 females) at a dose of 15.0 g/kg to assess the acute oral toxicity.  Animals were observed for mortality and toxic effects immediately and 1, 2, 3, 4, and 6 hours after dosing and daily for 14 days.  Necropsies were performed on all rats.  No deaths were observed.  Hair loss in 9/10 animals and darkened kidneys in 5/10 animals were observed at necropsy.  The oral LD50 for Hydrocarbons, C10-C13, n-alkanes, isoalkanes, cyclics, <2% aromatics was greater than 15.0 g/kg. Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations. 

 

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

In a key study (Exxon, 1989), the acute toxicity of the test material (Hydrocarbons, C11-C14, isoalkanes, <2% aromatics) was evaluated in rats via oral gavage at a dose of 5 g/kg bw. Observations were made as to the nature, onset, severity, and duration of toxicological signs once per day for a total of 14 days. All animals survived the entire observational period and displayed a low incidence of clinical symptoms.  The animals displayed little or no abnormalities. The LD50 for Hydrocarbons, C11-C14, isoalkanes, <2% aromatics) 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.

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

In a key study (Exxon, 1977), the test material (Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, <2% aromatics) was administered via oral gavage to ten albino Wistar rats (5 males and 5 females) at a dose of 15.0 g/kg to assess the acute oral toxicity.  Animals were observed for mortality and toxic effects immediately and 1, 2, 3, 4, and 6 hours after dosing and daily for 14 days.  Necropsies were performed on all rats.  No deaths or clinical signs of toxicity were observed.  Slight alopecia in the anogential area was observed in 9/10 animals and darkened ovaries in 3/5 female animals were observed at necropsy.  The oral LD50 for Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, <2% aromatics was greater than 15.0 g/kg. Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

 

Inhalation

 

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

In a key study (ExxonMobil Corp., 1995) the test material (Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics) was administered via individual inhalation chambers for four hours to ten Sprague-Dawley rats (5 males, 5 females) to an average actual vapor concentration of 6100 mg/m3for four hours to assess acute inhalation toxicity. Animals were observed for fourteen days following exposure.  There were no mortality or gross pathological alterations noted in any of the animals.  Based on the conditions of this study, The LC50for acute inhalation exposure was determined to be greater than 6100 mg/m3.

 

n-alkanes, C9-C13

In a key study (Nilsen OG, Haugen OA, Zahlsen K, Halgunset J, Helseth A, Aarset H, Eide I, 1988), individual alkanes (n-nonane (n-C9), n-decane (n-C10), n-undecane (n-C11), n-dodecane (n-C12), and n-tridecane (n-C13)) were administered via individual inhalation chambers to eight Sprague-Dawley rats at their respective maximum attainable vapor concentration (n-C9: 5280, 4438, 3560, 2414 ppm; n-C10: 1369 ppm; n-C11: 442 ppm, n-C12; 142 ppm; n-C13: 41 ppm) for eight hours to assess acute inhalation toxicity. There was no mortality and no gross pathological alterations noted in any of the animals treated with n-C10 to n-C13.  The LC50after an 8-hour exposure for n-C9 alkane vapors was determined to be 4467 ppm.  The LC50after an 8-hour exposure for acute inhalation exposure to n-C10 to n-C13 alkane vapors is greater than the highest obtainable vapor concentration. The LC50after an 8-hour exposure for n-C9 alkane vapors was determined to be 4467 ppm.

 

Dermal

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

In a key study (ExxonMobil Corp., 1984), the acute dermal toxicity of Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics 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 LD50was determined to be greater than 3160 mg/kg.

Justification for classification or non-classification

Based on available read across data, Tridecane is minimally toxic via ingestion where the LD50 is >5000 mg/kg, by inhalation where the LC50 is >6100 mg/m3, and via dermal exposure where the LD50 is >3160 mg/kg.  These findings do not warrant classification under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

Tridecane 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).