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Administrative data

Description of key information

For acute oral, dermal and inhalation toxicity studies, no mortality was observed at the highest doses tested, i. e. doses equal to or greater than 46.4 mL/Kg bw, 2000 mg/Kg bw and 5000 mg/m3, respectively.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted according to acceptable scientific conditions, not GLP and no guideline followed. Number of tested animals, dose range, observation time and observed parameters are ok, even if no LD50 was determined.
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:
no
Principles of method if other than guideline:
Guideline principles
GLP compliance:
not specified
Remarks:
study conducted before GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchstierzucht Hagemann GmbH and Co., D-4923 Exertal 1
- Age at study initiation: M: 52 days, F: 70 Days
- Weight at study initiation: Zwischen 165 and 185
- Fasting period before study: 16 hours
- Housing: MAKROLON-Cage (Type III)
- Diet (e.g. ad libitum): fasting during test period
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1.0 °C
- Humidity (%): 60 ± 5 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: August 1980
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
No vehicle

MAXIMUM DOSE VOLUME APPLIED: 46.4 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: not provided
Doses:
Doses: 2.15, 4.64, 10.0, 21.15, 31.6 and 46.4 mL/kg b.w:
No. of animals per sex per dose:
Doses: 2.15; 4.64; 10.0 mL/ kg b.w. administered in 5 M + 5 F
Doses: 21.15; 31.6; 46.4 mL/ kg b.w. administered in 10 M + 10 F
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 4 weeks
- Frequency of observations and weighing: every 24 h
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology

- Duration of observation period following administration: 14 days (or other?)
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: feed consumption, behavior, body weight increase
Statistics:
The LD50 was calculated using Litchfield and Wilcoxon method. Mortality rate based on 24h and 14 d was calculated.
Preliminary study:
No data
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 46.4 mL/kg bw
Mortality:
No mortality occurred up to test dose 46.4 mL/kg b.w.
Clinical signs:
Oily secretions in the area of anus from 4.64 mL/kg b.w. up to the highest dose.
Reduced food intake by female at 31.6 mL/kg bw.
No other proof of substance reaction.
Body weight:
10% decrease of female body weight intake at dose 46.4 mL/kg b.w. on first observation day.
Gross pathology:
no specific reaction
Other findings:
Oily secretion in the area of anus for tested dose from 4.64 mL/kg bw to 46.4 mL/kg bw
Decrease in daily food intake :
- at dose 31.6 mL/kg bw, female food intake decreased of 28 % on first observation day and 11 % on 2nd observation day.
- at dose 46.4 mL/kg bw, female food intake decreased of 32 % on first observation day and 49 % on 2nd observation day.

No additional data.

Interpretation of results:
other: no mortality up to 46.4 mL/kg b.w.
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
No mortality was observed in rats up to 46.4 mL/kg b.w., the highest dose tested.
Executive summary:

The toxicity of BP Solvent IH/Isohexadecan 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 LD50 was determined.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Quality of whole database:
Only key study available

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:
1995/07/28-1995/09/08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to or similar to guideline study OECD 403: GLP
Justification for type of information:
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
Limit test:
yes
Species:
rat
Strain:
other: Crl: CDBR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Kingston Facility, Stone Ridge, New York
- Age at study initiation: Group 1, approximately 6-7 weeks; Group 2, approximately 8-9 weeks
- Weight at study initiation: Group 1 males, 182 to 208 grams; Group 1 females, 171 to 184 grams; Group 2 males, 315 to 339 grams; Group 2 females, 220 to 232 grams
- Fasting period before study: none
- Housing: Single housed during study period, suspended stainless steel and wire mesh
- Diet (e.g. ad libitum): Certified Rodent Diet #5002 from PMI Feeds, Inc. Richmond, Indiana, ad libitum during non-exposure periods. Food was withheld while animals were in chamber.
- Water (e.g. ad libitum): Automatic watering system, ad libitum during non-exposure periods. Water withheld while animals were in chamber.
- Acclimation period: At least 12 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68-76 degrees F in animal room; 70-74 degrees F in exposure chamber
- Humidity (%): 40-70% relative humidity in animal room; 58-73% relative humidity in exposure chamber
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark


IN-LIFE DATES: From: 1995-08-08 To: 1995-09-08
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 150 liter stainless steel and acrylic whole-body inhalation exposure chamber
- System of generating particulates/aerosols: The test material was generated using a single-barrel Laskin nebulizer and a 3-neck round-bottom flask as a reservoir for the liquid test material. Compressed air was supplied to the nebulizer at approximately 3.5-4.0 psi back-pressure, producing a liquid droplet aerosol atmosphere within the 3-neck flask. The aerosol mixed with additional room air which was drawn through a glass mixing vessel prior to entering the exposure chamber.
- Method of particle size determination: The particle size distribution was determined once during each exposure using a Sierra Instruments Model 210 Cascade Impactor. Pre-weighed glass fiber filters were used to collect the aerosol on each stage. A bulk estimation technique was employed to characterize the particle size distribution of the atmosphere. The change in weight of the filter for each stage was measured and the cumulative percent of the sample collected on each stage was calculated. This information plus the stage constants for the impactor were used to calculate the 15.9%, 50.0%, and 84.1% particle sizes (equivalent aerodynamic diameter), the geometric standard deviation, and the estimated percent of the aerosol less than or equal to 1, 10, and 15 microns in size.
- Temperature, humidity, pressure in air chamber: Chamber airflow, temperature, and relative humidity were monitored continuously throughout the exposure and recorded approximately every 30 minutes.


TEST ATMOSPHERE
- Brief description of analytical method used: Analytical chamber concentrations were determined during each hour of the exposure by drawing a known volume of the test atmosphere through a sample train consisting of pre-weighed teflon (PTFE) (Group 1) or glass fiber (Group 2) filters for non-volatile aerosol and a charcoal sorbent tube for volatile hydrocarbons.

From Group 1, the filters were first weighed for gravimetric determination of total non-volatile aerosol; the analytical procedure then specified analyis of both filters and sorbent tubes by GC/FID for total and individual hydrocarbons. However, the filters were not weighed until 8 days after the exposure and it appeared that a significant portion of the collected test material had volatilized from the fibers. Exposure was repeated with a second group of animals.

From Group 2, non-volatile aerosol was collected on a glass-fiber filter and the gravimetric determination was performed immediately following sample collection. The filters and sorbent tube were analyzed by GC/FID, and total hydrocarbons and individual hydrocarbons (full scan) were reported as the sum of the gravimetric aerosol and total hydrocarbon vapor results.

PARTICLE SIZE DATA
-Mass median equivalent aerodynamic diameter (50% size): Group 1 and Group 2, 3.7 microns
-Geometric standard deviation: Group 1, 2.9; Group 2, 2.5
-Percent <= 15 microns: Group 1, 91%; Group 2, 93.5%
-Percent <= 10 microns: Group 1, 83%; Group 2, 85.9%
-Percent <= 1 micron: Group 1, 10.6%, Group 2, 8.3%
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetrically (aerosol); GC/FID (vapor)
Duration of exposure:
4 h
Concentrations:
Group 1: estimated aerosol concentration of 5247 mg/m3
Group 2: analytical chamber concentration of 5266 mg/m3 (5213 mg/m3 aerosol, 53 mg/m3 vapor)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: At 15 minute intervals during the first hour of exposure and once each hour thereafter through the termination of exposure.
- Necropsy of survivors performed: yes
Statistics:
Statistical analyses included means and standard deviations of body weight and body weight change by group and sex.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 266 mg/m³ air (analytical)
Exp. duration:
4 h
Remarks on result:
other: No mortality occurred.
Mortality:
No mortality in either Group 1 or Group 2.
Clinical signs:
other: other:
Body weight:
All animals displayed increased in body weight over their initial (Day 0) values, with the exception of two females in Group 2 that had slight weight losses.
Gross pathology:
All Group 1 animals were free of abnormalities at the gross postmortem evaluation.

In Group 2, 4 males/1 female exhibited red foci and/or slight discoloration on the lungs, 1 male displayed dark red nasal turbinates, 1 male had smaller than normal right kidney, and 3 males/1 female exhibited alopecia and/or scabs on the dorsal surface, extremities and/or head.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The LC50 for acute inhalation exposure (aerosol atmosphere) of MRD-95-247 is greater than 5266 mg/m3 (5213 mg/m3 aerosol, 53 mg/m3 vapor). This finding does not warrant classification of MRD-95-247 as an acute inhalation toxicant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

To assess acute inhalation toxicity, MRD-95 -247 was administered via individual whole-body inhalation chambers for four hours to two groups of ten Crl:CDBR rats at either an estimated aerosol concentration of 5247 mg/m3 or an analytical concentration of 5266 mg/m3 (5213 mg/m3 aersol, 53 mg/m3 vapor). Animals were observed for fourteen days following exposure. No mortality was observed, and all animals that received the estimated aerosol concentration of 5247 mg/m3 were free of gross pathological abnormalities. In the second group (5266 mg/m3 aerosol), 4 males and 1 female exhibited red foci on the lungs, one male displayed dark red nasal turbinates, and 3 males and 1 female had alopecia and/or scabs on the dorsal surface, extremities, and/or head. Based on the conditions of this study, the LC50 for acute inhalation exposure to an aerosol atmosphere of MRD-95 -247 is greater than 5266 mg/m3.

This finding does not warrant classification of MRD-95-247 as an acute inhalation toxicant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995-09-20 to 1995-10-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to or similar to guideline study OECD 403: GLP
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
Limit test:
yes
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Inc., Kingston, New York USA
- Age at study initiation: Males, approximately 6 weeks; Females, approximately 7 weeks
- Weight at study initiation: Males, 155 to 168 grams; Females, 157 to 177 grams
- Fasting period before study: none
- Housing: Single housed during the study period. Suspended stainless steel and wire mesh.
- Diet (e.g. ad libitum): Certified Rodent Diet #5002, from PMI Feeds, Inc., Richmond, Indiana, ad libitum, during non-exposure periods. Food withheld while animals were in chamber.
- Water (e.g. ad libitum): Automatic watering system, ad libitum, during non-exposure periods. Water withheld while animals were in chamber.
- Acclimation period: 8 days.


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


IN-LIFE DATES: From: 1995-09-21 To: 1995-10-05
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 150 liter stainless steel and acrylic whole-body inhalation exposure chamber.
- System of generating particulates/aerosols: The test atmosphere was generated using a Laskin nebulizer and a 3-neck round-bottom flask as a reservoir for the liquid test material. Compressed air was supplied to the nebulizer at approximately 4-5 psi back-pressure, producing a liquid droplet aerosol within the 3-neck flask. The aerosol was mixed with additional room air and then drawn into the exposure chamber.
- Method of particle size determination: Sierra Instruments Model 210 Cascade Impactor. Preweighed glass fiber filters were used to collect the aerosol on each stage. A bulk estimation technique was employed to characterize the particle size distribution of the test atmosphere. The change in weight of the filter for each stage was measured and the cumulative percent of the sample collected on each stage was calculated. This information plus the stage constants for the impactor were used to calculate the 15.9%, 50.0% and 84.1% particle sizes, the geometric standard deviation, and the estimated percent of the aerosol less than or equal to 1, 10, and 15 microns in size.
- Temperature, humidity, pressure in air chamber:

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

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

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

Analytical verification of test atmosphere concentrations:
yes
Remarks:
Gravimetrically (aerosol); GC/FID (vapor)
Duration of exposure:
4 h
Concentrations:
5991 mg/m3 (5428 mg/m3 aerosol, 562 mg/m3 vapor)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Approximately 15 minute intervals during the first hour of exposure and once each hour thereafter through the termination of exposure.
- Necropsy of survivors performed: yes
Statistics:
Means and standard deviations for body weight and body weight change by group and sex
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 991 mg/m³ air (analytical)
Exp. duration:
4 h
Remarks on result:
other: No mortalities.
Mortality:
No mortalities occurred.
Clinical signs:
other: other:
Body weight:
All animals displayed increases in body weight over their initial (Day 0) values.
Gross pathology:
All ten animals were free of internal macroscopic abnormalities at post-mortem examination.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The LC50 for acute inhalation exposure (aerosol atmosphere) to MRD-95-289 is greater than 5991 mg/m3 (5428 mg/m3 aerosol, 562 mg/m3 vapor). This finding does not warrant classification of Isopar M as an acute inhalation toxicant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

To assess acute inhalation toxicity, MRD-95 -289 was administered via individual whole-body inhalation chambers for four hours to ten Crl:CDBR rats at a total chamber concentration of 5991 mg/m3 (5428 mg/m3 aerosol, 562 mg/m3 vapor). Animals were observed for fourteen days following exposure. There were no mortality or gross pathological alterations in the animals, with the exception of two animals that displayed scabs and one with a necrotic and truncated tail. Based on the conditions of the study, the LC50 for acute inhalation exposure to an aerosol atmosphere of MRD-95 -289 is greater than 5991 mg/m3.

This finding does not warrant classification of MRD-95 -289 as an acute inhalation toxicant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 000 mg/m³
Quality of whole database:
Two key analogue read across studies available.

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:
Between 10th and 14th of May, 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted according to OECD guideline N°402 but not in compliance with GLP. Details on the substance provided by the manufacturer.
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 402 (Acute Dermal Toxicity)
Deviations:
no
Principles of method if other than guideline:
Guideline study
GLP compliance:
no
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: HC/CFY (Remote Sprague-Dawley)
- Source: Hacking and Churchill Limited, Huntington, Cambridgeshire, England
- Age at study initiation: approximately 6 to 8 weeks of age
- Weight at study initiation: 212 to 215 g
- Housing: individually in metal cages with wire mesh floors
- Diet: Standard laboratory rodent diet (Laboratory Diet No. 1, Spratt's Rodent Breeding Diet), ad libitum
- Water: ad libitum. Examination at source are conducted quarterly.
- Acclimation period: minimum 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): mean: 55%
- Air changes: approximately 15 per hour
- Photoperiod: artificial light, 12 hrs light, 12 hrs dark.


Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 10% of the total body surface.
Hair was removed one day prior to treatment, no shaving or chemical depilation was used.
- Type of wrap if used: gauze held with an impermeable dressing encircled firmly around the trunk


REMOVAL OF TEST SUBSTANCE
- Washing: in warm (30-40°C) water. Dry with absorbent paper
- Time after start of exposure: at the end of the 24-hour exposure


TEST MATERIAL
- Concentration (if solution): not exceeding 2.6 mL/kg
- Constant volume or concentration used: yes/no
Duration of exposure:
24 hours
Doses:
2000 mg/kg b.w. applied by spreading
No. of animals per sex per dose:
5 animals / sex / dose (see Table 7.2.3/1)
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: soon after dosing, then at frequent intervals for the remainder of Day 1. On subsequent days the animals were observed at least twice.
- Observation of treated areas: daily for signs or dermal irritation
- Necropsy of survivors performed: yes, after cervical dislocation animals were subjected to a macroscopic examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of abnormal organs, if present, was recorded.
- Other examinations performed:
clinical signs: recorded at each observation
body weight: on Day 1, 8 and 15
Statistics:
No data
Preliminary study:
Not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality was observed
Clinical signs:
No treatment related clinical signs were observed
Body weight:
No treatment related change has been observed. See Table 7.2.3/2 for details.
Gross pathology:
Two small areas of necrosis were observed at the treatment site on two male rats on Day 2. Recovery from this was complete on Day 6 and 9 respectively.
Other findings:
- Other observations:
Cutaneous reactions: Slight to well-defined erythema and slight oedema were observed at the treatment sites of all animals. Recovery was generally complete by Day 6 with the exception of one male rat which showed slight oedema until Day 9.
On Day 6 all the rats developed small, slightly raised erythematous areas at the dose site. Signs of recovery from this were indicated on Day 9 when small focal scab formations were observed. These persisted until Day 15 in all rats except two females which had completely recovered by Day 14.
See Table 7.2.3/3 for details.

No sign of systemic toxicity.
Terminal autopsy findings were normal.

Table 7.2.3/2: Individual bodyweights of rats dosed dermally with P-147:

Sex

Bodyweight (g) at Day

1

8

15

Females

250

308

378

248

291

354

250

300

375

250

297

364

250

312

383

Males

216

239

269

222

234

266

214

227

253

215

232

259

212

231

253

Table 7.2.3/3: Irritant/corrosive response data for each animal at each observation time

Score at time point

Erythema

Oedema

Max. score: 4

Max. score: 4

M

F

M

F

Day 2

2/2/1/2/2

1/2/1/1/1

0/0/0/0/0

0/0/0/0/0

Day 3/4/5

2/2/2/2/2

2/2/2/2/2

1/1/1/1/1

1/1/1/1/1

Day 6/7/8

0/0/0/0/0

0/0/0/0/0

1/0/0/0/0

0/0/0/0/0

Day 9 -14

0/0/0/0/0

0/0/0/0/0

0/0/0/0/0

0/0/0/0/0

Interpretation of results:
other: Practically nontoxic
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, Petrepar-147 is not classified according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation 1272/2008.
Executive summary:

Petrepar P-147 was tested for acute dermal toxicity in HC/CFY (remote Sprague-Dawley) rats in a limit dose assay according to OECD guideline N°402. The test substance, a liquid, was administered undiluted as supplied. A 10% total body surface of hair was removed from the dorso-lumbar region with clippers in every animal. The assay was conducted on a group of 10 rats (5 males, 5 females) with a dose of 2000 mg/kg b.w. administered by spreading in a single dermal dose (maximum dose volume of 2.6 mL/kg b.w). After test substance application an occlusive patch was held in place for 24 hours. Skin was washed with water at the end of the 24-hour exposure period.
Examinations for mortality, clinical signs and body weight gain were performed during the 14-day observation period. All surviving animals were necropsied at the end of the observation period.
No deaths and clinical signs occurred during the observation period.

Body weight gain was not affected by treatment. At necropsy, macroscopic examination of main organs showed no abnormalities.

Slight to well-defined and slight oedema was observed at the site of treatment in all animals. Reversibility was generally observed by day 6 with the exception of one animal showing slight oedema until Day 9. All rats developed small, slightly raised erythematous areas at the dose site on the day 6. Then, small focal scab formations persisted from day 9 to day 15 in all rats except two females which had recovered by day 14. Two small areas of necrosis were observed at the treatment site on two males on day 2 but not on day 6 and day 9, respectively.


As the acute dermal LD50 was greater than 2000 mg/kg b.w. under the test conditions, Petrepar P-147 is not classified according to the criteria of Annex VI to Directive 67/548/EEC and CLP Regulation 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Only key study available.

Additional information

There is no acute oral, inhalation, or dermal toxicity data available for Isoeicosane. However, data is available for structural analogues Hydrocarbons, C10-C12, isoalkanes, <2% aromatics, Hydrocarbons, C12-C16, isoalkanes, cyclics, <2% aromatics, hydrocarbons, C14-C17, n-alkanes, 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

One study was available for acute oral toxicity, dealing with the toxicity of isohexadecane. The study was conducted similarly to OECD guideline 401 without GLP compliance. The study showed no mortality at concentrations up to 46.4 mL/Kg bw.

Dermal

Percutaneous absorption of alkanes is inversely proportional to their carbon chain length. Pentane has higher permeation (0.52 nmoles/min/cm2) compared to that of octane (0.08 x 10E-3) (Tsuruta 1982). The permeability (cm/h) coefficients determined for 3 n-alkanes confirm that permeability is alkanes is low and decreases with increasing chain length: n-C10 = 6.5x10E-6; n-C11 = 4.5x10-7; and n-C12 = 1.6 x10E-6 (Kim et al. 2006). Accordingly, acute dermal data from lower carbon numbers that show no mortality can be read across to higher carbon numbers to fulfil information requirements indicating that no acute dermal toxicity is expected from these substances.

One study was available for acute dermal toxicity, dealing with the toxicity of hydrocarbons, C14-C17, n-alkanes. The study was conducted according to OECD guideline 402 without GLP compliance. This study showed no mortality at concentrations equal to or higher than 2000 mg/kg bw.

Inhalation

Vapors originating from hydrocarbon solvents decrease with increasing chain length. Experimentally the highest concentrations achieved in a 13-week study were with an isoparffinic C10-C12 solvent (Carrillo et al. 2013), achieving vapor concentrations of 10400 mg/m3, with no mortalities. For higher carbon numbers exposures will result in the generation of mists so that coalescence of droplets in the upper respiratory tract will result in aspiration hazard as the primary hazard.

 

Isohexadecane is a low volatile hydrocarbon solvent. For regulatory purposes, the substance was tested for acute inhalation following a standard procedure (OECD 403, nose only). Because of its low vapour pressure, the material had to be tested as an aerosol (Griffiths, 2014), this form of exposure may happen in the workplace, but aerosol concentrations will be several orders of magnitude below the tested concentrations.

 

Following GHS classification and labelling rules, the acute inhalation median lethal concentration (4 hr LC50 of 1.73 mg/L) of the tested solvent , is in the range of >1 - 5 mg/L, which would merit classification as acute inhalation toxicity category 4 – H332. A careful look at the histopathological examinations however, reveal that the deaths are attributed to aspiration rather than systemic or acute toxicity. The findings observed in the lungs (incompletely collapsed, isolated dark red foci on the cranial lobes, dark red or reddish discoloration, foamy fluid release from the bronchi) were all consistent with inflammation (i.e. a chemical pneumonitis) induced by hydrocarbon aspiration. Low viscosity hydrocarbon fluids, such as the tested hydrocarbon solvent, are hazardous by aspiration (chemical pneumonitis). Therefore, the LC50 value obtained by exposure to an aerosol is not acute toxicity in itself but aspiration, which is induced by exposure conditions following study design. This hazard is already recognised for low viscosity hydrocarbons and indicated as “Aspiration Hazard, category 1 – H304”, which may occur by accidental ingestion but not at regular occupational exposures that are orders of magnitude lower than the LC50 value ~1730 mg/m3.

Two key studies were available for acute inhalation, dealing with the toxicity of Hydrocarbons, C10-C12, isoalkanes, <2% aromatics and hydrocarbons, C12-C16, isoalkanes, cyclics, <2% aromatics. Both studies were conducted similarly to OECD guideline 403. They showed no mortality at concentrations equal to or higher than 5000 mg/m3.

Justification for classification or non-classification

Based on available read across data, Isoeicosane is minimally toxic via ingestion where the LD50 is >46.4 mL/Kg bw mg/Kg, via dermal exposure where the LD50 is >2000 mg/Kg bw, and by inhalation where the LC50> 5000 mg/m3.  These findings do not warrant classification under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

Isoeicosane 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).