Registration Dossier

Administrative data

Description of key information

Oral LD50 (rat) > 5000 mg/Kg bw

 

Inhalation LC50 (rat) >5991 mg/m³

 

Dermal LD50 (rabbit) > 2000 mg/Kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: OECD guideline N°401, not GLP. Substance identification: commercial name without any details on the substance but MSDS 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 401 (Acute Oral 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:
other: HC/CFY
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hacking and Churchill Limited, Huntington Cambridgeshire, England
- Age at study initiation: 4 to 6 weeks
- Weight at study initiation: 112 to 133g
- Fasting period before study: overnight prior to and approximately 4 hours after dosing
- Housing: by sex, randomly allocated to cages with wire mesh floors
- Diet (e.g. ad libitum): yes: standard laboratory rodent diet
- Water (e.g. ad libitum): yes
- Acclimation period: 8 days prior start of study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 23 °C
- Humidity (%): 56%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h artificial lightening


IN-LIFE DATES: From 18th of May from 1st of June 1984
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
No data
Doses:
5000 mg/kg b.w.
No. of animals per sex per dose:
10 rats (5 males + 5 females)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations at least twice a day; weighing: on days 1, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: Macroscopic post mortem examination was performed. Abdominal and thoracic cavities were opened. Macroscopic appearence of abnormal organs when present was recorded.
Statistics:
no data
Preliminary study:
No preliminary study
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
No mortality was observed at tested dose, see table 7.2.1/2.
Clinical signs:
Pilo-erection was observed at the tested dose for all exposed animals which was reversible at the third day of observation.
Body weight:
Body weight gain was recorded as normal.
Gross pathology:
No effect was observed at necropsy.
Other findings:
Terminal autopsy findings were normal

Table 7.2.1/2: Number of animals dead

Dose (g/kg)

Mortality ratio (No of death/No dosed)

Male

Female

Combined

5.0

0/5

0/5

0/10

Sex

Bodyweight (g) per day

1

8

15

Male

133

132

133

125

130

212

210

211

186

207

278

274

274

258

280

Female

121

114

112

123

126

164

174

166

170

184

198

204

204

198

216

Signs

No of rats in group of 5 showing signs

Male

Female

Pilo-erection

5

5

Interpretation of results:
other: Practically non toxic
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:

PETRAPAR 147 (P-147) was tested for acute oral toxicity in HC/CFY rats in a limit dose assay. The assay was conducted on a group of 10 rats (5 males, 5 females) with a dose of 5000 mg/kg b.w. administered by gavage, as supplied, in a single oral dose (maximum dose volume of 6.4 mL/kg b.w). 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 occurred. Pilo-erection
was observed in all animals shortly after dosing but not at 72-hour observation period. Body weight gain was not affected by treatment. At necropsy, macroscopic examination of main organs showed no abnormalities.


As the acute oral LD50 was found greater than 5000 mg/kg b.w. under the conditions of the test, PETREPAR 147
is not classified according to CLP Regulation 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
1 Key study and 1 supporting read across study from structural analogues available for assessment.

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:
1995-09-20 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:
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:
5 991 mg/m³
Quality of whole database:
1 Key read across study from a structural analogue available for assessment.

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:
1 Key read across study from a structural analogue available for assessment.

Additional information

There is no acute oral, inhalation, or dermal toxicity data available for Hydrocarbons, C17 -C19, n-alkanes, <2% aromatics. However, data is available for structural analogues, Hydrocarbons, C14-C17, n-alkanes, <2% aromatics; Hydrocarbons, C12-C16, isoalkanes, cyclics, <2% aromatics; and Isohexadecane. This data is read across to Hydrocarbons, C17 -C19, n-alkanes, <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, C14 -C17, n-alkanes, <2% aromatics

 

PETRAPAR 147 (P-147) was tested for acute oral toxicity in HC/CFY rats in a limit dose assay (Cepsa, 1984). The assay was conducted on a group of 10 rats (5 males, 5 females) with a dose of 5000 mg/kg b.w. administered by gavage, as supplied, in a single oral dose (maximum dose volume of 6.4 mL/kg b.w).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 occurred. Pilo-erectionwas observed in all animals shortly after dosing but not at 72-hour observation period. Body weight gain was not affected by treatment. At necropsy, macroscopic examination of main organs showed no abnormalities. As the acute oral LD50 was found greater than 5000 mg/kg b.w. under the conditions of the test, PETREPAR 147 is not classified according to CLP Regulation 1272/2008.

 

Isohexadecane

 

The toxicity of BP Solvent IH/Isohexadecan in Sprague-Dawley rats was tested by gavage of the undiluted liquid test substance as supplied (INEOS, 1980). 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.

 

Inhalation

 

Hydrocarbons, C12 -C16, isoalkanes, cyclics, <2% aromatics

 

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 (ExxonMobil, 1997).

 

Dermal

 

Hydrocarbons, C14 -C17, n-alkanes, <2% aromatics

 

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 (Petroquimica, 1984). 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 CLP Regulation 1272/2008.

Justification for classification or non-classification

Based on available read across data, Hydrocarbons, C17-C19, n-alkanes, <2% aromatics is minimally toxic via ingestion where the LD50 is > 5000 mg/Kg bw mg/Kg, via dermal exposure where the LD50 is >2000 mg/Kg bw, and by inhalation where the LC50> 5991 mg/m3.  These findings do not warrant classification under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Hydrocarbons, C17-C19, n-alkanes, <2% aromatics is classified under EU CLP guidelines as a Category 1 aspiration hazard based on its physical and chemical properties (hydrocarbon fluid, viscosity ≤ 20.5 mm2/s).