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EC number: - | CAS number: 1189173-49-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
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- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
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- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
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- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Oral LD50 (rat) > 5000 mg/Kg bw
Inhalation LC50 (rat) >6100 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
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 1989/03/01-1989/03/15
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: According to or similar to guideline study OECD 401: GLP .
- Justification for type of information:
- A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- yes
- Remarks:
- only one dose tested
- GLP compliance:
- yes
- Test type:
- acute toxic class method
- Limit test:
- yes
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River France
- Sex: Males (5); Females (5)
- Weight at study initiation: 102-146 g
- Housing: individual
- Diet (e.g. ad libitum): Biosure LAD 1, ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 13 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 50%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- A single dose of P-D 20/26 (5g/kg) was administered by oral gavage.
- Doses:
- 5 g/kg
- No. of animals per sex per dose:
- Male (5), Female (5)
- Control animals:
- no
- Details on study design:
- The acute oral toxicity of P-D 20/26 was investigated in a group of 5 male and 5 female rats. Each animal received a single oral dose of 5 g/kg administered by oral gavage. The condition of all animals was observed over a 14 day period following dosing.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 5 000 mg/kg bw
- Mortality:
- No mortality was observed in any of the animals treated with 5 g/kg P-D 20/26.
- Clinical signs:
- other: Pilo-erection was observed in all rats within five minutes of dosing and throughout the remainder of Day 1. There were no other clinical signs and recovery, as judged by external appearance and behavior, was complete by Day 2.
- Gross pathology:
- Terminal autopsy findings were normal.
- Interpretation of results:
- other: Not classified
- Remarks:
- Criteria used for interpretation of results: EU
- Conclusions:
- The LD50 for P-D 20/26 following oral gavage was >5 g/kg . Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
- Executive summary:
The acute toxicity of P-D 20/26 was evaluated in rats via oral gavage at a dose of 5 g/kg bw. Observations were made as to the nature, onset, severity, and duration of toxicological signs once per day for a total of 14 days. All animals survived the entire observational period and displayed a low incidence of clinical symptoms. The animals displayed little or no abnormalities. The LD50 for P-D 20/26 following oral gavage was >5 g/kg. Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 1977-06-16 to 1977-06-30
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: According to or similar to guideline study OECD 401: pre-GLP
- Justification for type of information:
- A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- GLP compliance:
- no
- Test type:
- standard acute method
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Housing: individually
- Diet (e.g. ad libitum): ad libitum except for 18 hours prior to dosing
- Water (e.g. ad libitum):ad libitum - Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Doses:
- 15g/kg
- No. of animals per sex per dose:
- 5 males and 5 females/dose
- Control animals:
- no
- Details on study design:
- Rats were observed for mortality and toxic effects immediately and 1, 2, 4, and 6 hours after dosing and daily for 14 days. Necropsies were performed on all rats. Weights were recorded pretest and weekly
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 15 000 mg/kg bw
- Mortality:
- No mortatlity
- Clinical signs:
- other: During the first 24h after hyperactivity to noise, dilated pupils, and slight lethargy were observed. Chromorhinorrhea was observed in 4 males and 1 female on day 1 after exposure and alopecia in anogenital region was observed in all females on Day 14 aft
- Gross pathology:
- Red ovaries in 3/5 females; portions of uterus red in 2/5 females.
- Other findings:
- Slight alopecia in anogenital area in 9/10 animals
- Interpretation of results:
- other: Not classified
- Remarks:
- Criteria used for interpretation of results: EU
- Conclusions:
- The LD50 following oral gavage of MRD 77-12 is greater than 15g/kg. Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
- Executive summary:
MRD 77-12 was administered via oral gavage to ten albino Wistar rats (5 males and 5 females) at a dose of 15.0 g/kg to assess the acute oral toxicity. Animals were observed for mortality and toxic effects immediately and 1, 2, 3, 4, and 6 hours after dosing and daily for 14 days. Necropsies were performed on all rats. No deaths or clinical signs of toxicity were observed. Slight alopecia in the anogential area was observed in 9/10 animals and darkened ovaries in 3/5 female animals were observed at necropsy. The oral LD50 for MRD 77-12 was greater than 15.0 g/kg. Classification as an oral toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 5 000 mg/kg bw
- Quality of whole database:
- Two key read across studies available from structural analogues.
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 1995
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well-documented study report equivalent or similar to OECD guideline 403 : GLP.
- Justification for type of information:
- A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- GLP compliance:
- yes
- Test type:
- standard acute method
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River
- Age at study initiation: 9-11 weeks
- Weight at study initiation: 245-325 g
- Housing:individually
- Diet (e.g. ad libitum): ad libitum during non-exposure, food withheld while in chamber
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-76
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Exposure apparatus: 150 liter stainless steel inhalation chamber
- Exposure chamber volume: 150 liter
- Temperature, humidity, pressure in air chamber: 75° F, 48%, slight negative pressure to the room
TEST ATMOSPHERE
- Brief description of analytical method used: calibrated infrared monitor
- Samples taken from breathing zone: no
CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: - Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- 4 h
- Concentrations:
- actual vapor concentration of6100 mg/m3
- No. of animals per sex per dose:
- 10 animals/dose (5 males; 5 females)
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Day 0, 7, and 14
- Necropsy of survivors performed: yes - Key result
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- >= 6 100 mg/m³ air (analytical)
- Exp. duration:
- 4 h
- Mortality:
- None
- Clinical signs:
- other: None
- 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:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- 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:
- The justification for read across is provided 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: During exposure, observed abnormalities included wet/matted fur, decreased activity, and eyes closed. Upon removal from the chamber, all animals exhibited wet and matted fur. All animals recovered by the first day post-exposure, with the exception of one
- 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.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LC50
- Value:
- 6 100 mg/m³ air
- Quality of whole database:
- One key and one weight of evidence study available from structural analogues.
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 1992/11/10-1992/11/24
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable well-documented study report which meets basic scientific principles: GLP
- Justification for type of information:
- The justification for read across is provided as an attachment in IUCLID Section 13.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Version / remarks:
- ; 1987 Guidelines
- Deviations:
- yes
- Remarks:
- occlusive dressing used
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Hazleton Research Products
-Sex: Male (3); Female (3)
- Age at study initiation: 12-13 weeks
- Weight at study initiation: Male: 2.01 to 2.21 kg; Female: 2.17 to 2.48 kg
- Housing: individually housed
- Diet (e.g. ad libitum): AgwayCertified Diet RCA Rabbit, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8-day acclimatization
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-70
- Humidity (%): 40 to 60
- Photoperiod (hrs dark / hrs light): 12/12 - Type of coverage:
- occlusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- On the day prior to application the trunk of each animal was clipped free of hair. For each treated animal, 5000 mg/kg of MRD-92-405 was applied to the trunk beneath a gauze patch and secured by an occlusive wrap to prevent evaporation. The whole patch assembly was held in place with tape. The patches were left in position for approximately 24 hours. Residual test material was removed and animals were observed 1, 2.5, and 4 hours after dosing and once per day thereafter for a total of 14 days.
- Duration of exposure:
- 24 hours
- Doses:
- 5000 mg/kg: (3) males; (3) female
- No. of animals per sex per dose:
- Animals: (3) males; (3) female
- Control animals:
- no
- Details on study design:
- SCORING SYSTEM: Draize scale
- Dermal response observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight - Statistics:
- Differences between treated and control group mean values for bodyweight gain were analysed by Student's t-test. Where individual variance ratios were significant (P <0.05 or less), Cochrans approximation was applied (Snedecor and Cochran, Statistical Methods, 6th Ed. Iowa State. 1973). Where zero variance was found in one or more groups, intergroup comparison was performed by the Wilcoxon Rank Sum Test.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 5 000 mg/kg bw
- Mortality:
- There were no animal deaths prior to study termination.
- Clinical signs:
- other: Well-defined erythema was noted upon removal of the test patches in all animals exposed to MRD-92-405, with edema noted in two animals. At Day 14, three animals were noted as having very slight erythema and only one animal was noted as having well-defined
- Gross pathology:
- One animal was free of macroscopic abnormalities. Five animals were observed with desquamation.
- Interpretation of results:
- other: Not classified
- Remarks:
- Criteria used for interpretation of results: EU
- Conclusions:
- The LD50 of MRD-92-405 was > 5000 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:
Three male and three female rabbits were exposed to MRD-92-405 for 24h via an occluded patch. Dermal evaluations occurred at 24 hours post patch removal and once daily until the study termination at day 14. Exposure had no affect on viability; all animals survived the exposure. The LD50 of MRD-92-405 was > 5000 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:
- acute toxicity: dermal
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 1989/01/27 - 1989/02/10
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: According to or similar to guideline study OECD 402: GLP .
- Justification for type of information:
- The justification for read across is provided as an attachment in IUCLID Section 13.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal 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 France
-Sex: Male (5); Female (5)
- Weight at study initiation: 209 to 254 g
- Housing: individually housed
- Diet (e.g. ad libitum): Labsure LAD 1, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 15 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 71%
- Photoperiod (hrs dark / hrs light): 12/12 - Type of coverage:
- occlusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- On the day prior to application the trunk of each animal was clipped free of hair. For each treated animal, 2000 mg/kg of P-D 20/26 was applied to the trunk beneath a gauze patch and secured by an occlusive wrap to prevent evaporation. The whole patch assembly was held in place with tape. The patches were left in position for approximately 24 hours. Residual test material was removed and animals were observed soon after dosing and twice per day thereafter for a total of 14 days.
- Duration of exposure:
- 24 hours
- Doses:
- 2000 mg/kg: (5) males; (5) female
- No. of animals per sex per dose:
- Animals: (5) males; (5) female
- Control animals:
- no
- Details on study design:
- SCORING SYSTEM: Draize scale
- Dermal response observations: daily
- Other examinations performed: clinical signs, body weight - Statistics:
- Differences between treated and control group mean values for bodyweight gain were analysed by Student's t-test. Where individual variance ratios were significant (P <0.05 or less), Cochran's approximation was applied (Snedecor and Cochran, Statistical Methods, 6th Ed. Iowa State. 1973). Where zero variance was found in one or more groups, intergroup comparison was performed by the Wilcoxon Rank Sum Test.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Mortality:
- There were no animal deaths prior to study termination.
- Clinical signs:
- other: Well-defined erythema accompanied by slight oedema was observed in all five males and one female after removal of the dressings. A small amount of test substance remained on the skin site in these animals. Slight erythema only was observed in the remainin
- Gross pathology:
- Terminal autopsy findings were normal.
- Interpretation of results:
- other: Not classified
- Remarks:
- Criteria used for interpretation of results: EU
- Conclusions:
- The LD50 of P-D 20/26 was > 2000 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:
Five male and five female rabbits were exposed to P-D 20/26 for 24h via an occluded patch. Dermal evaluations occurred at 24 hours post patch removal and twice daily until the study termination at day 14. Exposure had no affect on viability; all animals survived the exposure. The LD50 of P-D 20/26 was > 2000 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:
- acute toxicity: dermal
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 1984
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well-documented study report equivalent or similar to OECD guideline : GLP
- Justification for type of information:
- A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- GLP compliance:
- yes
- Test type:
- standard acute method
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Hazleton
- Age at study initiation: 19 weeks
- Weight at study initiation: 3.14-3.51
- Housing: individual
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 50 days
ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-71
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12
- Details on dermal exposure:
- TEST SITE
- Area of exposure: shoulder region to lumbar region
- Type of wrap if used: gauze and plastic sleeve
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing, wiped with gauze
- Time after start of exposure: 24h - Duration of exposure:
- The test material was applied to the skin at the appropriate dose, covered with a gauze patch, secured with tape, and covered with a plastic sleeve. After ca. 24h of exposure, the plastic sleeve, tape and gauze patch were removed. The skin was then wiped (but not washed) with gauze and water to remove any remaining test material.
- Doses:
- The test material was applied to the skin at the appropriate dose, covered with a gauze patch, secured with tape, and covered with a plastic sleeve. After ca. 24h of exposure, the plastic sleeve, tape and gauze patch were removed. The skin was then wiped (but not washed) with gauze and water to remove any remaining test material.
- No. of animals per sex per dose:
- 6 animals/dose (3 males; 3 females)
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:2, 4, 24 hours after dosing and daily for 14 days
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight - Statistics:
- The means and standard deviations of the body weights were calculated.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- >= 3 160 mg/kg bw
- Mortality:
- none
- Clinical signs:
- other: There was an overall low incidence of clinical in-life observations noted during the study. Observations included nasal discharge, dry rales, alopecia. Topical exposure elicited very slight to well defined erythema in all animals and very slight edema i
- Gross pathology:
- N/A
- Other findings:
- N/A
- Interpretation of results:
- other: Not classified
- Remarks:
- Criteria used for interpretation of results: EU
- Conclusions:
- The dermal LD50 for MRD-83-349 is greater than 3160 mg/kg. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
- Executive summary:
The acute dermal toxicity of MRD-83-349 was evaluated in rabbits following topical occlusive exposure. Test material was applied as a single dose of 3160 mg/kg to the clipped backs of 3 male and 3 female rabbits, covered with a gauze patch, and secured with non-irritating tape and a plastic sleeve. The test material remained in contact with the skin for 24 hours. Observations were made as to the nature, onset, severity, and duration of toxicological signs 2, 4, and 24 hours after dosing and once per day thereafter, for a total of 14 days. Dermal responses were evaluated 24 hours after topical application and on Days 3, 7, 10, and 14 according to the Draize method of scoring. Application of MRD-83-349 at a dose level of 3160 mg/kg showed no evidence of systemic toxicity under the conditions of this study and all animals survived to study termination. There were no deaths or treatment-related clinical signs. Topical exposure elicited very slight to well defined erythema in all animals and very slight edema in four animals. Desquamation was noted in five animals during the study. By Day 14, all animals were clear of erythema and edema. Based on the results of this study, the dermal LD50 for MRD-83-349 is greater than 3160 mg/kg. Classification as an acute dermal toxicant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- Three key read across studies available from structural analogues.
Additional information
There is no acute oral, inhalation, or dermal toxicity data available for Hydrocarbons, C14-C20 (even numbered), n-alkanes, isoalkanes, <2% aromatics. However, data is available for structural analogues, Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics; Hydrocarbons, C11-C14, n-alkanes, <2% aromatics, Hydrocarbons, C11-C14, isoalkanes, cyclics, <2% aromatics; Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, <2% aromatics; Hydrocarbons, C12-C16, isoalkanes, cyclics, <2% aromatics; C14-C16, n-Paraffins, Hydrocarbons, C14-C17, n-alkanes, <2% aromatics; and isohexadecane. This data is read across to based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.
Oral
Hydrocarbons, C11-C14, isoalkanes, cyclics, <2% aromatics
In a key study (ExxonMobil, 1989), the acute toxicity of the test material was evaluated in rats via oral gavage at a dose of 5 g/Kg bw. Observations were made as to the nature, onset, severity, and duration of toxicological signs once per day for a total of 14 days. All animals survived the entire observational period and displayed a low incidence of clinical symptoms. The animals displayed little or no abnormalities. The LD50 of the test material following oral gavage was >5 g/Kg.
Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, <2% aromatics
In a key study (ExxonMobil, 1977), the test material was administered via oral gavage to ten albino Wistar rats (5 males and 5 females) at a dose of 15.0 g/Kg to assess the acute oral toxicity. Animals were observed for mortality and toxic effects immediately and 1, 2, 3, 4, and 6 hours after dosing and daily for 14 days. Necropsies were performed on all rats. No deaths or clinical signs of toxicity were observed. Slight alopecia in the anogential area was observed in 9/10 animals and darkened ovaries in 3/5 female animals were observed at necropsy. The oral LD50 for the test material was greater than 15.0 g/Kg.
C14-C16 n-Paraffins
In a supporting toxicity study (Conoco, Inc., 1982), C14-C16 n-Paraffins was tested for acute oral toxicity in COX-SD rats in an acute dose assay. Animals were fasted overnight prior to treatment. The test substance, a liquid, was administered as supplied. The assay was conducted on a group of 10 rats (5 males, 5 females) with doses of 4750 mg/Kg b.w. or 5250 mg/Kg b.w. administered by gavage in a single oral dose. 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. One male died at the lowest test substance dose while no mortality was observed at the highest dose. Hypoactivity of the animals was observed within 24 hours post-treatment but not after. Diarrhea, diuresis, wet skin and fur of anogenital region and general weakness were also noted at both doses within one to three days post-treatment. Body weight gain was not affected by treatment. At necropsy, macroscopic examination of main organs showed no abnormalities. As the acute oral LD50was found greater than 5250 mg/Kg b.w. under the conditions of the test, C14-C16 n-Paraffins are not classified according to the criteria of CLP Regulation 1272/2008.
Hydrocarbons, C14-C17, n-alkanes, <2% aromatics
In a supporting study (Cepsa, 1984), the test material (Hydrocarbons, C14-C17, n-alkanes, <2% aromatics) 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 LD50was found greater than 5000 mg/Kg b.w. under the conditions of the test, the test material was not classified according to the criteria of CLP Regulation 1272/2008.
Isohexadecane
In a supporting study (INEOS, 1980), the toxicity of isohexadecane in Sprague-Dawley rats was tested by gavage of the undiluted liquid test substance as supplied. The animals were observed for 4 weeks after treatment. At the end of observation period, they were killed and a necropsy was performed. The test doses were 2.15, 4.64, 10.0, 21.15, 31.6 and 46.4 mL/Kg bw. Five males and five females were tested at the three lower doses while 10 rats of both sexes were treated at the three higher dose groups. No mortality was observed at any tested dose. Sublethal effects were noted such as oily secretion in the area of anus for tested dose from 4.64 mL/kg bw to 46.4 mL/kg bw. Moreover, 28% and 11% daily food intake decrease was recorded in females treated at 31.6 mL/kg bw on the first and the second day of observation, respectively. The same effects (32% and 49% food intake decreases) were observed at the 24 and 48-hour observation periods in females treated with the highest dose. Decrease of body weight intake was also observed on first observation day in treated females at 46.4 mL/kg bw, corresponding to 37 g/kg bw. No LD50 was determined.
Inhalation
Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics
In a key study (ExxonMobil, 1995), the test material was administered via individual inhalation chambers for four hours to ten Sprague-Dawley rats (5 males, 5 females) to an average actual vapor concentration of 6100 mg/m3 for four hours to assess acute inhalation toxicity. Animals were observed for fourteen days following exposure. There were no mortality or gross pathological alterations noted in any of the animals. Based on the conditions of this study, the LC50 for acute inhalation exposure to the test material vapor is greater than 6100 mg/m3.
Hydrocarbons, C12-C16, isoalkanes, cyclics, < 2% aromatics
In a key study (ExxonMobil, 1997), to assess acute inhalation toxicity, the test material (Hydrocarbons, C12-C16, isoalkanes, cyclics, < 2% aromatics) 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/m3vapor). 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 the test material was 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).
C14-C16 n-Paraffins
In a supporting study (Conoco, Inc., 1982), the toxicity of C14-C16 n-Paraffins was tested in COX-SD rats exposed by inhalation. Five males and five females were exposed to the test substance in the form of a mist at a delivery flow concentration of approximately 5.8 mg/L of air at a total flow rate of 9 L/min. The animals were observed for 2 weeks after treatment. At the end of observation period, they were killed and a pathology investigation was performed. No mortality occured during the study. Moderate rales were noted in 2 animals on day 2 to 7, that lasted 9 days or until termination. Moderate thinness was also recorded in 2 animals from day 1 or 2 and lasted 3 to 6 days. Necropsy showed slight congestion of the lungs in 2 rats and a slight decrease of visceral fatty tissues in one animal. As the acute LC50 by inhalation was found to be greater than 5.8 mg/L under the conditions of the test, C14-C16 n-Paraffins are not classified according to the criteria of EU GHS.
Dermal
Hydrocarbons, C9-C11, isoalkanes, cyclics, <2% aromatics
In a key acute dermal toxicity study (ExxonMobil, 1984), the acute dermal toxicity of the test material was evaluated in rabbits following topical occlusive exposure. Test material was applied as a single dose of 3160 mg/Kg to the clipped backs of 3 male and 3 female rabbits, covered with a gauze patch, and secured with non-irritating tape and a plastic sleeve. The test material remained in contact with the skin for 24 hours. Observations were made as to the nature, onset, severity, and duration of toxicological signs 2, 4, and 24 hours after dosing and once per day thereafter, for a total of 14 days. Dermal responses were evaluated 24 hours after topical application and on Days 3, 7, 10, and 14 according to the Draize method of scoring. Application of the test material at a dose level of 3160 mg/Kg showed no evidence of systemic toxicity under the conditions of this study and all animals survived to study termination. There were no deaths or treatment-related clinical signs. Topical exposure elicited very slight to well defined erythema in all animals and very slight edema in four animals. Desquamation was noted in five animals during the study. By Day 14, all animals were clear of erythema and edema. Based on the results of this study, the dermal LD50 for the test material was determined to be greater than 3160 mg/Kg.
Hydrocarbons, C11-C14, n-alkanes, < 2% aromatics
In a key acute dermal toxicity study (ExxonMobil, 1993), three male and three female rabbits were exposed to the test material (Hydrocarbons, C11-C14, n-alkanes, < 2% aromatics) for 24h via an occluded patch. Dermal evaluations occurred at 24 hours post patch removal and once daily until the study termination at day 14. Exposure had no effect on viability; all animals survived the exposure. The LD50 was > 5000 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).
Hydrocarbons, C11-C14, isoalkanes, cyclics, < 2% aromatics
In a key acute dermal toxicity study (Cepsa Quimica, 1989), five male and five female rabbits were exposed to the test material (Hydrocarbons, C11-C14, isoalkanes, cyclics, < 2% aromatics) for 24h via an occluded patch. Dermal evaluations occurred at 24 hours post patch removal and twice daily until the study termination at day 14. Exposure had no effect on viability; all animals survived the exposure. The LD50was > 2000 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).
C14 -C16 n-paraffins
In a supporting study (Conoco, Inc., 1982), the acute dermal toxicity of C14 -C16 n-paraffins was determined in male and female adults New Zealand White rabbits. The test substance was applied at 500 or 2000 mg/Kg b.w. concentration on abraded skin of rabbits exposed for 24 hours by an occlusive dressing. At the end of exposure, the remaining test substance was wiped by means of absorbent paper. 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 nor clinical signs occurred during the observation period. Body weight gain was not affected by treatment.
At the 24 hour observation interval, all of the animals showed very slight to marked erythema and edema of the skin at the treatment site. The initial dermal reaction was followed by thickening and/or wrinkling, fissuring, dryness and desquamation of which residual effects persisted in each through termination of the study. As the acute dermal LD50 was greater than 2000 mg/Kg b.w. under the test conditions, C14 -C16 n-paraffins are not classified according to the criteria of CLP Regulation 1272/2008.
Hydrocarbons, C14-C17, n-alkanes, <2% aromatics
In a supporting study (Petroquimica, 1984), the test material (Hydrocarbons, C14-C17, n-alkanes, <2% aromatics) was tested for acute dermal toxicity in HC/CFY (remote Sprague-Dawley) rats in a limit dose assay according to OECD guideline 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, the test material 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, C14-C20 (even numbered), n-alkanes, isoalkanes, <2% aromatics is minimally toxic via ingestion where the LD50 is >5000 mg/Kg, via dermal exposure where the LD50 is >2000 mg/Kg, and by inhalation where the LC50 >6100 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, C14-C20 (even numbered), n-alkanes, isoalkanes, <2% aromatics is classified under EU CLP guidelines as a Category 1 aspiration hazard based on its physical and chemical properties (hydrocarbon fluid, viscosity ≤ 20.5 mm2/s).
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