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EC number: 215-662-8 | CAS number: 1338-24-5
- 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
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- 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
For acute oral toxicity no key study could be put forward. Instead the available studies were considered in a Weight of Evidence approach, all resulting in LD50 values above limit dose (3.0 - 5.88 g/kg bw). From the available studies the most detailed study was kept as for the chemical safety assessment.
For acute dermal toxicity the LD50 was obtained from 2 studies, both showing LD50 values above limit dose (3.16 & 20.0 g/kg bw).The study with the lowest values was considered as Key study and the other served as supporting study.
The endpoint acute inhalation toxicity has been waived based on the very low vapour pressure of the substance. Inhalation exposure is very unlikely under normal handling and use.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- This study is reported in a 'Reclamed Substances Testplan' for Naphthenic acids in the frame of the High Production Volume Chemical Challende Program of US EPA and hence considered as secondary literature. Because no access to the original report was obtained a Klimisch score 4 for reliability has been assigned. However, this study has been evaluated by the American Petroleum Institute (API) and was found to be reliable without restriction. The following conclusion was drawn by the API: 'it appeared to be comparable to a guideline study with adequate experimental details provided. Although the investigators used male rats only, there is sufficient experimental detail to make a conclusion on the study's validity, and the results can be used to assess the potential acute toxicity of naphthenic acid.'
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- not specified
- Principles of method if other than guideline:
- Male rats only
- GLP compliance:
- not specified
- Test type:
- standard acute method
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
- Route of administration:
- oral: unspecified
- Vehicle:
- unchanged (no vehicle)
- Doses:
- Rats were dosed at 1.0, 1.47, 2.15, 3.16, 4.64, 6.81 and 10 g/kg of body weights.
- No. of animals per sex per dose:
- Seven groups of 5 male rats
- Control animals:
- not specified
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed 1, 2, 4 and 6 hours ,after dosing and once daily for 14 days. Mortality, toxicity and pharmacological effects were recorded. Body weights were recorded pretest and in the survivors at 14 days.
- Necropsy of survivors performed: yes
All animals were examined for gross pathology - Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 5 880 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 4.31 - <= 8.02
- Mortality:
- Deaths occurred at the four highest dose levels: 3.26, 4.64, 6.81 and 10 g/kg bw. 8/10 animals died at the two highest dose levels.
- Clinical signs:
- other: Significant predeath toxic signs included tremors, lethargy, ptosis, ataxia, prostration, negative righting reflex, flaccid muscle tone, piloerection, diarrhea, chromodacryorrhea. dyspnea and chromorhinorrhea. Body weight changes were noted in the survivo
- Gross pathology:
- Significant necropsy findings in the animals that died during the study included dilated hearts and gastrointestinal irregularities.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LD50 was determined to be 5.88 (4.31-8.02) g/kg bw
- Executive summary:
Seven groups of 5 male rats were dosed at 1.0, 1.47, 2.15, 3.16, 4.64, 6.81, and 10 g/kg of body weights. Mortality, toxicity and pharmacological effects were recorded. Body weights were recorded pretest and in the survivors at 14 days. At 14 days the survivors were sacrificed. All animals were examined for gross pathology.
Deaths occurred at the four highest dose levels: 3.26, 4.64, 6.81, and 10 g/kg bw. 8/10 animals died at the two highest dose levels. Significant predeath toxic signs included tremors, lethargy, ptosis, ataxia, prostration, negative righting reflex, flaccid muscle tone, piloerection, diarrhea, chromodacryorrhea, dyspnea and chromorhinorrhea. Body weight changes were noted in the survivors. Significant necropsy findings in the animals that died during the study included dilated hearts and gastrointestinal irregularities.
The LD50 was determined to be 5.88 (4.31-8.02) g/kg bw.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 5 880 mg/kg bw
- Quality of whole database:
- Klimisch value of the studies varied from 3-4. All information was based on published data, including secondary sources; therefore details were missing. On the other hand, LD50 values were consistently higher than 2000 mg/kg bw.
Acute toxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1979
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Although no indication that it is a GLP study, the availeble robust study summary published in the "robust study information on reclaimed substances: Naphthenic acid" by the API sufficient detail is provided to make a conclusion about its validity.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- yes
- Remarks:
- This study is a combined study where Accute Dermal Toxicity is considered together with skin irritation.
- Principles of method if other than guideline:
- This study is a combined study where Accute Dermal Toxicity is considered together with skin irritation.
- GLP compliance:
- not specified
- Test type:
- standard acute method
- Limit test:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Type of coverage:
- occlusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- 3.16 g/kg naphthenic acid was applied dermally to the clipped abraded abdomens of each animal. The area was covered with gauze and secured by a thick plastic binder, which was removed atfter 24 hours, and the skin washed with water or corn oil.
- Duration of exposure:
- 24 hours
- Doses:
- 3.16 g/kg naphthenic acid was applied dermally to the clipped abraded abdomens of each animal
- No. of animals per sex per dose:
- 2 per sex
- Control animals:
- not specified
- Details on study design:
- According to experimental protocol, if no deaths occurred at the initial level, no addition animals were dosed. If one animal died, the experiment was to be repeated using 3 more groups of animals dosed at varying levels.
Following the skin wash, animals were observed for mortality and toxic effects at 2 hr and 4 hr, and once daily thereatter. Body weights were recorded pretest and at termination. Dermal irritation was recorded at 24 hr, 3, 7, 10 and 14 days.
The rabbits were observed 1, 2, 4 and 6 hours after dosing and once daily for 14 days. Mortality, toxicity and pharmacological effects were recorded. Body weights were recorded pretest and in the survivors at 14 days. At 14 days the survivors were sacrificed. Ananimals were examined for gross pathology. - Sex:
- male/female
- Dose descriptor:
- approximate LD50
- Effect level:
- > 3 160 mg/kg bw
- Based on:
- test mat.
- Mortality:
- no
- Clinical signs:
- other: lethargy, diarrhea, ptosis, adipsia, anorexia, and few feces
- Gross pathology:
- No
- Other findings:
- No deaths occurred at the 3.16 mg/kg dose level. Most of the animals (3/4) appeared normal during the first 2 to 4 hours of dosing, after which symptoms of toxicity were observed. 3 out of 4 animals (1 male, 2 female) showed signs of toxicity until day 12 or 13. During the first 5 days, all animals displayed one or more of the following symptoms: lethargy, diarrhea, ptosis, adipsia, anorexia, and few feces.
The LD50 was determined to be greater than 3.16 g/kg bw
Redness and irritation scores were recorded at 24 hr, 3, 7, 10 and 14 days post-washing. 4 Hour occluded sites (DOT, OECD methods)
Mean values (24, 48 & 72 hours) for erythema and edema at the intact sites were 1.69 and 1.3 respectively. The initial response of the skin to the test material was slight, with little difference in response between intact or abraded sites. - Interpretation of results:
- GHS criteria not met
- Executive summary:
New Zealand white rabbits were dermally treated with 3.16 g/kg Naphthenic acids under occlusive dressing for 24 hours, afeter which the skin was washed with water or corn oil. The rabbits were observed 1, 2, 4 and 6 hours after dosing and once daily for 14 days. No deaths occurred at the 3.16 mg/kg dose level. Most of the animals (3/4) appeared normal during the first 2 to 4 hours of dosing, after which symptoms of toxicity were observed. 3 out of 4 animals (1 male, 2 female) showed signs of toxicity until day 12 or 13. During the first 5 days, all animals displayed one or more of the following symptoms: lethargy, diarrhea, ptosis, adipsia, anorexia, and few feces.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 3 160 mg/kg bw
- Quality of whole database:
- High quality study
Additional information
Acute oral toxicity was obtained from various studies, that were considered as Weight of Evidence information. There were various studies with limited to moderate information, however all providing consistent LD50 values:
- LD50 = 5.88 g/kg bw in male rats; male rats were dosed from 1 to 10 g/kg of body weights (HPVIS, 2003; Exxon, 1979). Deaths occurred at the four highest dose levels of 3.26, 4.64, 6.81, and 10 g/kg bw. 8/10 animals died at the two highest dose levels. Significant predeath toxic signs included tremors, lethargy, ptosis, ataxia, prostration, negative righting reflex, flaccid muscle tone, piloerection, diarrhea, chromodacryorrhea, dyspnea and chromorhinorrhea. Body weight changes were noted in the survivors. Necropsy findings in the animals that died during the study included dilated hearts and gastrointestinal irregularities.
- LD50 = 3.0 -5.2 g/kg bw in rats; this was based on fraction from crude kerosene acids and a fraction from mixed crude oils, respectively (Rockhold, 1955) . Death appeared to result from gastrointestinal disturbances, with the mortality peak occurring on the third to fourth day after administration. The animals exhibited anorexia, inanition, diarrhea, and asthenia.
- LD50 = 3.55 g/kg bw in mice (HPVIS, 2003; Penissi & Lynch, 1977). Clinical observations included CNS depression, corneal eye opacity,dryness of mouth, convulsions, diarrhea, and death due to respiratory arrest
- Finally acute oral toxicity testing was performed in Wistar rats with a mixture of naphthenic acids isolated from Althabasca oils sand (AOS). Single dosages of 3, 30 and 300 mg/kg bw were given to female rats and 300 mg/kg bw was given to male rats by oral gavage. Food consumption was temporarily suppressed in the high dose groups of both sexes. Histopathology 14 days after dosing revealed a significant incidence of pericholangitis in the high dose group of both sexes, suggesting hepatotoxicity as an acute effect. Other histological lesions included brain haemorrhage in the high dosed males, and cardiac perioarteriolar necrosis and fibrosis in female rats. *
Acute inhalation toxicity testing was waived according 8.5.2 column 2 of Annex VIII: Vapour pressure of Naphthenic acids is very low (<0.001 Pa at 25°C), thus inhalation of vapors is considered to be improbable and aerosols are not expected to be formed with standard uses.
Acute dermal toxicity was studied after 24 hours occlusive dressing in 2 studies in New Zealand rabbits:
- LD50 >3.16 g/kg (HPVIS, 2003; Exxon, 1979). No deaths occurred at the 3.16 mg/kg dose level and most of the animals (3/4) appeared normal during the first 2 to 4 hours of dosing, after which symptoms of toxicity were observed, e.g. lethargy, diarrhea, ptosis, adipsia, anorexia, and few feces.
- LD50> 20 g/kg bw (Auletta, 1979). Ataxia and motor activity decrease were evident throughout the fourteen day observation period; from Day 2 through Day 14 of the study these signs were noted at least once in all animals; abdominal griping and soft stool were noted in a few animals and oral, ocular and nasal discharge, alopecia, aggressiveness and fecal staining of the abdomen were noted sporadically in one or two animals.
* The oil sands extracts used in testing described in Rogers et al. (2002) was composed of a greater proportion of higher molecular weight naphthenic acid isomers than the registered sample. Three and four ring constituents comprised 38% of their test sample whereas they totalled 7% of the registered (and HPV) substance. The higher molecular weight naphthenic acid constituents in the oil sands extracts may have implications to the interpretation of effects. Rogers drew attention to the fact that the material he had isolated from oil sands had properties that differed from those of commercial materials that he was using for standards. In fact, there were differences in toxic properties and possible contaminants present in the samples of Rogers or methodological differences which were not representative for the commercial products, so the extent to which these are due to differences in the test protocols is not known (EPA, 2012; see attachment).
Justification for classification or non-classification
Available data suggest values for acute oral and dermal toxicity that warrant no classification for acute toxicity under Regulation 1272/2008 (CLP) nor under Directive 67/548/EC (DSD).
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