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EC number: 220-864-4 | CAS number: 2921-88-2
- 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
Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 988
- Report date:
- 1988
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 82-2 (Repeated Dose Dermal Toxicity -21/28 Days)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Chlorpyrifos
- EC Number:
- 220-864-4
- EC Name:
- Chlorpyrifos
- Cas Number:
- 2921-88-2
- Molecular formula:
- C9H11Cl3NO3PS
- IUPAC Name:
- O,O-diethyl O-3,5,6-trichloropyridin-2-yl phosphorothioate
- Test material form:
- solid
Constituent 1
- Specific details on test material used for the study:
- Chlorpyrifos (DURSBAN R)
Lot AGR 219646
Purity: 99.98%
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- female
Administration / exposure
- Type of coverage:
- semiocclusive
- Vehicle:
- unchanged (no vehicle)
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 21 days
- Frequency of treatment:
- 6 hours/day
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 0.1 mg/kg bw/day (nominal)
- Dose / conc.:
- 0.5 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 mg/kg bw/day (nominal)
- Dose / conc.:
- 5 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent no treatment
Examinations
- Observations and examinations performed and frequency:
- Clinical signs, Functional Observational Battery, Cholinesterase (CHE) activity in plasma, red blood cell (RBC), and brain homogenate.
Hematology (hematocrit (HCT), hemoglobin concentration (HGB), erythocyte count (RBC), total leukocyte count (WBC), and platelet count (PLAT). Differential leukocyte counts were obtained from stained blood smears of all rats.
Clinical chemistry: alanine aminotransferase activity (ALT), aspartate aminotransferase activity (AST), urea nitrogen (UN), alkaline phosphatase activity (AP), glucose (GLUC), creatinine activity (CREAT), total protein (TP), albumin (ALB), globulin (GLOB), cholesterol (CHOL), triglycerides (TRIG), calcium (CALC) and phosphorous (PHOS). Sodium (Na), potassium (K) and chloride (Cl) were also measured.
Urinalysis: bil irubin, glucose, ketones, blood, pH, protein, and urobilinogen. In addition, the color and appearance of the urine were noted and determinations of specific gravity and microsediment were conducted (determinations of specific gravity were done on individual samples; microsediment was done on pooled urine samples from each dose group). - Sacrifice and pathology:
- All surviving animals were sacrificed the day following the last application; rats were fasted prior to the sacrifice. Each animal was weighed, anesthetized, the trachea was clamped and the animal was decapitated. Weights of adrena1s, brain, liver, kidneys and testes were recorded for each animal at the scheduled sacrifice. All animals were examined for gross pathological alterations by a veterinary pathologist. The necropsy included in situ examination of the eyes by a glass-slide technique with fluorescent illumination. A complete set of tissues was collected from each animal and preserved in neutral, phosphate-buffered 10% formalin. The brain was bissected longitudinally and one half was utilized for cholinesterase determination. The lungs were infused with buffered formalin to their approximate normal inspiratory volume and the nasal cavity was flushed with formalin via the pharyngeal duct to ensure rapid fixation of the tissue. The adrenals, brain, kidneys, liver, peripheral nerve (sciatic), skin (from the treated portion of the back and an untreated site from the dorsal portion of the neck), spinal cord (cervical, thoracic, and lumbar areas), and a few selected tissues which had gross pathologic observations were prepared for histopathological examination by standard methods from all controls and rats treated with 5 mg/kg/day. The tissues were stained with hematoxylin and eosin and examined microscopically by a veterinary pathologist. Although tissues weresimilarly prepared from rats treated with 0.1, 0.5 or 1 mg/kg/day, they were not examined microscopically due to a lack of lesions at the highest dose level.
- Statistics:
- The statistical analysis outlined below was conducted on parameters measured during the 21-day study; no statistical analysis was conducted on data from the 4-day probe. Descriptive statistics (mean and standard deviation) were calculated for white blood cell differential counts and feed consumption data. Body weights,absolute and relative organ weights, cholinesterase activity, clinical chemistry data, urinary gravity and hematology data (except white blood cell differential counts) were evaluated by Bartlett's test for equality of variances followed by a parametric analysis of variance (ANOVA) and Dunnett's test. Statistical outliers were identified by a sequential outlier test. Only feed consumption outliers were routinely excluded from analysis.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Red-brown exudate (staining) around the eyes was noted for most female rats (including controls) throughout the course of the study; a few male rats (including controls) exhibited this red-brown stain around eyes on days 2 and 21 of the study. No other clinical observations were noted.
- Dermal irritation:
- no effects observed
- Description (incidence and severity):
- There were no indications of skin irritation based on dermal scores.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- All groups of rats lost weight (2-4%) during the first week of the study. During the second week, however, all groups recovered the lost weight and continued to gain until study termination. Mean body weights were comparable between dose groups ,throughout the course of the study. The initial weight loss was probably the result of stress from the increased handling associated with the bandaging technique.
- Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- Mean feed consumption values were comparable between groups over the study period. Feed consumption was lower for all groups during the first week of the study but increased during the last 2 weeks of the study supporting the theory of initial stress associated with acclimation to the application technique.
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- There were no toxicologically significant effects observed in routine hematology parameters.
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- There were no toxicologically significant effects observed in routine clinical chemistry parameters.
- Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- Urinalysis values for chlorpyrifos treated groups of animals were comparable to controls.
- Behaviour (functional findings):
- effects observed, non-treatment-related
- Description (incidence and severity):
- Results of the functional observational battery indicate no appreciable difference between dose groups and control groups. Observations of decreased muscle tone noted for two female rats of the 5 mg/kg/day dose group and increased fecal staining for one male rat of the 0.5 mg/kg/day group were considered incidental findings since no treatment-related effects were observed in other parameters (specifically cholinesterase data).
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Description (incidence and severity):
- There were no indications of systemic toxicity based on terminal body weight or organ weight data.
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No indication of toxicity was observed during gross pathologic examination of animals treated dermally with chlorpyrifos for 21 days. Likewise, histopathologic examination did not reveal evidence of toxicity. Each of the few observations made at necropsy was present only in a single rat and all observations were considered to be spontaneous changes unrelated ·to treatment. In addition, all histopathologic observations (except for one control female rat) were of a minimal nature and were considered to be typical spontaneous changes normally present in rats of this strain and age. One female control rat had ureteral and urinary bladder calculi with associated hyperplasia and inflammation of the associated tissues and kidney.
- Other effects:
- no effects observed
- Description (incidence and severity):
- There were no statistically identified differences in mean values of brain, plasma, or RBC cholinesterase activity for any group treated with chlorpyrifos. While values for 5.0 mg/kg/day male plasma and RBC cholinesterase and female plasma cholinesterase activities were 7, 11 and 17% lower, respectively, than their concurrent control groups, these values were within the range observed for recent historical controls in this laboratory.
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 5 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: no adverse effects noted after 21 day dermal exposure at highest level tested
Applicant's summary and conclusion
- Conclusions:
- 21-day dermal NOEL (female rat) > 5 mg/kg/day
However, application of 10 mg chlorpyrifos/kg body weight/day for 4 days, produced decreases in plasma (45%) and RBC (16%) cholinesterase activity without evidence of toxicity. - Executive summary:
In a probe study, female Fischer 344 rats {4/dose group) were exposed dermally to chlorpyrifos in corn oil solution at dose levels of 0 (corn oil), 1, 10, 100 or 500 mg/kg body weigh~/day, approximately 6 hours/day, for 4 consecutive days. Clinical observations were recorded daily, body weights were recorded on days 1 and 4, plasma and red blood cell (RBC) cholinesterase activities were measured and a gross necropsy conducted on day 5. There were substantial dose-related decreases relative to control in plasma cholinesterase activities (45, 91, or 98%) for animals that received 10, 100 or 500 mg/kg/day, respectively; RBC cholinesterase activities were also decreased in these groups (16, 49 or 75%, respectively). Animals that received 1 mg/kg/day were unaffected by treatment. Decreases in plasma cholinesterase activity as high as 98%
were not asociated with any changes in body weight, in-life clinical signs, or gross
pathologic alterations.
Based on the results of the probe study, 5 rats/sex/exposure group were subsequently exposed to a (corn oil), 0.1, 0.5, 1 or 5 mg chlorpyrifos/kg body weight/day in corn oil solution for approximately 6 hours/day, 5 days/week for 3 consecutive weeks. Body weight, feed consumption, in-life clinical observations, clinical laboratory studies, gross pathology and histopathology were evaluated and found to be unaffected. Plasma, RBC and brain cholinesterase activities measured at necropsy were comparable in treated and control groups. In addition, nothing remarkable was observed in a functional observational battery conducted immediately prior to necropsy.
Daily dermal application of up to 5 mg chlorpyrifos/kg body weight/day over 21 days (15
applications) was well tolerated by rats with no indication of systemic toxicity and no decrease in cholinesterase activity, the most sensitive indicator of exposure. However, application of 10 mg chlorpyrifos/kg body weight/day for 4 days, produced decreases in plasma (45%) and RBC (16%) cholinesterase activity without evidence of toxicity.
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