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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
Immunotoxicity
Administrative data
Description of key information
Study Type |
Species |
Findings |
Guideline |
Reliability |
28-Day Rat Diet |
Rat |
NOAEL: 10 mg/kg/day; no humoral immune response |
EPA OPPTS 870.7800 |
1 |
Key value for chemical safety assessment
Effect on immunotoxicity: via oral route
Link to relevant study records
- Endpoint:
- immunotoxicity: sub-chronic oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.7800
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
- Specific details on test material used for the study:
- Chlorpyrifos Technical
Lot# KC28161419, TSN101285
Purity: 99.8% - Species:
- rat
- Strain:
- other: Crl:CD(SD)
- Sex:
- female
- Route of administration:
- oral: feed
- Vehicle:
- acetone
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- continuous
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 0.4 mg/kg bw/day (nominal)
- Dose / conc.:
- 2 mg/kg bw/day (nominal)
- Dose / conc.:
- 10 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Observations and clinical examinations performed and frequency:
- A cage-side examination was conducted at least once a day, at approximately the same time each day (usually in the morning). Detailed clinical observations (DCO) were conducted on all animals pre-exposure and once per week throughout the study.
All rats were weighed pre-exposure, twice weekly throughout the study, and at necropsy (terminal).
Feed consumed was determined pre-exposure, twice during the first week and at least weekly thereafter for all animals by weighing feed containers at the start and end of a measurement cycle.
The following clinical chemistry parameters were evaluated: Hematocrit (HCT), Hemoglobin (HGB) concentration, Red blood cell (RBC) count, Total white blood cell (WBC) count, Differential WBC count, Platelet (PLT) count, Reticulocyte (RET) count. RBC indices measured included: Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin Concentration (MCHC).
Red Blood Cell (RBC) and brain cholinesterase activity were measured. - Sacrifice and pathology:
- A limited gross necropsy was conducted on all animals (including positive control animals) by a veterinary pathologist assisted by a team of trained individuals. The necropsy included an examination of the external tissues and all orifices. The eyes were examined in situ by application of a moistened microscope slide to each cornea. All animals had the head removed, although the vehicle control and treated animals also had the cranial cavity opened and the brain removed, rinsed with saline, and blotted dry. The brain was then dissected into the right and left hemispheres. The right hemisphere was weighed. Both sections were individually quick frozen in liquid nitrogen (see the assessment of brain acetyl cholinesterase activity section of protocol for further details). The skin, on all animals, was thenvcreflected from the carcass, the thoracic and abdominal cavities opened and the viscera examined. All visceral tissues were dissected from the carcass, re-examined and selected tissues were incised. For all study animals (including the positive control animals) spleen and thymus were trimmed and weighed immediately. The ratios of organ weight to terminal body weight were calculated.
- Specific cell-mediated immunity:
- The immunotoxic potential of chlorpyrifos was assessed through the evaluation of the primary antibody response to sheep red blood cells (SRBC) using an enzyme-linked immunosorbant assay (ELISA) approach that measured the concentration of serum anti-SRBC IgM.
- Positive control:
- Cyclophosphamide monohydrate
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no treatment-related observations in the ranked parameters throughout the study. Clinical observations consisted of a few animals in the
low and high dose group with dermatitis. These observations were considered spurious and unrelated to treatment due to the isolated occurrence and lack of dose response. - Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Details on results:
- There were no treatment related effects on body weight, body weight gain, feed consumption, hematology or absolute and relative spleen and thymus weights. RBC and brain cholinesterase activities were inhibited by chlorpyrifos in a dose-dependent manner. The response for RBCs was inhibited to a greater extent and at lower dose levels when compared to the response for the brain. RBC cholinesterase activity was significantly decreased at all dose levels when compared to the vehicle control and values were 53.7%, 0.9% and 0.2% of the control value for the 0.4, 2, and 10 mg/kg/day dose groups, respectively. Brain cholinesterase activity was unchanged in the 0.4 mg/kg/day dose group, relative to control, but was significantly decreased in the intermediate and high-dose groups. Brain cholinesterase activities were 91.3% and 18.2% of the control value for the 2 and 10 mg/kg/day dose groups, respectively. Analysis of the anti-SRBC IgM ELISA data did not reveal a statistically significant difference between the three doses of chlorpyrifos and the vehicle control. Despite the lack of statistical significance, a 64% and 41% decrease in the mean anti-SRBC IgM concentration, relative to control, was observed for the 2 and 10 mg/kg/day dose groups, respectively. The interpretation of the biological significance of these decreases was confounded by several factors including the biological variability in the control group, the lack of a clear dose response, and the lack of any correlative evidence on other immune parameters (e.g., spleen and thymus weights and hematology). Based on these considerations, a clear assessment of the antibody response could not be made, and it was determined that the evidence for the immunotoxicity potential of chlorpyrifos was equivocal.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: no immunotox effects at highest dose tested
- Conclusions:
- A clear assessment of the antibody response could not be made, and it was determined that the evidence for the immunotoxicity potential of chlorpyrifos was equivocal.
- Executive summary:
Ten female Crl:CD(SD) rats per group were given test diets formulated to supply 0, 0.4, 2.0, or 10 mg/kg/day chlorpyrifos for 28 days to evaluate the potential for immunotoxicity. Actual time-weighted average doses were 0, 0.416, 2.13, or 10.7 mg/kg/day, respectively. An additional group of ten female Crl:CD(SD) rats exposed to 0 mg/kg/day was included to serve as positive immunosuppressive controls and received intraperitoneal doses of 20 mg/kg cyclophosphamide (CP) on study days 24-28. The immunotoxic potential of chlorpyrifos was assessed through the evaluation of the primary antibody response to sheep red blood cells (SRBC) using an enzyme-linked immunosorbant assay (ELISA) approach that measured the concentration of serum anti-SRBC IgM. Additional parameters evaluated included daily cage-side observations, weekly detailed clinical observations, body weights, feed consumption, hematology, selected organ weights, gross examinations of selected tissues and red blood cell (RBC) and brain cholinesterase activities.
There were no treatment related effects on body weight, body weight gain, feed consumption, hematology or absolute and relative spleen and thymus weights. RBC and brain cholinesterase activities were inhibited by chlorpyrifos in a dose-dependent manner. The response for RBCs was inhibited to a greater extent and at lower dose levels when compared to the response for the brain. RBC cholinesterase activity was significantly decreased at all dose levels when compared to the vehicle control and values were 53.7%, 0.9% and 0.2% of the control value for the 0.4, 2, and 10 mg/kg/day dose groups, respectively. Brain cholinesterase activity was unchanged in the 0.4 mg/kg/day dose group, relative to control, but was significantly decreased in the intermediate and high-dose groups. Brain cholinesterase activities were 91.3% and 18.2% of the control value for the 2 and 10 mg/kg/day dose groups, respectively.
Analysis of the anti-SRBC IgM ELISA data did not reveal a statistically significant difference between the three doses of chlorpyrifos and the vehicle control. Despite the lack of statistical significance, a 64% and 41% decrease in the mean anti-SRBC IgM concentration, relative to control, was observed for the 2 and 10 mg/kg/day dose groups, respectively. The interpretation of the biological significance of these decreases was confounded by several factors including the biological variability in the control group, the lack of a clear dose response, and the lack of any correlative evidence on other immune parameters (e.g., spleen and thymus weights and hematology). Based on these considerations, a clear assessment of the antibody response could not be made, and it was determined that the evidence for the immunotoxicity potential of chlorpyrifos was equivocal.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Effect on immunotoxicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Effect on immunotoxicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
In a rat immunotoxicity study, diets formulated to supply 0, 0.4, 2.0, or 10 mg/kg/day chlorpyrifos for 28 days was provided. There were no treatment related effects on body weight, body weight gain, feed consumption, hematology or absolute and relative spleen and thymus weights. RBC and brain cholinesterase activities were inhibited by chlorpyrifos in a dose-dependent manner. The response for RBCs was inhibited to a greater extent and at lower dose levels when compared to the response for the brain. RBC cholinesterase activity was significantly decreased at all dose levels when compared to the vehicle control and values were 53.7%, 0.9% and 0.2% of the control value for the 0.4, 2, and 10 mg/kg/day dose groups, respectively. Brain cholinesterase activity was unchanged in the 0.4 mg/kg/day dose group, relative to control, but was significantly decreased in the intermediate and high-dose groups. Brain cholinesterase activities were 91.3% and 18.2% of the control value for the 2 and 10 mg/kg/day dose groups, respectively. Based on these considerations, a clear assessment of the antibody response could not be made, and it was determined that the evidence for the immunotoxicity potential of chlorpyrifos was equivocal.
Justification for classification or non-classification
The test substance did not produce a humoral response in rats in a 28-day immunotoxicity study. Therefore, the substance does not need to be classified for mutagenicity according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.
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