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EC number: 249-109-7 | CAS number: 28629-66-5
- 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
Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Study period:
- July 1980 - December 1980
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- other: Secondary effects due to irritation. Thus, meets definition "This includes studies or data from the literature/reports in which there are interferences [i.e. irritation] between the measuring system and the test substance".
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 980
- Report date:
- 1980
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
- Deviations:
- yes
- Remarks:
- Only two dose groups (plus vehicle control) were used; toxicity occured at both doses. The study report indicates that the test substance application site remained uncovered.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Zinc bis(O,O-diisooctyl) bis(dithiophosphate)
- EC Number:
- 249-109-7
- EC Name:
- Zinc bis(O,O-diisooctyl) bis(dithiophosphate)
- Cas Number:
- 28629-66-5
- Molecular formula:
- Too complex
- IUPAC Name:
- zinc bis(O,O-diisooctyl) bis(dithiophosphate)
- Details on test material:
- - Substance type: Clear, oil-like liquid
- Physical state: Liquid
- Analytical purity: Assumed to be 100% for the purposes of dosing
- Lot/batch No.: ECA-6371
- Expiration date of the lot/batch: July 1981
- Stability under test conditions: No data
- Storage condition of test material: Room temperature
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: HARE rabbits for Research, Marland Breeding Farms Inc., 521 Burnet Meadow Road, P.O. Box X, Hewitt, New Jersey, 07421
- Age at study initiation: No data
- Weight at study initiation: Males 1.7–2.8 kg; Females 1.6-2.9 kg.
- Fasting period before study: No data
- Housing: Individually in stainless steel cages.
- Diet: ad libitum
- Water: e.g. ad libitum
- Acclimation period: 16 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 60-78 deg F (
- Humidity (%): 43-75%
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light
IN-LIFE DATES: From: 11 August 1980 To: 8 September 1980
Administration / exposure
- Type of coverage:
- open
- Vehicle:
- other: Primol 185 (mineral oil)
- Details on exposure:
- TEST SITE
- Area of exposure: the dorsal surface was clipped from the suprascapular area to the hind quarters, approximately 10cm
- % coverage: No data
- Type of wrap if used: To avoid the possibility of applying test substance to the control dorsal area (untreated), a folded paper towel was held over the left suprascapular dorsal surface of all treated and control animals during the application of the vehicle and test substance
- Time intervals for shavings or clipplings: Rabbits were reclipped on Monday and Thursday of each week throughout the study
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The backs of rabbits were gently wiped with paper towels approximately 6 hours after exposure to remove excessive test substance if necessary.
- Time after start of exposure: Approximately 6 hours.
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2mL of test substance in vehicle per kg body weight
- Concentration (if solution): 5 and 25% (based on previous toxicity studies conducted with this substance)
- Constant volume or concentration used: Constant volume used.
VEHICLE
- Justification for use and choice of vehicle (if other than water): No data
- Amount(s) applied (volume or weight with unit): 2mL/kg body weight
- Lot/batch no. (if required): 2938
- Purity: No data
USE OF RESTRAINERS FOR PREVENTING INGESTION: Yes, all rabbits were fitted with Elizabethan collars - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- Duplicate 10mL samples were taken from each weekly batch of dosing solutions prepared and sent to the study Sponsor for analytical confirmation of test substance concentration.
- Duration of treatment / exposure:
- 28 days
- Frequency of treatment:
- 5 days/week
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
approx. 100mg/kg body weight
Basis:
nominal per unit body weight
- Remarks:
- Doses / Concentrations:
approx. 500 mg/kg body weight
Basis:
nominal per unit body weight
- No. of animals per sex per dose:
- 10 males and 10 females per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Based on previous toxicity studies with the test substance
- Rationale for animal assignment (if not random): Random - Positive control:
- No
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Observations for mortality and gross signs of toxicologic or pharmacologic effects were performed twice daily.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Detailed physical examination for signs of local or systemic toxicity, pharmacologic effects and palpation of tissues masses was performed weekly.
DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: Recorded daily, 7 days/week. Observations were made immediately prior to the application of the test substance.
BODY WEIGHT: Yes
- Time schedule for examinations: Once pretest, weekly during treatment and terminally (after fasting).
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION: No data
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Pretest and on Days 27-30.
- Anaesthetic used for blood collection: No
- Animals fasted: Yes
- How many animals: All survivors
- Parameters checked in List 1 were evaluated
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Pretest and on Days 28-30
- Animals fasted: Yes
- How many animals: All survivors
- Parameters checked in List 2 were examined.
URINALYSIS: No data
NEUROBEHAVIOURAL EXAMINATION: No data - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Complete gross pstmortem examinations were performed on all survivors at termination as well as on all animals either dying spontaneously or killed in extremis during the study. The examinations included examination of the external surface, all orifices, the cranial cavity, carcass, the external and cut surface of the brain and spinal cord, the thoracic, abdominal and pelvic cavities and their viscera, and the cervical tisses and organs.
ORGAN WEIGHTS: Yes (see List 3)
HISTOPATHOLOGY: Yes (see List 4). Control and high-dose animals only, except for testes where low-dose animals also examined. - Statistics:
- Body weight, haematology and clinical chemistry parameters, terminal organ and body weights and organ/body weight ratios were analysed. Mean values of all dose groups were compared to control at each time interval.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Dermal irritation:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- CLINICAL SIGNS AND MORTALITY
All low-dose animals (treated with 5% test substance) survived to terminal sacrifice.
In the high-dose group (25% test substance concentration), one male and three females died during the study between Days 17 and 30.
Low- and high-dose males and females exhibited a greater incidence and severity of emaciation than did control animals throughout the period of test substance administration. Thickening of the outer layer of the skin was observed during the last two weeks of the study in low- and high-dose males and females. A greater incidence of lacrimation was observed in the low- and high-dose males (Week 2) and females (Week 2-4) than in the control animals. All animals treated with the test substance also displayed a higher incidence of mucoidal nasal discharge and staining of the anogenital regio compared to controls.
Both low- and high-dose animals generally exhibited marked, dose-related increases in the incidence and severity of erythema, odema, atonia, desquamation, fissuring, eschar formation and exfoliation. Many of the observations were recorded as being moderate to extreme in severity, particularly in the high-dose group.
BODY WEIGHT AND WEIGHT GAIN
Slight to statistically significant, dose-related decreases in body weight were generally exhibited in treated males and females throughout the course of the study.
FOOD CONSUMPTION
No data.
FOOD EFFICIENCY
No data.
WATER CONSUMPTION
No data.
OPHTHALMOSCOPIC EXAMINATION
No data.
HAEMATOLOGY
Low- and high-dose males and females exhibited slight or statistically significantly lower mean haemoglobin, haematocrit and erythrocyte values than did corresponding control animals after four weeks of treatment.
CLINICAL CHEMISTRY
Low- and high-dose males and females exhibited slight or statistically significant, dose-related increases in mean cholesterol values and slight to statistically significant dose-related reductions in albumin. Although these differences were within normal physiological limits, albumin was considered to be borderline low. Total protein and albumin/globulin ratios were normal.
Slight reductions were generally evident in the terminal plasma, erythrocyte and brain cholinesterase values of the low- and high-dose males and females.
URINALYSIS
No data.
NEUROBEHAVIOUR
No data.
ORGAN WEIGHTS
The absolute and relative (organ/body weight ratio) weights of the testes and epididymides of the low- and high-dose males were markedly lower than control weights, showed a dose-related pattern, and were considered to be indicative of a treatment-related effect. high-dose males and low- and high-dose females displayed slight to statistically significant, dose-related increases in mean absolute and relative weights of the adrenals. Slight to statistically significant, dose-related increases in mean absolute and relative kidney weights were also evident in treated males and females.
GROSS PATHOLOGY
Results of the gross postmortem examinations confirmed a higher incidence of exfoliation, fissuring, eschar formation and desquamation in treated animals. The testes of low- and high-dose males were observed to be markedly smaller than those of control males. Other grossly visible morphologic abnormalities observed during the gross postmortem examinations occurred sporadically and were not considered to be treatment-related.
HISTOPATHOLOGY
The results of the microscopic evaluations revealed that the topical administration of the test substance produced irritating skin lesions in both males and females at both the low and high concentrations. In addition, treatment-related testicular effects were evident in the low- and high-dose males. These testicular changes were characterised by morphologic abnormalities in the seminiferous tubules that consisted primarily of aspermatogenesis, diffuse tubular hypoplasia and a reduced mitotic activity.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Basis for effect level:
- other: Adverse effects, both systemic and local to the site of administration, were observed at both test substance concentrations (5% and 25%)
- Remarks on result:
- not determinable
- Remarks:
- no NOAEL identified
- Dose descriptor:
- LOAEL
- Effect level:
- 5 other: %
- Based on:
- test mat.
- Sex:
- male/female
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Daily application of the test substance (and 5% and 25% concentration) to the clipped skin of rabbits caused local effects at the site of administration rated as moderate to extreme, as well as systemic effects including decreased body weight, emaciation, slight to statistically significant alterations to some haematoligical and clinical chemistry parameters, slight to statistically significant increases in kidney and adrenal weights and, in males, markedly decreased testes weights, which under microscopic assessment revealed morphologic abnormalities in the seminiferous tubules that consisted primarily of aspermatogenesis, diffuse tubular hypoplasia and a reduced mitotic activity. In the high-dose group (25% concentration), one male and three females died during the study. Based on these findings, a no-observed adverse effect level (NOAEL) cannot be identified from this study.
- Executive summary:
In a study of repeated dermal toxicity, test substance CAS 28629-66-5 at concentrations of 5% and 25% in mineral oil was applied to the clipped dorsal skin of groups of 10 male and 10 female New Zealand White rabbits, five days per week for four weeks. The dose volume applied was 2mL/kg body weight. A control group of 10 males and 10 females were treated with mineral oil vehicle alone. Animals were observed daily for mortality, gross signs of toxicity and local irritation, and given a more detailed physical examination weekly. Body weight was measured weekly. Blood for haematology and clinical chemistry was taken pretest and at termination. All animals underwent gross pathological examination at necropsy. Selected organs were weighed and a number of tissues examined microscopically.
One high-dose male and three high-dose females died during the study. There were no deaths in the low-dose group. The test substance caused local skin effects at the site of administration ranked from moderate to severe. Clinical signs of toxicity in treated animals included decreased body weight and emaciation, lacrimation, mucoidal nasal discharge and staining of the anogenital region. Haematology revealed slight or statistically significantly lower mean haemoglobin, haematocrit and erythrocyte values in treated animals compared to control animals. Clinical chemistry found slight to statistically significant increases in cholesterol and decreases in albumin. Slight decreases in terminal plasma, erythrocyte and brain cholinesterase was also generally evident in treated animals. At postmortem, gross examination revealed markedly decreased testes size in both low- and high-dose males, and a higher incidence of exfoliation, fissuring, eschar formation and desquamation in all treatment groups. Testes and epididymides of treated males were found to be markedly lower in weight than in control males. Slight to statistically significant, dose-related increases in kidney and adrenal weight were also seen in treated animals. Histological examination showed testicular changes characterised by morphologic abnormalities in the seminiferous tubules that consisted primarily of aspermatogenesis, diffuse tubular hypoplasia and a reduced mitotic activity.
[The study report documents the testing of three separate test substances for 28-day dermal toxicity; however, only the information relating to the study of CAS 28629-66-5 is presented in this Endpoint Study Record.]
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