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EC number: 227-824-5 | CAS number: 5994-61-6
- 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
- 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
- Study period:
- From Aug. 28, 1985 to July 23, 1987
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study conducted equivalent or similar to OECD Guideline 410.
- Justification for data waiving:
- other:
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to other study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 987
- Report date:
- 1987
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
- Deviations:
- no
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- N-(carboxymethyl)-N-(phosphonomethyl)glycine
- EC Number:
- 227-824-5
- EC Name:
- N-(carboxymethyl)-N-(phosphonomethyl)glycine
- Cas Number:
- 5994-61-6
- Molecular formula:
- C5H10NO7P
- IUPAC Name:
- 2-[(carboxymethyl)(phosphonomethyl)amino]acetic acid
- Details on test material:
- - Name of test material (as cited in study report): glyphosate intermediate
- Physical state: Off-white solid
- Analytical purity: 97.97 %
- Lot/batch No.: Batch 900
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratory, Portage, MI
- Age at study initiation: Approximately 7 wk
- Weight at study initiation: Males- 208.0-230.8 g; Females- 149.4-177.1 g
- Fasting period before study:
- Housing: Individual suspended stainless steel cages, over paper bedding
- Diet: Basal Diet (Ralston Purina RODENT CHOW No. 5002), ad libitum
- Water: St. Louis public water supply, ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature: 70-74 °F
- Humidity: 35-60 %
- Photoperiod: 12 h light/12 h dark cycle
IN-LIFE DATES: From: Aug. 28, 1985 To: Sept. 27, 1985
Administration / exposure
- Type of coverage:
- open
- Vehicle:
- other: Mineral oil
- Details on exposure:
- TEST SITE
- Area of exposure: 25 cm2
USE OF RESTRAINERS FOR PREVENTING INGESTION: Yes (plastic neck collar) - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Test material was stable over a 4 week test period as analysed by a flow injection mode, liquid chromatographic procedure. The homogeneity of the test material/ mineral oil slurry was determined to be adequate for study use. Data obtained from analyses of weekly mixture samples indicated 7 % or less difference from the target level
- Duration of treatment / exposure:
- 28 d
- Frequency of treatment:
- 6 h/d, 5d/wk
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 25, 150 and 500 mg/kg bw/d
Basis:
analytical per unit body weight
- No. of animals per sex per dose:
- Ten
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Dosage levels were based upon the results of a range-finding study.
- Positive control:
- Not reported
Examinations
- Observations and examinations performed and frequency:
- MORTALITY AND MORIBUNDITY: Yes
- Time schedule: Twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Once weekly
DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: Once per wk
BODY WEIGHT: Yes
- Time schedule for examinations: Once weekly
FOOD CONSUMPTION: Yes
- Time schedule for examinations: Once weekly
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At termination of study
- Animals fasted: Yes (Food withheld overnight prior to blood collection)
- How many animals: All surviving animals
- Parameters checked: Total erythrocyte count (RBC), total leukocyte count (WOC), platelet count, hematocrit (Ret), level of hemoglobin (Hgb), and red blood cell indices (mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC)), Leukocyte differential, Reticulocyte count,
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At termination of study
- Animals fasted: Yes (Food withheld overnight prior to blood collection)
- How many animals: All surviving animal
- Parameters checked: Albumin, total protein, blood urea nitrogen (BUN), total bilirubin, direct bilirubin, glucose, glutamic pyruvic transaminase (S-GPT/ALT), alkaline phosphatase, glutamic oxaloacetate transaminase (S-GOT/AST), globulin, gamma glutamyl transpeptidase (gamma-GT), creatinine, cholesterol (Chol), calcium, phosphorus, chloride, sodium, and potassium.
- Sacrifice and pathology:
- SACRIFICE: At termination of study
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (High dose group was sacrificed on Day 16 due to severe dermal irritation; gross pathology and tissue analysis was done in mid dose group and control animals; histopathological analysis of only skin tissue was done in low dose group). - Other examinations:
- None
- Statistics:
- - Dunnett's Multiple Comparison Test (two-tailed) (for body weights, food consumption, noncategorical clinical pathology data, absolute organ weights)
- Mann-Whitney Test with Bonferroni Inequality Procedure (for organ weight/body weight ratios)
- Fisher's Exact Test with Bonferroni Inequality Procedure (for incidence of microscopic lesions)
- Bartlett'sTest (to evaluate homogeneity of variances)
- Grubb's Test (to detect outliers)
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Dermal irritation:
- effects observed, treatment-related
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY: There were no mortalities during the study. However the highest exposure group was sacrificed prematurely (Day 16) due to severe dermal lesions.
BODY WEIGHT AND WEIGHT GAIN: Prior to their sacrifice on Day 16, males from the highest exposure level had slightly reduced body weights (14 % less than controls). Females at the same exposure level were not similarly affected. Both sexes at the low and mid exposure levels gained weight comparable to the control group.
FOOD CONSUMPTION: During the wk prior to their sacrifice, males from the highest exposure level ate significantly less diet (>25 % less than
controls). Food consumption in females at the same exposure level were not affected. Rats of both sexes at the low and mid exposure levels consumed similar amounts of diet as did the control level rats.
DERMAL IRRITATION: Dryness, redness, flaking/peeling, scabs, bleeding, necrosis and sloughing of skin observed at site of application. Males were more affected than females. The incidence and severity were dose related. However, low dose females were not affected and low dose males were only mildly affected. However, it is possible that the frequency and severity of lesion was enhanced by skin preparation (such as shaving nicks) and application of the vehicle.
HAEMATOLOGY: Both sexes at the mid dose group had increased WBC counts which appeared primarily due to lymphocytosis and may have been secondary to the skin lesions. Increased absolute neutrophils were noted for mid dose males, but with no statistical significance. Other statistically significant changes including mean corpuscular volume for low dose males, and absolute neutrophils for low dose females, were not dose related and were therefore not considered biologically significant. Furthermore, all of the hematologic parameters, including the increased WHC counts, were within the historical control range.
CLINICAL CHEMISTRY: Serum chemistry changes such as BUN, SGPT, calcium and sodium, although statistically significant, were within the normal historical range and were therefore not considered biologically significant or related to treatment.
GROSS PATHOLOGY: Sporadic differences in organ weight/body weight ratios (brain, heart, kidneys, liver) were not accompanied by other correlative findings. Hence, these changes were not considered biologically significant or treatment related. The incidence of exudate/scab formation and enlargement of elbow lymph node were increased in males at all dose levels and in females at the two highest doses. Enlarged elbow lymph nodes in all dose group males and in mid and high dose group females were probably secondary to the skin lesions. Histologically, the elbow lymph nodes from test and control animals were hyperplastic and did not appear microscopically different from each other.
HISTOPATHOLOGY: NON-NEOPLASTIC: The predominant finding in sections of treated skin from all mid dose males was significant ulceration with an overlying crust and underlying moderate, chronic active dermatitis, granulation tissue, loss of underlying hair follicles and adnexa, and with occasional follicular abscess. Moderate to marked acanthosis and hyperkeratosis were usually limited to the epithelium immediately adjacent to the ulcer. Histologically, treatment related severe ulcerative dermatitis occurred in mid dose animals but not in vehicle control animals. The intermittent distribution of moderately severe dermal lesions in low dose males and mid dose females suggests that some individuals may be more sensitive to the test material than others, or that the test material requires another factor (such as a prior break in the skin) to be irritating. Males were more severely affected than females, which may have reflected a sex related sensitivity to the test material or differences in behavioral response to dermal irritation.
Effect levels
- Dose descriptor:
- NOEL
- Effect level:
- 150 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: Overall effects (Clinical signs; mortality; body weight; food consumption; haematology; clinical chemistry; gross pathology; histopathology)
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
None
Applicant's summary and conclusion
- Conclusions:
- Treatment-related skin lesions, often accompanied by secondary reactions, occurred at all exposure levels for males and at the two highest exposure levels for females. No evidence of systemic toxicity was observed at any of the tested dose levels. All of the abnormalities observed were probably attributable to localized irritation at the application site. Therefore, the mid dose level (150 mg/kg bw/d) was considered the no observed effect Ievel (NOEL) for systemic toxicity.
- Executive summary:
A study was conducted to evaluate the repeated dermal toxicity of test material in Sprague Dawley rats.
10 animals/sex were exposed to test material (suspended in mineral oil) dermally at a concentration of 0, 25, 150, and 500 mg/kg/d for 4 wk (frequency: 6 h/d, 5 d/wk). Animals treated with mineral oil served as control.
Application of test material resulted in treatment-related dermal lesions at all exposure levels in males and at 150 and 500 mg/kg/d in females. The severity of the dermal lesions observed prompted the premature termination of the high dose group on Day 16 of the study. Additional effects observed at the low and mid dose evels, which were considered to be secondary responses to the dermal irritation, were decreased body weight and food consumption and elevated white blood cell and lymphocyte counts. No signs of systemic toxicity were observed at any exposure level.
In conclusion, treatment related skin lesions, often accompanied by secondary reactions occurred at all exposure levels for males and at the two highest exposure levels for females. All of the abnormalities observed were probably attributable to localized irritation at the application site. Therefore, the mid dose level (150 mg/kg bw/d) was considered the no observed effect Ievel (NOEL) for systemic toxicity.
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