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EC number: 266-719-9 | CAS number: 67564-91-4
- 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
The 4 week short term oral toxicity of fenpropimorph is characterised by reduced body weight in rats, mice and to a lesser extent in dogs. At high dose levels (1600 ppm) in rats clinical signs of toxicity were observed, in mice dosed 4000 ppm clinical signs of toxicity as well as mortality was noted. Dogs dosed up to 1600 ppm did not demonstrate clinical signs of toxicity.
Haematological examinations revealed reduced haemoglobin and increased bilirubin in rats only. Clinical-chemical parameters such as cholesterol, triglycerides, total protein, calcium and glucose were decreased in high dose rats. Increased liver weights were observed in rats, mice and dogs. A histopathological correlate was not detected, suggesting an adaptive effect.
The 90 day oral toxicity studies, performed in rats and dogs revealed reduced body weights in high dose rats but not in dogs. Haematology demonstrated decreased haemoglobin and increased bilirubin, just as in the 4 weeks study, in high dose rats. In both species alanine aminotransferase was increased. Also similar to the 4 week rat study, triglycerides and cholesterol were decreased in the high dose rats of the 90 day study. In the 90 day feeding studies, liver weight was found to be increased in rats. Similar to the 4 week studies, a histopathological correlate was not observed. In the two 90 day rat studies the NOAELs for systemic toxicity, excluding cholinesterase reduction (see below), were 10 ppm (0.7 / 0.8 mg/kg bw/d for males and females) and 12.5 ppm (0.78 / 0.93 mg/kg bw/d). As the next higher dose level was 100 ppm, the NOAEL of 12.5 ppm can be used as an overall NOAEL for systemic toxicity, excluding cholinesterase reduction.
The determination of plasma/serum-, erythrocyte- and brain cholinesterase in the short-term studies showed that only serum/plasma cholinesterase was reduced and exclusively in rats. The overall NOAEL for cholinesterase reduction was 0.39 mg/kg bw/d (males) and 0.47 mg/kg bw/d (females).
In the 4 week inhalation study in rats there were no effects on body weight, but several clinical chemical parameters were altered; e.g. increased alanine aminotransferase and alkaline phosphatase as well as decreased cholesterol. These changes have also been observed in the oral studies in rats. Plasma cholinesterase activity was reduced in the high and mid dose level. The NOAEL was determined to be 0.01 mg/l (2.5 mg/kg bw/d – males, 3.4 mg/kg bw/d – females).
In a 4-week dermal study in Wistar rats the NOAEL for systemic toxicity was 2.0 mg/kg bw/d (0.05 % concentration), the highest dose applied in this study. Signs of local irritation were not observed. The selection of the concentrations was based on the results of a pretest in which significant dermal changes (scale formation) were observed at a concentration of 0.1 %.
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 06 June 1995 - 26 Sep 1995
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Version / remarks:
- May 12, 1981
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- Chbb: THOM (SPF)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach/Riss, FRG.
- Females (if applicable) nulliparous and non-pregnant: not specified
- Age at study initiation: 26 - 29 days
- Weight at study initiation: mean 194 g (male) / 147 g (female)
- Housing: single housing
- Diet (e.g. ad libitum): Kliba rats/mice/hamsters maintenance diet (343 meal, Klingentalmühle AG, Kaiseraugust, Switzerland), ad libitum
- Water (e.g. ad libitum): from water bottles, ad libitum
- Acclimation period: yes
DETAILS OF FOOD AND WATER QUALITY:
The food used in the study was assayed for chemical and microbiological contaminants.
The drinking water is regularly assayed for chemical contaminants as well as for the absence of microorganisms.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C (air-conditioned)
- Humidity (%): 30 - 70%
- Air changes (per hr): not specified
- Photoperiod: 12 hrs dark / 12 hrs light
IN-LIFE DATES: From: June 06, 1995 To: Sep. 26, 1995 - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet (frequency): not specified
- Mixing appropriate amounts with (Type of food): Kliba rats/mice/hamsters maintenance diet (343 meal, Klingentalmühle AG, Kaiseraugust, Switzerland) - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The concentration control analyses yielded 128% -130% for the 1 ppm samples. Due to the small amount of the test substance and the determination limits of the analytical method, these values for the 1 ppm samples are assessed as being acceptable.
For the samples with nominal concentrations between 100 and 1,000 ppm, mean recoveries in the range of 93.3% - 99.9% were obtained thus confirming the theoretical contents. - Duration of treatment / exposure:
- 3 months
- Frequency of treatment:
- continuously
- Dose / conc.:
- 1 ppm
- Remarks:
- corresponds to 0.1 mg/kg bw/d in males and females
- Dose / conc.:
- 10 ppm
- Remarks:
- corresponds to 0.7 mg/kg bw/d in males, 0.8 mg/kg bw/d in females
- Dose / conc.:
- 100 ppm
- Remarks:
- corresponds to 7.1 mg/kg bw/d in males, 8.5 mg/kg bw/d in females
- Dose / conc.:
- 1 000 ppm
- Remarks:
- corresponds to 71.0 mg/kg bw/d in males, 77.7 mg/kg bw/d in females
- No. of animals per sex per dose:
- 15 animals / sex in dose groups 0, 10, 100 and 1000 ppm
10 animals / sex in dose group 1 ppm - Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale:
The 0, 1, 10, 100 and 1000 ppm dosages were selected on the basis of the results of the results of a 4-week repeated dose toxicity study and two 3-month feeding studies with the test substance where no animals died.
- Rationale for animal assignment (if not random): The animals were randomly assigned to the groups based upon body weight, separated by sex prior to the
first functional observational battery. The randomization list was drawn up by a computer.
- Fasting period before blood sampling for clinical biochemistry: yes, for about 16-20 hours - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: on days -7, 22, 50 and 85
CLINICAL OBSERVATIONS: Yes
- Time schedule: Monday to Friday twice a day and Saturday, Sunday and public holidays once a day
BODY WEIGHT: Yes
- Time schedule for examinations: on day 0 and thereafter in weekly intervals
FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
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: Yes
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: before the start and at the end of administration (study day 78 females and study day 80 males)
- Dose groups that were examined: each test group was examined before and the control and the high dose group were examined at the end of administration
HAEMATOLOGY: Yes
- Time schedule for collection of blood: on study day 91 (female) and 92 (male)
- Anaesthetic used for blood collection: No
- Animals fasted: Yes
- How many animals: 10 / dose group
- The following parameters were examined: leukocytes, erythrocytes, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, prothrombin time
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on study day 91 (female) and 92 (male)
- Animals fasted: Yes
- How many animals: 10 / dose
- The following parameters were examined: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum cholinesterase. erythrocyte cholinesterase, brain cholinesterase, sodium, potassium, chloride, inorganic phosphate, calcium, urea, creatinine, glucose, total bilirubin, total protein, albumin, globulins, triglycerides, cholesterol, magnesium, gamma-glutamyltransferase
PLASMA/SERUM HORMONES/LIPIDS: Not specified
URINALYSIS: Yes
- Time schedule for collection of urine: on study day 87 (male) and 89 (female)
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- The following parameters were examined: volume, color, turbidity, nitrite, pH, protein, glucose, ketones, urobilinogen, bilirubin, blood, specific gravity, sediment
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: on study days -7, 22, 50 and 85
- Dose groups that were examined: all dose groups
- Battery of functions tested: sensory activity, grip strength, motor activity
IMMUNOLOGY: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
1. All gross lesions
2. Brain
3. Pituitary gland
4. Thyroid glands/ parathyroid glands
5. Thymus
6. Trachea
7. Lungs
8. Heart
9. Aorta
10. Salivary glands (mandibular gland, sublingual gland)
11. Liver
12. Spleen
13. Kidneys
14. Adrenal glands
15. Pancreas
16. Testes/ Ovaries
17. Uterus, oviducts, vagina
18. Epididymides, prostate, seminal vesicle
19. Skin
20. Esophagus
21. Stomach (fore- and glandular stomach)
22. Duodenum, jejunum, ileum
23. Cecum, colon, rectum
24. Urinary bladder
25. Lymph nodes (mesenteric and mandibular lymph node)
26. Female mammary gland
27. Skeletal muscle
28. Sciatic nerve
29. Sternum with sternal marrow
30. Bone marrow (femur)
31. Eyes
32. Femur with knee joint
33. Spinal cord (cervical, thoracic and lumbar cord)
34. Extraorbital lacrimal glands - Statistics:
- Mean and standard deviations, the Kruskal-Wallis Test (two sided), Mann-Whitney U test (two-sided), Anova (two-sided), Fishers´s exact test and Dunnett´s test (two sided) were used.
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No substance related effects were obtained. The findings (loss of tail end in each one female of test groups 0 and 3) were spontaneous in nature.
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- In high dose (1,000 ppm ) males and females, body weight was statistically significantly impaired during the entire study. The impairment on day 91 in comparison to the control group was 14.7% in males and 12.2% in females. This was assessed as being substance-related. Corresponding body weight change
values were 24.9% and 25.3% below controls, respectively.
In 100 ppm females, body weight was statistically significantly impaired on days 21, 35, 42, 49, and 77; the values on day 91 was still 6.9% below control, although without statistical significance.
Nevertheless, this was assessed as being substance related. Corresponding body weight change values were 14.9% below controls. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- In high dose (1,000 ppm ) males and females, food consumption was statistically significantly impaired during the entire study. The impairment on day 91 in
comparison to the control group was 9.8% in males and 18.1% in females. This was assessed as being substance-related.
In the 10 ppm group males, statistically significantly increased values were seen on days 63, 77 and 84, and in the 100 ppm group females a statistically significantly decreased value was seen on day 21. Due to the isolated occurrence and the
lack of a dose-response relationship this was assessed as being incidental. - Food efficiency:
- effects observed, treatment-related
- Description (incidence and severity):
- Food efficiency was statistically significantly impaired on single occasions in males and females treated with 1,000 ppm and in females treated with 100 ppm. This was assessed as being substance-related.
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No substance-related findings were obtained. All findings (corneal stipplings, remainders of the pupillary membrane) were equally distributed between
the groups and thus spontaneous in nature. - Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- At the end of the study slightly but statistically significantly decreased hemoglobin concentrations were found in the peripheral blood of the high dose females. The other hematological examinations and the clotting analyses did not reveal any substance-related changes.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- After 3 months of test substance administration alanine aminotransferase activities were significantly increased in the sera of the high dose males and females. Moreover, marked decreases in serum cholinesterase activities were measured in test group 3 (68% of the control value) and 4 (69% of the control value) males and in test group 2 (71% of the control value), 3 (46% of the control value) and 4 (31% of the control value) females. The other serum enzymes as well as the erythrocyte and brain cholinesterase in the animals of either sex remained unaffected.
Blood chemistry examinations revealed increases in total bilirubin concentrations and decreases in triglyceride and cholesterol levels in the sera of the high dose males and females. However, the increase in total bilirubin seen in the high dose
males was not statistically significantly different to the corresponding control but appeared as a trend towards elevated concentrations. - Endocrine findings:
- not examined
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- effects observed, treatment-related
- Description (incidence and severity):
- Open field observations:
In high, mid and low dose males rearing was statistically significantly decreased on day -7. This was clearly incidental in nature.
On day 22, each one male of test group 2 (10 ppm) and 3 (100 ppm) showed slight resistance against handling (rank 2) when removed from home cage. On day 50, 2 males of test group 2 and one male of test group 3 also showed slight resistance
against handling (rank 2). On day 85, one male of test group 2 was slightly apathetic when removing from home cage (rank 1) and one male showed slight resistance against handling (rank 2). However, as slight resistance against handling (rank 2) and "difficult to handle" (rank 3), was also observed sporadically in control animals, these findings were assessed as being incidental and not substance-related.
Sensorimotor tests / Reflexes:
The pupillary reflex test was retarded (rank 1) on day 22 in 1 high dose female, on day 50 in 8 high dose males and 5 high dose females, and on day 85 in 8 high
dose males and 5 high dose females.
Grip strength of forelimbs was statistically significantly reduced in high dose females on day 22.
The values of landing foot splay test were statistically significantly decreased in high dose males on day 50, in high dose females on days 22, 50 and 85 and in mid dose females day 22.
All these findings were assessed as being treatment-related. - Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- In the male test animals, the relative organ weights of testes and brain of the high dose group and of the liver of the third dose group were statistically significantly increased (p <= 0.01, testes approximately 20%, brain approximately 20%, and liver
approximately 18%).
In the female test animals, the mean liver weights of the third and high dose group were statistically significantly increased (p <= 0.01, approximately 21% in the high dose group and approximately 13% in the third dose group).
Also the relative brain weights of the female third and high dose test animals were statistically significantly increased (p <= 0.01, approximately 13% in the high dose group and p <= 0.05, approximately 9% in the third dose group). - Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Liver: A "Focus" was found in one male test animal of the second dose group.
Forestomach: The macroscopic finding "Margo plicatus thickened" was recorded for one female test animal of the control group.
Kidney: A macroscopically visible "Cyst" was diagnosed for one high dose female test animal. - Neuropathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The mean absolute brain weight of the females in dose group 3 (100 ppm) showed a slight, significant decrease (p <= 0.05, approximately 6%).
The brain weight change is not seen to be of any biological significance.
A minimal (single, grade 1) axonal degeneration was found in one lumbar dorsal root of one male control. Minimal axonal degeneration was also found in the
tibial nerve of one male control and in the proximal sciatic nerve of another male control as well as in the proximal sciatic nerve of one high dose female and in the sural nerve of another high dose female. - Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- For the macroscopic observation of a red brown "Focus" no histopathological correlate was found. All histopathological findings noted for the liver are seen to be spontaneous or incidental in nature.
The macroscopic finding "Margo plicatus thickened" of one female control test animal is caused by a focal, submucosal inflammation, histopathologically.
All histopathological findings noted for the forestomach are seen to be spontaneous or incidental in nature.
The macroscopic finding "Cyst" is verified by the histopathological examination.
All histopathological findings noted for the kidneys are seen to be spontaneous or incidental in nature. - Histopathological findings: neoplastic:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- 10 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- body weight and weight gain
- clinical biochemistry
- food consumption and compound intake
- food efficiency
- haematology
- organ weights and organ / body weight ratios
- Key result
- Critical effects observed:
- not specified
Reference
Additional information
Justification for classification or non-classification
As fenpropimorph did not lead to significant organ toxicity, a classification is not warranted.
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