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EC number: 217-210-5 | CAS number: 1777-82-8
- 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: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1984-05 to 1989-03
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Experimental study conducted similar to OECD guideline and according to GLP
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1989
- Reference Type:
- review article or handbook
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1989
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Principles of method if other than guideline:
- The test substance was orally administered to rats for 13 weeks.
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 2,4-dichlorobenzyl alcohol
- EC Number:
- 217-210-5
- EC Name:
- 2,4-dichlorobenzyl alcohol
- Cas Number:
- 1777-82-8
- Molecular formula:
- C7H6Cl2O
- IUPAC Name:
- (2,4-dichlorophenyl)methanol
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, Portage, Michigan, USA
- Age at study initiation: 28+/-1 d
- Weight at study initiation: mean body weights of groups were comparable
- Fasting period before study:
- Housing: polypropylene cages with stainless steel grids and lids
- Diet: ad libitum, Labsure CRM pelleted diet (autoclaved)
- Water: ad libitum
- Acclimation period: 4 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/-2
- Humidity (%): 50+/-10
- Air changes (per hr): 30
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- propylene glycol
- Details on oral exposure:
- For 7 days before treatment the animals were dosed daily with water to become accustomed to the oral dosing procedure.
The dose volume was 0.5 mL/100 g bw for all animals. - Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
200, 400 mg/kg bw/d
Basis:
actual ingested
- No. of animals per sex per dose:
- 16
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Post-exposure period: none
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: allocation, day before first treatment, day of first treatment and afterwards once weekly
BODY WEIGHT: Yes
- Time schedule for examinations: allocation and afterwards once weekly
FOOD CONSUMPTION:
- Recorded for each cage weekly
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: 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 AND COMPOUND INTAKE (if drinking water study): No data
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: during week before dosing, during week 13
- Dose groups that were examined: all
HAEMATOLOGY: Yes
- Time schedule for collection of blood: timepoint 1: week 7, timepoint 2: after dosing period (from cardiac puncture)
- Anaesthetic used for blood collection: timepoint 1+2: No data
- Animals fasted: timepoint 1+2: No data
- How many animals: timepoint 1: 8 of each sex from each group, timepoint 2: all animals
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: timepoint 1: week 7, timepoint 2: after dosing period (from cardiac puncture)
- Animals fasted: timepoint 1+2: No data
- How many animals: timepoint 1: 8 of each sex from each group, timepoint 2: all animals
URINALYSIS: Yes
- Time schedule for collection of urine: week 7 and 13
- Metabolism cages used for collection of urine: No data
- Animals fasted: Yes, partially. First collection overnight (16 h) and subsequent 6 h period without water
NEUROBEHAVIOURAL EXAMINATION: No
OTHER:
Femoral bone marrow samples were taken from all rats and smears prepared for examination after the dosing period. - Sacrifice and pathology:
- Animals were sacrificied after 1, 2, 4, 6 or 24 h after final dose. The cardiac blood samples were collected afterwards.
GROSS PATHOLOGY: Yes, organs weighted: adrenals, brain, heart, kidneys, liver, pituitary, spleen, thyroids (with parathyroids) and, either testes, prostate with seminal vesicles, or ovaries.
HISTOPATHOLOGY: Yes, samples taken from adrenals, aorta, bone (femur), brain, caecum, cochleae, colon, duodenum, eyes, heart, ileum, kidneys, liver, lungs (after inflation with fixative), lymph nodes (cervical, mesenteric and inguinal), mammary gland, oesophagus, pancreas, pituitary, salivary gland (submaxillary), sciaric nerve, skeletal muscle (biceps femoris), skin, spinal cord, spleen, stomach (secretory and forestomach), thyroids (with parathyroids), trachea, thymus, tongue, urinary bladder, and either: testes and prostate with seminal vesicles or ovaries and uterus with cervix and vagina.
All the organs and tissues listed above, with the exception of cochlea, were examined from all control rats and all rats given 400 mg/kg bw/d. In addition, sections of the stomach and liver were examined from all rats given 200 mg/kg bw/d. The right cochlea from five male and five female rats in each of the control and high-dose groups were examined by light microscopy. - Other examinations:
- One day after arrival, five rats of each sex were killed and a comprehensive microbiological examination was conducted. A similar examination was carried out on five male and five female Sprague-Dawley rats obtained from the Clinical Research Centre (CRC). A further five male and five female CRC rats were housed in the same room as the study, as sentinels, under identical conditions. These rats were killed during week 14 and a comprehensive microbiological examination conducted. The findings of the examination on the Charles River CD rats indicated that their health status was good, and that they were of a suitable high quality for the study. Results of the examinations of the CRC rats indicated that they had not been exposed to any subclinical infections during the course of the study.
- Statistics:
- The methods used are as described by Chappell and Scott. Significance testing was performed at p < 0.05 and p < 0.01.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- 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:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- not examined
- 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:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Two deaths occured. One animal from 400 mg/kg bw treatment group on day 3 and one animal from 200 mg/kg bw/d treatment group on day 80. Reasons for death were not determined.
Increased salvation and stained coats were observed in all groups.
Rales and uneven breathing were observed occasionally in 12 males and 13 females of 400 mg/kg bw/d group and for 2 males and 4 females in 200 mg/kg bw/d group. One controll animal was once observed with rales.
2 females of 400 mg/kg bw /dgroup collapsed after treatment on day 81 but recovered during the same day.
BODY WEIGHT AND WEIGHT GAIN
Slightly lower bodyweight gains were recorded for treated females in comparison to the controls, though the differences were not statistically significant and not dose dependent. The weight gains of males were not affected by treatment.
FOOD CONSUMPTION
Slightly higher mean weekly food consumption was recorded throughout the dosing period for treated males in comparison to the controls. Food consumption of female rats was not affected by treatment.
OPHTHALMOSCOPIC EXAMINATION
No effects detected.
HAEMATOLOGY
There was no clear effect of treatment on haematological parameters. At week 7, treated females had slightly increased erythrocyte size, as evidenced by high PCV and MCV values, and low MCHC. These differences were greater for females given 200 mg/kg bw/d than those given 400 mg/kg bw/d. Furthermore, erythrocyte size was normal in treated males at week 7, and normal in both sexes after 13 weeks' treatment. Consequently, the difference at week 7 is considered to be of doubtful significance. There were no other differences between treated and control rats. There was no effect of treatment on myelograms.
CLINICAL CHEMISTRY
Higher alkaline phosphatase (ALB) and cholesterol values were recorded for treated males after 6 and 13 weeks of treatment in all dose groups. A trend towards higher ALB values was also noted for treated females, though the differences from controls were not statistically significant. Treated males had higher serum urea and creatinine levels at week 7, but not after 13 weeks' treatment. Lower gamma globulin levels were recorded for males and females given 400 mg/kg bw/d at both investigations, and for males and females given 200 mg/kg bw/d after 13 weeks of treatment. Minor changes in other protein fractions were recorded for females at the higher dose. These small changes were not consistent and were not considered to be a response to treatment. At the terminal investigations, blood samples were collected over two days. Urea, triglyceride and potassium values were affected by the day of sampling. However, there was no difference between treated and control rats an each occasion.
URINALYSIS
Treatment was associated with slightly lower urinary pH in males, and there was a tendency towards higher urinary flow rate for rats given 400 mg/kg bw/d. Examination of the urinary sediment revealed increased epithelial cell counts for treated males at week 7, and of cellular detritus in the samples of treated males at both investigations. Males given 200 mg/kg bw/d showed poor concentrating ability at both collections but, since this appeared to result from high initial specific gravity in rats given 200 mg/kg bw/d and was not apparent at the higher dosage, it was considered not to be due to treatment.
ORGAN WEIGHTS
Liver and kidney weights were elevated in treated males, and liver weights were elevated in females given 400 mg/kg bw/d. Statistical analysis also revealed significantly lower pituitary weights for treated females. Since the differences were not dosage-related and all individual values were normal, this was considered to be of no biological significance.
GROSS PATHOLOGY
Treatment-related changes were found in the stomachs. The changes comprised discrete or diffuse raised areas on the mucosal surface (particularly in the forestomach), a wrinkled, rough or discoloured appearance of the forestomach mucosa, thickening of the limiting ridge and prominence of the stomach blood vessels. The most marked change was the presence of raised areas, and this was recorded for all males given 400 mg/kg bw and killed after 13 weeks treatment, for six females given this dose, and for one female given 200 mg/kg bw/d. Other changes were seen in all but one of the remaining females given 400 mg/kg bw/d and in 11 males and twelve females given 200 mg/kg bw/d. Discolorations of the mucosa of the secretory region of the stomach, either generally or as discrete foci or areas, were also recorded in a few treated rats. There was no macroscopic finding in other tissues that was considered to be related to treatment.
HISTOPATHOLOGY:
In the liver, centrilobular hepatocyte enlargement or centrilobular glycogen loss were recorded for most rats given 400 mg/kg bw/d. These changes were not present in rats given 200 mg/kg bw/d or in control rats.
In the stomach, treatment-related changes were seen in the forestomach. There were no changes in the secretory stomach. The lesions comprised epithelial damage and submucosal oedema, thickening of the epithelium, and changes in the keratin layer. Epithelial damage, that is ulceration, erosion or necrosis, was seen in one male and five females given 400 mg/kg bw/d. Submucosal oedema was seen in several rats given 400 mg/kg bw/d. In the females it was associated with epithelial damage. Thickening of the forestomach epithelium, apparent as plaques or diffuse areas, and resulting from hyperplasia, was seen in rats given 400 mg/kg bw/d. This hyperplasic change was not seen in rats given the vehicle or 200 mg/kg bw/d. Minimal generalized thickening of the forestomach epithelium was apparent in one rat given 400 mg/kg bw, nine given 200 mg/kg bw and one propylene glycol control. The higher incidence of this feature in the 200 mg/kg bw/d group may have been related to treatment. Changes in the keratin of the forestomach comprised hyperkeratosis, swelling of the keratin layers and, in one female given 400 mg/kg bw/d, a marked hydropic change. Hyperkeratosis, was recorded for most rats given 400 mg/kg bw/d, for two males given 200 mg/kg bw/d and for one control male. The distinctive swelling of the keratin, often associated with separation of the keratin layers, was seen in most treated rats but was not present in the controls.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 400 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: systemic toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- < 200 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: local effects in forestomach
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.