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EC number: 700-188-0 | CAS number: 1333481-90-5
- 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
Endpoint summary
Administrative data
Description of key information
A study was conducted to assess the toxic potential of the test substance, when administered to rats by daily oral gavage for a period of 7 consecutive days. It was concluded that the test substance has no toxic potential when administered to rats by daily oral gavage for a period of up to 7 consecutive days up to 1000 mg/kg/day.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 24 January 2008 to 01 February 2008
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP study based on OECD Guideline 407 and EU Directive B.7 but dosed for only 7 days rather than the guideline 28 days.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- dosed for 7 days only
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
- Deviations:
- yes
- Remarks:
- dosed for 7 days only
- Principles of method if other than guideline:
- Based on OECD 407 Guideline and EU Directive B.7., but animals were dosed for 7 days rather than 28 days
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: ca. 9 weeks
- Weight at study initiation: Males: 262 - 296 grams; Females: 186 - 204 grams
- Fasting period before study:
- Housing: Group housing of 3 animals per sex in Macrolon cages (MIV type, height 18 cm) with sterilised sawdust as bedding material (Litalabo,
S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lilico & Son (Wonham Mill Ltd), Surrey, U.K.)
- Diet (e.g. ad libitum): Free access (ad libitum) to pelleted rodent diet (SM R/M-Z from SSNIFF, Spezialdiaten GmbH, Soest, Germany).
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3.0°C (actual range 19.9 - 21.5°C)
- Humidity (%): 30 - 70% (actual range 38 - 55%)
- Air changes (per hr): approx. 15/hr
- Photoperiod (hrs dark / hrs light): 12 hrs
IN-LIFE DATES: From: 24 January 2008 To: 01 February 2008 - Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
Formulations (w/w) were prepared daily within 4 hours prior to dosing, and were homogenized to visually acceptable levels.
VEHICLE
- Justification for use and choice of vehicle (if other than water): 1% Aqueous carboxymethylcellulose; based on trial formulations performed at
NOTOX and on information from the sponsor
- Concentration in vehicle: 0.0mg/kg/day (controls); 150, 300 & 1000mg/kg/day
- Amount of vehicle (if gavage): 5ml/kg
- Lot/batch no. (if required): Not reported
- Purity: Not reported - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 7 consecutive days
- Frequency of treatment:
- Once per day
- Remarks:
- Doses / Concentrations:
150 mg/kg/day
Basis:
actual ingested - Remarks:
- Doses / Concentrations:
300mg/kg/day
Basis:
actual ingested - Remarks:
- Doses / Concentrations:
1000mg/kg/day
Basis:
actual ingested - No. of animals per sex per dose:
- 3/sex/dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Dose levels were based on results of the acute oral toxicity study (NOTOXproject 486674) and information from the
sponsor.
- Rationale for animal assignment (if not random): Random
- Rationale for selecting satellite groups: N/A
- Post-exposure recovery period in satellite groups: N/A
- Section schedule rationale (if not random): N/A - Positive control:
- N/A
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: At least once/day
BODY WEIGHT: Yes
- Time schedule for examinations: Days 1, 4 & 7
FOOD CONSUMPTION:
- Over Days 1-4 and 4-7
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Immediately prior to scheduled post-mortem
- Anaesthetic used for blood collection: Yes (identity) iso-flurane
- Animals fasted: Yes
- How many animals: All
- Parameters examined: White blood cells, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, Red blood cells, Reticulocytes, red blood cell distribution width, Haemoglobin, Haematocrit, Mean corpuscuiar volume, Mean corpuscular haemoglobin, Mean corpuscular haemoglobin concentration, Platelets, Prothrombin time and Activated Partial thromboplastin time.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Immediately prior to scheduled post-mortem
- Animals fasted: Yes
- How many animals: All
- Parameters examined: Alanine aminotransferase, Aspartate aminotransferase, Alkaline phosphatase, Total Protein, Albumin, Total bilirubin, Urea,
Creatinine, Glucose, Cholesterol, Triglycerides, Sodium, Potassium, Chloride, Calcium and Inorganic Phosphate
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (all animals)
HISTOPATHOLOGY: Yes (groups 1 & 4 plus all gross lesions) - Other examinations:
- Organ weights
- Statistics:
- Means, SD and/or median
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- 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:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY :
No mortalities occurred during the study and no clinical signs of toxicity were noted during the observation period
BODY WEIGHT AND WEIGHT GAIN
No toxicologically significant changes in body weights and body weight gain were noted.
FOOD CONSUMPTION
No toxicologically significant changes in food consumption before or after allowance for body weight were noted. Food consumption corrected for
body weight of females at 1000 mg/kg/day appeared slightly lower during treatment. Absolute food intake of these animals was essentially similar to control levels. As this change was of a minor nature, this was considered to be of no toxicological relevance.
FOOD EFFICIENCY N/A
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study) N/A
OPHTHALMOSCOPIC EXAMINATION Not conducted
HAEMATOLOGY
Haematological parameters of treated rats were considered not to have been affected by treatment.
CLINICAL CHEMISTRY
Clinical biochemistry parameters of treated rats were considered not to have been affected by treatment.
URINALYSIS Not conducted
NEUROBEHAVIOUR Not conducted
ORGAN WEIGHTS
No toxicologically significant changes were noted in organ weights and organ to body weight ratios.
Liver weights of two males at 1000 mg/kg/day (nos. 10 and 12) appeared slightly higher than control levels. However, these values (and those of
the liver to body weight ratios) were within the range considered normal for rats of this age and strain. Moreover, there were no concurrent
histopathological changes in the liver. Therefore, no toxicological relevance was ascribed to these variations.
GROSS PATHOLOGY
Necropsy did not reveal any toxicologically relevant alterations. Necropsy findings were considered to be of no toxicological significance since they
occurred in the absence of a treatment-related distribution, and are occasionally seen among rats used in these types of studies. These findings
included pelvic dilation of the kidneys, yellowish foci or nodules on the epididymides and fluid in the uterus.
HISTOPATHOLOGY: NON-NEOPLASTIC
There were no microscopic findings recorded which could be attributed to treatment with the test substance.
HISTOPATHOLOGY: NEOPLASTIC (if applicable) N/A
HISTORICAL CONTROL DATA (if applicable)
All microscopic findings were within the range of background pathology encountered in Wistar rats of this age and strain and occurred at similar
incidences and severity in both control and treated rats.
OTHER FINDINGS None - Dose descriptor:
- NOAEL
- Effect level:
- > 1 000 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Remarks on result:
- not determinable
- Remarks:
- no NOAEL identified
- Critical effects observed:
- not specified
- Conclusions:
- From the results presented in this report it was concluded that Lactol has no toxic potential when administered to rats by daily oral gavage for a
period of up to 7 consecutive days up to 1000 mg/kg/day. - Executive summary:
A study was conducted at NOTOX, The Netherlands, on behalf of Pfizer Ireland Pharmaceuticals Ltd., to assess the toxic potential of the test substance Lactol, when administered to rats by daily oral gavage for a period of 7 consecutive days. The study was conducted to GLP and based on OECD Guideline 407 and EU Directive B.7. However, the animals were dosed for seven days only rather than the 28 days in the guidelines. Lactol was administered by oral gavage to four groups of Wistar rats (each of three rats per sex) at doses of 150, 300 & 1000mg/kg bodyweight/day; a concurrent control group was treated with vehicle only.
Animals were subjected to clinical observations which were undertaken at least once per day and body weights were recorded on days 1, 4 & 7 of the study; food consumption was recorded over days 1-4 and 4-7. Macroscopic examinations were performed and major organs were weighed after terminal sacrifice (Day 7). Immediately prior to post-mortem, blood samples were collected for haematology and clinical biochemistry evaluations. No toxicologically significant changes were noted in any of the parameters investigated in this study (i.e. clinical appearance, body weight, food consumption, clinical laboratory investigations, macroscopic examination, organ weights, and microscopic examination). From the results presented in this report it was concluded that Lactol has no toxic potential when administered to rats by daily oral gavage for a period of up to 7 consecutive days up to 1000 mg/kg/day.
Reference
Slight weight loss was observed among female dose groups (see Tables 1 & 2 below), but the incidence of this slight weight loss was unrelated to the dose and was considered to be related to the age of the animals.
Table 1: Body weights (Grams) summary
MALES |
|
||||
Treatment |
Group 1 (control) |
Group 2 (150mg/kg) |
Group 3 (300mg/kg) |
Group 4 (1000mg/kg) |
|
Day 1 Week 1 |
MEAN |
282 |
284 |
284 |
285 |
S.D. |
13.3 |
19.3 |
5.1 |
10.0 |
|
N |
3 |
3 |
3 |
3 |
|
Day 4 Week 1 |
MEAN |
293 |
292 |
292 |
293 |
S.D. |
13.8 |
20.6 |
9.2 |
15.7 |
|
N |
3 |
3 |
3 |
3 |
|
Day 7 Week 1 |
MEAN |
299 |
301 |
296 |
301 |
S.D. |
17.4 |
18.9 |
10.7 |
19.1 |
|
N |
3 |
3 |
3 |
3 |
|
|
|||||
FEMALES |
|
||||
Treatment |
Group 1 (control) |
Group 2 (150mg/kg) |
Group 3 (300mg/kg) |
Group 4 (1000mg/kg) |
|
Day 1 Week 1 |
MEAN |
194 |
192 |
197 |
197 |
S.D. |
3.6 |
9.3 |
8.9 |
6.5 |
|
N |
3 |
3 |
3 |
3 |
|
Day 4 Week 1 |
MEAN |
191 |
194 |
198 |
196 |
S.D. |
5.5 |
11.8 |
10.5 |
11.6 |
|
N |
3 |
3 |
3 |
3 |
|
Day 7 Week 1 |
MEAN |
197 |
202 |
203 |
198 |
S.D. |
6.4 |
13.4 |
10.8 |
10.5 |
|
N |
3 |
3 |
3 |
3 |
N: number of animals
Table 2: Body weight Gain (%) summary
MALES |
|
||||
Treatment |
Group 1 (control) |
Group 2 (150mg/kg) |
Group 3 (300mg/kg) |
Group 4 (1000mg/kg) |
|
Day 1 Week 1 |
MEAN |
0 |
0 |
0 |
0 |
S.D. |
0.0 |
0.0 |
0.0 |
0.0 |
|
N |
3 |
3 |
3 |
3 |
|
Day 4 Week 1 |
MEAN |
4 |
3 |
3 |
3 |
S.D. |
0.5 |
0.7 |
1.7 |
1.9 |
|
N |
3 |
3 |
3 |
3 |
|
Day 7 Week 1 |
MEAN |
6 |
6 |
4 |
5 |
S.D. |
1.2 |
1.7 |
2.8 |
3.0 |
|
N |
3 |
3 |
3 |
3 |
|
|
|||||
FEMALES |
|
||||
Treatment |
Group 1 (control) |
Group 2 (150mg/kg) |
Group 3 (300mg/kg) |
Group 4 (1000mg/kg) |
|
Day 1 Week 1 |
MEAN |
0 |
0 |
0 |
0 |
S.D. |
0.0 |
0.0 |
0.0 |
0.0 |
|
N |
3 |
3 |
3 |
3 |
|
Day 4 Week 1 |
MEAN |
-2 |
1 |
1 |
0 |
S.D. |
1.8 |
1.3 |
1.7 |
2.6 |
|
N |
3 |
3 |
3 |
3 |
|
Day 7 Week 1 |
MEAN |
2 |
5 |
3 |
1 |
S.D. |
1.5 |
2.4 |
2.8 |
2.0 |
|
N |
3 |
3 |
3 |
3 |
S.D: standard deviation
N: number of animals
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- 2 (reliable with restrictions)
Additional information
A study was conducted to assess the toxic potential of the test substance, when administered to rats by daily oral gavage for a period of 7 consecutive days. The study was conducted to GLP and based on OECD 407 and EC B.7. However, the animals were dosed for seven days only. No toxicologically significant changes were noted in any of the parameters investigated in this study (i.e. clinical appearance, body weight, food consumption, clinical laboratory investigations, macroscopic examination, organ weights, and microscopic examination). It was concluded that the test substance has no toxic potential when administered to rats by daily oral gavage for a period of up to 7 consecutive days up to 1000 mg/kg/day.
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
GLP study based on OECD Guideline 407 and EU Directive B.7 but dosed for only 7 days rather than the guideline 28 days.
Justification for classification or non-classification
According to the results of the tests and the Official Journal of the European Communities, Annex VI, 'General Classification and Labelling Requirements for Dangerous Substances and Preparations' the substance cannot be classified on the basis of its subacute toxicity as the guidelines stipulate 28 days dose exposure and not the 7 days as in the present study.
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