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EC number: 266-235-8 | CAS number: 66204-44-2
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- one-generation reproductive toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- April 14, 2008 to March 30, 2009
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- Well performed Guideline study according to good scientific standards
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 009
- Report date:
- 2009
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: EEC 88/302; L 133/43 (1988)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- 3,3’-methylen-bis-(5-methyloxazolidine) (MBO)
- IUPAC Name:
- 3,3’-methylen-bis-(5-methyloxazolidine) (MBO)
- Details on test material:
- - Name of test material (as cited in study report): 3,3’-methylen-bis-(5-methyloxazolidine) (MBO) (Grotan OX)
- Substance type: Formaldehyde releaser
- Physical state: Liquid, colorless to light yellow
- Analytical purity: 90 - 100%
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date: Oct 22, 2007
- Lot/batch No.: 0001129974
- Stability under test conditions: The application formulations investigated during the study were found to comprise MBO in the range of 61.0% to 84.5%. Due to a challenging development of a suitable analytical method, for which the validation took more time than planned, the samples were stored for more than one year. Certain degradation of the formulated test item cannot be completely excluded due to this long storage time of samples. Therefore, the NOEL was not corrected according to the measured recovery concentrations.
- Storage condition of test material: Dry and at room temperature (20 ± 5 °C)
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- HanRcc (SPF)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Laboratories Ltd., 4414 Füllinsdorf, Switzerland
- Age at study initiation: (P) 7 wks
- Weight at study initiation: (P) Males: 192 to 229 g; Females: 135 to 177 g;
- Fasting period before study: no
- Housing: Individually in Makrolon type-3 cages with wire mesh tops and sterilized standard softwood bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period:Under test conditions after health examination. Only animals without any visible signs of illness were used for the study
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (12 hrs dark / 12 hrs light):
IN-LIFE DATES: From April 14, 2008 to August 19, 2008
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: 3,3’-methylen-bis-(5-methyloxazolidine) (MBO) was weighed into a glass beaker on a tared precision balance and the vehicle was added (w/v). Using an appropriate homogenizer, a homogeneous suspension was prepared. Separate formulations were prepared for each concentration.
Homogeneity of the test item in the vehicle was maintained during the daily administration
period using a magnetic stirrer.
VEHICLE
- Justification for use and choice of vehicle (if other than water): Cornoil was used to prepare a homogeneous suspension
- Concentration in vehicle: 0, 0.1, 0.3 and 0.9
- Amount of vehicle (if gavage): 5 mL/kg bw
- Lot/batch no. (if required): Roth / 13890412 - Details on mating procedure:
- - M/F ratio per cage: 1.1
- Length of cohabitation: 14 days maximum
- Proof of pregnancy: [a) The daily vaginal smear was sperm positive, or b) A copulation plug was observed. Referred to as day 0 of pregnancy
- After 14 days of unsuccessful pairing replacement of first male by another male with proven fertility.
- Further matings after two unsuccessful attempts: No. If mating was not recorded during this additional pairing period of a maximum of 14 days, the female was sacrificed and the reproductive organs examined histopathologically in order to ascertain the reason for the infertility.
- After successful mating each pregnant female was caged individually
- Any other deviations from standard protocol: None - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- On the first treatment day samples from the control group as well as three samples (top, middle and bottom) of about 2 g of each concentration were taken prior to dosing for analysis of concentration and homogeneity. In addition, samples of about 2 g of each concentration were taken from the middle to confirm stability (6 hours). During the last week of the treatment, samples were taken from the middle to confirm concentration. The aliquots for analysis of dose
formulations were frozen (-20 ± 5 °C) and delivered on dry ice to Dr. D. Flade (Harlan Laboratories Ltd., Itingen / Switzerland) and stored there at -20 ± 5 °C until analysis.
The test item concentrations were determined by LC-MS developed at Harlan Laboratories. - Duration of treatment / exposure:
- Pre-Pairing 70 days
Pairing 14 days maximum
Gestation approximately 21 days
Lactation 21 days
Treatment ended on day 20 post partum - Frequency of treatment:
- Once daily
- Details on study schedule:
- - Selection of pups: All dams were allowed to give birth and rear their litters (F1 pups) up to day 21 post partum. Day 0 was designated as the day on which a female had delivered all her pups. The offspring was examined as soon as possible after completion of delivery for litter size, number of live and still births, and any gross anomalies. On day 4 post partum, the number of offspring was reduced to 8 per litter (when possible equally divided as to sex). On the day of weaning (day 21 post partum), the dams were separated from their litters.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 5, 15, and 45 mg/kg bw/day
Basis:
nominal conc.
- No. of animals per sex per dose:
- 24 males/24 females per sex and dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: The dose levels were selected based on a previous non-GLP compliant dose range finding toxicity study in Han Wistar Rats, Harlan Laboratories Study B50916, using dose levels of 30, 60 and 120 mg/kg/ day, resulting in a NOEL of 30 mg/kg/day.
- Rationale for animal assignment: Computer-generated random algorithm. In addition body weights (recorded on the day of allocation) were taken into consideration in order to ensure similar mean body weights in all groups. - Positive control:
- No
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily cage-side clinical observations (once daily, during acclimatization and up to day of necropsy).
Additionally females were observed for signs of difficult or prolonged parturition, and behavioral abnormalities in nesting and nursing.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: Was recorded daily from treatment start to day of necropsy.
FOOD CONSUMPTION
Males: Weekly during pre-pairing and after pairing periods
Females: Weekly from treatment start to delivery and on days 1, 7 and 14 post partum.
No food consumption was recorded during the pairing period.
WATER CONSUMPTION No - Oestrous cyclicity (parental animals):
- Determined in all femal parental animals
- Sperm parameters (parental animals):
- Parameters examined in all P male parental generations:
- Weights of seminal vesicles, with coagulating glands and their fluids (as one unit)
Epididymides (total weight and cauda separately)
Testes
Prostate
Histopathology from testis and epididymis - Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: yes
- If yes, maximum of 8 pups/litter (equally dividedas to sex as possible); excess pups were killed and discarded.
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
Number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities
GROSS EXAMINATION OF DEAD PUPS:
yes, F1 pups were sacrificed on day 4 p.p., examined macroscopically for possible defects and preserved in neutral phosphate buffered 4% formaldehyde solution. All the remaining pups were sacrificed and examined macroscopically for defects after weaning. If indicated, skeletal development of the pups were examined by staining with alizarin red S after clearing in potassium hydroxide (a slightly modified technique of Dawson.
Dead young, except those excessively cannibalized, were autopsied and/or preserved in fixative for possible further examination. - Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All surviving animals [at or shortly after weaning, P generation females and the remaining pups were sacrificed. P generation males were sacrificed when they were no longer needed for the assessment of reproductive effects..]
- Maternal animals: All surviving animals [females which lost their litter were sacrificed and necropsied together with the dams after weaning of the pups or if considered appropriate, at any time after litter loss. If birth did not occur on the expected date (day 21 p.c.), the female was sacrificed on day 25 p.c. and examined as described.]
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera
HISTOPATHOLOGY / ORGAN WEIGHTS
Histopathology
(from Parental animals)
Gross lesions
Ovaries
Pituitary
Prostate
Seminal vesicles with coagulating gland
Testes with epididymides (in Bouin’s fixative)
Uterus and cervix
Vagina
Stomach
Slides of all organs and tissues (see list above) from all animals of the control and high dose group (group 1 and 4, respectively), and all gross lesions from all animals of all groups were processed, embedded in paraffin, cut at a nominal thickness of 2-4 micrometers, stained with hematoxylin & eosin (H&E) and examined by light microscope by the study pathologist. As histomorphologic changes were observed in the stomach of high dose animals of both sexes, examination of this organ was extended to the assigned animals of the mid- and low-dose groups
Organ weights (P)
Seminal vesicles, with coagulating glands and their fluids (as one unit)
Epididymides (total weight and cauda separately)
Testes
Prostate
Ovaries
Uterus (including cervix and vagina, excluding oviducts)
[Paired organs were weighed individually] - Postmortem examinations (offspring):
- SACRIFICE
- F1 offspring
F1 pups selected for litter size standardization were sacrificed on day 4 p.p., examined macroscopically for possible defects and preserved in neutral phosphate buffered 4% formaldehyde solution. All the remaining pups were sacrificed and examined macroscopically for defects after weaning. If indicated, skeletal development of the pups were examined by staining with alizarin red S after clearing in potassium hydroxide (a slightly modified technique of Dawson).
Dead young, except those excessively cannibalized, were autopsied and/or preserved in fixative for possible further examination. - Statistics:
- The following statistical methods were used to analyze food consumption, body weights and reproduction data:
• Means and standard deviations of various data were calculated and included in the report.
• The Dunnett-test (many to one t-test) based on a pooled variance estimate was applied if the variables could be assumed to follow a normal distribution for the comparison of the treated groups and the control groups for each sex.
• The Steel-test (many-one rank test) was applied instead of the Dunnett-test when the data could not be assumed to follow a normal distribution.
• Fisher's exact-test was applied if the variables can be dichotomized without loss of information - Reproductive indices:
- Estrus Cycle
Duration of Gestation
Implantation Rate
Post-implantation Loss and Postnatal Loss Days 0 - 4 Post Partum - Offspring viability indices:
- External Examination at First Litter Check and during Lactation
Sex Ratios
Litter Size at First Litter Check
Breeding Loss Days 5 - 21 Post Partum
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- All animals survived until the scheduled necropsy.
No clinical signs or signs of discomfort were noted during the treatment period in any group in
males and females.
As an exception, one female in group 4 was lethargic, lost body weight and had diarrhea, ruffled
fur and a hunched posture on day 22 post coitum, indicating a dystocia. After giving birth (all
pups were cannibalized), no clinical sings were noted anymore. - Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Males
In group 4, mean body weight gain was slightly although not statistically significantly reduced
during the pre-pairing period resulting in slightly reduced mean body weights. Mean body weights remained reduced until the end of the treatment period.
In groups 2 and 3, mean body weights were similar to the control group.
Females
Mean body weight and mean body weight gain were not affected by treatment with the test item in any group.
In groups 2 and 3, mean body weights were similar to the control group. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Males
In group 4, mean food consumption was slightly and occasionally statistically significantly
reduced during the pre-pairing period.
In groups 2 and 3, mean food consumption was similar to the control
group.
Females
In group 4, mean food consumption was slightly although not statistically significantly reduced
in the last week of the gestation period (-6.3% compared to the control group).
In groups 2 and 3, mean food consumption and mean was similar to the control
group. - Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- HISTOPATHOLOGY (PARENTAL ANIMALS)
Microscopically, MBO induced test item-related changes in the forestomach. They consisted of moderate to massive ulcerations of the forestomach in many male animals of group 4 as well as moderate to marked ulcerations in females of group 4. Minimal to slight vacuolar degeneration of the squamous epithelium was recorded only in group 4 males. Furthermore, there was minimal to moderate squamous hyperplasia along with different severity degrees of hyperkeratosis, submucosal inflammation and submucosal edema in animal of both sexes of group 4. In group 3, minimal to slight vacuolar degeneration as well as minimal degrees of squamous hyperplasia, hyperkeratosis, submucosal inflammation and edema were recorded in the forestomach of males but not in females. In addition, one male showed minimal focal erosion and minimal epithelial inflammatory infiltrates were observed in few males of group 3. - Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- Test substance intake: 0, 5, 15, and 45 mg/kg bw/day
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- effects observed, treatment-related
- Description (incidence and severity):
- REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
In group 4, there were indications for an undetected postnatal loss, which means pups were cannibalized directly after birth by its mother before their number and sex have been recorded. Combined total number of post implantation loss and number of postnatal loss between days 0 -4 were 47, 45, 48 and 66 pups in order of ascending dose levels. Since the number in groups 2 and 3 was similar than in the control group this finding was considered to be not test item-related.
In group 4, the high number of 66 lost pups and the high number of dead pups at first litter check were considered to be test item-related
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- >= 5 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
- Dose descriptor:
- NOAEL
- Effect level:
- >= 15 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: A systemic NO(A)EL for the parental animals was considered to be 15 mg/kg body weight/day, based on the reduced body weights at 45 mg/kg body weight/day.
- Dose descriptor:
- NOAEL
- Effect level:
- >= 15 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: The NOAEL for reproduction/ developmental toxicity was considered to be 15 mg/kg/day, based on the increased incidence of the post implantation and postnatal loss at 45 mg/kg body weight/day.
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
Details on results (F1)
Pup Weights to Weaning (to Day 21 Post Partum)
Mean pup weights on day 1 post partum and during the lactation period were not affected by treatment with the test item.
Macroscopical Findings
At necropsy of pups, there were no abnormal findings.
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- >= 45 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No effects were noted in the F1 progeny during the weaning phase and at necropsy.
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
Table 1 Table for animal assignment for mating |
|||||
|
Number of animals |
||||
Controls |
Low Dose |
Medium Dose |
High Dose |
||
Parents |
m |
24 |
24 |
24 |
24 |
f |
24 |
24 |
24 |
24 |
|
F1 |
Litters (total) |
21 |
22 |
21 |
22 |
Table 2 Table for reproductive toxicity study (Only relevant findings presented) |
||||||||||
Parameter |
|
control |
low dose |
medium dose |
High dose |
|||||
Generation |
m |
f |
m |
f |
m |
f |
m |
f |
||
Mortality |
incidence |
P |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Food consumption(pre-pairing period, days 1-70) |
% of control |
P |
|
|
-1.5 |
+1.5 |
-1% |
+2.9 |
-5.8 |
+1.5 |
Food consumption(females, last gestational week, day 14-21) |
% of control |
P |
|
|
|
+5.2 |
|
+2.9 |
|
-6.3 |
Differences in mean body weight gain(pre-pairing period, from day 1 to 70) |
% of control |
P |
+108 |
+55 |
+103 |
+54 |
+107 |
+56 |
+101 |
+57 |
Clinical Observations |
Incidence |
P |
n.s.f. |
n.s.f. |
n.s.f. |
n.s.f. |
n.s.f. |
n.s.f. |
n.s.f. |
1# |
Pathology |
|
P |
|
|
|
|
|
|
|
|
Macroscopic findings |
|
P |
|
|
|
|
|
|
|
|
Cratiform retractions |
Incidence, (%) |
P |
0 |
0 |
0 |
0 |
0 |
0 |
9 (38) |
1 (4) |
Isolated cratiform retractions |
Incidence, (%) |
P |
0 |
0 |
0 |
0 |
0 |
0 |
3 (13) |
1 (4) |
Nodules |
Incidence, (%) |
P |
0 |
0 |
0 |
0 |
0 |
0 |
5 (21) |
0 |
Several cratiform retractions |
Incidence, (%) |
P |
0 |
0 |
0 |
0 |
0 |
0 |
1 (4) |
0 |
n.s.f.: no specific findings
#: one high-dosed female showed lethargia, diarrhea and dystocia and had cannibalized its pups
Parameter |
|
control |
low dose |
medium dose |
High dose |
|||||
Generation |
m |
f |
m |
f |
m |
f |
m |
f |
||
Histopathologic examination |
|
|
|
|
|
|
|
|
|
|
No. animals examined |
|
P |
24 |
24 |
24 |
24 |
24 |
24 |
24 |
24 |
Ulcerations |
Incidence |
P |
0 |
0 |
0 |
0 |
0 |
0 |
19 |
4 |
Vacuolar degeneration |
Incidence |
P |
0 |
0 |
0 |
0 |
4 |
0 |
5 |
0 |
Squamous hyperplasia |
Incidence |
P |
0 |
0 |
0 |
0 |
5 |
0 |
10 |
5 |
Hyperkeratosis |
Incidence |
P |
0 |
0 |
1 |
0 |
5 |
|
18 |
7 |
Submucosal inflam. |
Incidence |
P |
0 |
0 |
0 |
0 |
2 |
0 |
4 |
2 |
Reproductive Performance |
|
|
|
|
|
|
|
|
|
|
Implantations |
Group means |
P |
|
12.8 |
|
13.0 |
|
13.3 |
|
13.1 |
Post implanation loss |
% of implantations |
P |
|
7.5 |
|
12.3 |
|
14.7 |
|
16.3 |
Litters affected |
F1 |
|
12 |
|
12 |
|
14 |
|
10 |
|
Total |
F1 |
|
20 |
|
35* |
|
41** |
|
47** |
|
Mean |
F1 |
|
1.0 |
|
1.6 |
|
2.0 |
|
2.1 |
|
N |
F1 |
|
21 |
|
22 |
|
21 |
|
22 |
|
Post natal loss (days 0-4 p.p.) |
% of living pups |
F1 |
|
10.9 |
|
4.0 |
|
2.9 |
|
7.9 |
Litters affected |
F1 |
|
4 |
|
8 |
|
3 |
|
5 |
|
Total |
F1 |
|
27 |
|
10** |
|
7** |
|
19 |
|
Mean |
F1 |
|
1.3 |
|
0.5 |
|
0.3 |
|
0.9 |
|
N |
F1 |
|
21 |
|
22 |
|
21 |
|
22 |
|
Dead pups at first litter check |
Litters affected |
F1 |
|
3 |
|
3 |
|
3 |
|
3 |
|
Total |
F1 |
|
3 |
|
2 |
|
12 |
|
24 |
|
Mean |
F1 |
|
0.1 |
|
0.1 |
|
0.6 |
|
1.1 |
|
N |
F1 |
|
21 |
|
22 |
|
21 |
|
22 |
* or **: Fisher’s Exact test at 5% or 1% level
Applicant's summary and conclusion
- Conclusions:
- Based on histopathological test-item related toxicological relevant effects in the forestomach in male and female rats administered at 15 and 45 mg/kg, a general local No-Observed-Adverse-Effect-Level (NOAEL) for the parental animals was considered to be 5 mg/kg body weight/day. A systemic NO(A)EL for the parental animals was considered to be 15 mg/kg body weight/day, based on the reduced body weights at 45 mg/kg body weight/day. The NOAEL for reproduction/ developmental toxicity was considered to be 15 mg/kg/day, based on the increased incidence of the post implantation and postnatal loss at 45 mg/kg body weight/day. No effects were noted in the F1 progeny during the weaning phase and at necropsy.
- Executive summary:
One generation reproductive toxicity study according to OECD Guideline 415.
MBO was administered in corn oil as vehicle at dosages of 5, 15, and 45 mg/kg body weight/day.
In group 2 (5 mg/kg bw), no test item-related findings were noted.
In group 3 (15 mg/kg bw), histopathological changes were recorded in the forestomach of males but not in females.
In group 4 (45 mg/kg bw) in males, mean food consumption and mean body weight gain were slightly reduced during the pre-pairing period, resulting in slightly reduced mean body weights. In females, only mean food consumption was slightly although not statistically significantly reduced in the last week of the gestation period.
The sum of the post implantation loss, the number of dead pups at first litter check and the postnatal loss between days 0 - 4 was increased.
Macroscopically, test item-related crateriform retractions and/or nodules in the forestomach mucosa of many males and of few females were recorded. These findings were histopathologically confirmed.
The NOAEL (parental) for reproduction was 15 mg/kg bw. No effectes were detected in the F1 progeny.
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