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EC number: 209-264-3 | CAS number: 563-80-4
- 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
Key value for chemical safety assessment
Effects on fertility
Effect on fertility: via inhalation route
- Dose descriptor:
- NOAEC
- 5 000 mg/m³
Additional information
The potential for methyl isopropyl ketone to cause reproductive toxicity is well understood. In the key study, a reproduction/developmental toxicity screening study conducted according to OECD Guideline 421, both sexes were exposed to target concentrations up to 5.0 mg/L via inhalation for 6 hr/day, 7 days/wk. Animals were exposed for 51 (males) or 35-41 (females) consecutive days during premating, mating and up to Gestation Day 19. There were no gross or microscopic effects on any reproductive organ in either sex and no treatment-related effects on sexual function, fertility, or any reproductive parameters. There were no adverse effects on sperm motility, epididymal spermatozoa count, or testicular sperm count. There were also no gross or microscopic effects on any reproductive organ in a repeat-exposure inhalation study in which groups of male and female Sprague-Dawley rats were exposed to up to 3000 ppm methyl isopropyl ketone for 6 hr/day, 5 days/wk for a total of 22 exposures. The NOEC for reproductive toxicity was 5.0 mg/L in the reproduction/developmental toxicity screening test, an exposure concentration that caused severe CNS depression and significant decreases in body weight and body weight gain and feed consumption and food utilization in both sexes.
Effects on developmental toxicity
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2/2012 - 5/2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study was conducted to OECD protocols in a GLP-compliant lab
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- not applicable
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- Sexually mature, virgin female Sprague Dawley [Crl:CD(SD)] rats were used as the test system on this study. This species and strain of animal is recognized as appropriate for developmental toxicity studies. This animal model has been proven to be susceptible to the effects of developmental toxicants. The number of animals selected for this study was based on the United States EPA Health Effects Test guidelines OPPTS 870.3700, Prenatal Developmental Toxicity Study, August 1998 and the OECD Guideline for Testing of Chemicals Guideline 414, Prenatal Developmental Toxicity Study January 2001.
All rats were housed throughout the acclimation period and during the study in an environmentally controlled room. The room temperature and humidity controls were set to maintain environmental conditions of 71°F ± 5°F (22°C ± 3°C) and 50% ± 20%, respectively. Room temperature and relative humidity data were monitored continuously and were scheduled for automatic collection on an hourly basis. Actual mean daily temperature ranged from 71.1°F to 72.1°F (21.7°C to 22.3°C) and mean daily relative humidity ranged from 38.2% to 57.0% during the study. Fluorescent lighting provided illumination for a 12-hour light (0600 hours to 1800 hours)/12-hour dark photoperiod. The light status (on or off) was recorded once every 15 minutes. Air handling units were set to provide a minimum of 10 fresh air changes per hour. - Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- air
- Details on exposure:
- The test substance or filtered air was administered via a daily 6-hour whole-body exposure during gestation days 0-19. All rats were exposed at approximately the same time each day.
The following table presents the study group assignment:
Group
Number Treatment Target Exposure Level (ppm) Number of Females
1 Filtered Air 0 25
2 MIPK 300 25
3 MIPK 750 25
4 MIPK 1500 25
Exposure levels were based on the results of a previous reproductive screening study in rats at dosage levels of 1.0, 2.5, and 5.0 mg/L (approximate levels of 300, 750, and 1500 ppm, respectively). In this study, concentration-dependent reductions in activity level were noted at 2.5 and 5.0 mg/L and partially closed eyes were noted at 5.0 mg/L. In addition, mean body weights and food consumption were reduced at 2.5 and 5.0 mg/L for the first 2-3 weeks of the pre-mating dosing period and continued to be slightly decreased in the gestational phase at 5.0 mg/L. Developmentally, a decrease in the live litter size and a decrease in postnatal survival from postnatal day (PND) 0-4 were noted at 5.0 mg/L. Therefore, the same exposure levels were chosen for the current study and the dosing regimen was extended (gestation days 0-19) to cover the pre-implantation period (gestation days 0-5) to assess any impact on litter size from exposure during this period.
The selected route of administration for this study was whole-body inhalation exposure because the intended use of the test substance indicated that this would be a likely route of human exposure. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analyzed exposure concentrations were determined at approximately 30-minute intervals using a gas chromatograph (GC) under the control of the WINH data acquisition software application. Samples were collected from the approximate animal-breathing zone of the inhalation exposure chamber via heated stainless steel sampling lines. Test atmosphere samples were collected automatically using a heated external multi-position valve. For each sample, the chromatograph was displayed and the area under the sample peak was calculated and stored. The concentration in parts per million (ppm) was calculated using a ln-quadratic equation based on the GC calibration curve.
- Details on mating procedure:
- At the conclusion of the acclimation period, all available females were weighed and examined in detail for physical abnormalities. At the discretion of the Study Director, each animal judged to be in good health and meeting acceptable body weight requirements was placed in a suspended wire-mesh cage with a resident male from the same strain and source for breeding. Resident males were untreated, sexually mature rats utilized exclusively for breeding. These rats were maintained under similar laboratory conditions as the females. A breeding record containing the male and female identification numbers and the dates of cohabitation was maintained. The selected females were approximately 13 weeks old when paired for breeding.
Positive evidence of mating was confirmed by the presence of a vaginal copulatory plug or the presence of sperm in a vaginal lavage and verified by a second biologist. Each mating pair was examined daily. The day on which evidence of mating was identified was termed gestation day 0 and the animals were separated.
The experimental design consisted of 3 test substance-exposed groups and 1 control group, composed of 25 rats per group. The bred females were assigned to groups using a WTDMS™ computer program which randomized the animals based on stratification of the gestation day 0 body weights in a block design. Animals not assigned to study were transferred to the WIL Research stock colony or euthanized by carbon dioxide inhalation and discarded. Body weight values ranged from 219 g to 286 g on gestation day 0. - Duration of treatment / exposure:
- The test substance or filtered air was administered via a daily 6-hour whole-body exposure during gestation days 0-19. All rats were exposed at approximately the same time each day.
- Frequency of treatment:
- The test substance or filtered air was administered via a daily 6-hour whole-body exposure during gestation days 0-19. All rats were exposed at approximately the same time each day.
- Duration of test:
- The test substance or filtered air was administered via a daily 6-hour whole-body exposure during gestation days 0-19. All rats were exposed at approximately the same time each day.
- No. of animals per sex per dose:
- 25
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Treatment from day 0 was used as this study was designed to answer questions regarding information from ACGIH that MiPK exposure results in preimplantation loss. The normal test paradigm of days 6-19 would not account for this observation. While most studies are conducted from days 6-19, the guideline clearly states that the entire period of gestation can be used.
- Maternal examinations:
- All rats were observed twice daily, once in the morning and once in the afternoon, for moribundity and mortality. Individual clinical observations were recorded daily from gestation days 0 through 20 (prior to exposure during the treatment period). Animals were also observed for signs of toxicity approximately 1 hour following exposure. The absence or presence of findings was recorded for individual animals.
Special attention was given to the state of arousal and response to novel stimuli during exposure (as close as possible to the end of the exposure period each day) by producing a loud-noise stimulus. The noise was produced by allowing an approximately 50 g item to strike the steel side of the exposure chamber at the approximate level of the cage rack. The stimulus item was attached to a length of cotton rope that was held against the steel side of the chamber approximately 45 cm from the item. The stimulus item was raised until the rope was approximately perpendicular to the side of the chamber, and the item was released. Each animal’s response to the stimulus was recorded as: no reaction, slight reaction (ear flick or some evidence that the stimulus was heard), or more energetic response (jump, flinch, and/or vocalization). - Ovaries and uterine content:
- Laparohysterectomies and macroscopic examinations were performed blind to treatment group. All females were euthanized on gestation day 20 by carbon dioxide inhalation. The thoracic, abdominal, and pelvic cavities were opened by a ventral mid-line incision, and the contents were examined. In all instances, the postmortem findings were correlated with the antemortem comments, and any abnormalities were recorded. The uterus and ovaries were then exposed and excised. The number of corpora lutea on each ovary was recorded. The trimmed uterus was weighed and opened, and the number and location of all fetuses, early and late resorptions, and the total number of implantation sites were recorded. The placentae were also examined. The individual uterine distribution of implantation sites was documented using the following procedure. All implantation sites, including resorptions, were numbered in consecutive order beginning with the left distal to the left proximal uterine horn, noting the position of the cervix, and continuing from the right proximal to the right distal uterine horn.
Uteri with no macroscopic evidence of implantation were opened and subsequently placed in 10% ammonium sulfide solution for detection of early implantation loss - Fetal examinations:
- Fetal examinations were performed blind to treatment group. Each viable fetus was examined externally, individually sexed, weighed, euthanized by a subcutaneous injection of sodium pentobarbital in the scapular region, and tagged for identification. Fetal tags contained the WIL Research study number, the female number, and the fetus number. The detailed external examination of each fetus included, but was not limited to, an examination of the eyes, palate, and external orifices, and each finding was recorded. Crown-rump measurements and degrees of autolysis were recorded for late resorptions, a gross external examination was performed (if possible), and the tissues were discarded.
Each viable fetus was subjected to a visceral examination using a modification of the Stuckhardt and Poppe fresh dissection technique to include the heart and major blood vessels. The sex of each fetus was confirmed by internal examination. Fetal kidneys were examined and graded for renal papillae development. Heads from approximately one-half of the fetuses in each litter were placed in Bouin’s fixative for subsequent soft-tissue examination by the Wilson sectioning technique. The heads from the remaining one-half of the fetuses were examined by a midcoronal slice. All carcasses were eviscerated and fixed in 100% ethyl alcohol.
Following fixation in alcohol, each fetus was macerated in potassium hydroxide and stained with Alizarin Red S and Alcian Blue. Fetuses were then examined for skeletal malformations and developmental variations.
External, visceral, and skeletal findings were recorded as developmental variations (alterations in anatomic structure that are considered to have no significant biological effect on animal health or body conformity and/or occur at high incidence, representing slight deviations from normal) or malformations (those structural anomalies that alter general body conformity, disrupt or interfere with normal body function, or may be incompatible with life). - Statistics:
- All statistical tests were performed using WTDMS™ unless otherwise noted. Analyses were conducted using two-tailed tests (except as noted otherwise) for minimum significance levels of 1% and 5%, comparing each test substance-exposed group to the control group. Each mean was presented with the standard deviation (S.D.), standard error (S.E.), and the number of animals (N) used to calculate the mean. Data obtained from nongravid animals were excluded from statistical analyses. Due to the use of significant figures and the different rounding conventions inherent in the types of software used, the means and standard deviations on the summary and individual tables may differ slightly. Therefore, the use of reported individual values to calculate subsequent parameters or means will, in some instances, yield minor variations from those listed in the report data tables. Where applicable, the litter was used as the experimental unit.
Mean maternal body weights (absolute and net), body weight changes (absolute and net), and food consumption, gravid uterine weights, organ weights (absolute and relative to brain weights), numbers of corpora lutea, implantation sites, and viable fetuses, and fetal body weights (separately by sex and combined) were subjected to a parametric one-way ANOVA to determine intergroup differences. If the ANOVA revealed significant (p<0.05) intergroup variance, Dunnett’s test was used to compare the test substance-exposed groups to the control group. Mean litter proportions (percent per litter) of prenatal data (viable and nonviable fetuses, early and late resorptions, total resorptions, pre and postimplantation loss, and fetal sex distribution), total fetal malformations and developmental variations (external, visceral, skeletal, and combined) and each particular external, visceral, and skeletal malformation or variation were subjected to the Kruskal-Wallis nonparametric ANOVA test to determine intergroup differences. - Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Test substance-related lower mean body weight gains and reduced food consumption were noted for the 750 and 1500 ppm groups generally throughout the exposure period (gestation days 0-20). As a result, mean body weights in these groups were up to 11.5% and 12.3% lower than the control group. In addition, mean net body weights, net body weight gains, and gravid uterine weights in the 750 and 1500 ppm groups were lower than the control group. In the 300 ppm group, a test substance-related lower mean body weight gain was noted during gestation days 0-3. Although mean body weight gains in this group were similar to the control group throughout the remainder of the exposure period (gestation days 3-20), the initial lower mean body weight gain was of sufficient magnitude to result in a lower overall mean body weight gain (gestation days 0-20), slightly lower (within 5% of the control group values) mean body weights during gestation days 3-20, and a lower mean net body weight gain. Reduced food consumption was also noted for the 300 ppm group throughout the treatment period.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- no effects observed
- Immunological findings:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed - Changes in number of pregnant:
- no effects observed
- Other effects:
- no effects observed
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
In this study, reduced reactivity to noise stimulus, lower mean body weights and body weight gains, and corresponding reduced mean food consumption were noted for females in the 300, 750, and 1500 ppm groups. - Key result
- Dose descriptor:
- LOAEC
- Effect level:
- < 300 ppm (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Remarks on result:
- not determinable
- Remarks:
- no NOAEC identified
- Dose descriptor:
- NOAEC
- Effect level:
- > 1 500 ppm (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Key result
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed - Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Other effects:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 1 500 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- fetal/pup body weight changes
- changes in litter size and weights
- changes in postnatal survival
- external malformations
- skeletal malformations
- visceral malformations
- Key result
- Abnormalities:
- no effects observed
- Key result
- Developmental effects observed:
- no
- Lowest effective dose / conc.:
- 1 500 ppm
- Treatment related:
- no
- Conclusions:
- In this study, reduced reactivity to noise stimulus, lower mean body weights and body weight gains, and corresponding reduced mean food consumption were noted for females in the 300, 750, and 1500 ppm groups. Based on these results, an exposure level of less than 300 ppm was considered to be the no-observed-adverse-effect level (NOAEL) for maternal toxicity. Based on the absence of developmental toxicity at any exposure level tested, 1500 ppm, the highest exposure level tested, was considered to be the NOAEL for embryo/fetal development when MIPK was administered by whole-body inhalation to bred Crl:CD(SD) rats.
- Executive summary:
Objective
The objective of the study was to determine the potential of the test substance to induce developmental toxicity after maternal exposure from conception to 1 day prior to expected parturition, to characterize maternal toxicity at the exposure levels tested, and to determine a no-observed-adverse-effect level (NOAEL) for maternal and developmental toxicity.
Design
Methyl isopropyl ketone (hereafter referred to as MIPK) was administered via whole body inhalation exposure to 3 groups of 25 bred female Crl:CD(SD) rats for 6 hours daily from gestation days 0 through 19. Target exposure levels were 300, 750, and 1500 ppm, corresponding to mean measured exposure concentrations of 304, 757, and 1529 ppm, respectively. A concurrent control group composed of 25 bred females was exposed to filtered air on a comparable regimen. The females were approximately 13 weeks of age at the initiation of exposure. All animals were observed twice daily for mortality and moribundity. Clinical observations, body weights, and food consumption were recorded at appropriate intervals. On gestation day 20, a laparohysterectomy was performed on each female and selected organs were collected and weighed. The uteri, placentae, and ovaries were examined, and the numbers of fetuses, early and late resorptions, total implantations, and corpora lutea were recorded. Gravid uterine weights were recorded, and net body weights and net body weight changes were calculated. The fetuses were weighed, sexed, and examined for external, visceral, and skeletal malformations and developmental variations.
Results
All females survived to the scheduled euthanasia. Test substance-related reduced reactivity to a noise stimulus near the end of exposure was noted for females in all test substance‑exposed groups when compared to the control group. No test substance‑related clinical findings were noted for females in the 300, 750, or 1500 ppm groups at the daily examinations or approximately 1 hour following exposure.
Test substance-related lower mean body weight gains and reduced food consumption were noted for the 750 and 1500 ppm groups generally throughout the exposure period (gestation days 0-20). As a result, mean body weights in these groups were up to 11.5% and 12.3% lower than the control group. In addition, mean net body weights, net body weight gains, and gravid uterine weights in the 750 and 1500 ppm groups were lower than the control group. In the 300 ppm group, a test substance-related lower mean body weight gain was noted during gestation days 0-3. Although mean body weight gains in this group were similar to the control group throughout the remainder of the exposure period (gestation days 3-20), the initial lower mean body weight gain was of sufficient magnitude to result in a lower overall mean body weight gain (gestation days 0-20), slightly lower (within 5% of the control group values) mean body weights during gestation days 3-20, and a lower mean net body weight gain. Reduced food consumption was also noted for the 300 ppm group throughout the treatment period.
No test substance-related macroscopic findings were noted at any exposure level.
Test substance-related higher mean adrenal gland weights (absolute and relative to brain weight) were noted at 1500 ppm when compared to the control group. Mean adrenal weights at 300 and 750 ppm and mean liver and kidney weights at 300, 750, and 1500 ppm were unaffected by test substance exposure.
Intrauterine growth and survival in the 300, 750, and 1500 ppm groups were unaffected by test substance exposure. There were no test substance-related effects on fetal morphology noted at any exposure level.
Conclusion
In this study, reduced reactivity to noise stimulus, lower mean body weights and body weight gains, and corresponding reduced mean food consumption were noted for females in the 300, 750, and 1500 ppm groups. Based on these results, an exposure level of less than 300 ppm was considered to be the no-observed-adverse-effect level (NOAEL) for maternal toxicity. Based on the absence of developmental toxicity at any exposure level tested, 1500 ppm, the highest exposure level tested, was considered to be the NOAEL for embryo/fetal development when MIPK was administered by whole-body inhalation to bred Crl:CD(SD) rats.
Reference
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEC
- 5 284 mg/m³
- Study duration:
- subacute
- Species:
- rat
Additional information
In an OECD 414 prenatal developmental test, methyl isopropyl ketone (hereafter referred to as MIPK) was administered via whole body inhalation exposure to 3 groups of 25 bred female Crl:CD(SD) rats for 6 hours daily from gestation days 0 through 19. Target exposure levels were 300, 750, and 1500 ppm, corresponding to mean measured exposure concentrations of 304, 757, and 1529 ppm, respectively. A concurrent control group composed of 25 bred females was exposed to filtered air on a comparable regimen. The females were approximately 13 weeks of age at the initiation of exposure. All animals were observed twice daily for mortality and moribundity. Clinical observations, body weights, and food consumption were recorded at appropriate intervals. On gestation day 20, a laparohysterectomy was performed on each female and selected organs were collected and weighed. The uteri, placentae, and ovaries were examined, and the numbers of fetuses, early and late resorptions, total implantations, and corpora lutea were recorded. Gravid uterine weights were recorded, and net body weights and net body weight changes were calculated. The fetuses were weighed, sexed, and examined for external, visceral, and skeletal malformations and developmental variations.
In this study, reduced reactivity to noise stimulus, lower mean body weights and body weight gains, and corresponding reduced mean food consumption were noted for females in the 300, 750, and 1500 ppm groups. Based on these results, an exposure level of less than 300 ppm was considered to be the no-observed-adverse-effect level (NOAEL) for maternal toxicity. Based on the absence of developmental toxicity at any exposure level tested, 1500 ppm, the highest exposure level tested, was considered to be the NOAEL for embryo/fetal development when MIPK was administered by whole-body inhalation to bred Crl:CD(SD) rats.
Justification for classification or non-classification
There were no adverse effects on reproductive organs in either sex of rats exposed to methyl isopropyl ketone by the inhalation route for 4 weeks in a repeat-exposure study and no adverse effects on reproductive organs or any reproductive parameters in a reproductive/developmental screening study in which both sexes were exposed to methyl isopropyl ketone via whole body inhalation at concentrations up to 5.0 mg/L for 6 hr/day, 7 days/wk from the beginning of premating through Day 19 of gestation. Based on a weight-of-the-evidence assessment, methyl isopropyl ketone is not classified for "Reproductive Toxicity" according to GHS. Methyl isopropyl ketone has caused fetotoxicity but only in the presence of maternal toxicity. Based on a weight-of-the-evidence assessment, methyl isopropyl ketone is not selectively toxic to the fetus and is not classified for "Developmental Toxicity" according to GHS.
Additional information
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