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EC number: 201-818-2 | CAS number: 88-30-2
- 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:
- three-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- other information
- Study period:
- 1971 to 1973
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 973
- Reference Type:
- review article or handbook
- Title:
- Unnamed
- Year:
- 1 999
- Report date:
- 1999
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
- Version / remarks:
- 2001-01-22
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- α,α,α-trifluoro-4-nitro-m-cresol
- EC Number:
- 201-818-2
- EC Name:
- α,α,α-trifluoro-4-nitro-m-cresol
- Cas Number:
- 88-30-2
- Molecular formula:
- C7H4F3NO3
- IUPAC Name:
- α,α,α-trifluoro-4-nitro-m-cresol
- Reference substance name:
- 5-chloro-α,α,α-trifluoro-2-nitrotoluene
- EC Number:
- 204-280-7
- EC Name:
- 5-chloro-α,α,α-trifluoro-2-nitrotoluene
- Cas Number:
- 118-83-2
- Molecular formula:
- C7H3ClF3NO2
- IUPAC Name:
- 4-Chloro-1-nitro-2-(trifluoromethyl)benzene
- Reference substance name:
- Water
- EC Number:
- 231-791-2
- EC Name:
- Water
- Cas Number:
- 7732-18-5
- Molecular formula:
- H2O
- IUPAC Name:
- Dihydrogen oxide
- Reference substance name:
- 3-Carboxy-4-nitrophenol
- Cas Number:
- 610-37-7
- Molecular formula:
- C7H5NO5
- IUPAC Name:
- 3-Carboxy-4-nitrophenol
- Test material form:
- liquid
Constituent 1
impurity 1
impurity 2
impurity 3
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source of test material:
Samples of TFM used for this study carried the following label information:
1-21-5479 C31 51315/1
JFK AIRPORT ATTN AMERICAN HOECHST CORP SOMMERVILLE N. J. MR. KUFAHL CHEM. DEPT.
MADE IN WEST GERMANY
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Sprague-Dawley, Madison, Wisconsin, USA
- Females nulliparous and non-pregnant: yes
- Age at study initiation: (P0) ~3 - 4 weeks
- Housing: individually, in metal screen bottom cages, 7" x 7" x 9 3/4"
- Diet: ad libitum, Purina Laboratory Chow from specially capped clear glass jars that limit spillage and contamination of feed and provide visibility of amount and condition of feed.
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: The appropriate amount of TFM (85.6 %) was brought up to 1 % by weight of the diet with corn oil. The TFM and corn oil were thoroughly mixed, then totally admixed with the basal diet. The negative control diet consisted of the basal diet with a 1 % by weight addition of corn oil.
DIET PREPARATION
- Mixing appropriate amounts with: Purina Laboratory Chow (pellets)
VEHICLE
- Justification for use and choice of vehicle: In addition to facilitating good distribution of the test materials, the addition of the corn oil eliminated dusting, thus preventing personnel contamination and cross contamination of test animals from different diet groups. - Details on mating procedure:
- - M/F ratio per cage: 1/1
- Length of cohabitation: one week
- Proof of pregnancy: vaginal plug referred to as day 1 of pregnancy.
- After seven days of unsuccessful pairing replacement of first male by another male with proven fertility.
- After successful mating each pregnant female was caged: Approximately five days prior to parturition, females were placed in plastic shoe box cages equipped with a stainless steel topf food jar, and water bottle. Bedding (AB-SORB-DRI) was changed three times weekly or more often if needed through weaning. After being placed in shoe boxes, females were allowed to deliver and care for their own young with a minimum of disturbance. - Duration of treatment / exposure:
- After approximately 13 weeks on test diets, (18 weeks for the F0 generation), females were mated one to one with males from the same diet group.
- Frequency of treatment:
- continously
- Details on study schedule:
- The following description pertains to animals selected for reproduction studies from the F0, F1a, and F2b generations.
After approximately 13 weeks on test diets, (18 weeks for the Fo generation), females were mated one to one with males from the same diet group.
One week after weaning of the F2a or F3a litters, the parent generation was mated again in the described manner to produce a second litter.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 300 ppm
- Remarks:
- Group 8, conversion with generic animal data according to "Reproductively Active Chemicals" (factor for adult rats: 0.08)
300 ppm = 24 mg/kg bw/day
- Dose / conc.:
- 1 250 ppm
- Remarks:
- Group 9, conversion with generic animal data according to "Reproductively Active Chemicals" (factor for adult rats: 0.08)
1250 ppm = 100 mg/kg bw/day
- Dose / conc.:
- 5 000 ppm
- Remarks:
- Group 10, conversion with generic animal data according to "Reproductively Active Chemicals" (factor for adult rats: 0.08)
5000 ppm = 400 mg/kg bw/day
- No. of animals per sex per dose:
- 40 (F0), 20 (F1, F2)
- Control animals:
- yes, concurrent vehicle
Examinations
- Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: yes
- If yes, maximum of 40 pups/litter (20/sex/litter as nearly as possible); excess pups were killed and discarded.
PARAMETERS EXAMINED
The following parameters were examined in [F1 / F2 / F3] offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain
GROSS EXAMINATION OF DEAD PUPS:
Yes - Reproductive indices:
- mating index, fertility index, gestation index
- Offspring viability indices:
- viabilty index, survival index, lactation index
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- 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):
- not examined
- Food efficiency:
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
Details on results (P0)
Effect levels (P0)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 400 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reproductive performance
Target system / organ toxicity (P0)
- Key result
- Critical effects observed:
- no
Results: P1 (second parental generation)
General toxicity (P1)
- 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):
- not examined
- Food efficiency:
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
Reproductive function / performance (P1)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
Details on results (P1)
Data from the second litter of the F1a generation (F2b litter) showed no changes in Fertility index and Mating index in the treament groups cmpared to the control group.
The number of newborn pups was not affected by the treatment.
Effect levels (P1)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 400 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reproductive performance
Target system / organ toxicity (P1)
- Key result
- Critical effects observed:
- no
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- mortality observed, non-treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Group 10 (high level TFM) revealed reduced weaning weights in all litters (3 - 6 g) when compared to group 7 (negative control).
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- 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
- Other effects:
- not examined
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not examined
Details on results (F1)
Effect levels (F1)
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1a
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
Target system / organ toxicity (F1)
- Key result
- Critical effects observed:
- no
Results: F2 generation
General toxicity (F2)
- Clinical signs:
- no effects observed
- Mortality / viability:
- mortality observed, non-treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Group 10 (high level TFM) revealed reduced weaning weights in all litters (3 - 6 g) when compared to Group 7 (negative control).
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Ophthalmological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- 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
- Other effects:
- not examined
Developmental neurotoxicity (F2)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F2)
- Developmental immunotoxicity:
- not examined
Details on results (F2)
Effect levels (F2)
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F2b
- Effect level:
- 100 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
Target system / organ toxicity (F2)
- Key result
- Critical effects observed:
- no
Overall reproductive toxicity
- Key result
- Reproductive effects observed:
- no
Any other information on results incl. tables
Additionally, the effects on a third generation were observed:
F3a: First litter data for the F2b generation revealed generally normal values for most groups. Group 10 showed a slightly lower number of pregnancies, Fertility index - 74 %, when compared to Group 7 (94 %). Mating indexes are essentially equal for all groups. Smaller average numbers of pups were born in Groups 10 and 12 (10.5 and 9.7) when compared to Group 7 (12.0). Viability was good (89 - 97 %) for all groups. Survival was good for all groups at day 4. Average pup weights at day 4 were normal for all groups. Survival was good in all groups at weaning (day 21). Weaning weights were slightly smaller in Group 10 than Group 7 (45 g vs. 48 g).
F3b: Fertility indexes were down or unchanged in all groups when compared with indexes of F3a litters. Mating indexes were, in general, up for all groups. Though within a normal range, smaller average numbers of pups were born in Groups 10 compared with Group 7. Groups 10 averaged 10.9 pups per litter compared with 13.0 pups in Group 7. Survival was good in all groups through weaning. Pup weights at day 4 were normal and revealed no differences among the groups. At 21 days a smaller average pup weight was seen in Group 10 (47 g) when compared with Group 7 (52 g).
Summary:
Overall reproductive performance in rats was generally good for most groups in all five litters (representing 3 generations) examined. Though some slight variations from litter to litter were seen, all average data and reproductive indexes were essentially normal and no significant reproductive differences were observed between the low level TFM or mid level TFM groups and the negative control group. A slightly lower Fertility index was observed in one or two groups from various litters. General overall fertility showed no abnormal variations between control and test groups, however. Gestation indexes were good throughout the study; essentially all positive pregnancies resulted in live births. Viability (Viability index) and survival through weaning (Survival index, Lactation index) were good for all groups through 3 generations. The average numbers of pups born per litter were, in most cases, within the normal range for this laboratory of approximately 9 - 12. Approximately half of the individual litters born in any given reproduction showed reduced number of pups born when compared to a normal range. Group 10 (high level TFM) revealed slightly reduced average numbers of pups born in both F3 litters when compared to the negative control. Average pup weights at day 4 showed slight variations among the groups, but all average weights were normal and no trend exists through 3 generations. At 21 days, weaning weights were normal and no consistent differences existed between the negative control group and the low and mid TFM groups. Group 10 (high level TFM) revealed reduced weaning weights in all litters (3 - 6 g) when compared to Group 7 (negative control).
Applicant's summary and conclusion
- Conclusions:
- In this 3-generation study similar to OECD guideline 416 in rats, no effect of the test substance on fertility was observed.
- Executive summary:
In this study, the test substance was administered to 40 sex/dose (F0), or 20 sex/dose (F1, F2) Sprague-Dawley rats in diet at dose levels of 0, 300.0, 1250.0, and 5000.0 ppm (0, 24, 100, or 400 mg/kg bw/day). No changes in the reproductive indices of the treatment groups compared to the control group were observed in any generation. The only treatment-related effect observed was a reduction of weaning weights in the high dose group in the F1 and F2 generation.
Based on these observation, following NOAEL were determined:
P0: 5000 ppm (400 mg/kg bw/day) based on reproductive performance
P1:5000 ppm (400 mg/kg bw/day) based on reproductive performance
F1: 1250 ppm (100 mg/kg bw/day) based on body weight and weight gain
F2b:1250 ppm (100 mg/kg bw/day) based on body weight and weight gain
However, it can be assumed, that the observed weight difference between untreated control animals and treated animals (400 mg/kg bw/day) at weaning, is a transient effect. Comparing the weight gain of the femal P0, P1 and P2 animals of the corresponding treatment groups, no differences in bodyweight can be observed. Therefore, the observed weight difference at weanlings is not an adverse effect.
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