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EC number: 700-903-6 | CAS number: 255830-15-0
- 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:
- two-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 29.10.1976 to 15.08.1978
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 979
- Report date:
- 1979
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Three generation reproduction toxicity study with the following restrictions: no assessment of estrus cycle, sperm parameters, sexual milestones and no analytical confirmation of exposure levels.
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Nitrilotrimethylenetris(phosphonic acid)
- EC Number:
- 229-146-5
- EC Name:
- Nitrilotrimethylenetris(phosphonic acid)
- Cas Number:
- 6419-19-8
- Molecular formula:
- C3H12NO9P3
- IUPAC Name:
- [nitrilotris(methylene)]tris(phosphonic acid)
- Test material form:
- solid: crystalline
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Long-Evans
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Blue Spruce Farms, Altamont, New York.
- Age at study initiation: (P) 6-7 weeks
- Weight at study initiation: (P) males approximately 370 grams, females approximately 240 grams at mating
- Fasting period before study: No data
- Housing: Individually (except during mating and lactation) in elevated stainless steel wire mesh cages.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 14 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data
IN-LIFE DATES: From: 12.11.1976 To: 15.08.1978
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with (Type of food): Purina Laboratory Chow (standard laboratory diet)
- Storage temperature of food: No data - Details on mating procedure:
- - M/F ratio per cage: 1/2 (See table 1)
- Length of cohabitation: Overnight for up to 15 days.
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy.
- Remated (for F1b/F2b/F3b generation) following a 14 d rest period.
- Further matings after two unsuccessful attempts: no data
- After successful mating each pregnant female was caged: individually in elevated stainless steel wire mesh cages.
- Any other deviations from standard protocol: None apparent. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Diet samples were taken from control and treated groups weekly. Samples were stored frozen and sent to the sponsor at regular intervals throughout the study. No further details.
- Duration of treatment / exposure:
- From 60 days prior to first mating of P generation then continuous over 3 generations . Duration of test in total was approximately 21 months.
- Frequency of treatment:
- Daily
- Details on study schedule:
- - F1 and F2 parental animals not mated until after a growth period (unspecified duration) following selection from the F1b and F2b litters.
- Selection of parents from F1 and F2 generation when pups were 7 days post weaning.
- Age at mating of the mated animals in the study: Not clear, but there was a 14 day rest period between matings.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 300 ppm (nominal)
- Remarks:
- nominal in diet
See table 3 for conversion to mg/kg bw/day
- Dose / conc.:
- 1 000 ppm (nominal)
- Remarks:
- nominal in diet
See table 3 for conversion to mg/kg bw/day
- Dose / conc.:
- 3 000 ppm (nominal)
- Remarks:
- nominal in diet
See table 3 for conversion to mg/kg bw/day
- No. of animals per sex per dose:
- 12 male and 24 females (see Table 1)
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: No data
- Rationale for animal assignment (if not random): Random - Positive control:
- None
Examinations
- Parental animals: Observations and examinations:
- Examination conducted on F0, F1, F2 AND F3 (all adult generations)
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Gross examination occurred twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Weekly
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly during growth and rest periods of all animals. As well as pregnant females (F0, F1b, F2b) on GD 0, 6, 15 and 20 and lactating females (F0, F1) on LD 0, 4, 14 and 21.
FOOD CONSUMPTION AND COMPOUND INTAKE: Weekly for males and non-pregnant females.
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
WATER CONSUMPTION AND COMPOUND INTAKE: No
OPHTHALMOSCOPIC EXAMINATION: F0 parents after weaning of F1b litter. - Oestrous cyclicity (parental animals):
- Not investigated.
- Sperm parameters (parental animals):
- Not investigated.
- Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: yes
- If yes, to 10 pups/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, physical or behavioral abnormalities. See Tables 4, 5 and 6 for pup survival data.
GROSS EXAMINATION OF DEAD PUPS:
yes, sex determined and stomach checked for presence of milk. Cause of death was not determined. - Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All surviving animals after completion of pup selection for the F0 and F1 generations, and after weaning of last litters for the F2 generation.
- Maternal animals: All surviving animals after completion of pup selection for the F0 and F1 generations, and after weaning of last litters for the F2 generation. Additionally, non-pregnant dams from first mating.
- Dead and moribund animals examined as death occurred.
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.
- Dams uterine contents examined for the presence of implantation sites and/or scars.
HISTOPATHOLOGY / ORGAN WEIGHTS: None scheduled for adults. Only grossly abnormal tissues were examined. - Postmortem examinations (offspring):
- SACRIFICE
- The F1a/F2a/F3a offspring not selected as parental animals were sacrificed at 21 days of age.
- F1b and F2b progeny (non-parental): sacrificed after pup selection for next generation.
- F3b sacrificed at weaning.
- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows:
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.
HISTOPATHOLOGY / ORGAN WEIGTHS
The tissues indicated in Table 2 were prepared for microscopic examination from 10 pups/sex/group of the F3b generation. In addition, any grossly abnormal tissues were examined. - Statistics:
- Offspring body weights, off-spring numbers (LD 0 LD 4): F-test and Student's T-test.
Offspring survival, litter deaths, litters weaned, mortality, mating rates, pregnancy rates, fertility rates: Chi square.
Body weights, body weight change, food intake: Dunnett's test. - Reproductive indices:
- Mating indices (%), pregnancy rates (%) and fertility (%). No details given.
- Offspring viability indices:
- No details given.
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- F0: One mid dose male was sacrificed in a moribund state during mating for F1b litter ("severely tilted head"). One high dose female was sacrificed post-weaning of F1b litter with "extremely distended abdomen". There was no dose response and the deaths were considered sporadic, therefore not related to treatment. Physical observations were comparable between all groups.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- There was no effect in either sex on mean body weight or body weight gain during growth or rest periods. There were no effects on maternal body weight or body weight change during gestation or lactation periods.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The ophthalmoscopic examination revealed four rats (one control female, two mid dose males and one high dose male) with ocular abnormalities. However, these were not considered to be treatment related.
- 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
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- Gestation length, mean number of live and dead pups at birth and percentage of live pups at birth were comparable between groups.
Effect levels (P0)
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- F0
- Effect level:
- >= 3 000 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed
Target system / organ toxicity (P0)
- Critical effects observed:
- no
Results: P1 (second parental generation)
General toxicity (P1)
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Red and swollen ears on the tagged ear were noted in F1 and F2 adults. Physical observations were comparable between all groups.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- F1: One mid dose male died during mating. One high dose female died during post-weaning interval, prior to sacrifice. One control male and one high dose female sacrificed with "severely tilted heads" (male sacrificed wk 4, female in rest period between matings). There was no dose response and the deaths were considered sporadic and therefore, not related to treatment.
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Immunological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Other effects:
- no effects observed
- Description (incidence and severity):
- A high number of dead pups within a single mid dose litter lead to a significant decrease in the survival index at birth in the mid dose group for F1b.
Reproductive function / performance (P1)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
Effect levels (P1)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- F1 / P1
- Effect level:
- >= 3 000 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- F2 / P2
- Effect level:
- >= 3 000 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed
Target system / organ toxicity (P1)
- Critical effects observed:
- no
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- Physical observations comparable were between all groups.
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- mortality observed, non-treatment-related
- Description (incidence and severity):
- F2: One low dose female died during week 3 of the growth period. One mid dose male died during week 8 of the growth period. One mid dose female died on GD 21 for the F3b litter. One high dose male died during the mating interval to produce the second litter. There was no dose response and the deaths were considered sporadic and therefore, not related to treatment.
- Body weight and weight changes:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
- Other effects:
- no effects observed
- Description (incidence and severity):
- No adverse effect was concluded. There was no effect on mating indices (%), pregnancy rates (%) or fertility (%).
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not examined
Effect levels (F1)
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- F1
- Generation:
- F1
- Effect level:
- >= 3 000 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed
Target system / organ toxicity (F1)
- Critical effects observed:
- no
Results: F2 generation
General toxicity (F2)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- no mortality observed
- Description (incidence and severity):
- Significant decrease (P<0.01) in survival index at birth in the second mid dose litter (F1 for F2b). This was not considered indicative of a treatment-related effect by the study authors since comparable changes this was not replicated in other phases of the study, nor was any dose/response relationship present. Survival at birth was significantly increased (P<0.01) for the high dose F3b litter. Some statistically significant differences were apparent in postnatal survival indices between control and treated groups, however these were not considered adverse by the authors since no trend was present. These differences generally reflected a statistically significant enhancement in survival relative to the controls (9 instances), while decreased survival was relatively infrequent (2 instances). The percentages of litters with offspring deaths and litters weaned were comparable between control and treated groups.
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Water consumption and compound intake (if drinking water study):
- not examined
- Gross pathological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Scattered red foci was present in the lung from some F2b offspring from the mid and high dose groups. This was not present in controls and the low dose group. The effects were considered as not treatment-related by the authors due to the absence of this in the other generations. All other necropsy observations were similar for the control and the treated litters. Evaluation of selected tissues from 10 control weanlings and 10 high dose weanlings from the F3b generation revealed no abnormalities. Changes present in the lung were consistent with minimal to mild interstital pneumonia. The microscopic appearance of the gonads was unremarkable and consistent with sexually immature rats.
- Histopathological findings:
- no effects observed
- Other effects:
- no effects observed
- Description (incidence and severity):
- The sex ratio was not affected by treatment.
Developmental immunotoxicity (F2)
- Developmental immunotoxicity:
- not examined
Effect levels (F2)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- F2
- Generation:
- F2
- Effect level:
- >= 3 000 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- F3
- Generation:
- other: F3
- Effect level:
- >= 3 000 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects observed
Target system / organ toxicity (F2)
- Critical effects observed:
- no
Overall reproductive toxicity
- Reproductive effects observed:
- no
Any other information on results incl. tables
Table 3 - Test substance intake based on food intake (weekly mean data) measurements .
Males (mg/kg bw/day) | Males (mg/kg bw/day) | Males (mg/kg bw/day) | Females (mg/kg bw/day) | Females (mg/kg bw/day) | Females (mg/kg bw/day) | |
Group (ppm) | II (300) | III (1000) | IV (3000) | II (300) | III (1000) | IV (3000) |
F0 growth | 33.4 | 111.6 | 342.3 | 37.3 | 117.1 | 362.5 |
F0 rest | 18.4 | 60.7 | 182.9 | 24.3 | 75.7 | 247.2 |
F1 growth | 26.3 | 89.6 | 270.2 | 28.1 | 98.4 | 290.2 |
F1 rest | 14.4 | 41.7 | 141.0 | 20.1 | 67.3 | 201.1 |
F2 growth | 29.6 | 95.4 | 296.6 | 34.3 | 112.6 | 337.8 |
F2 rest | 17.6 | 58.3 | 171.9 | 25.0 | 81.4 | 243.9 |
Table 4 - Summary of offspring
survival for the F1 generation.
Group (ppm) | Mean gestation length | % pups born alive | Mean no weaned/litter | Postnatal survival (%) | Postnatal survival (%) | Postnatal survival (%) | % litters with death (days 0 -21)c | % litters weanedc | Sex ratio (M/F) |
0 -4a | 4 -14b | 14 -21 | |||||||
F0 to F1a | |||||||||
I (0) | 22.5 | 98.8 | 9.1 | 92.0 | 94.3 | 100 | 57.1 | 95.2 | 0.87 |
II (300) | 22.4 | 98.2 | 8.6 | 97.3* | 90.5 | 100 | 65 | 100 | 0.87 |
III (1000) | 22.5 | 98.1 | 7.6* | 96.2 | 85.4** | 100 | 47.6 | 95.2 | 0.88 |
IV (3000) | 22.3 | 98.1 | 8.7 | 99.2** | 91.4 | 99 | 52.2 | 100 | 1.24 |
F0 to F1b | |||||||||
I (0) | 22.1 | 93.0 | 8.9 | 87.2 | 96.0 | 99.3 | 61.1 | 88.9 | 1.07 |
II (300) | 22.1 | 96.0 | 8.7 | 91.7 | 91.3 | 99.4 | 83.3 | 100 | 1.12 |
III (1000) | 22.1 | 97.2 | 9.3 | 94.8* | 93.7 | 100 | 56.3 | 100 | 0.84 |
IV (3000) | 22.1 | 95.8 | 9.2 | 97.6** | 96.5 | 99.5 | 28.6 | 100 | 0.96 |
Significantly different from control *p≤0.05; **p≤0.01
aComparison between days for postnatal offspring survival are calculated using Day 4 pre-cull data.
bComparison between days for postnatal offspring survival are calculated using Day 4 post-cull data.
cOnly those pups found alive at Day 0 of lactation are used in calculations.
Table 5 - Summary of offspring survival for the F2 generation.
Group (ppm) | Mean gestation length | % pups born alive | Mean no weaned/litter | Postnatal survival (%) | Postnatal survival (%) | Postnatal survival (%) | % litters with death (days 0 -21)c | % litters weanedc | Sex ratio (M/F) |
0 -4a | 4 -14b | 14 -21 | |||||||
F1 to F2a | |||||||||
I (0) | 22.2 | 99.5 | 9.2 | 96.2 | 93.5 | 100 | 33.3 | 94.4 | 1.09 |
II (300) | 22.3 | 100 | 9.5 | 96.8 | 99.5** | 100 | 35.0 | 100 | 1.18 |
III (1000) | 22.1 | 99.6 | 9.4 | 95.4 | 99.5** | 98.6 | 40.9 | 100 | 1.06 |
IV (3000) | 22.3 | 97.4 | 9.1 | 97.3 | 100** | 100 | 30.4 | 100 | 0.92 |
F1 to F2b | |||||||||
I (0) | 22.4 | 99.3 | 8.8 | 78.5 | 100 | 100 | 35.7 | 85.7 | 0.89 |
II (300) | 22.1 | 96.1 | 8.8 | 93.6** | 92.5 | 98.1 | 61.1 | 100 | 1.11 |
III (1000) | 22.1 | 92.5** | 8.2 | 92.4** | 88.5** | 58.8 | 93.8 | 93.8 | 0.95 |
IV (3000) | 22.5 | 99.1 | 9.0 | 96.6** | 97.8 | 98.9 | 50.0 | 100 | 0.94 |
Significantly different from control *p≤0.05; **p≤0.01
aComparison between days for postnatal offspring survival are calculated using Day 4 pre-cull data.
bComparison between days for postnatal offspring survival are calculated using Day 4 post-cull data.
cOnly those pups found alive at Day 0 of lactation are used in calculations.
Table 6 - Summary of offspring survival for the F3 generation.
Group (ppm) | Mean gestation length | % pups born alive | Mean no weaned/litter | Postnatal survival (%) | Postnatal survival (%) | Postnatal survival (%) | % litters with death (days 0 -21)c | % litters weanedc | Sex ratio (M/F) |
0 -4a | 4 -14b | 14 -21 | |||||||
F2 to F3a | |||||||||
I (0) | 22.3 | 97.9 | 7.8 | 89.5 | 94.3 | 99.4 | 54.5 | 95.5 | 0.91 |
II (300) | 22.4 | 91.3 | 6.4 | 87.2 | 89.5 | 100 | 75.0 | 100 | 1.13 |
III (1000) | 22.2 | 96.2 | 7.7 | 85.9 | 89 | 100 | 57.1 | 87.7 | 1.09 |
IV (3000) | 22.2 | 98.6 | 8.8 | 96.7** | 91.9 | 99.4 | 66.7 | 94.7 | 1.11 |
F2 to F3b | |||||||||
I (0) | 22.2 | 92.9 | 9.1 | 89.5 | 97.4 | 98.6 | 50.0 | 88.9 | 1.00 |
II (300) | 22.4 | 96.1 | 8.7 | 92.4 | 98.5 | 99.2 | 43.8 | 93.8 | 1.06 |
III (1000) | 22.1 | 92.7 | 8.3 | 93.5 | 97.3 | 100 | 38.5 | 100 | 0.83 |
IV (3000) | 22.2 | 98.5** | 9.2 | 89.9 | 98.7 | 100 | 52.9 | 94.1 | 1.45 |
Significantly different from control *p≤0.05; **p≤0.01
aComparison between days for postnatal offspring survival are calculated using Day 4 pre-cull data.
bComparison between days for postnatal offspring survival are calculated using Day 4 post-cull data.
cOnly those pups found alive at
Day 0 of lactation are used in calculations.
Applicant's summary and conclusion
- Conclusions:
- The key reproductive study is a multigenerational study for the category member, ATMP-H, conducted prior to the adoption of OECD test guidelines and pre-GLP. Male and female Long-Evans rats were administered ATMP 60 days prior to mating (F0) and continuously thereafter (F1, F2, F3) in the diet at fixed concentrations of 0, 300, 1000 and 3000 ppm for three consecutive generations. The NOAEL for general toxicity and reproductive toxicity was greater than the highest dose tested of 3000 ppm. The concentration of the test substance and mean weekly food intake values were used to determine the approximate doses received by the animals. The dose of 3000 ppm was approximately equal to a dose of 275 mg/kg bw/day in males and 310 mg/kg bw/day in females (Biodynamics Inc., 1979a).
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