Registration Dossier
Registration Dossier
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 200-240-8 | CAS number: 55-63-0
- 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:
- three-generation reproductive toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1976-1978
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Meets generally accepted scientific standards, well documented and acceptable for assessment.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 978
- Report date:
- 1978
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: U.S.F.D.A Guidelines (1966)
- Deviations:
- yes
- Remarks:
- See Overall remarks
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
- Deviations:
- yes
- Remarks:
- See Overall remarks
- Principles of method if other than guideline:
- GUIDELINE FOLLOWED (U.S.F.D.A Guidelines (1966))F0 group consisted of 10 males and 20 females cohabited for 14 days. F1a group was discarded and the F0 group remated. Twenty to 24 apparently normal offspring (F1b) of each sex were randomly selected in approx. equal numbers from each group and mated 1 / 1 with rats from the same group.The same procedure was followed with the F2 group. The F3b group was sacrificed after weaning and the overt physical and reproductive parameters called for in the FDA Guideline were evaluated. The results are shown in the tables on the pages 4 and5. As usual, rats in each cage were examined daily.
- GLP compliance:
- no
- Remarks:
- Unlikely
- Limit test:
- no
Test material
- Reference substance name:
- Glycerol trinitrate
- EC Number:
- 200-240-8
- EC Name:
- Glycerol trinitrate
- Cas Number:
- 55-63-0
- Molecular formula:
- C3H5N3O9 C3H5(NO3)3
- IUPAC Name:
- propane-1,2,3-triyl trinitrate
- Details on test material:
- - Name of test material (as cited in study report): Nitroglycerin, TNG
- Substance type: technical product
- Physical state: a 10 % mixture on lactose
- Analytical purity: 9.72% +/- 0.09%
- Lot/batch No.: D17-H3
- Source: Atlas Chemical Division, ICI America Inc., Wilmington, DE
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Charles River CD
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS- Source: Charles River Breeding Laboratory, Wilmington, Massachusetts, USA- Age at study initiation: All animals were maturing- Fasting period before study: no data- Housing: plastic cages with metal lids, filter tops, 4 male or 5 female in each cage, some groups were subdivided to prevent fighting.- Identification of animals: ear-punches- Bedding: with hardwood chip- Diet: ad libitum, Diets were prepared weekly- Water: ad libitum- Acclimation period: 2 weeksENVIRONMENTAL CONDITIONS- Temperature (°F): 75+/-5- Humidity (%): 50+/-10%- Air changes (per hr): 10 air changes per hour- Photoperiod (hrs dark / hrs light):12 hour light/12 hour dark
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- With the rodents, dosage levels of 0,01% (100 ppm), 0,1% (1000 ppm) and 1% (10 000 ppm) in the diet were used.DIET PREPARATION- Rate of preparation of diet (frequency): Diets were prepared weekly. - Mixing appropriate amounts with (Type of food): 10% concentrate was mixed with feed in a rotating box on a modified mixer to provide the diet mixture by successive dilutions. The control rodents received a mixture containing 10% dried feed in ordinary feed.With the rodents, dosage levels of 0,01% (100 ppm), 0,1% (1000 ppm) and 1% (10 000 pm) in the diet werer used.
- Details on mating procedure:
- - Length of cohabitation: Mating periods for F1 and F2 generations were 14 – 15 days.Reproductive performance for each parental generation was quantified by: the mating ratio and fertility ratios of each sex.- Proof of pregnancy: vaginal smears- Each male was housed with two females for 14 days.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Test levels of diet were prepared fresh weekly by dilution of the concentrate with unheated feed and were analyzed after preparation. Control analyses were carried out over eight-day periods to measure evaporation of NG from the diet under cage conditions during the week. GC also was used for these analyses, but with a 63Ni detector. This information was used to calculate actual dosage received by the rats.
- Duration of treatment / exposure:
- six months for males and five months for females
- Frequency of treatment:
- daily in the diet
Doses / concentrations
- Remarks:
- Doses / Concentrations:0.0, 0.01, 0.1, and 1.0 % (w/w) in the diet. Basis:actual ingested
- No. of animals per sex per dose:
- The begining number of rats was 38 of each sex per group. Additional rats were icluded for the three-generation (20 females in each dosage group) and metabolism (12 males and 12 females, each in the control, low doasge and high dose group) studies.
- Control animals:
- yes
- Details on study design:
- DOSES: 0.0, 0.01, 0.1, and 1.0 % (w/w) in the diet. Corresponding average TNG intakes for six months pretreatment (six months for males and five months for females) were, respectively, 0.00(M & F); 3.60 ± 0.28(M), 5.00 ± 0.17(F); 39.0 ± 1.8(M), 46.0 ± 0.9(F); and 408 ± 18(M), 452 ± 9(F) mg TNG / kg of rat / day. Females were dosed during pregnancy and between matings. Males were dosed until successful delivery of each "b" generation
Examinations
- Litter observations:
- litter size, the livebornindex, the weight of liveborn pups at birth, viability index, the weight at weaning and sex ratio.
Results and discussion
Results: P0 (first parental generation)
Effect levels (P0)
- Remarks on result:
- not measured/tested
Results: P1 (second parental generation)
Effect levels (P1)
- Remarks on result:
- not measured/tested
Results: F1 generation
General toxicity (F1)
- Mortality / viability:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
Details on results (F1)
Effect levels (F1)
open allclose all
- Dose descriptor:
- NOEL
- Generation:
- F1a
- Effect level:
- 39 mg/kg bw/day (actual dose received)
- Sex:
- male
- Basis for effect level:
- other: Dietary intakes of 39 ± 1.8 mg TNG / kg / day were no-effect levels for males.
- Dose descriptor:
- NOEL
- Generation:
- F1a
- Effect level:
- 46 mg/kg bw/day (actual dose received)
- Sex:
- female
- Basis for effect level:
- other: Dietary intakes of 46 ± 0.9 mg TNG / kg / day were no-effect levels for females.
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The high dose (1.0 % in the diet; 6-month average daily male intake = 408 mg ± 18 mg TNG / kg / day) caused severe aspermatogenesis with resulting severe infertility in the F2a generation of males. The high dose in the females (452 ± 9 mg TNG / kg / day caused a slight reduction in the parameters measured in the high dose F1b litter. Measurement of the dams' food intake during the F1b gestation period indicated a 35 % reduction of food intake vs. the control rats. This probably was responsible for the 38 % reduction in the individual total litter weights observed in the high dose F1b litter.Negative dominant lethal mutagenic and teratogenic studies (Robust Summaries included in this set), suggested strongly that these reduced litter parameters were not due to mutagenic or teratogenic effects as measured by those studies in intact rodents.Male daily dietary intake of an average 408 ± 18 mg TNG / kg / day was an effect level in male rats as measured by aspermatogenesis in the F2 generation of males. Female dietary intake of 452 ± 9 mg TNG / kg / day was an effect level in females as measured by litter size and birth weights. Dietary intakes of 39 ± 1.8 and 46 ± 0.9 mg TNG / kg / day, respectively, were no-effect levels for males and females.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
