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EC number: 244-959-5 | CAS number: 22398-80-7
- 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
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- 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
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- Nanomaterial specific surface area
- Nanomaterial Zeta potential
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- Endpoint summary
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- 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
Description of key information
A two-year study assessing the testicular damage induced following intratracheal instillations of Indium phosphide was conducted. Male Syrian golden hamsters were instilled with 3.0 mg/kg bw of Indium Phosphide twice a week for 8 weeks.
Animals were periodically sacrificed at 0, 8, 16, 40, 64 and 88 weeks after the last instillation.
Observed effects included those on the weight loss of animals and reproductive organs(testes and epididymis), decrease in sperm cell count and histopathological lesions in the seminiferous tubules.
From week 0 to 8 body weights and organ weights (epididymis and testes) of hamsters were comparable to those of chamber controls and changed significantly from week 16 to 64 where body weights diminished to 80-90% of control animals and organ weights to 60-70%. Both the body weights and organ weights returned to compatibility on week 88.
Similarly incidences of histopathologic changes in the seminiferous tubules were comparable to control values up till week 8 and changes occurred at week 16 to week 64.
The caudal sperm count in treated animals significantly decreased immediately after the last instillation and continued to decrease from week 16 to 64 where it was between 40-50%. Recovery of the caudal sperm count to the control level was seen at week 88 when serum indium concentrations were decreased by half.
Testicular damages were seen to recover in week 88 in line with the decrease in serum indium.
Considering the severity of the effects on reproductive organs and caudal sperm count compared to the generic toxic effects, they were not considered as non-specific, secondary effects. The authors concluded Indium Phosphide to be a testicular toxicant.
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 2000
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- - Principle of test:
Effects of indium phosphide on male genital organs were observed in hamsters after intra-tracheal instillation of 3 mg/kg bw of Indium Phosphide twice a week for 8 weeks. Testicular damage was evaluated 0, 8, 16, 40, 64 and 88 weeks after instillation.
- Short description of test conditions: Male Syrian golden hamsters six weeks of age were housed in stainless steel cages at temperatures of 22-25°C, air humidity 50-60% and a light cycle of 12 hrs day and 12 hrs night. Food and water were provided ad libitum. Following a two week acclimation period hamsters 8 weeks of age were randomised by weight in to groups (controlled and exposed). Hamsters were intratracheally instilled with a 2.0 mL suspension/kg body weight under ether anaesthesia. A single instillation dose of the tests material was 3.0 mg/kg body weight. Hamsters in the control group were given phosphate buffer solution only. Hamsters were treated twice daily for 8 weeks.
- Parameters analysed / observed: Testes and epididymis were removed and weighted, sperm counter was performed using the right cauda epididymis, and histopathological changes in the right testis were investigated. - GLP compliance:
- no
- Limit test:
- no
- Species:
- hamster, Syrian
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Japan SLC,Inc.
- Age at study initiation: 8 weeks
- Weight at study initiation: mean body weight of 111.6 g
- Housing: stainless steel cage
- Diet : CE-2 feed (ad libitum)
- Water: Tap water (ad libitum):
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25
- Humidity (%): 50-60
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light - Route of administration:
- intratracheal
- Mass median aerodynamic diameter (MMAD):
- 1.06 µm
- Geometric standard deviation (GSD):
- 1.8
- Vehicle:
- other: Pathogen free Phosphate bufer solution
- Details on exposure:
- VEHICLE
- Concentration in vehicle: 1.5 mg/mL - Details on mating procedure:
- Not applicable
- Analytical verification of doses or concentrations:
- no
- Details on analytical verification of doses or concentrations:
- Not reported
- Duration of treatment / exposure:
- 8 weeks
- Frequency of treatment:
- twice weekly
- Details on study schedule:
- Not applicable
- Dose / conc.:
- 3 other: mg/kg bw, twice a week
- Dose / conc.:
- 0 other: mg/kg bw, twice a week
- No. of animals per sex per dose:
- 48 males / dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Rationale for animal assignment (if not random): randomised by weight
- Positive control:
- No
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Not reported
DETAILED CLINICAL OBSERVATIONS: Not reported
BODY WEIGHT: Yes
- Time schedule for examinations: 0, 8, 16, 40,64 and 88 weeks after the last instillation - Oestrous cyclicity (parental animals):
- Not applicable
- Sperm parameters (parental animals):
- Parameters examined in [all/P/F1/F2] male parental generations: Testes and epididymis were removed and weighted, sperm counter was performed using the right cauda epididymis, and histopathological changes in the right testis were investigated.
- Litter observations:
- Not applicable
- Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All surviving animals were sacrificed 0, 8,1 6, 40, 64 and 88 weeks after the last instillation.
HISTOPATHOLOGY / ORGAN WEIGHTS: Organ weights for reproductive organs such as the testis and epididymis were recorded. Histopathological analysis of testis were undertaken. - Postmortem examinations (offspring):
- Not applicable
- Statistics:
- The F test was performed to evaluate the equality of variance.If a significant difference was found,a t test with Welch's correction was used for the statistical analysis otherwise a t test without a correction was used. Differences were considered significant at p<0.05
- Reproductive indices:
- Not reported
- Offspring viability indices:
- Not applicable
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- Three hamsters died of thinness, four were cannibalized (control group) and four were accidentally killed before examination (control group) during the observation period.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weights were comparable to chamber controls instantly succeeding instillation. However, they significantly diminished to 80-90% of chamber control from week 16 to week 64 prior to returning to compatibility with the control group at 88 weeks after the last instillation.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Serum indium concentration decreased by approximately half starting from the 8 week period and continuing to week 88 after the last instillation.
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- The incidences of seminiferous tubules with histopathologic changes were comparable to the control value up till week 8 following instillation. Vacuolization of seminiferous epithelium was frequently observed as an early histopathologic change.
Spermatogonia remained in the seminiferous tubules with severe histopathologic changes.
Significant changes occurred from week 16 to 64.
From weeks 16 to 88 after instillation, 30-50% of seminiferous tubules have histopathologic alterations, while abnormalities linked to age are observed in 14% of seminiferous tubules in controls at week 88. Histologic alterations included exfoliation and disarrangement of seminiferous epithelium, degeneration and loss of germ cells, and atrophy of seminiferous tubules without alteration of spermatogonia. - Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- effects observed, treatment-related
- Description (incidence and severity):
- The caudal sperm count in the Indium exposed group decreased significantly immediately after the last instillation before effects on bodyweights were observed, suggesting that it is not secondary to other toxic effects. The caudal sperm count decreased further from week 16 to 64 and was between 40-50% during this period post instillation. The caudal sperm count recovered to the control level 88 weeks after the last instillation.
- Reproductive performance:
- not specified
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 3 other: mg/kg bw, twice weekly
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- body weight and weight gain
- histopathology: non-neoplastic
- reproductive function (sperm measures)
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 3 mg/kg bw/day (nominal)
- System:
- male reproductive system
- Organ:
- cauda epididymis
- seminiferous tubules
- testes
- Treatment related:
- yes
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- not examined
- Body weight and weight changes:
- not examined
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- 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:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- not examined
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- not examined
- Body weight and weight changes:
- not examined
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Anogenital distance (AGD):
- not examined
- Nipple retention in male pups:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
- Other effects:
- not examined
- Behaviour (functional findings):
- not examined
- Developmental immunotoxicity:
- not examined
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- not examined
- Body weight and weight changes:
- not examined
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Anogenital distance (AGD):
- not examined
- Nipple retention in male pups:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
- Other effects:
- not examined
- Behaviour (functional findings):
- not examined
- Developmental immunotoxicity:
- not examined
- Key result
- Reproductive effects observed:
- yes
- Lowest effective dose / conc.:
- 3 other: mg/kg bw, twice weekly
- Treatment related:
- yes
- Relation to other toxic effects:
- reproductive effects occurring together with other toxic effects, but not as a secondary non-specific consequence of other toxic effects
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- Effects on male genital organs and caudal sperm count were observed following an exposure to Indium Phosphide, which were not considered as secondary to other adverse effects.
- Executive summary:
A two-year study assessing the testicular damage induced following intratracheal instillations of Indium phosphide was conducted. Male Syrian golden hamsters were instilled with 3.0 mg/kg bw of Indium Phosphide twice a week for 8 weeks.
Animals were periodically sacrificed at 0, 8, 16, 40, 64 and 88 weeks after the last instillation.
Observed effects included those on the weight loss of animals and reproductive organs(testes and epididymis), decrease in sperm cell count and histopathological lesions in the seminiferous tubules.
From week 0 to 8 body weights and organ weights (epididymis and testes) of hamsters were comparable to those of chamber controls and changed significantly from week 16 to 64 where body weights diminished to 80-90% of control animals and organ weights to 60-70%. Both the body weights and organ weights returned to compatibility on week 88.
Similarly incidences of histopathologic changes in the seminiferous tubules were comparable to control values up till week 8 and changes occurred at week 16 to week 64.
The caudal sperm count in treated animals significantly decreased immediately after the last instillation and continued to decrease from week 16 to 64 where it was between 40-50%. Recovery of the caudal sperm count to the control level was seen at week 88 when serum indium concentrations were decreased by half.
Testicular damages were seen to recover in week 88 in line with the decrease in serum indium.
Considering the severity of the effects on reproductive organs and caudal sperm count compared to the generic toxic effects, they were not considered as non-specific, secondary effects. The authors concluded Indium Phosphide to be a testicular toxicant.
Reference
Additional information
A toxicity reproduction study was performed using intratracheal instillation for 8 weeks (two instillations per week) with an observation period of 88 weeks.
Based on the observations, it was concluded that treatment-related adverse effects occurred impacting on the fertility of animals without being secondary to generic toxic effects.
Justification for classification or non-classification
The study performed and reported by Omura et al. (2000) was used as basis by the ECHA Committee for Risk Assessment to set the Harmonised Classification of Indium Phosphide as Repr. 2; H361f: Suspected of damaging fertility.
Despite the interpretation of the study being limited by the single dose administrated and the lack of assessment of the fertility function, the observed adverse effects to caudal sperm count and male reproductive organs were considered as sufficient to conclude on the toxicity of the substance to fertility. In addition, while this study was performed using intratracheal instillation, testing performed via the inhalation route showed that indium can accumulate in testes following chronic exposure, thus supporting the classification as Repr. 2.
Additional information
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