Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
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: 231-767-1 | CAS number: 7722-88-5
- 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
Description of key information
One key study is available (Seo D, 2011) for the sub-chronic toxicity endpoint. This study is considered to be a reliability 2 study as it has been conducted to the appropriate guideline (OECD 408) and under the conditions of GLP. On the basis of this study the NOAEL was determined to be 500 mg/kg bw/day.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- Deficiencies: No indication of GLP compliance is reported and only group mean data are provided in the report
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- yes
- Remarks:
- Animals were only dosed for 5 days / week, Individual animal data not reported
- GLP compliance:
- not specified
- Remarks:
- Study published in the literature. No information on GLP is given.
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Orient Bio Co., Ltd. (Gyeonggi-do, Korea)
- Age at study initiation: 5 weeks old
- Weight at study initiation: between 150 and 200 g
- Housing: The animals were housed in groups of two to three in stainless steel wire mesh cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum - commercial rodent chow (2.0 Mrad gamma-ray sterilized EP pellet, Cargill Agri Purina Korea Ltd, Korea).
- Acclimation period: 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 3°C
- Humidity (%): 55 ± 5%
- Air changes (per hr): 10 to 18
- Photoperiod (hrs dark / hrs light): 10/14 - Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- distilled
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- Once a day, 5 days a week
- Remarks:
- Doses / Concentrations:
250, 500, 1000 mg/kg bw
Basis:
nominal in water - No. of animals per sex per dose:
- 10 per sex per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: 14-day range-finder study; No toxicity or mortality was observed in any of the five male and female rats treated with tetrasodium pyrophosphate for 14 days.
- Positive control:
- Not applicable
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once a day
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once a day
BODY WEIGHT: Yes
- Time schedule for examinations: once a week
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): yes (time scale for measurements not recorded: Food consumption by each group was measured at the start of treatment and during the 90-day administration period.
FOOD EFFICIENCY: Not applicable
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not applicable
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: Yes; isoflurane
- Animals fasted: Yes
- How many animals: all
- Parameters checked in table 1 were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: No data
- Animals fasted: Yes
- How many animals: all
- Parameters checked in table 2 were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: During dosing week 13 (last week)
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- The following parameters were examined: glucose, bilirubin, ketone body, specific gravity, blood, pH, protein, urobilinogen, nitrite and leukocyte levels, using the Multistix 10SG (Bayer, U.S.A.) and urine analyser (Clinitek 500, U.S.A.).
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes - Statistics:
- Statistical Analysis
The differences in parameters (BWs, organ weights, and the results of the blood biochemistry and haematology) were assessed by a standard two-way analysis of variance (ANOVA). If these showed statistical significance, Duncan’s or Dunnett’s multiple range test were used to compare groups (SPSS version 12.0 [SPSS Inc., Chicago, IL, USA]). P-values < 0.05 were considered statistically significant. - Clinical signs:
- no effects observed
- Description (incidence and severity):
- No mortality. Slight clinical signs noted in female rat treated with 500 and 1,000 mg/kg bw/ day (see 'details on results')
- Mortality:
- no mortality observed
- Description (incidence):
- No mortality. Slight clinical signs noted in female rat treated with 500 and 1,000 mg/kg bw/ day (see 'details on results')
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Male rats treated with 1,000 mg/kg bw/day had a lower terminal bodyweight than the control animals. No other effects noted and no treatment-related effects were noted in female dose groups.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- A significant decrease was noted in the top dose males during weeks 8 and 9 and a significant increase in food consumption was noted for females dosed with 1,000 mg/kg bw/day during week 4.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- See 'details on results' for a description of the effects noted.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- See 'details on results' for a description of the effects noted.
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- The relative weight of the liver in both male and females dosed with 500 and 1,000 mg/kg bw/day was significantly increased.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- There were no grossly visible findings or lesions in any dose group.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Effects were noted in the kidneys in the high dose groups (see ' details on results' for a full description)
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- Mortality and clinical signs
There was no treatment-related mortality in the animals treated with the test substance during the study. Female rats treated with 500 and 1,000 mg/kg of test substance showed hair loss. No significant clinical signs were observed in any other group.
Body weight
The terminal bodyweights of male rats treated with 1,000 mg/kg of test substance were lower than that of the control group, while there were no differences in body weight between the 250, 500 mg/kg, and control group. There was no treatment-related change in body weight in female rats
Food consumption
A significant decrease in food consumption was observed in the 1,000 mg/kg group of males at week 8 and 9. Food consumption in females increased significantly in the 1,000 mg/kg group at week 4. There were no significant changes in food consumption in the other groups .
Urinalysis and haematology
There were no specific symptoms in urinalysis at the doses of 250, 500, and 1,000 mg/kg. There were no significant changes in haematology in the 250 mg/kg group. WBC and neutrophil counts were significantly increased in males and females of the 1,000 mg/kg group, whereas the lymphocyte count was significantly lower in males and females of the 1,000 mg/kg group. RBC, HB, HCT, PT, and
APTT were significantly reduced in the males of the 1,000 mg/kg group, and PT was significantly reduced in males of the 500 mg/kg group.
Biochemistry
There were no significant changes in the serum biochemistry of males and females in the 250 mg/kg group. Total protein was significantly reduced in both sexes in the 500 and 1,000 mg/kg group. Albumin was significantly reduced in males of the 500 and 1,000 mg/kg group, and in females of the 1,000 mg/kg group. The A/G ratio was significantly increased in females of the 500 and 1,000 mg/kg group. T-BIL was significantly increased in females of the 1,000 mg/kg group, and ALP was significantly reduced in females of the 1,000 mg/kg group. AST was significantly increased in males of the 1,000 mg/kg group, but ALT was significantly reduced in females of the 1,000 mg/kg group. TG was significantly increased in both sexes in the 1,000 mg/kg group, while Ca, IP, Na, K, and Cl were significantly reduced in both sexes in this group. IP was also reduced in males of the 500 mg/kg group.
Necropsy findings and organ weight
There were no grossly visible findings or lesions in any group. There were no significant changes in organ weight in males and females of the 250 mg/kg group. The relative weight of the liver in the males of the 500 mg/kg and 1,000 mg/kg groups showed a significant increase. The absolute and relative weight of the liver in females of the 500 mg/kg and 1,000 mg/kg groups were also significantly increased
Histopathology
No exposure-related histopathological changes were observed in any of the organs examined in SD rats, with the exception of kidney lesions. Cortical tubular basophilia of the renal tubule was more evident in males of the 1,000 mg/kg group and mineralization of the kidney was evident in females of the 1,000 mg/kg group. Other background lesions were observed in the 0, 250, 500, and 1,000 mg/kg groups in both sexes. - Dose descriptor:
- NOEL
- Effect level:
- 250 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Haematological parameters were altered in the rats receiving 500 and 1000 mg/kg bw/day. These changes were not considered to be of toxicological relevance.
- Dose descriptor:
- NOAEL
- Effect level:
- 500 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Tubular basophilia was noted at 1000 mg/kg bw/day in both male and female rats.
- Critical effects observed:
- not specified
- Conclusions:
- The NOAEL was determined to be 500 mg/kg bw/day on the basis of changes observed in the kidneys of the rats in the high dose group.
Rats in general and particularly female rats are known to be susceptible to nephrocalcinosis when administered high doses of phosphates (typically starting at about 0.5 – 1.0 % in the diet).The effects are only seen in high dose animals (well above the recommended classification limits for STOT RE as defined in the Guidance on the Application of Regulation (EC) No 1272/2008) and therefore classification for STOT RE is not justified and no classification is proposed.
Reference
Table 3. Food consumption
Week |
Male |
Female |
||||||
Control |
250 (mg/kg bw/day) |
500 (mg/kg bw/day) |
1000 (mg/kg bw/day) |
Control |
250 (mg/kg bw/day) |
500 (mg/kg bw/day) |
1000 (mg/kg bw/day) |
|
1 |
27.1± 1.0 |
27.0± 1.6 |
26.7± 0.9 |
27.1± 1.8 |
19.1± 1.4 |
20.6± 1.7 |
19.9± 1.5 |
20.2± 1.0 |
2 |
30.4± 0.9 |
28.5± 6.4 |
30.7± 1.7 |
29.2± 1.4 |
21.1± 2.6 |
21.3± 3.9 |
21.4± 2.1 |
20.3± 2.1 |
3 |
33.8± 1.9 |
34.1± 2.2 |
32.9± 3.1 |
30.4± 3.6 |
22.6± 2.2 |
22.6± 2.7 |
21.8± 2.1 |
21.7± 1.0 |
4 |
30.9± 1.2 |
31.6± 2.5 |
31.8± 6.6 |
28.5± 3.2 |
19.7± 2.5 |
20.5± 1.4 |
21.3± 1.5 |
22.7± 1.3* |
5 |
33.4± 2.8 |
30.8± 1.2 |
31.8± 2.7 |
30.5± 2.1 |
21.7± 0.6 |
20.3± 3.3 |
19.3± 2.5 |
22.9± 2.7 |
6 |
29.3± 3.9 |
27.9± 2.6 |
29.2± 1.9 |
27.9± 2.9 |
18.1± 2.0 |
17.1± 3.7 |
18.2± 1.8 |
19.2± 1.3 |
7 |
33.1± 2.7 |
33.3± 2.6 |
33.8± 1.2 |
32.9± 3.2 |
24.3± 2.0 |
21.9± 2.0 |
23.2± 2.8 |
23.9± 2.9 |
8 |
31.5± 2.1 |
31.3± 2.1 |
33.0± 1.6 |
28.3± 0.5** |
20.8± 2.0 |
20.3± 2.9 |
21.7± 2.8 |
21.0± 2.2 |
9 |
31.8± 2.1 |
31.2± 1.7 |
30.5± 1.1 |
28.2±2.5* |
20.6± 3.8 |
18.8± 2.7 |
19.9± 1.4 |
19.8± 2.1 |
10 |
32.7± 2.0 |
31.6± 2.3 |
31.9± 1.1 |
28.8± 1.8 |
21.2± 1.3 |
18.9± 3.8 |
21.2± 2.4 |
19.4± 1.7 |
11 |
29.8± 2.7 |
30.3± 3.0 |
29.6± 2.0 |
27.8± 1.6 |
20.5± 3.5 |
19.5± 2.3 |
21.1± 3.7 |
21.0± 3.9 |
12 |
33.8± 0.5 |
33.5± 0.5 |
33.2± 0.6 |
33.4± 0.5 |
20.2± 1.8 |
19.7± 3.1 |
21.5± 2.0 |
20.3± 2.9 |
13 |
30.1± 2.2 |
29.4± 2.3 |
31.2± 1.8 |
28.5± 1.7 |
20.1± 1.5 |
18.6± 1.9 |
20.4± 3.6 |
21.1± 2.5 |
*p<0.05, **p<0.01.
Table 4. Haematology
Parameter measured |
Male |
Female |
||||||
Control |
250 (mg/kg bw/day) |
500 (mg/kg bw/day) |
1000 (mg/kg bw/day) |
Control |
250 (mg/kg bw/day) |
500 (mg/kg bw/day) |
1000 (mg/kg bw/day) |
|
WBC (K) |
7.20± 1.830 |
6.62± 0.71 |
7.76± 1.580 |
9.35± 1.31* |
3.72± 1.860 |
6.84± 2.090 |
4.44± 0.660 |
6.39± 1.83** |
Neutrophil (%) |
14.2± 4.600 |
18.6± 6.20 |
20.1± 6.600 |
24.8± 4.900 |
12.2± 3.700 |
17.7± 5.000 |
17.3± 7.300 |
20.9± 6.3*0 |
Lymphocyte (%) |
80.1± 4.500 |
74.8± 6.20 |
73.6± 6.900 |
68.7± 6.000 |
81.4± 5.000 |
74.4± 6.100 |
75.4± 7.400 |
73.2± 7.0*0 |
Monocyte (%) |
3.6± 1.100 |
3.9± 1.60 |
3.4± 1.100 |
4.1± 1.800 |
3.6± 1.500 |
3.7± 0.200 |
3.8± 1.700 |
3.3± 0.900 |
Eosinophil (%) |
1.4± 0.500 |
1.9± 0.50 |
2.3± 0.7*0 |
1.8± 0.600 |
2.1± 0.900 |
1.9± 0.300 |
2.6± 1.100 |
2.1± 0.600 |
Basophil (%) |
0.2± 0.100 |
0.2± 0.10 |
0.2± 0.100 |
0.3± 0.100 |
0.2± 0.100 |
0.2± 0.000 |
0.2± 0.100 |
0.2± 0.100 |
RBC (M) |
8.56± 0.190 |
8.43± 0.34 |
8.55± 0.420 |
8.19± 0.19** |
7.82± 0.280 |
8.16± 0.400 |
7.96± 0.230 |
7.82± 0.250 |
Hb (g/dl) |
15.3± 0.500 |
14.9± 0.70 |
14.8± 0.800 |
14.4± 0.3** |
14.4± 0.500 |
14.5± 0.600 |
14.6± 0.400 |
14.1± 0.400 |
Hct (%) |
45.5± 1.400 |
44.3± 1.80 |
44.4± 2.200 |
43.1± 0.8** |
42.3± 1.500 |
43.1± 2.000 |
42.8± 1.300 |
42.0± 1.200 |
MCV (fL) |
53.1± 1.100 |
52.5± 1.30 |
52.0± 2.700 |
52.7± 0.900 |
54.1± 1.200 |
52.0± 2.400 |
53.8± 1.300 |
53.7± 0.900 |
MCH (pg) |
17.9± 0.400 |
17.6± 0.50 |
17.3± 1.000 |
17.6± 0.400 |
18.5± 0.500 |
17.5± 0.900 |
18.3± 0.500 |
18.1± 0.200 |
MCHC (g/dL) |
33.8± 0.500 |
33.5± 0.50 |
33.2± 0.600 |
33.4± 0.500 |
34.1± 0.400 |
33.0± 1.400 |
34.1± 0.200 |
33.7± 0.400 |
Reticulocyte (%) |
2.04± 0.340 |
2.1± 0.30 |
2.38± 0.520 |
2.37± 0.380 |
1.79± 0.410 |
2.11± 0.260 |
2.02± 0.490 |
2.27± 0.420 |
PLT (K) |
1148.2± 124.4 |
1071.6± 98.4 |
1213.9± 123.4 |
1264.5± 110.5 |
1153.7± 171.4 |
1153.2± 105.1 |
1169.5± 427.3 |
1441.4± 210.2 |
PT (sec) |
17.7± 0.500 |
17.6± 0.60 |
16.7± 0.6**0 |
16.5± 0.6**0 |
16.9± 0.800 |
17.1± 0.600 |
17.1± 1.000 |
16.4± 0.900 |
APTT (sec) |
20.3± 1.200 |
19.5± 1.90 |
19.4± 1.200 |
18.4± 1.1*0 |
16.4± 0.800 |
18.8± 1.500 |
16.5± 0.900 |
16.7± 0.8 |
WBC: white blood cell, RBC: red blood cell, Hb: hemoglobin, Hct: hematocrit, MCV: mean corpuscular volume,
MCH: mean corpuscular haemoglobin, MCHC: mean corpuscular hemoglobin concentration, PLT: platelet. PT: prothrombin time,
APTT: activated partial thromboplastin time.
*p<0.05,**p<0.01
See attachment for the following tables:
- Table 5. Biochemistry
- Table 6. Absolute organ weights
- Table 7. Relative organ weights
See Figures for information on changes in bodyweight.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 500 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- The key study was performed in accordance with an appropriate guideline (OECD 408) and with few deficiencies. No indication of GLP compliance is reported and only group mean data are provided in the report however, this study is considered to meet the regulatory requirements for repeated dose toxicity in accordance with Annex XI, Section 1 of Regulation (EC) No.1907/2006 (REACH). Additional literature data were available, however these were considered to be most useful as supporting data only.
- System:
- urinary
- Organ:
- kidney
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
REPEATED DOSE: INHALATION
In vivo repeated dose toxicity studies via the inhalation route are not considered to be required for the following reasons:
Inhalable dusts, including the test material, may be absorbed directly from the respiratory tract or, through the action of clearance mechanisms. The material can be cleared from the respiratory tract by the muco-cillary escalator and then swallowed, adding to systemic toxicity via the oral route. It has already been concluded that sodium and potassium pyrophosphates are of low systemic toxicity via the oral route. Therefore the potential risk from inhaled dust that is cleared from the airways and subsequently swallowed is considered to be minimal.
With regards to systemic absorption via the epithelial lining of the lungs; water-soluble substances (i.e.sodium and potassium pyrophosphates) would, to a certain extent, diffuse/dissolve into the mucus lining of the respiratory tract, however, sodium and potassium pyrophosphates are not considered to be lipophilic and therefore absorption via the respiratory tract epithelium is unlikely. Another consideration of systemic absorption are the aqueous pores lining the respiratory tract, absorption via aqueous pores is possible.
Some sodium and potassium pyrophosphates are however classified as irritating to the eyes and as such the possibility of irritation to the mucus membranes of the lungs has been considered.
In order to assess the effects of exposure to sodium and potassium pyrophosphates companies involved with the manufacture of sodium and potassium pyrophosphates have provided medical data to support the hypothesis that there is no concern for workers exposed to quantities of these products at doses close to the derived DNEL. Inhalation exposure is the only relevant route of exposure during manufacture and packaging activities.
The substances covered by this investigation were:
- Disodium dihydrogenpyrophosphate (EC: 231-835-0, CAS: 7758-16-9)
- Trisodium hydrogen diphosphate (EC: 238-735-6, CAS: 14691-80-6)
- Tetrasodium pyrophosphate (EC: 231-767-1, CAS: 7722-88-5)
- Tetrapotassium pyrophosphate (EC: 230-785-7, CAS: 7320-34-5)
Medical data from five sites; two in Western Europe, one in Eastern Europe and 2 in North America / Canada, covering both manufacturing and packaging activities associated with sodium and potassium pyrophosphates were provided in an anonymous form. The data reported consists of the following measurements: FEV-1 value (Forced Expiratory Volume in 1 Second), FVC (Forced Vital Capacity). In addition, the age, smoker status, weight, asthma status, lung cancer status, number of years exposed to inorganic pyrophosphates and other unspecified personal factors that may influence the health of the subject were also recorded in the data.
From this data the Tiffeneau index (FEV-1 / FCV x 100) was calculated. This ratio is often used as a measure of the pulmonary function of an individual and is expressed as a percentage of the vital capacity. Assessment of the degree of airflow obstruction according to the reduction in post-bronchodilator forced expiratory volume in 1 second (FEV1) is made using spirometry. Reduced FEV-1 values can also be indicative of restrictive lung disease in cases where the Tiffeneau index is not also reduced; however it is worth noting that in adults it is known that the FEV-1 will decline with age.
For the purpose of this investigation FEV -1 measurements of between 80% – 120% are considered to be normal and Tiffeneau index values of <80% were considered to be indicative of reduced pulmonary function.
Analysis of Results:
MANUFACTURING ACTIVITIES:
Of the 102 workers on which data were collected, 19 workers were found to have a Tiffeneau ratio of <80%. However the following confounding factors were noted: 5 of these workers were smokers, 9 were overweight (3 smoked and were overweight), 1 had asthma and 3 had a history of bronchitis. 2 of remaining 4 workers had low FEV-1 values when first measured thus suggesting the effects were not related to pyrophosphate inhalation and only 2 cases were unexplained.
In addition, only 3 cases had a FEV-1 of <80% and a normal Tiffeneau ratio; 2 of which were smokers (1 was also overweight) and 1 was unexplained.
PACKAGING ACTIVITIES:
Of the 56 workers on which data were collected, 3 workers were found to have a Tiffeneau ratio of <80%. However all 3 of these workers were smokers. No workers had a FEV-1 of <80% and a normal Tiffeneau ratio. It is worth nothing however that 33 workers did not have FEV-1 or FVC values reported for them as it was not considered necessary to check pulmonary functions as no risk was anticipated due to a lack of reported problems for workers exposed to pyrophosphates.
Conclusions:
The data collected do not suggest a hazard for workers involved in the manufacture of use of sodium and potassium pyrophosphates. In the cases of reduced pulmonary function where no confounders were recorded it impossible to say whether other environmental factors (e.g. genetics) would have contributed to the results as the lack of correlation between reduced pulmonary function and exposure is not indicative of an effect.
Therefore, this data is considered to be sufficient adequacy and relevance to negate the need for further animal testing for REACH registration in accordance with Annex XI, Section 1.1.3 of Regulation (EC) No. 1907/2006 (REACH) and the DNEL calculated from the oral data is considered to be sufficiently protective.
Justification for classification or non-classification
The NOAEL was determined to be 500 mg/kg bw/day on the basis of changes observed in the kidneys of the rats in the high dose group.
Rats in general and particularly female rats are known to be susceptible to nephrocalcinosis when administered high doses of phosphates (typically starting at about 0.5 – 1.0 % in the diet).The effects are only seen in high dose animals (well above the recommended classification limits for STOT RE as defined in the Guidance on the Application of Regulation (EC) No 1272/2008) and therefore classification for STOT RE is not justified and no classification is proposed.
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.