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EC number: 200-272-2 | CAS number: 56-40-6
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Comparable to guideline study with restrictions (only two dose levels, limited documentation (clinical signs, gross pathology))
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- only two dose levels, limited documentation (clinical signs, gross pathology)
- Reason / purpose for cross-reference:
- reference to same study
- Principles of method if other than guideline:
- The carcinogenicity of glycine was assessed in rats by application in the drinking water.
- GLP compliance:
- no
- Species:
- rat
- Strain:
- Fischer 344/DuCrj
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Co. Japan, Inc. Atsugi
- Age at study initiation: 6 wks
- Housing: in plastic cages (3/sex/cage)
- Diet (ad libitum): pellet diet (CRF-1, Charles River, Japan)
- Water (ad libitum)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 2
- Humidity (%): 55 ± 5 - Route of administration:
- oral: drinking water
- Vehicle:
- unchanged (no vehicle)
- Duration of treatment / exposure:
- 108 wks
- Frequency of treatment:
- continuously via drinking water
- Dose / conc.:
- 2.5 other: % (nominal in water)
- Remarks:
- equivalent to 1534 mg/kg bw/day for males and 1587 mg/kg bw/day for females (actual ingested)
- Dose / conc.:
- 5 other: % (nominal in water)
- Remarks:
- equivalent to 3280 mg/kg bw/day for males and 3082 mg/kg bw/day for females (actual ingested)
- No. of animals per sex per dose:
- 50
- Control animals:
- other: drinking water without test substance
- Details on study design:
- - Dose selection rationale: on the basis of a preliminary subacute experiment (not further specified)
- Observations and examinations performed and frequency:
- BODY WEIGHT: Yes
- Time schedule for examinations: every one or two weeks
FOOD CONSUMPTION: Yes
- Time schedule for examinations: every four weeks
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: daily
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at week 108
- How many animals: all survivors
- Parameters checked: white/red blood cells, heamoglobin (Hb), haematocrit (Ht)
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at week 108
- How many animals: all survivors
- Parameters checked: glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), creatine phosphokinase (CPK), blood urea nitrogen (BUN), creatinine (CRE), Urea (UA), total protein (TP), albumin/globulin rate (A/G rate), blood glucose (BG), phospholipid (PL), total cholesterol (Tch), triglyceride (TG), natrium, potassium, calcium, chloride
URINALYSIS: Yes
- Parameters checked: leukocytes, nitrite, urobilinogen, protein, pH, ketone, glucose - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (all animals, including those that died or were sacrificed upon becoming moribund during the experiment)
HISTOPATHOLOGY: Yes (all organs were examined and samples were fixed in 10% buffered neutral formalin, embedded in paraffin, and routinely stained with hematoxylin and eosin; histological analysis of tumors in renal pelvis) - Statistics:
- Wilcoxon t-test or chi-squared test
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- 5% dose group: slightly increased mortality in females compared to controls
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- 5% dose group: slightly increased mortality in females compared to controls
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- 2.5 and 5% dose group: slight dose-dependent inhibition of mean body weight gain in both sexes
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 5% dose group: significant changes of Hb and HT in males and females
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 2.5 and 5% dose group, males and females: significantly changes in CPK, BUN, TP, Tch and TG were observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- 2.5 and 5% dose group: papillary necrosis and transitional hyperplasia was observed in male and female animals (no cases seen in the controls)
- Histopathological findings: neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- 2.5 and 5% dose group, females: kidney papillomas were seen, which were not observed in controls
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Mortality of females of the high dose group was slightly increased when compared to controls (number of surviving females and males: 31, 46, 41 and 40, 45, 40 for the high, low, control group).
BODY WEIGHT AND WEIGHT GAIN
2.5 and 5% dose group, males and females: Mean body-weights were slightly but dose-dependently inhibited when compared to controls over the hole study period (only growth curves were given).
HAEMATOLOGY
5% dose group, males: A slight but not significant increase in white blood cells was observed. The Hb was significantly increased when compared to controls.
5% dose group, females: A slight but not significant increase in white blood cells and a slight but not significant decrease in red blood cells was observed. The Hb and HT were significantly decreased when compared to controls.
2.5% dose group, females: A slight but not significant increase in white blood cells and a slight but not significant decrease in red blood cells was observed.
CLINICAL CHEMISTRY
2.5 and 5% dose group, males and females: The CPK values were significantly decreased when compared to controls in both sexes and both dose groups. BUN was significantly increased in both sexes of the 5% dose group.
2.5 and 5% dose group, females: A significant and dose-dependent decrease of TP and Tch and a significant and dose-dependent increase in TG was observed.
Some sporadic effects on isolated parameters were observed which were considered as not treatement-related (see Table 1 "Any other information on results incl. tables").
URINALYSIS
No significant differences in urinalysis data between treated and control male and female animals were observed. The only change was increased numbers of erythrocytes in glycine-treated male and female rats. This was expected from haemorrhage in necrotic renal papillae (see histopathology).
ORGAN WEIGHTS
No significant effects on the relative organ weights were observed in the treated groups when compared to controls.
HISTOPATHOLOGY: NON-NEOPLASTIC
The incidences of papillary necrosis in the kidney of male rats fed 2.5 and 5% glycine were 4 and 7%, while the corresponding figures for females were 30 and 32%. Since necrosis of the renal papillae was limited to glycine-treated rats it was very likely linked to the induction of papillomas. Transitional hyperplasia in renal pelvis was observed in 2 female animals of the 2.5% dose group. Calcification indices in kidney were 39, 32 and 42% of the 0, 2.5 and 5% groups. Endometrial polyps in the uterus were increased in both treatment group females (see Table 2/3 "Any other information on results incl. tables").
Overall, for the males, tumors were found in 90% of the high dose group, 97% of the low dose group and in 90% of the controls, while the corresponding figures for females were 59, 65 and 39%. These tumors were considered to be spontaneous in nature (see Table 3 "Any other information on results incl. tables").
HISTOPATHOLOGY: NEOPLASTIC (if applicable)
One renal cell tumor was seen in one male of the high dose group. Renal pelvis papillomas were found in 8% of the low dose group and in 6% of the high dose group females, but not in the controls. Since spontaneous tumors in this tissues are very rare, they were considered as treatment-related (see Table 3 "Any other information on results incl. tables"). - Dose descriptor:
- LOAEL
- Remarks:
- carcinogenicity
- Effect level:
- 1 561 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: histopathology
- Dose descriptor:
- NOAEL
- Remarks:
- carcinogenicity
- Effect level:
- < 1 561 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: histopathology
- Critical effects observed:
- not specified
Table 1: Clinical chemistry data for rats treated with the test substance (mean values ± standard deviation)
|
Males |
Females |
||||
Group (%) |
0 |
2.5 |
5 |
0 |
2.5 |
5 |
No. of rats |
40 |
45 |
40 |
41 |
46 |
31 |
GOT (K-U) |
122 ± 72 |
120 ± 57 |
114 ± 27 |
130 ± 53 |
117 ± 40 |
136 ± 68 |
GPT (K-U) |
51 ± 34 |
55 ± 37 |
53 ± 12 |
59 ± 22 |
56 ± 12 |
66 ± 16 |
LDH (K-U) |
2879 ± 772 |
2710 ± 972 |
2514 ± 819 |
2572 ± 1369 |
2666 ± 836 |
2556 ± 952 |
ALP (KA-U) |
16 ± 6 |
15 ± 5 |
17 ± 5 |
19 ± 9 |
19 ± 5 |
25 ± 7* |
CPK (IU/L) |
754 ± 321 |
563 ± 217* |
509 ± 197* |
706 ± 392 |
545 ± 160* |
446 ± 158* |
BUN (mg/dL) |
18 ± 3 |
17 ± 2 |
21 ± 3* |
18 ± 2 |
17 ± 2 |
21 ± 3* |
CRE (mg/dL) |
0.6 ± 0.07 |
0.5 ± 0.10* |
0.5 ± 0.11* |
0.5 ± 0.06 |
0.5 ± 0.06 |
0.5 ± 0.07 |
UA (mg/dL) |
2.3 ± 1.5 |
1.9 ± 0.6 |
2.5 ± 1.3 |
2.8 ± 1.8 |
2.0 ± 0.9* |
2.5 ± 1.7 |
TP (g/dL) |
6.9 ± 0.5 |
6.6 ± 0.3* |
6.8 ± 0.4 |
7.5 ± 0.7 |
7.1 ± 0.5* |
6.8 ± 0.7* |
A/G (rate) |
0.6 ± 0.09 |
0.7 ± 0.06* |
0.7 ± 0.06* |
0.8 ± 0.07 |
0.8 ± 0.06 |
0.8 ± 0.09 |
BG (mg/dL) |
131 ± 46 |
127 ± 30 |
140 ± 51 |
136 ± 35 |
127 ± 15 |
125± 27 |
PL (mg/dL) |
216 ± 62 |
205 ± 54 |
214 ± 61 |
211 ± 37 |
205 ± 36 |
202 ± 34 |
Tch (mg/dL) |
150 ± 51 |
130 ± 39 |
129 ± 42 |
117 ± 22 |
104 ± 19* |
98 ± 17* |
TG (mg/dL) |
175 ± 82 |
162 ± 59 |
198 ± 78 |
154 ± 73 |
209 ± 102* |
226 ± 105* |
Na (mEq/L) |
144 ± 2 |
141 ± 2* |
143 ± 2 |
141 ± 3 |
139 ± 1* |
141 ± 4 |
K (mEq/L) |
5.3 ± 0.7 |
4.6 ± 0.8* |
5.3 ± 1.0 |
5.0 ± 0.9 |
4.4 ± 0.5* |
4.7 ± 0.8 |
Ca (mg/dL) |
11.1 ± 0.9 |
10.3 ± 0.5* |
11.2 ± 1.1 |
11.2 ± 1.4 |
10.6 ± 0.6* |
10.7 ± 1.1 |
Cl (mEq/L) |
99 ± 1.9 |
101 ± 2.3* |
99 ± 3.5 |
99 ± 2.0 |
98 ± 2.3 |
97± 4.3 |
*p<0.05, compared to control
Table 2: Histological findings for the urinary system for rats treated with the test substance
No. of affected rats (%) |
|||||||
|
Males |
Females |
|||||
Test substance concentration (%) |
0 |
2.5 |
5 |
0 |
2.5 |
5 |
|
Effective No. of rats |
40 |
45 |
40 |
41 |
46 |
31 |
|
Urinary system |
|
|
|
|
|
|
|
Kidney
|
renal cell tumor |
0 |
0 |
1(2) |
0 |
0 |
0 |
papillary necrosis |
0 |
2(4) |
3(7) |
0 |
14(30) |
10(32) |
|
calcification |
0 |
0 |
0 |
16(39) |
15(32) |
13(42) |
|
Pelvis
|
transitional hyperplasia |
0 |
0 |
0 |
0 |
2(4) |
0 |
transitional cell tumor |
1(2) |
0 |
0 |
0 |
0 |
0 |
|
papilloma |
0 |
0 |
0 |
0 |
4(8) |
2(6) |
Table 3: Organ distribution and histological diagnosis for tumors in rats treated with the test substance
|
No. of affected rats (%) |
||||||
|
Males |
Females |
|||||
Test substance concentration (%) |
0 |
2.5 |
5 |
0 |
2.5 |
5 |
|
Effective No. of rats |
40 |
45 |
40 |
41 |
46 |
31 |
|
Tumor development |
36(90) |
44(97) |
36(90) |
27(59) |
30(65) |
12(39) |
|
Genital system |
|||||||
Testis |
interstitial cell tumor |
35(87) |
44(97) |
36(90) |
- |
- |
- |
Prostate |
adenoma |
1(2) |
2(4) |
2(4) |
- |
- |
- |
calcification |
- |
- |
- |
- |
- |
- |
|
Uterus |
endometrial polyp |
- |
- |
- |
5(12) |
18(39) |
12(38) |
endometrial sarcoma |
- |
- |
- |
0 |
1(2) |
0 |
|
adenocarcinoma |
- |
- |
- |
1(2) |
0 |
0 |
|
Mammary gland |
firboma |
0 |
0 |
0 |
1(2) |
0 |
0 |
adenoma |
0 |
0 |
0 |
0 |
1(2) |
1(3) |
|
Endocrine system |
|||||||
Pituitary gland |
adenoma |
9(22) |
6(13) |
7(17) |
13(31) |
12(26) |
9(29) |
Thyroid gland |
C-cell adenoma |
4(10) |
1(2) |
3(7) |
4(9) |
3(6) |
2(6) |
C-cell carcinoma |
0 |
2(4) |
1(2) |
1(2) |
1(2) |
0 |
|
papillary adenoma |
1(2) |
0 |
1(2) |
0 |
2(4) |
0 |
|
papillary adenocarcinoma |
0 |
1(2) |
0 |
0 |
0 |
0 |
|
Adrenal gland |
pheochromocytoma |
5(13) |
7(15) |
5(13) |
0 |
1(2) |
0 |
Pancreas |
islet cell tumor |
6(15) |
1(2) |
2(4) |
0 |
1(2) |
0 |
Digestive system |
|||||||
Liver |
neoplastic nodule |
1(2) |
0 |
0 |
0 |
0 |
1(3) |
Respiratory system |
|||||||
Lung |
adenoma |
0 |
2(4) |
0 |
0 |
1(2) |
0 |
Urinary system |
|||||||
Kidney |
renal cell tumor |
0 |
0 |
1(2) |
0 |
0 |
0 |
transitional cell tumor |
1(2) |
0 |
0 |
0 |
0 |
0 |
|
papilloma |
0 |
0 |
0 |
0 |
4(8) |
2(6) |
|
Urinary bladder |
papilloma |
0 |
0 |
0 |
0 |
0 |
0 |
Body cavity |
|||||||
Peritoneum |
mesothelioma |
2(5) |
2(4) |
1(2) |
0 |
0 |
0 |
Hematopoietic system |
|||||||
Leukemia |
|
4(10) |
6(13) |
3(7) |
6(14) |
9(17) |
3(9) |
Integument, musculoskeletal system |
|||||||
Subcutis |
fibroma |
3(8) |
0 |
0 |
4(10) |
2(4) |
0 |
|
lipoma |
0 |
1(2) |
0 |
0 |
0 |
1(2) |
|
preputial/clitoral gland tumor |
3(6) |
2(4) |
2(4) |
0 |
0 |
1(2) |
|
fibrosarcoma |
0 |
0 |
1(2) |
0 |
0 |
0 |
Data source
Reference
- Reference Type:
- publication
- Title:
- Carcinogenicity study of glycine in Fischer 344 rats
- Author:
- Kitahori, Y. et al.
- Year:
- 1 994
- Bibliographic source:
- J Toxicol Pathol 7: 471-480
Materials and methods
- Principles of method if other than guideline:
- The carcinogenicity of glycine was assessed in rats by application in the drinking water.
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Glycine
- EC Number:
- 200-272-2
- EC Name:
- Glycine
- Cas Number:
- 56-40-6
- Molecular formula:
- C2H5NO2
- IUPAC Name:
- glycine
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344/DuCrj
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Co. Japan, Inc. Atsugi
- Age at study initiation: 6 wks
- Housing: in plastic cages (3/sex/cage)
- Diet (ad libitum): pellet diet (CRF-1, Charles River, Japan)
- Water (ad libitum)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 2
- Humidity (%): 55 ± 5
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- unchanged (no vehicle)
- Duration of treatment / exposure:
- 108 wks
- Frequency of treatment:
- continuously via drinking water
Doses / concentrationsopen allclose all
- Dose / conc.:
- 2.5 other: %
- Remarks:
- nominal in water
- Dose / conc.:
- 5 other: %
- Remarks:
- nominal in water
- Dose / conc.:
- 1 534 mg/kg bw/day (actual dose received)
- Remarks:
- males
- Dose / conc.:
- 3 280 mg/kg bw/day (actual dose received)
- Remarks:
- males
- Dose / conc.:
- 1 587 mg/kg bw/day (actual dose received)
- Remarks:
- females
- Dose / conc.:
- 3 082 mg/kg bw/day (actual dose received)
- Remarks:
- females
- No. of animals per sex per dose:
- 50
- Control animals:
- other: drinking water without test substance
- Details on study design:
- - Dose selection rationale: on the basis of a preliminary subacute experiment (not further specified)
Examinations
- Observations and examinations performed and frequency:
- BODY WEIGHT: Yes
- Time schedule for examinations: every one or two weeks
FOOD CONSUMPTION: Yes
- Time schedule for examinations: every four weeks
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: daily
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at week 108
- How many animals: all survivors
- Parameters checked: white/red blood cells, heamoglobin (Hb), haematocrit (Ht)
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at week 108
- How many animals: all survivors
- Parameters checked: glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), creatine phosphokinase (CPK), blood urea nitrogen (BUN), creatinine (CRE), Urea (UA), total protein (TP), albumin/globulin rate (A/G rate), blood glucose (BG), phospholipid (PL), total cholesterol (Tch), triglyceride (TG), natrium, potassium, calcium, chloride
URINALYSIS: Yes
- Parameters checked: leukocytes, nitrite, urobilinogen, protein, pH, ketone, glucose - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (all animals, including those that died or were sacrificed upon becoming moribund during the experiment)
HISTOPATHOLOGY: Yes (all organs were examined and samples were fixed in 10% buffered neutral formalin, embedded in paraffin, and routinely stained with hematoxylin and eosin; histological analysis of tumors in renal pelvis) - Statistics:
- Wilcoxon t-test or chi-squared test
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- 5% dose group: slightly increased mortality in females compared to controls
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- 5% dose group: slightly increased mortality in females compared to controls
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- 2.5 and 5% dose group: slight dose-dependent inhibition of mean body weight gain in both sexes
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 5% dose group: significant changes of Hb and HT in males and females
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- 2.5 and 5% dose group, males and females: significantly changes in CPK, BUN, TP, Tch and TG were observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- 2.5 and 5% dose group: papillary necrosis and transitional hyperplasia was observed in male and female animals (no cases seen in the controls)
- Histopathological findings: neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- 2.5 and 5% dose group, females: kidney papillomas were seen, which were not observed in controls
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Mortality of females of the high dose group was slightly increased when compared to controls (number of surviving females and males: 31, 46, 41 and 40, 45, 40 for the high, low, control group).
BODY WEIGHT AND WEIGHT GAIN
2.5 and 5% dose group, males and females: Mean body-weights were slightly but dose-dependently inhibited when compared to controls over the hole study period (only growth curves were given).
HAEMATOLOGY
5% dose group, males: A slight but not significant increase in white blood cells was observed. The Hb was significantly increased when compared to controls.
5% dose group, females: A slight but not significant increase in white blood cells and a slight but not significant decrease in red blood cells was observed. The Hb and HT were significantly decreased when compared to controls.
2.5% dose group, females: A slight but not significant increase in white blood cells and a slight but not significant decrease in red blood cells was observed.
CLINICAL CHEMISTRY
2.5 and 5% dose group, males and females: The CPK values were significantly decreased when compared to controls in both sexes and both dose groups. BUN was significantly increased in both sexes of the 5% dose group.
2.5 and 5% dose group, females: A significant and dose-dependent decrease of TP and Tch and a significant and dose-dependent increase in TG was observed.
Some sporadic effects on isolated parameters were observed which were considered as not treatement-related (see Table 1 "Any other information on results incl. tables").
URINALYSIS
No significant differences in urinalysis data between treated and control male and female animals were observed.
ORGAN WEIGHTS
No significant effects on the relative organ weights were observed in the treated groups when compared to controls.
HISTOPATHOLOGY: NON-NEOPLASTIC
The incidences of papillary necrosis in male rats fed 2.5 and 5% glycine were 4 and 7%, while the corresponding figures for females were 30 and 32%. Since necrosis of the renal papillae was limited to glycine-treated rats it was very likely linked to the induction of papillomas. Transitional hyperplasia in renal pelvis was observed in 2 female animals of the 2.5% dose group. Calcification indices in kidney were 39, 32 and 42% of the 0, 2.5 and 5% groups (see Table 2 "Any other information on results incl. tables").
HISTOPATHOLOGY: NEOPLASTIC (if applicable)
For the males, tumors were found in 90% of the high dose group, 97% of the low dose group and in 90% of the controls, while the corresponding figures for females were 59, 65 and 39%. These tumors were considered to be spontaneous in nature (see Table 3 "Any other information on results incl. tables").
One renal cell tumor was seen in one male of the high dose group. Kidney papillomas were found in 8% of the low dose group and in 6% of the high dose group females, but not in the controls. Since spontaneous tumors in this tissues are very rare, they were considered as treatment-related (see Table 3 "Any other information on results incl. tables").
Effect levels
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- 1 561 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: clinical chemistry; histopathology
- Dose descriptor:
- NOAEL
- Effect level:
- < 1 561 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- histopathology: neoplastic
- histopathology: non-neoplastic
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 1: Clinical chemistry data for rats treated with the test substance (mean values± standard deviation)
|
Males |
Females |
||||
Group (%) |
0 |
2.5 |
5 |
0 |
2.5 |
5 |
No. of rats |
40 |
45 |
40 |
41 |
46 |
31 |
GOT (K-U) |
122 ± 72 |
120 ± 57 |
114 ± 27 |
130 ± 53 |
117 ± 40 |
136 ± 68 |
GPT (K-U) |
51 ± 34 |
55 ± 37 |
53 ± 12 |
59 ± 22 |
56 ± 12 |
66 ± 16 |
LDH (K-U) |
2879 ± 772 |
2710 ± 972 |
2514 ± 819 |
2572 ± 1369 |
2666 ± 836 |
2556 ± 952 |
ALP (KA-U) |
16 ± 6 |
15 ± 5 |
17 ± 5 |
19 ± 9 |
19 ± 5 |
25 ± 7* |
CPK (IU/L) |
754 ± 321 |
563 ± 217* |
509 ± 197* |
706 ± 392 |
545 ± 160* |
446 ± 158* |
BUN (mg/dL) |
18 ± 3 |
17 ± 2 |
21 ± 3* |
18 ± 2 |
17 ± 2 |
21 ± 3* |
CRE (mg/dL) |
0.6 ± 0.07 |
0.5 ± 0.10* |
0.5 ± 0.11* |
0.5 ± 0.06 |
0.5 ± 0.06 |
0.5 ± 0.07 |
UA (mg/dL) |
2.3 ± 1.5 |
1.9 ± 0.6 |
2.5 ± 1.3 |
2.8 ± 1.8 |
2.0 ± 0.9* |
2.5 ± 1.7 |
TP (g/dL) |
6.9 ± 0.5 |
6.6 ± 0.3* |
6.8 ± 0.4 |
7.5 ± 0.7 |
7.1 ± 0.5* |
6.8 ± 0.7* |
A/G (rate) |
0.6 ± 0.09 |
0.7 ± 0.06* |
0.7 ± 0.06* |
0.8 ± 0.07 |
0.8 ± 0.06 |
0.8 ± 0.09 |
BG (mg/dL) |
131 ± 46 |
127 ± 30 |
140 ± 51 |
136 ± 35 |
127 ± 15 |
125± 27 |
PL (mg/dL) |
216 ± 62 |
205 ± 54 |
214 ± 61 |
211 ± 37 |
205 ± 36 |
202 ± 34 |
Tch (mg/dL) |
150 ± 51 |
130 ± 39 |
129 ± 42 |
117 ± 22 |
104 ± 19* |
98 ± 17* |
TG (mg/dL) |
175 ± 82 |
162 ± 59 |
198 ± 78 |
154 ± 73 |
209 ± 102* |
226 ± 105* |
Na (mEq/L) |
144 ± 2 |
141 ± 2* |
143 ± 2 |
141 ± 3 |
139 ± 1* |
141 ± 4 |
K (mEq/L) |
5.3 ± 0.7 |
4.6 ± 0.8* |
5.3 ± 1.0 |
5.0 ± 0.9 |
4.4 ± 0.5* |
4.7 ± 0.8 |
Ca (mg/dL) |
11.1 ± 0.9 |
10.3 ± 0.5* |
11.2 ± 1.1 |
11.2 ± 1.4 |
10.6 ± 0.6* |
10.7 ± 1.1 |
Cl (mEq/L) |
99 ± 1.9 |
101 ± 2.3* |
99 ± 3.5 |
99 ± 2.0 |
98 ± 2.3 |
97± 4.3 |
*p<0.05, compared to control
Table 2: Histological findings for the urinary system for rats treated with the test substance
No. of affected rats (%) |
|||||||
|
Males |
Females |
|||||
Test substance concentration (%) |
0 |
2.5 |
5 |
0 |
2.5 |
5 |
|
Effective No. of rats |
40 |
45 |
40 |
41 |
46 |
31 |
|
Urinary system |
|
|
|
|
|
|
|
Kidney
|
renal cell tumor |
0 |
0 |
1(2) |
0 |
0 |
0 |
papillary necrosis |
0 |
2(4) |
3(7) |
0 |
14(30) |
10(32) |
|
calcification |
0 |
0 |
0 |
16(39) |
15(32) |
13(42) |
|
Pelvis
|
transitional hyperplasia |
0 |
0 |
0 |
0 |
2(4) |
0 |
transitional cell tumor |
1(2) |
0 |
0 |
0 |
0 |
0 |
|
papilloma |
0 |
0 |
0 |
0 |
4(8) |
2(6) |
Table 3: Organ distribution and histological diagnosis for tumors in rats treated with the test substance
No. of affected rats (%) |
|||||||
|
Males |
Females |
|||||
Test substance concentration (%) |
0 |
2.5 |
5 |
0 |
2.5 |
5 |
|
Effective No. of rats |
40 |
45 |
40 |
41 |
46 |
31 |
|
Tumor development |
|
|
|
|
|
|
|
Genital system |
|||||||
Testis |
interstitial cell tumor |
36(90) |
44(97) |
36(90) |
27(59) |
30(65) |
12(39) |
Prostate |
adenoma |
35(87) |
44(97) |
36(90) |
- |
- |
- |
calcification |
1(2) |
2(4) |
2(4) |
- |
- |
- |
|
Uterus |
endometrial polyp |
- |
- |
- |
5(12) |
18(39) |
12(38) |
endometrial sarcoma |
- |
- |
- |
0 |
1(2) |
0 |
|
adenocarcinoma |
- |
- |
- |
1(2) |
0 |
0 |
|
Mammary gland |
firboma |
0 |
0 |
0 |
1(2) |
0 |
0 |
adenoma |
0 |
0 |
0 |
0 |
1(2) |
1(3) |
|
Endocrine system |
|||||||
Pituitary gland |
adenoma |
9(22) |
6(13) |
7(17) |
13(31) |
12(26) |
9(29) |
Thyroid gland |
C-cell adenoma |
4(10) |
1(2) |
3(7) |
4(9) |
3(6) |
2(6) |
C-cell carcinoma |
0 |
2(4) |
1(2) |
1(2) |
1(2) |
0 |
|
papillary adenoma |
1(2) |
0 |
1(2) |
0 |
2(4) |
0 |
|
papillary adenocarcinoma |
0 |
1(2) |
0 |
0 |
0 |
0 |
|
Adrenal gland |
pheochromocytoma |
5(13) |
7(15) |
5(13) |
0 |
1(2) |
0 |
Pancreas |
islet cell tumor |
6(15) |
1(2) |
2(4) |
0 |
1(2) |
0 |
Digestive system |
|||||||
Liver |
neoplastic nodule |
1(2) |
0 |
0 |
0 |
0 |
1(3) |
Respiratory system |
|||||||
Lung |
adenoma |
0 |
2(4) |
0 |
0 |
1(2) |
0 |
Urinary system |
|||||||
Kidney |
renal cell tumor |
0 |
0 |
1(2) |
0 |
0 |
0 |
transitional cell tumor |
1(2) |
0 |
0 |
0 |
0 |
0 |
|
papilloma |
0 |
0 |
0 |
0 |
4(8) |
2(6) |
|
Urinary bladder |
papilloma |
0 |
0 |
0 |
0 |
0 |
0 |
Body cavity |
|||||||
Peritoneum |
mesothelioma |
2(5) |
2(4) |
1(2) |
0 |
0 |
0 |
Hematopoietic system |
|||||||
Leukemia |
|
4(10) |
6(13) |
3(7) |
6(14) |
9(17) |
3(9) |
Integument, musculoskeletal system |
|||||||
Subcutis |
fibroma |
3(8) |
0 |
0 |
4(10) |
2(4) |
0 |
|
lipoma |
0 |
1(2) |
0 |
0 |
0 |
1(2) |
|
preputial/clitoral gland tumor |
3(6) |
2(4) |
2(4) |
0 |
0 |
1(2) |
|
fibrsarcoma |
0 |
0 |
1(2) |
0 |
0 |
0 |
Applicant's summary and conclusion
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.
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