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EC number: 249-636-2 | CAS number: 29450-45-1
- 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: dermal
Administrative data
- Endpoint:
- sub-chronic toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 13.07.1999 - 19.08.1999
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Cross-reference
- Reason / purpose for cross-reference:
- read-across source
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 999
- Report date:
- 2009
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- yes
Test material
- Reference substance name:
- (4-chloro-2-methylphenoxy)acetic acid
- EC Number:
- 202-360-6
- EC Name:
- (4-chloro-2-methylphenoxy)acetic acid
- Cas Number:
- 94-74-6
- Molecular formula:
- C9H9ClO3
- IUPAC Name:
- (4-chloro-2-methylphenoxy)acetic acid
- Reference substance name:
- Water
- EC Number:
- 231-791-2
- EC Name:
- Water
- Cas Number:
- 7732-18-5
- Molecular formula:
- H2O
- IUPAC Name:
- water
- Test material form:
- solid
Constituent 1
impurity 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Wistar rats Imp-Wist (male and female) were used. The animals were obtained from the conventional breeding in Institute of Occupational Medicine in Łódź. Prior to the start of the study the animals were acclimated in the test conditions for 14 days. At the start of the test the animals were 2 months old. The average body weight was 253.9 g for males and 183.2 g for females.
Results and discussion
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- clinical biochemistry
- haematology
- organ weights and organ / body weight ratios
Target system / organ toxicity
- Critical effects observed:
- no
Any other information on results incl. tables
1. Clinical observation
All the animals survived the experiment. The rats exposed to MCPA didn't vary from the rats from control group. The dressing put on the animals made moving difficult for the rats from both groups. From 3th day of the experiment slight blush and peeling of the cuticle were observed in the rats exposed to test substance in the place of its application. At the end of the experiment no dermal changes were noticed.
1.2. Body weight and fodder consumption
In the second half of the experiment body weight of males exposed to test substance was lower than body weight of control males — the difference was significant statistically
Table 1. MCPA: Repeated Dose Dermal Toxicity (21-day study) Body weight (g) - males
Day of experiment |
|
Group |
|
|
|
0 |
|
1 |
|
1 |
254.4 |
± 12.5 |
253.4 |
± 8.7 |
4 |
263.2 |
± 11.0 |
257.0 |
± 10.1 |
8 |
275.6 |
± 9.6 |
266.0 |
± 11.1 |
11 |
284.6 |
± 12.4 |
268.8 |
± 10.6* |
15 |
297.2 |
± 15.0 |
279.8 |
± 11.7* |
18 |
304.4 |
± 18.8 |
290.6 |
± 8.2* |
21 |
323.6 |
± 22.8 |
301.6 |
± 8.9* |
* p≤0.05
No statistic differences were stated in the females
Table 2. MCPA: Repeated Dose Dermal Toxicity (21-day study) Body weight (g) – females
Day of experiment |
|
Group |
|
|
|
0 |
1 |
|
|
1 |
183.2 |
± 12.9 |
183.2 |
± 11.6 |
4 |
187.6 |
± 16.3 |
182.6 |
± 10.5 |
8 |
196.0 |
± 21.9 |
189.8 |
± 8.3 |
11 |
200.0 |
± 19.7 |
196.4 |
± 7.6 |
15 |
205.8 |
± 20.3 |
200.4 |
± 7.9 |
18 |
211.2 |
± 26.1 |
208.8 |
± 8.1 |
21 |
223.2 |
± 26.8 |
216.2 |
± 8.9 |
In the second half of the experiment fodder consumption of males exposed to test substance was lower than fodder consumption of control males – the difference was significant statistically
Table 3. MCPA: Repeated Dose Dermal Toxicity (21-day study) Food intake (g/rat/day) - males
Week of experiment |
Group |
|
0 |
1 |
|
1 |
25.3 ± 0.9 |
24.2 t 0.9 |
2 |
24.7 ± 1.8 |
22.2 ± 0.8* |
3 |
27.6 ±2.2 |
26.4 ± 1.2 |
* p≤0.05
Fodder consumption of females exposed to the substance and from the control group was on the same level during entire experiment.
Table 4. MCPA: Repeated Dose Dermal Toxicity (21-day study) Food intake (g/rat/day) — females
Week of experiment |
|
Group |
|
|
|
0 |
|
1 |
|
1 |
19.9 |
± 1.7 |
18.7 |
± 1.4 |
2 |
18.0 |
± 1.7 |
18.4 |
± 1.0 |
3 |
21.3 |
± 2.5 |
20.0 |
± 3.0 |
2. Hematology
The hematologic values are listed in the tables 5 and 6. No statistically significant differences were stated between rats exposed to the substance and control animals.
Table 5. MCPA: Repeated Dose Dermal Toxicity (21-day study) Hematologic examination after 21 days
Parameter |
Group |
||
0 |
1 |
||
|
Male |
||
Hemoglobin |
g/l |
168.40 ± 12.80 |
167.00 ± 9.57 |
Hematocrit |
l/l |
0.38 ± 0.05 |
0.39 ± 0.04 |
Erythrocytes |
x 1012/l |
7.48 ± 1.06 |
7.82 ± 0.89 |
Thrombocytes |
x 1012/l |
0.85 ± 0.07 |
0.76 ± 0.12 |
Leukocytes |
x 1012/l |
8.02 ± 0.69 |
9.40 ± 2.29 |
|
Female |
||
Hemoglobin |
g/l |
157,60 ± 7,50 |
158.60 ± 5.27 |
Hematocrit |
l/l |
0,35 ± 0,04 |
0.37 ± 0.03 |
Erythrocytes |
x 1012/l |
6,93 ± 0,75 |
7.31 ± 0.53 |
Thrombocytes |
x 1012/l |
0,88 ± 0,20 |
0.88 ± 0.17 |
Leukocytes |
x 1012/l |
5,52 ± 1,26 |
5.68 ± 0.99 |
Table 6. MCPA: Repeated Dose Dermal Toxicity (21-day study) Hematologic examination after 21 days Leukogram
Parameter |
|
Group |
|
0 |
1 |
||
|
Male |
||
Neutrocytes |
l/l |
0.13 ± 0.05 |
0,14 ± 0.06 |
Eosinocytes |
l/l |
0.01 ± 0.01 |
0,01 ± 0.01 |
Bazocytes |
l/l |
0.00 ± 0.00 |
0,00 ± 0.00 |
Limphocytes |
l/l |
0.86 ± 0.06 |
0,84 ± 0.06 |
Monocytes |
l/l |
0.01 ± 0.00 |
0,01 ± 0.01 |
Other cells |
l/l |
0.00 ± 0.00 |
0,00 ± 0.00 |
|
Female |
||
Neutrocytes |
l/l |
0.18 ± 0.03 |
0.15 ± 0.06 |
Eosinocytes |
l/l |
0.01 ± 0.01 |
0.02 ± 0.01 |
Bazocytes |
l/l |
0.00 ± 0.00 |
0.00 ± 0.00 |
Limphocytes |
l/l |
0.79 ± 0.03 |
0.81 ± 0.07 |
Monocytes |
l/l ll |
0,01 ± 0.01 |
0.01 ± 0.01 |
Other cells |
l/l |
0.00 ± 0.00 |
0.00 ± 0.00 |
3. Clinical biochemistry
The biochemical parameters are listed in the table 7.
Only one statistically significant difference was stated: the proportion of albumins to globulins was lower in the case of males exposed to MCPA than in case of males from the control group (table 7). No statistic differences were stated as far as females are concerned.
Table 7. MCPA: Repeated Dose Dermal Toxicity (21-day study) Clinical biochemistry after 21 days
Parameter |
Group |
|
0 |
1 |
|
Male |
||
Protein glob. g/l |
68.60 ± 1.02 |
69.94 ± 3.35 |
Albumin g/l |
45.14 ± 1.72 |
44.42 ± 2.10 |
Globulin g/l |
23.46 ± 1.60 |
25.52 ± 1.56 |
Ratio AJG |
1.93 ± 0.20 |
1.74 ± 0.08* |
Glucose mmol/l |
8.38 ± 2.11 |
11.38 ± 2.99 |
Cholesterol mmol/l |
1.61 ± 0.25 |
1.44 ± 0.48 |
Urea nitrogen mmo1/1 |
7.36 ± 1.07 |
6.82 ± 1.81 |
Creatynine mmol/l |
42.92 ± 2.71 |
42.26 ± 4.61 |
Natrium mmo1/1 |
145.40 ± 1.82 |
143.60 ± 1.52 |
Callum mmol/l |
4.86 ± 0.38 |
5.44 ± 0.89 |
Female |
||
Protein glob. g/l |
69.36 ± 3.23 |
71.10 ± 4.87 |
Albumin g/l |
44.34 ± 1.59 |
44.10 ± 3.39 |
Globulin g/l |
25.02 ± 2.52 |
27.00 ± 4.25 |
Ratio AJG |
1.79 ± 0.17 |
1.67 ± 0.31 |
Glucose mmol/l |
5.78 ± 2.00 |
5.76 ± 1.12 |
Cholesterol mmol/l |
1.75 ± 0.31 |
1.66 ± 0.28 |
Urea nitrogen mmol/l |
8.52 ± 0.79 |
8.90 ± 1.36 |
Creatynine mmol/l |
40.94 ± 2.90 |
39.66 ± 3.55 |
Natrium mmol |
144.00 ± 1.41 |
143.20 ± 2.17 |
Callum mmol/l |
5.08 ± 0.72 |
5.18 ± 0.48 |
* p≤0.05
4. Enzyms
The enzymatic values are given in the table 8.
Table 8. MCPA: Repeated Dose Dermal Toxicity (21-day study) Enzymatic examination after 21 days
Parameter |
Group |
||
0 |
1 |
||
|
Male |
||
Asp AT |
IU |
103.00 ± 28.31 |
117.80 ± 18.51 |
Al AT |
IU |
41.20 ± 4.32 |
59.00 ± 21.30 |
SDH |
1U |
2.50 ± 1.86 |
2.60 ± 0.88 |
AP |
IU |
177.00 ± 38.09 |
205.00 ± 43.03 |
LAP |
IU |
30.40 ± 3.71 |
32.60 ± 2.19 |
B-GR |
IU |
1.11 ±0.14 |
1.10 ± 0.08 |
CHE |
mIU |
0.51 ± 0.06 |
0.52 ± 0.05 |
|
Female |
||
Asp AT |
IU |
99.20 ± 20.54 |
88.40 ± 7.70 |
Al AT |
IU |
35.00 ± 9.03 |
37.40 ± 8.65 |
SDH |
IU |
2.52 ± 0.81 |
2.02 ± 1.04 |
AP |
IU |
102.40 ± 14.28 |
127.40 ± 23.94 |
LAP |
IU |
26.20 ± 3.90 |
30.00 ± 7.91 |
B-GR |
IU |
1.22 ± 0.16 |
1.03 ± 0.54 |
CHE |
mIU |
1.37 ± 0.23 |
1.19 ± 0.31 |
The activity of particular enzymes in the animals exposed to MCPA and the control animals showed considerable individual differences, but no statistically significant difference was stated in the mean values in both groups.
5. Pathology
In the macroscopic examination of skin and internal organs no pathologic changes were stated. In the absolute weight of internal organs a statistically significant decrease in the weight of adrenals was stated in case of females. In the relative weight of organs statistically significant increase in the weight of males' kidneys and fall in the weight of females' adrenals were observed (table 9 and 10).
Microscopic examination showed circulatory disturbances in the case of animals exposed to MCPA as well as control animals. The heart, liver, adrenals and hypophysis were congested.
Table 9. MCPA: Repeated Dose Dermal Toxicity (21-day study) Absolute organ weight (mg)
Organ |
Number of rats |
Sex |
Group |
|
0 |
1 |
|||
Liver |
5 |
Male |
9778.400 ± 596.798 |
9042.800 ± 580.195 |
5 |
Female |
6521.000 ± 996.234 |
6342.600 ± 253.917 |
|
Kidneys |
5 |
Male |
2183.800 ± 175.076 |
2208.600 ± 126.396 |
5 |
Female |
1477.800 ± 150.556 |
1462.800 ± 145.741 |
|
Adrenals |
5 |
Male |
77.600 ± 10.171 |
74.400 ± 10.092 |
5 |
Female |
93.600 ± 9.478 |
74.000 ± 2.828* |
|
Testicles |
5 |
Male |
3464.200 ± 230.417 |
3187.800 ± 220.112 |
* p≤0.05
Table 10. MCPA: Repeated Dose Dermal Toxicity (21-day study) Relative organ weight (mg)
Organ |
Number of rats |
Sex |
Group |
|
0 |
1 |
|||
Liver |
5 |
Male |
3.024 ± 0.107 |
2.997 ± 0.151 |
5 |
Female |
2.910 ± 0.185 |
2.940 ± 0.204 |
|
Kidneys |
5 |
Male |
0.675 ± 0.041 |
0.732 ± 0.033* |
5 |
Female |
0.663 ± 0.021 |
0.676 ± 0.055 |
|
Adrenals |
5 |
Male |
0.024 ± 0.003 |
0.025 ± 0.003 |
5 |
Female |
0.042 ± 0.003 |
0.034 ± 0.002* |
|
Testicles |
5 |
Male |
1.072 ± 0.056 |
1.056 ± 0.056 |
* p≤0.05
6. Discussion
In the repeated dose dermal study (21 applications) of MCPA in a dose of 1000 mg/kg b.w./day in rats the test substance didn't cause any deaths in the tested group. On the skin in a place of application a temporary blush and slight peeling of the cuticle were observed. The rats from the exposed group didn't vary either in behavior or in appearance from control rats. Smaller discrease in body weight in case of males exposed to MCPA was probably caused by smaller fodder consumption of these animals.
In the hematologic parameters no statistically significant differences were stated between both groups.
In the biochemical parameters only one statistically significant difference was stated. It didn't concern examined biochemical parameters but only calculated proportion of albumins to globulins in case of males exposed to MCPA. Because obtained values of A/G indicator are contained in the range of values observed in the bigger historic control group, it should be accounted for accidental, resulting from low number of animals in a group.
The activity of examined enzymes was on the similar level in the group of animals exposed to MCPA and in the control group.
Some changes in the weight of internal organs (kidneys, adrenals) may be result of slight decrease in the body weight caused by temporary decrease in the fodder consumption.
The pathomorphologic examination didn't show any macroscopicall changes. Microscopically, some circulatory disturbances were observed, but the frequency was similar in the control and exposed group. They are not bound to the tested substance.
On the basis of the results of the clinical, hematologic, biochemical, enzymatic and pathomorphologic parameters it can be stated that MCPA in a dose of 1000 mg/kg b.w./day didn't have negative influence on rats' organism.
Applicant's summary and conclusion
- Executive summary:
Conclusions:
1) MCPA applied during 21 days on the skin of rats in a dose of 1000 mg/kg b.w./day didn't have negative impact on organism of rats.
2) The no-observed-adverse-effect-level (NOAEL) is. 1000 mg/kg b.w./day.
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