Strontium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate

Endpoint summary

Description of key information

The NOAEL for chronic oral toxicity is established at 25 mg/kg bw based on repeated dose toxicity studies with analogue substances. Higher doses result in kidney damage. This is derived from subacute gavage studies with Pigment Red 57:1(Ca) (OECD 422, GLP, MHLW 1993), Pigment Red 48:2(Ca) (OECD 422, GLP, MHLW 2009) and Pigment Red 57(Sr) (OECD 407, GLP, DIC 2006). In a chronic feeding study with the sodium salt of Pigment Red 57(Na), exacerbation of spontaneous renal disease in aged rats was observed with a NOAEL of 0.05 % (CTFA 1981). The dietary concentration of 0.05% corresponds to an average dose of 26 mg/kg bw for males and 31 mg/kg bw for females.

No histopathology findings on kidneys were reported after a two-year skin painting study with mice with Pigment Red 57:1(Ca) (Carson 1984).

Regarding the cation, available data indicate that the data available for the Pigments covers the hazard of both the related anion and cation.

The amine that would be liberated from azo reduction caused no adverse effects upon subacute oral toxicity at the limit dose of 1000 mg/kg bw (MHLW).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Reference 1

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2005 - 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

study that followed OECD testing guideline 407, adopted in 1995. Parameters required in updated guideline of 2008 are not investigated.

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Japan (Hino Breeding center)
- Age at study initiation: 5 weeks
- Weight at study initiation: 120 – 137 g and 105 – 122 g
- Fasting period before study: no statement
- Housing: Individually housed in a stainless wire cage after grouping ( group of 3 to 5/ cage before grouping)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 7 days including 6 days for quarantine


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21- 25°C
- Humidity (%): 40 – 70%
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: Sept.27,20005 To: Oct.25, 2005 and Nov.8, 2005 (recovery group)

Route of administration:

oral: gavage

Vehicle:

olive oil

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Concentration, homogeneity and stability (immediately and after 3 days 7 days) of the dose formulations were determined in samples taken after experimental start. Concentration and homogeneity of the dose formulations were confirmed during treatment. Analysis was performed with an HPLC method and UV detection at 520 nm. Identity was confirmed by IR.

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily

Dose / conc.:

25 mg/kg bw/day (actual dose received)

Dose / conc.:

75 mg/kg bw/day (actual dose received)

Dose / conc.:

200 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

5; additional 5 animal for control and high dose group for 14-day recovery sacrifice

Control animals:

yes, concurrent vehicle

Details on study design:

For dose selection, 14-day oral repeat study was performed at doses of 50, 250, 500, and 1000 mg/kg/day. Basophilic tubules were noted in the 50 mg/kg/day group. Decreases in body weight, increases in kidney weight, degeneration and necrosis in kidney were recorded in dose groups of 250 mg/kg/day and higher.

Positive control:

not applicable

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: All animals were checked daily (three times a day throughout administration period, and twice a day during recovery).

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
- Parameters checked in table No.4 were examined (see 'Any other information on materials and methods incl. tables').

BODY WEIGHT: Yes
- Time schedule for examinations: days -1, 1 ,3 , 8 ,12 ,17 , 26, 28

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: day after final administration (4wks) and after the recovery period (6 wks)
- Anaesthetic used for blood collection: Yes : ether anaesthesia
- Animals fasted: Yes, overnight
- How many animals: all (except one dead animal)
- Parameters checked in table No.1 were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: after 4 and 6 weeks
- Animals fasted: Yes, overnight
- How many animals: all animals
- Parameters checked in table No 2 and 3 were examined (see 'Any other information on materials and methods incl. tables').

URINALYSIS: Yes
- Time schedule for collection of urine: after 4 and 6 weeks
- Metabolism cages used for collection of urine: Yes (housed individually in a metabolism cage)
- Animals fasted: Yes (Water ad libitum)
- Parameters checked: urine volume and specific gravity, colour, turbidity, pH, protein, glucose and occult blood, red blood cells, white blood cells, epithelial cells, casts, crystals

NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: during week 4
- Dose groups that were examined: all
- Battery of functions tested: sensory activity, grip strength, motor activity

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

HISTOPATHOLOGY: Yes;
- Necropsy (samples of the following tissues and organs were collected from all animals and fixed in neutral phosphate buffered 4% formaldehyde solution and processed for histopathology):
Adrenal glands ,Ovaries, Bone (femur),Bone marrow, Brain,Cecum, Cerebellum Colon, Duodenum, Epididymides, Eyes with optic nerve, Heart, Ileum, Jejunum, Kidneys, Liver, Lungs, Lymph nodes (mesenteric, axillary), , Pituitary gland, Prostate gland, Pons, Rectum, Sciatic nerve, Seminal vesicles, Spinal cord, Spleen, Stomach, Testes, Thymus, Thyroid (incl. parathyroid gland),Trachea, Urinary bladder, Uterus, Vagina, Gross lesions

Fetermination of organ weight (absolute and relative): Brain, Heart, Liver, Thymus, Kidneys, Adrenals, Spleen, Testes, Epididymides,Ovaries

Statistics:

x squared test was conducted for copulation and fertility indices. For all the other parameters, Bartlett's test was used to examine uniformity of distribution in each group, and one-way statistical analysis was performed when the distribution is uniform. Where significant differences were observed, Duneett's test was performed to examine differences in averages between each test group and control groups. Kruskal-Wallis's test was conducted when the distribution was not uniform. Significant testing was carried out at the 5% and the 1% levels.

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Description (incidence):

One high dose female was found emaciated and dead.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Body weight was not affected during the treatment period.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

Food intake was not affected during the treatment period. During the recovery period, males of treatment group showed an increased food in take compared to control rats.

Food efficiency:

no effects observed

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Reversible increase in absolute and relative kidney weight in males at 200 mg/kg bw. Absolute and relative kidney weights were increased after 4 weeks, but not at the end of the treatment-free recovery period.

Gross pathological findings:

no effects observed

Description (incidence and severity):

No macroscopic findings were observed.

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

- Histopathology examinations showed that kidneys of males receiving 200 mg/kg bw had an increase in atypical and typical basophilic tubules and that kidneys of males receiving 75 and 200 mg/kg bw showed a dose-dependent increase in degeneration and necrosis of tubular epithelium and dilation of distal and collecting tubules. All males of the highest dose group had orange coloured pigments in the cell debris. These were still visible in two of five animals at the recovery sacrifice.
- In females, slight degeneration and necrosis of tubular epithelium was observed only in the animals of the high dose group (200 mg/kg bw) after treatment. Females of the lower dose or recovery groups did not show histopathology findings.

Histopathological findings: neoplastic:

not examined

Other effects:

effects observed, treatment-related

Description (incidence and severity):

Animals excreted reddish stool and orange urine during the treatment. Whereas reddish stool was observed for all dose groups, orange urine was only observed in the mid and high dose group and not during the recovery period. The only treatment related clinical sign was salivation. It was no longer observed during the recovery period. One animal showed soft stool.

Details on results:

Effects of the test article were mainly observed in kidney, but were reversible within 14 days of recovery. 25 mg/kg bw/day was inferred as NOEL based on the findings observed in males at dose groups of 75 mg/kg/day and higher (i.e. degeneration and necrosis of tubular epithelium; dilation of distal and collecting tubules).

Dose descriptor:

NOEL

Effect level:

25 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

histopathology: non-neoplastic

Dose descriptor:

NOEL

Effect level:

75 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Critical effects observed:

yes

Lowest effective dose / conc.:

75 mg/kg bw/day (nominal)

System:

urinary

Organ:

kidney

Treatment related:

yes

Relevant for humans:

not specified

Table 1: Values for BUN (mg/dL) and Creatinine (mg/dL), SD given in parentheses
	BUN		Creatinine
	male	female	male	female
control	8.3 (0.2)	9.5 (0.3)	0.21 (0.02)	0.21 (0.03)
control (recovery)	15.0 (1.5)	15.8 (1.1)	0.3 (0.03)	0.3 (0.03)
25 mg/kg bw	8.6 (1.1)	11.5 (2.0)	0.18 (0.01)	0.23 (0.05)
70 mg/kg bw	10.0 (3.2)	9.2 (1.0)	0.18 (0.03)	0.18 (0.03)
200 mg/kg bw	16.4 (8.7)	10.2 (3.1)	0.42 (0.31)	0.15 (0.04)
200 mg/kg bw after recovery	14.1 (1.0)	17.6 (2.1)	0.29 (0.02)	0.3 (0.02)
* Significantly different from vehcle control at p < 0.05

Supporting information: Results of Dose-range-finder

For dose selection, 14-day oral repeat study was performed at doses of 50, 250, 500, and 1000 mg/kg/day. Basophilic tubules were noted in the 50 mg/kg/day group. Decreases in body weight, increases in kidney weight, degeneration and necrosis in kidney were recorded in dose groups of 250 mg/kg/day and higher.

Supporting information: Findings on the female of the high dose group that died on day 6

Clinical signs

Soft feces, diarrhea, anorexia, decreased feces, decease in locomotor activities, small feces, lid closure, no-feces, slow respiration, side-lying position, subnormal temperature, emaciation, moist fur. 

 

Macroscopic findings :

Reddish region in lung, reddish contents in stomach and cecum, apparent spotty pattern of surface in kidney, pale kidney, small thymus

 

Microscopic findings:

Congestion in lung; mineralization in glandular stomach; degeneration and necrosis of tubular epithelium; mineralization in kidney cortex; mucification of epithelium in vagina; atrophy in axillary lymph node, spleen, and thyroid; hypertrophy of chief cells in parathyroid; increased osteoclast in femur.  

Reference 2

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Justification for type of information:

Please see the category read-across justification in the category object.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Dose descriptor:

NOEL

Effect level:

< 100 mg/kg bw/day (actual dose received)

Based on:

other: read-across

Sex:

male/female

Dose descriptor:

LOEL

Effect level:

40 mg/kg bw/day (actual dose received)

Based on:

other: read-across

Sex:

male/female

Critical effects observed:

yes

Lowest effective dose / conc.:

40 mg/kg bw/day (nominal)

System:

urinary

Organ:

kidney

Treatment related:

yes

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

25 mg/kg bw/day

Study duration:

subacute

Species:

rat

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

Link to relevant study records

Reference

Endpoint:

chronic toxicity: dermal

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Justification for type of information:

Please see the category read-across justification in the category object.

Reason / purpose for cross-reference:

read-across source

Dose descriptor:

NOEL

Effect level:

> 50 other: mg/kg bw twice weekly

Based on:

other: read-across

Basis for effect level:

other: no adverse effects expected

Critical effects observed:

no

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

50 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: dermal

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Justification for type of information:

Please see the category read-across justification in the category object.

Reason / purpose for cross-reference:

read-across source

Dose descriptor:

NOEL

Effect level:

> 50 other: mg/kg bw twice weekly

Based on:

other: read-across

Basis for effect level:

other: no adverse effects expected

Critical effects observed:

no

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Oral exposure

Pigment Red 57:1(Ca) 5281-04-9

The study with Pigment Red 57:1(Ca) for repeated dose oral gavage toxicity was performed in Crj: CD(SD) rats with a product of 98% purity following OECD testing guideline 422 (MHLW, 1993) and the principles of GLP. Applied doses were 100, 300 and 1000 mg/kg/day using 5% Gum Arabic solution as vehicle. All animals survived to the end of the study. No clinical findings indicative of chemical toxicity were observed; red-stained faeces of dosed animals were due to the colour of the pigment. The mean body weight gain and food consumption in both sexes of dosed groups were comparable to those in the control groups throughout the study. No biologically significant changes in hematological parameters were noted in any dosed male groups. Males that received 300 mg/kg or more showed significantly decreased serum calcium and phosphorus levels. Further, significant decreases in serum potassium and total cholesterol levels, and significant increases in chloride and GOT levels were shown in the males that received 1000 mg/kg. Males that received 1000 mg/kg showed significant increases in relative kidney weights. Females that received 100 or 1000 mg/kg showed decreases in thymus weights in comparison with the controls. No other significant differences in organ weights were observed in either the males or the females. On the histopathology examination, predominant alterations suggesting effects in dosed rats were observed in the kidney. The lesions included an increased incidence of renal tubular epithelium regeneration in males receiving 300 mg/kg or more, and this and necrotic or foamy tubular epithelial cells in females that received 100 mg/kg or more. These lesions increased in severity and incidence in a dose-dependent manner.NOELsfor repeat dose toxicity are considered to be100 mg/kg bw/day for males and less than 100 mg/kg bw/day for females.

In another study rats were exposed 5 days a week to 1000 mg/kg bw/day for 30 days (22 doses in total). Half of the animals were not exposed during a recovery period, the other animals were sacrificed after the last exposure. No clinical signs except coloration of the feces was observed. No mortality, changes in food and water consumption, and effects on hematology, clinical biochemistry and urinalysis findings was observed. Slight inhibition of bodyweight gain which recovered during the recovery period was observed. Kidney weights were increased, although recovered after the recovery period. Morphological changes to the tubules of the kidney were observed, although no longer visible after the recovery period. TheNOAELwas determined to beless than 1000 mg/kg bw/day.

Pigment Red 57(Sr) 73612-29-0

Reversible kidney toxicity with a NOEL of 25 mg/kg bw and a LOAEL of 75 mg/kg bw was observed in the subacute oral toxicity study (OECD 407) with Pigment Red 57(Sr) using olive oil as vehicle (DIC 2006). Absolute and relative kidney weights were increased after four weeks, but not at the end of the treatment-free recovery period. No macroscopic findings were observed, but histopathology examinations showed that kidneys had a dose-dependent increase in atypical and typical basophilic tubules, degeneration and necrosis of tubular epithelium and dilation of distal and collecting tubules with a NOEL of 25 mg/kg bw. All males of the highest dose group of 200 mg/kg bw had orange coloured pigments in the cell debris. The pigment were still visible in two of five animals at the recovery sacrifice, all other histopathology findings were absent. Kidney findings occurred in females at a lower extent - slight degeneration and necrosis of tubular epithelium was observed only for the high dose group (200 mg/kg bw). Histopathology findings were not observed in animals of the recovery group. Body weight and food intake were not affected during the treatment period. During the recovery period, males of treatment group showed an increased food intake compared to control rats. Clinical signs consisted of salivation at the highest dose group during treatment.

Pigment Red 48:2(Ca) 7023-61-2

In the subacute oral toxicity study with Pigment Red 48:2(Ca) (OECD 422, MHLW 2009) using 1% Tween 80 in water as vehicle, the NOEL was determined to be 40 and less than 40 mg/kg bw for males and females, respectively. The test dosages were 40, 200, and 1000 mg/kg bw/day. In the histological examination of animals sacrificed after the dosing period, degeneration/necrosis of the proximal tubular epithelium in the kidney was noted in males of the 1000 mg/kg group and females of the 40 mg/kg group and higher. Moreover, degeneration/necrosis of the papillary ductal epithelium in females of the 1000 mg/kg group and mild basophilic tubule in males of the 1000 mg/kg group and females of the 200 and 1000 mg/kg groups were noted. Increased kidney weight was noted in males of the 1000 mg/kg group. These changes disappeared after a 2-week recovery period. Test substance-colored stool (red) was observed in all animals of the 40 mg/kg group and higher. Abnormal contents (test substance-colored reddish contents) the digestive organs such as cecum and colon and reddish urine in males were also noted. However, there were no abnormal changes in the digestive system or other organs/tissues in the histological examination. In other parameters, there were no changes attributed to the test substance on behavior test, body weight, food consumption, hematology, or blood chemistry.

4-aminotoluene-3-sulphonic acid (CAS 88-44-8) Moiety for Pigment Red 57

In an OECD 407 Guideline study, 5 male and female rats per dose group were exposed via oral gavage to 100, 300, or 1000 mg/kg bw test substance for 28 days (ECHA disseminated dossier). Toxicological effects included decreases in white blood cell count, total cholesterol and urine pH, and enlargement of cecum in male at 1000 mg/kg bw/day; increases in GPT, decreases in glucose and enlargement of cecum in female at 1000 mg/kg bw/day. Since all findings were reversible within 14 days, the NOAEL can be set at 300 mg/kg bw/day for both sexes.

Strontium

The long-term hazard of the strontium cation is derived from hazard data published for inorganic strontium salts. The relevant data is summarized in the Concise International Chemical Assessment Document on Strontium and Strontium Compounds (UNEP 2010). Strontium is part of the environment and consumed with food and drinking water and the total daily intake is estimated to be up to about 4 mg/day. In accordance with the chemical and physiologic similarity to calcium, strontium is almost exclusively detected in the skeleton, the strontium to calcium ratio in the bone being 0.0003 at birth and 0.0005 in adults.

At high doses, strontium causes numerous bone and cartilage abnormalities in experimental animals. In a study, using Strontium carbonate (CAS 1633-05-2), in young animals, which are most sensitive to skeleton effects, minor effects were seen after drinking water application at 350 mg strontium/kg bw/day for 20 days; but clear effects were seen at 750 and 1500 mg/kg bw/day (Storey 1961). In a study using, Strontium chloride (CAS 10025-70-4), no effects on bone were seen in a dietary study with weaning rats at 160 mg strontium per kg bw/day for 90 days (Kroes 1977) and in that study, 40 mg Strontium/kg bw/day was identified as the NOAEL based on changes in thyroid structure and weight, liver content and pituitary weight. For strontium sulfate (CAS 7759-02-6) the NOAEL was identified as less than 240 mg strontium/kg bw/day based on reduced spleen weights in female rats upon gavage application. At 480 mg strontium/kg bw/day, epididymis and testis weights were increased and at 950 mg/kg bw, females showed reductions in reticulocyte counts and activity of aspartate aminotransferase (NIER 2006).

 

Conclusion

Results for all analogue pigments are largely comparable. Kidney effects are clearly the most sensitive endpoint for the BONA metal laked pigments. Bolus dosing results in high peak exposures and high local concentrations and may overload the local detoxification capacities. The colourant is quickly taken up and eliminated via the kidney as indicated by dose-dependent urine coloration occurring within the first day of dosing. The regeneration of the renal epithelium indicates a cytotoxic effect, probably by the azo moiety or a metabolite.

In reproductive toxicity screening studies with Pigment Red 48:2(Ca) and 57:1(Ca) , pregnant females seemed somewhat more susceptible than males or non-pregnant females. However, the reported LOAELs of 40 and 100 mg/kg/day (lowest tested doses in each study, respectively) and the limited severity of the kidney effects at the LOAELs are considered compatible with the derived NOAEL of 25 mg/kg bw/day and no further adjustment is considered necessary. The cytotoxic effect of the Pigments Red lead to a constant regeneration of tubular epithelial cells as long as exposure continues. No pronounced increase in toxicity with dose was observed in any of the studies, i.e. higher doses did not induce qualitatively different kidney effects. Also, prolonged exposure up to 2 years did not increase kidney toxicity or induced qualitatively different effects. It appears that continuous application is better tolerated than bolus application. All kidney effects were completely reversible within tested recovery periods of 14 days. Effects at 40, 100, 200 or 300 mg/kg bolus dosing did not induce severe or serious damage, i.e., clear functional disturbance or morphological changes.

Strontium salts of Bona metal laked pigments contain strontium at about 17% of their molecular weight. Comparing the effective doses of the metal part and the organic part, the hazard profile is dominated by the organic part as can be observed in the subacute oral toxicity study with Pigment Red 57(Sr) (DIC 2006). Effects were observed at concentrations as low as 75 mg/kg bw, but these renal effects present in all studies with Bona pigments irrespectively of the metal present. Furthermore, these effects are absent in the studies performed with the different Strontium salts described above. Therefore, taking 25 mg/kg bw for chronic exposure of rats as a starting point for DNEL calculation covers hazards both related anion and cation.

Taking all repeated-dose studies into account both the most relevant NOAELs are the one from a guideline 28-day study with Pigment Red 57(Sr) (25 mg/kg bw) and from the chronic feeding study with sodium salt of Pigment Red 57(Na) (26 mg/kg/bw). Twenty-five mg/kg bw is used as starting point for DNEL derivation because the value stems from the newest study with the most extensive analysis of parameters (including urinalysis) and is the lowest value.

Dermal exposure

Absence of histopathology findings in kidney upon 18 month skin painting study with mice was published (1984). The study was designed between the US FDA and an industry association to assess the safety of the use of Pigment Red 57:1(Ca) in lipstick and therefore, a limit dose of 50 mg/kg bw was chosen. Limited details are given in the literature. The main focus of the study was local effects, but a set of organs for each five males and females was investigated by histopathology. As kidney histopathology was the most sensitive endpoint, this investigation contributes to hazard assessment.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for repeated dose toxicity according to Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008.