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EC number: 204-881-4 | CAS number: 128-37-0
- Life Cycle description
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- Endpoint summary
- Appearance / physical state / colour
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- 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
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- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
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- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
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- Specific investigations
- Exposure related observations in humans
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- Additional toxicological data
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 03 September 2013 - 15 December 2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2014
Materials and methods
- Principles of method if other than guideline:
- The aim of the study was to evaluate the tolerance of weaned piglets to Butylated Hydroxytoluene (BHT) as technological feed additive (E 321). The trial was carried out with 144 weaned piglets weighing 7.66 (± 0.89) kg/head at the start of the study. The feeding treatments were: 1) Control group T1: animals fed basal diet; 2) T2: animals fed basal diet (T1) supplemented with BHT at 150 g/tonne feed (recommended dose); 3) T3: animals fed basal diet (T1) supplemented with BHT at 1000 g/tonne feed (6.7x
recommended dose) and 4) T4: animals fed basal diet (T1) supplemented with BHT at 1500 g/tonne feed (10x recommended dose). The feeds were issued to the appropriate pens for 42 consecutive days (between day 0 and day 42 of the trial). Each feeding treatment was replicated in 9 pens (5 pens of castrated males and 4 pens of female piglets) with 4 animals of the same gender per pen. The data recorded during the feeding phase were live weight (LW) at 0, 14 and 42 days from the start of the study; average daily gain (ADG), daily feed intake and feed:gain ratio (F:G) during the periods 0-14; 14-42 and 0-42 days from the start of the study; blood haematology and biochemistry parameters at D0 and D43. - GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
Constituent 1
Test animals
- Species:
- pig
- Strain:
- other: Goland x Italian Duroc boar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Az. Agr. Guida di Valtulini Cristina – Fabio e Giovanna S.S. Soc. Agricola, Cascina Guida – 26020 Cappella Cantone (CR), Farm code: 076 CR 032.
- Age at study initiation: 28 days of age approx.
- Weight at study initiation: 7.66 (± 0.89) kg
- Fasting period before study:
- Housing: Grouped, 4 piglets per pen (total of 36 pens). The animals were placed in 5 cleaned, disinfected weaning rooms. In rooms 1 to 4 six pens are aligned in one row with a lateral corridor, 1.0 m wide. In room 5 there are 12 pens arranged in two rows separated by a corridor of 1.0 m wide. For animal health reasons, the weaning rooms are managed according to an “all in – all out” system, with at least 7 days between weaning batches.
- Diet (e.g. ad libitum): Ad libitum (steel feeders).
- Water (e.g. ad libitum): Ad libitum (nipple drinkers).
- Acclimation period: 4 days (medicated feed with amoxicillin and colisting).
DETAILS OF FOOD AND WATER QUALITY: See Table no. 1 below.
ENVIRONMENTAL CONDITIONS :
- Temperature (°C): Within specifications.
- Humidity (%): Within specifications.
*The temperature and relative humidity was recorded every 30 minutes during each day of the trial by a computerised automatic system.
- Air changes (per hr): The ventilation rate varied from 0 m3/hour to the maximum ventilation rate required, according to the desired temperature and the age of the
piglets.
- Photoperiod (hrs dark / hrs light): During the whole study period the lighting scheme was natural.
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- - PREPARATION OF DOSING SOLUTIONS:
The test producttreated feeds differed only in test product addition from the T1 control feed. The test product was included as dry product by mixing with part of the basal diet. This mixture was added to the rest of the basal diet. All control feeds (those containing no test products) were made before the test product containing feeds.
- Duration of treatment / exposure:
- 42 days (pre-starter period from day 0 to 14 and starter period from day 14 to 42).
- Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 other: g/tonne feed
- Dose / conc.:
- 150 other: g/Tonne feed (recommended use level)
- Remarks:
- ca. 4.6-6.5 mgBHT/kg bw
- Dose / conc.:
- 1 000 other: g/Tonne feed (6.7 x recommended use level)
- Remarks:
- ca. 29.7-42.1 mgBHT/kg bw
- Dose / conc.:
- 1 500 other: g/tonne feed (10 x recommended use level)
- Remarks:
- ca. 47.2-61.0 mgBHT/kg bw
- No. of animals per sex per dose:
- 20 castrated pigs and 16 females per dose (divided in 4 replicates each).
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: Not available.
- Rationale for animal assignment (if not random): Random.
- Rationale for selecting satellite groups: Not applicable.
- Post-exposure recovery period in satellite groups: Not applicable.
- Section schedule rationale (if not random): Random.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS/CLINICAL OBSERVATIONS: Yes
- Time schedule: Twice daily, in the morning and in the afternoon.
- Parameters: General health status, ensuring constant feed and water supply as well as checking for the correct temperature and ventilation.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Health/illness and diarrhoea was scored daily. Culling and mortality alongside the reason for culling and probable cause of mortality were recorded.
BODY WEIGHT: Yes
- Time schedule for examinations: Individual and mean pen weight of the animals at day 0, 14, and 42.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes.
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
Mean pen feed intake at days 14 and 42 for to calculate the feed intake in the periods D0-D14, D14-D42 and D0-D42
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. Mean daily gain and feed:gain ratio, calculated per pen
HAEMATOLOGY: Yes / No / Not specified
- Time schedule for collection of blood: At time 0 and at the end of the trial (D43).
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- How many animals: At time 0: randomly 20 piglets in total, 10 per sex. At D43: 12 piglets per treatment, 6 per sex.
- Parameters checked: RBC, Haemoglobin, Haematocrit, MCV, MCH, MCHC, WBC, Lymphocytes, Monocytes, Neutrophils, Eosinophils, Basophils, Platelets, reticulocyte count, RPI, MPV, PCT, PDW.
CLINICAL CHEMISTRY: Yes / No / Not specified
- Time schedule for collection of blood: At time 0 and at the end of the trial (D43).
- Animals fasted: Not specified
- How many animals: At time 0: randomply 20 piglets in total, 10 per sex. At D43: 12 piglets per treatment, 6 per sex.
- Parameters checked: Glucose, Calcium, Inorganic P, Cholesterol, Triglycerides, Phospholipids, Uric acid, Urea, Creatinine, Lactate dehydrogenase, Alkaline Phosphatase, GOT (Aspartate Transaminase), GPT (Alanine Transaminase), Total Bilirubin, GGT, haptoglobin, serum albumin, serum total protein, blood clotting: quick/INR value, prothrombin time (PT), thyroid hormones (TSH, T3, T4).
OTHER:
DIETARY ANALYSIS:
- Time schedule: Nine representative samples of at least 250 g were taken from each diet and for each growing period: 3 in the beginning, 3 in the middle and 3 in the end of the production process (during the bagging-of the feeds). These 9 samples were pooled to 3 samples in such a way that 1 sample from the beginning, middle and end were pooled together and thoroughly mixed.
- Parameters checked: Feed moisture, crude protein content, crude fat content, crude fibre content, crude ash, starch, digestible energy. - Statistics:
- All data were analysed by the GLM (General Linear Model) procedure of SAS (SAS, 2002-2008, release 9.2) using ANOVA (Analysis of Variance) as the main statistical test. Student’s “t” Test was used to compare the means of each group. The level of significance to indicate differences stated in the ANOVA model was P≤0.05 when the difference was statistically significant, while 0.05
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- The general performance parameters were good and similar to those expected under commercial rearing of weaned piglets in Italy. The veterinarian considered piglet health and husbandry to be generally good with no mortality and normal consistency of the faeces.
- Mortality:
- no mortality observed
- Description (incidence):
- No mortality was observed throughout the study.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- No statistically-significant differences were found for live weight and average daily gain among feeding treatments. See Table no. 2. below.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- No statistically significant differences were found for daily feed intake among feeding treatments in the all phases of the study. See Table no. 3 below.
- Food efficiency:
- no effects observed
- Description (incidence and severity):
- No statistically significant differences were found for feed: gain ratio among feeding treatments in the all phases of the study. See Table no. 3 below.
- 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):
- No statistical differences were found among feeding treatments with the exception of haemoglobin and haematocrit that were higher in T2 vs. T1, T3 and T4 groups (respectively 11.14 vs. 10.23, 10.46 and 10.46 %; P=0.0457 and 38.60 vs. 35.73, 36.23 and 35.94 %; P=0.0432) but no difference occurred between T1 and T4 group. Tendentially higher was WBC in T2 vs. T1 and T3 groups (9.90 vs. 8.27 and 8.27 1,000/ml respectively; P=0.0503). All measured blood haematological parameters on D0 and D43 were within the respective reference ranges. See Table no. 4.
For MCV and MCH statistically significant (treatment x gender) interactions were found. See Table no. 5. In females, both MCV and MCH parameters resulted higher in the T3 and T4 vs. T1 group (MCV: 60.53 and 59.65 vs. 56.23 fl; P=0.0225) (MCH: 17.72 and 17.32 vs. 16.28 pg; P=0.0222). See Table no. 6. In castrated males, MCV resulted higher in the T1 and T2 vs. T3 group (respectively 59.43 and 61.13 vs. 54.20 fl; P=0.0354) and MCH resulted tendentially higher in the T2 and T4 vs. T3 group (respectively 17.53 and 17.13 vs. 15.43 pg; P=0.0618). See Table no. 7. - Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Statistical significant differences were found for lactate dehydrogenase higher in T4 vs. T1, T2 and T3 groups (respectively 370.58 vs. 334.50, 344.92 and 335.08 U/l; P = 0.0066), while for triglycerides, GPT and serum total protein the differences were only tendentially. Triglycerides were tendentially lower in T2 and T3 vs. T1 group (respectively 72.67 and 71.67 vs. 80.17 mg/dl; P = 0.0976). GPT was tendentially higher in T2 and T4 vs. T1 group (respectively 44.75 and 44.17 vs.
35.42 U/l; P = 0.0959). Serum total protein was tendentially higher in T4 vs. T1, T2 and T3 groups (respectively 7.81 vs. 7.41, 7.44 and 7.47 g/dl; P = 0.0739). All measured blood biochemical parameters on D0 and D43 were within the respective reference ranges. For none of the blood biochemical parameters statistically significant (treatment x gender) interactions were found. See Table no. 8 below. It is important to point out that no differences were observed between the control and the treatment groups regarding neither the thyroid hormones (TSH, T3, T4) nor hepatic function related enzymes (GOT, GPT, GGT). Individual results for thyroid hormones have been included in Table no. 9. - Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 61 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No significant adverse effects observed at the highest dose tested.
- Remarks on result:
- other: 1500 g/tonne feed (ca. 47.2-61.0 mgBHT/kg bw)
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Any other information on results incl. tables
Table 1. Feed analysis:
BHT, mg/kg (mean ± standard deviation; n=4) |
||||
Experimental period |
T1 Control |
T2 BHT 150 g/ton. feed |
T3 BHT 1000 g/ton. feed |
T4 BHT 1500 g/ton. feed |
D0 - D14 |
Not detected |
149.2± 5.4 |
1007.3± 40.0 |
1424.9± 50.2 |
D14 - D42 |
Not detected |
149.5±4.6 |
1005.6± 26.5 |
1413.8± 75.4 |
The actual BHT content was within the nominal values and within the tolerance limits given.
Table 2. Body weight:
Zootechnical performance: live weight and average daily gain (mean; n = 36) |
||||||
Experimental period |
T1 Control |
T2 BHT 150 g/ton. feed |
T3 BHT 1000g/ton. feed |
T4 BHT 1500 g/ton. feed |
Treatment Effect (P) |
Standard error of the mean |
Live weight (kg) |
||||||
D0 |
7.55 |
7.83 |
7.60 |
7.68 |
0.5815 |
0.1458 |
D14 |
10.31 |
10.56 |
10.26 |
10.53 |
0.6433 |
0.2008 |
D42 |
20.76 |
20.89 |
20.27 |
20.93 |
0.2064 |
0.2400 |
Average daily gain (g) |
||||||
D0-D14 |
196.63 |
195.04 |
189.88 |
203.57 |
0.7952 |
9.6637 |
D14-D42 |
373.31 |
386.71 |
357.34 |
371.43 |
0.4259 |
12.2961 |
D0-D42 |
314.42 |
322.82 |
301.52 |
315.48 |
0.3358 |
8.1768 |
Table 3. Food intake and feed:gain ratio:
Daily feed intake and feed:gain ratio (mean, n = 9) |
||||||
Experimental period |
T1 Control |
T2 BHT 150 g/ton. feed |
T3 BHT 1000g/ton. feed |
T4 BHT 1500 g/ton. feed |
Treatment Effect(P) |
Standard error of the mean |
Feed intake (g) |
||||||
D0-D14 |
274.78 |
282.86 |
263.53 |
301.87 |
0.1819 |
12.3017 |
D14-D42 |
677.36 |
678.39 |
639.36 |
673.22 |
0.3470 |
17.4249 |
D0-D42 |
543.17 |
546.55 |
514.08 |
549.44 |
0.1324 |
11.5380 |
Feed:Gain ratio |
||||||
D0-D14 |
1.42 |
1.46 |
1.39 |
1.49 |
0.4217 |
0.0480 |
D14-D42 |
1.82 |
1.77 |
1.79 |
1.82 |
0.8459 |
0.0403 |
D0-D42 |
1.73 |
1.70 |
1.71 |
1.74 |
0.8188 |
0.0314 |
Table 4. Haematology:
Blood haematological parameters at D43 days from the start of the study (mean; n =12 [6 castrated males + 6 females]) |
||||||
|
T1 Control |
T2 BHT 150 g/ton. feed |
T3 BHT 1000 g/ton. feed |
T4 BHT 1500 g/ton. feed |
Treatment effect (P) |
Standard error of the mean |
WBC (1,000/ml) |
8.27 x |
9.90 y |
8.27 x |
9.27 xy |
0.0503 |
0.4789 |
RBC (1,000,000/ml) |
6.20 |
6.47 |
6.32 |
6.07 |
0.1171 |
0.1187 |
Haemoglobin(%) |
10.23a |
11.14b |
10.46a |
10.46a |
0.0457 |
0.2314 |
Haematocrit(%) |
35.73a |
38.60b |
36.23a |
35.94a |
0.0432 |
0.7774 |
MCHC(%) |
28.68 |
28.85 |
28.83 |
29.12 |
0.6196 |
0.2375 |
Neutrophils(%) |
42.58 |
36.75 |
35.17 |
36.67 |
0.2665 |
0.8061 |
Lymphocytes(%) |
45.38 |
50.50 |
53.08 |
51.00 |
0.3436 |
3.0663 |
Monocytes(%) |
7.08 |
8.42 |
7.67 |
8.25 |
0.5848 |
0.7497 |
Eosinophils(%) |
3.42 |
3.00 |
2.92 |
3.21 |
0.9151 |
0.5410 |
Basophils(%) |
1.54 |
1.33 |
1.17 |
0.88 |
0.3939 |
0.2791 |
Platelets (1,000/mmc) |
332.92 |
303.08 |
308.67 |
304.50 |
0.4431 |
14.6137 |
Reticulocyte(%) |
0.94 |
0.97 |
0.98 |
1.01 |
0.6718 |
0.0390 |
RPI(%) |
0.95 |
1.05 |
1.01 |
1.02 |
0.4108 |
0.0446 |
MPV (fl) |
7.57 |
7.85 |
9.02 |
7.60 |
0.1606 |
0.5107 |
PCT(%) |
0.40 |
0.35 |
0.44 |
0.40 |
0.5880 |
0.0452 |
PDW |
20.09 |
20.19 |
21.09 |
19.86 |
0.2699 |
0.4654 |
WBC = white blood cells; RBC = red blood cells; MCHC = mean concentration of haemoglobin in erythrocytes; RPI = Reticulocyte production index; MPV = mean platelet volume; PCT = platelet crit (percent volume of the blood occupied by platelets); PDW = platelet distribution width.
a,b.: Different letters in the same row = differences significant (P<0.05)
x,y.: Different letter in the same row = differences tendentially significant (0.0.5 < P < 0.1)
Table 5. Haematology - MCV and MCH (treatment x gender)
Blood haematological parameters at D43 days from the start of the study (mean; n = 6) |
|||||||
|
T1 Control |
T2 BHT 150 g/ton. feed |
T3 BHT 1000 g/ton. feed |
T4 BHT 1500 g/ton. feed |
Treatment effect (P) |
Treatment * sex interaction (P) |
Standard error of the mean |
MCV (fl) |
57.83 |
59.80 |
57.37 |
59.14 |
0.2281 |
0.0054 |
0.3092 |
MCH (pg) |
16.55 |
17.24 |
16.58 |
17.23 |
0.2151 |
0.0099 |
0.2314 |
MCV = mean volume of erythrocytes; MCH = mean content of haemoglobin.
Table 6. Haematology - MCV and MCH (treatment x females)
Blood haematological parameters at D43 days from the start of the study - females (mean; n = 6) |
||||||
|
T1 Control |
T2 BHT 150 g/ton. feed |
T3 BHT 1000g/ton. feed |
T4 BHT 1500 g/ton. feed |
Treatment Effect (P) |
Standard error of the mean |
MCV (fl) |
56.23a |
58.47ab |
60.53b |
59.65b |
0.0225 |
0.9334 |
MCH (pg) |
16.28a |
16.95ab |
17.72b |
17.32b |
0.0222 |
0.3047 |
MCV = mean volume of erythrocytes; MCH = mean content of haemoglobin.
a,b.: Different letters in the same row = differences significant (P<0.05)
Table 7. Haematology - MCV and MCH (treatment x castrated males)
Blood haematological parameters at D43 days from the start of the study - castrated males (mean; n = 6) |
||||||
|
T1 Control |
T2 BHT 150 g/ton. feed |
T3 BHT 1000g/ton. feed |
T4 BHT 1500 g/ton. feed |
Treatment Effect (P) |
Standard error of the mean |
MCV (fl) |
59.43b |
61.13b |
54.20a |
58.63ab |
0.0354 |
1.5871 |
MCH (pg) |
16.82xy |
17.53y |
15.43x |
17.13y |
0.0618 |
0.5381 |
MCV = mean volume of erythrocytes; MCH = mean content of haemoglobin.
a,b.: Different letters in the same row = differences significant (P<0.05)
x,y.: Different letter in the same row = differences tendentially significant (0.05 < P < 0.1)
Table 8. Biochemistry
Blood biochemical parameters at D43 days from the start of the study (mean; n =12 [6 castrated males + 6 females]) |
||||||
|
T1 Control |
T2 BHT 150 g/ton. feed |
T3 BHT 1000g/ton. feed |
T4 BHT 1500 g/ton. feed |
Treatment effect (P) |
Standard error of the mean |
Glucose (mg/dl) |
89.17 |
94.33 |
93.83 |
94.58 |
0.6725 |
3.5603 |
Urea (mg/dl) |
23.80 |
22.24 |
22.78 |
23.02 |
0.7618 |
13.0450 |
Uric acid (mg/dl) |
0.34 |
0.32 |
0.34 |
0.32 |
0.8398 |
0.0177 |
Creatinine (mg/dl) |
1.34 |
1.39 |
1.41 |
1.33 |
0.2992 |
0.0341 |
Cholesterol (mg/dl) |
85.33 |
76.08 |
77.92 |
85.00 |
0.1618 |
3.5634 |
Triglycerides (mg/dl) |
80.17y |
72.67x |
71.67x |
73.83xy |
0.0976 |
2.5601 |
Bilirubin (mg/dl) |
0.13 |
0.14 |
0.13 |
0.12 |
0.8483 |
0.0119 |
GOT (U/l) |
43.08 |
42.75 |
44.08 |
46.08 |
0.8780 |
3.1572 |
GPT (U/l) |
35.42x |
44.75y |
42.00xy |
44.17y |
0.0959 |
2.8527 |
GGT (U/l) |
28.22 |
28.95 |
28.40 |
32.24 |
0.2057 |
1.4945 |
Alkaline phosphate (U/l) |
280.17 |
319.33 |
295.75 |
301.42 |
0.3014 |
14.4340 |
Lactate dehydrogenase (U/l |
334.50a |
344.92a |
335.08a |
370.58b |
0.0066 |
7.8378 |
Calcium (mg/dl) |
10.66 |
10.06 |
10.61 |
10.02 |
0.2558 |
0.2889 |
Inorganic P (mg/dl) |
8.47 |
9.10 |
9.28 |
9.34 |
0.1128 |
0.2761 |
Phospholipides (mg/dl) |
110.25 |
103.95 |
105.17 |
113.78 |
0.2255 |
3.7170 |
Haptoglobin (mg/dl) |
1.12 |
1.13 |
1.12 |
1.12 |
0.9907 |
0.0290 |
Serum albumin (g/dl) |
2.48 |
2.63 |
2.49 |
2.41 |
0.5113 |
0.1041 |
Serum total protein (g/dl) |
7.41 x |
7.44 x |
7.47 x |
7.81 y |
0.0739 |
0.0173 |
INR value |
0.96 |
0.97 |
0.95 |
0.95 |
0.6826 |
0.0099 |
Prothrombin value (sec) |
10.73 |
10.72 |
10.83 |
10.80 |
0.9178 |
0.1320 |
TSH (mU/ml) |
0.02 |
0.02 |
0.02 |
0.02 |
0.9474 |
0.0011 |
T3 (pg/ml) |
2.47 |
2.44 |
2.48 |
2.56 |
0.9067 |
0.1171 |
T4 (ng/dl) |
1.38 |
1.34 |
1.27 |
1.27 |
0.6250 |
0.0672 |
GOT = Aspartate Transminase; GPT = Alanine Transminase, GGT = gamma-glutamyl transpeptidase, INR value = International Normalised Ratio; TSH = Thyroid stimulating hormone; T3 = Triiodothyronine; T4 = Thyroxine.
a,b.: Different letters in the same row = differences significant (P<0.05)
x,y.: Different letter in the same row = differences tendentially significant (0.05 < P < 0.1)
Table 9: Individual results on T3, T4 and TSH (thyroid hormones):
Treatment |
Sex |
Room |
Pen |
FT3 |
FT4 |
TSH |
T1 |
F |
1 |
5 |
2.5 |
1.29 |
0.015 |
T1 |
F |
1 |
5 |
2.1 |
1.27 |
0.019 |
T1 |
F |
4 |
2 |
2.6 |
1.36 |
0.026 |
T1 |
F |
4 |
2 |
2.9 |
1.06 |
0.021 |
T1 |
F |
4 |
6 |
2.1 |
1.36 |
0.019 |
T1 |
F |
5 |
5 |
2.7 |
1.6 |
0.017 |
T1 |
M |
1 |
1 |
2 |
1.9 |
0.015 |
T1 |
M |
1 |
1 |
2.2 |
1.6 |
0.018 |
T1 |
M |
2 |
3 |
3.1 |
1.41 |
0.017 |
T1 |
M |
5 |
1 |
2.5 |
1.15 |
0.021 |
T1 |
M |
5 |
10 |
2.8 |
1.26 |
0.021 |
T1 |
M |
5 |
10 |
2.1 |
1.26 |
0.028 |
T2 |
F |
1 |
2 |
2.4 |
1.2 |
0.024 |
T2 |
F |
2 |
4 |
2.5 |
1.26 |
0.025 |
T2 |
F |
3 |
5 |
2.1 |
1.6 |
0.015 |
T2 |
F |
3 |
5 |
2.3 |
1.15 |
0.018 |
T2 |
F |
5 |
6 |
2.1 |
1.8 |
0.024 |
T2 |
F |
5 |
6 |
2.4 |
1.4 |
0.015 |
T2 |
M |
1 |
6 |
2.3 |
1.29 |
0.021 |
T2 |
M |
1 |
6 |
2.2 |
1.31 |
0.024 |
T2 |
M |
3 |
1 |
3 |
1.15 |
0.019 |
T2 |
M |
4 |
3 |
3 |
1.19 |
0.016 |
T2 |
M |
5 |
2 |
2.4 |
1.29 |
0.024 |
T2 |
M |
5 |
9 |
2.6 |
1.41 |
0.015 |
T3 |
F |
2 |
1 |
2.6 |
1.02 |
0.022 |
T3 |
F |
2 |
1 |
2.6 |
1 |
0.021 |
T3 |
F |
3 |
2 |
2.9 |
1.12 |
0.023 |
T3 |
F |
4 |
4 |
3.1 |
1.26 |
0.019 |
T3 |
F |
5 |
8 |
2 |
1.45 |
0.016 |
T3 |
F |
5 |
8 |
2.5 |
1.66 |
0.021 |
T3 |
M |
1 |
3 |
2 |
1.23 |
0.027 |
T3 |
M |
1 |
3 |
2 |
1.22 |
0.018 |
T3 |
M |
2 |
5 |
2.1 |
1.27 |
0.014 |
T3 |
M |
3 |
6 |
2.5 |
1.81 |
0.019 |
T3 |
M |
5 |
3 |
3.2 |
1.11 |
0.027 |
T3 |
M |
2 |
12 |
2.3 |
1.12 |
0.015 |
T4 |
F |
1 |
4 |
2.1 |
1.7 |
0.02 |
T4 |
F |
1 |
4 |
2.5 |
1.36 |
0.019 |
T4 |
F |
1 |
4 |
2.1 |
1.24 |
0.027 |
T4 |
F |
2 |
6 |
3.1 |
0.99 |
0.022 |
T4 |
F |
4 |
5 |
2.7 |
1.27 |
0.017 |
T4 |
F |
5 |
11 |
2 |
1.15 |
0.021 |
T4 |
M |
2 |
4 |
2.4 |
1.09 |
0.019 |
T4 |
M |
2 |
2 |
3 |
1.35 |
0.015 |
T4 |
M |
3 |
3 |
2.4 |
0.96 |
0.014 |
T4 |
M |
4 |
1 |
2.1 |
1.45 |
0.022 |
T4 |
M |
5 |
7 |
3.7 |
1.7 |
0.019 |
T4 |
M |
5 |
2 |
2.6 |
1 |
0.016 |
Applicant's summary and conclusion
- Conclusions:
- The administration of BHT to piglets for fattening for 35 consecutive days up to 1500 g/tonne feed (ca. 47.2-61.0 mgBHT/kg bw), did not cause any adverse effects under the test conditions. No adverse effects were observed related neither to the thyroid hormones (TSH, T3, T4) nor hepatic function (GOT, GPT, GGT).
- Executive summary:
In the present study, the tolerance of weaned piglets to Butylated hydroxytoluene (BHT) at technological feed additive was evaluated (GLP study). The trial was carried out with 144 weaned piglets weighing 7.66 (± 0.89) kg/head at the start of the study. The feeding treatments were: 1) Control group T1: animals fed basal diet; 2) T2: animals fed basal diet (T1) supplemented with BHT at 150 g/tonne feed (recommended dose, ca. 4.6 -6.5 mgBHT/kg bw); 3) T3: animals fed basal diet (T1) supplemented with BHT at 1000 g/tonne feed (6.7x recommended dose, ca. 29.7 -42.1 mgBHT/kg bw) and 4) T4: animals fed basal diet (T1) supplemented with BHT at 1500 g/tonne feed (10x recommended dose, ca. 47.2 -61.0 mgBHT/kg bw). The feeds were issued to the appropriate pens for 42 consecutive days (between day 0 and day 42 of the trial). Each feeding treatment was replicated in 9 pens (5 pens of castrated males and 4 pens of female piglets) with 4 animals of the same gender per pen. The data recorded during the feeding phase were live weight (LW) at 0, 14 and 42 days from the start of the study; average daily gain (ADG), daily feed intake and feed:gain ratio (F:G) during the periods 0-14; 14-42 and 0-42 days from the start of the study; blood haematology and biochemistry parameters at D0 and D43. The piglets were considered of good health, no mortality was observed and the faeces were of normal consistency. No statistically significant differences were found for piglets performance (LW, ADG, daily feed intake and feed:gain ratio) among feeding treatments in all phases of the study. No statistical differences were found for haematological parameters at D43 among feeding treatments with the exception of haemoglobin and haematocrit that were higher in T2 vs. T1, T3 and T4 groups but no difference occurred between T1 and T4 group. Tendentially higher was WBC in T2 vs. T1 and T3 groups. Some statistically significant treatment * gender interactions were found for MCV and MCH and a statistical analysis for each gender was performed. In female pigs both MCV and MCH resulted higher in the T3 and T4 vs. T1 group while in castrated male pigs MCV resulted higher in the T1 and T2 vs. T3 group and MCH resulted tendentially higher in the T2 and T4 vs. T3 group. Concerning the biochemical parameters at D43 LDH was lower in T1, T2 and T3 vs. T4 group; triglycerides were tendentially higher in T1 vs. T2 and T3 groups; GPT was tendentially lower in T1 vs. T2 and T4 groups and serum total protein was tendentially higher in T4 vs. T1, T2 and T3 groups. All measured blood haematological and biochemical parameters were within the respective reference ranges. In conclusion, the administration of BHT to weaned piglets for 42 consecutive days up to 1500 g/tonne fed (ca. 47.2 -61.0 mgBHT/kg bw), did not cause significant adverse effects under the test conditions. It should be highlighted that no test item related adverse effects were observed regarding neither the thyroid hormones (TSH, T3, T4) nor the hepatic function (GOT, GPT, GGT).
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