Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
10 Dec 1950 - 14 Apr 1954
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication meeting basic scientific principles.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1955

Materials and methods

Objective of study:
absorption
distribution
excretion
Principles of method if other than guideline:
Fly ash derived from coal combustion was fed at 0, 300 and 1500 g / animal / day to cows over a period of 2 years.
After two years, the chemical composition of milk, blood, urine and faeces samples were analysed.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Fly ash from (black) coal combustion, Scholven, Germany
- Other: Further details are given in the tables below
Radiolabelling:
no

Test animals

Species:
cattle
Strain:
other: Schwarzbunte Niederungsrasse
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Oldenburg, Germany (a geographical region which was assumed to be free of fly ash from coal combustion)
- Age at study initiation: 2.75 - 6.75 years
- Weight at study initiation: 535 - 710 kg
- Housing: Cattle pen; the animals were allowed to graze.
- Diet (e.g. ad libitum): fodder beed, hay and straw (ad libitum) supplemented with mash.
At their arrival the animals were carefully clinically examined. All animals were in good nutritional state and showed no symptoms of illness.
Some animals were seropositive for tuberculosis.

ENVIRONMENTAL CONDITIONS
All animals were kept on farm without contact to other cattle.
The cattle pen was always kept clean, dry and ventilated with fresh air.

IN-LIFE DATES:
Exposure period: From: December 10th, 1950 To: December 15th, 1953
Post exposure observation period: From: December 16th, 1953 To: April 14th, 1954

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
The test substance was mixed with the daily food.
Animals were fed twice a day in individual boxes to assure the intake of the individual portions.

DIET PREPARATION
In the high dose group, the fly ash was mixed with soaked fodder beed and mash, to improve the taste and to ascertain the daily intake of the high amounts of fly ash.
Duration and frequency of treatment / exposure:
2 years, twice daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 300 and 1500 g/animal/day (2 high-dose animals received temporarily up to 1800 g/animal/day)
No. of animals per sex per dose:
3
Control animals:
yes, concurrent no treatment
Positive control:
not applicable
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Body fluids sampled: urine, faeces, blood, milk
- Time and frequency of sampling: once on December 10, 1952
Statistics:
not applicable

Results and discussion

Any other information on results incl. tables

Analysis of milk samples collected on December 10th, 1952:

(Average values in % determined from two different laboratories in parallel)

Animal

Treatment up to the sampling date

Dry residue

Ash

CaO

MgO

P2O5

1

concurrent no treatment

12.9

0.74

0.172

0.0144

0.212

2

concurrent no treatment

15.8

0.89

0.267

0.0222

0.276

3

concurrent no treatment

10.3

0.71

0.136

0.0155

0.185

4

300 g fly ash per day

11.2

0.78

0.173

0.0170

0.235

5

300 g fly ash per day

14.7

0.82

0.197

0.0194

0.299

6

300 g fly ash per day

14.1

0.71

0.152

0.0204

0.159

7

1500 - 1800 g fly ash per day

15.3

0.69

0.161

0.0161

0.220

8

1500 - 1800 g fly ash per day

14.1

0.73

0.155

0.0144

0.213

9

1500 - 1800 g fly ash per day

10.3

0.73

0.151

0.0153

0.224

Applicant's conclusion:

Two years of oral administration of two different doses of fly ash did not influence the composition of the milk regarding the analysed parameters.

 

Analysis of blood samples collected on December 10th, 1952:

(Average values in % determined from two different laboratories in parallel)

Animal

Treatment up to the sampling date

Dry residue

Ash

CaO

MgO

P2O5

Fe2O3

1

concurrent no treatment

19.2

1.37

0.0127

0.0058

0.0374

0.0534

2

concurrent no treatment

19.9

1.03

0.0110

0.0060

0.0380

0.0544

3

concurrent no treatment

18.7

1.15

0.0116

0.0061

0.0371

0.0435

4

300 g fly ash per day

19.5

1.22

0.0133

0.0062

0.0396

0.0502

5

300 g fly ash per day

19.2

1.36

0.0094

0.0077

0.0333

0.0572

6

300 g fly ash per day

19.6

1.13

0.0101

0.0068

0.0350

0.0430

7

1500 - 1800 g fly ash per day

20.3

1.16

0.0105

0.0071

0.0359

0.0480

8

1500 - 1800 g fly ash per day

18.3

0.98

0.0112

0.0062

0.0362

0.0489

9

1500 - 1800 g fly ash per day

19.3

1.12

0.0116

0.0077

0.0345

0.0547

Applicant's conclusion:

Two years of oral administration of two different doses of fly ash did not influence the composition of the blood regarding the analysed parameters.

 

Analysis of urine samples collected on December 10th, 1952

(Average values in % determined from two different laboratories in parallel)

Animal

Treatment up to the sampling date

pH

Glucose

Protein

Dry residue

CaO

MgOa

P2O5

1

concurrent no treatment

8.14

neg.

neg.

6.84

0.0055

0.0170

0.0027

2

concurrent no treatment

8.20

neg.

neg.

5.18

0.0018

0.0221

0.0024

3

concurrent no treatment

8.18

neg.

neg.

5.41

0.0011

0.0261

0.0016

4

300 g fly ash per day

8.36

neg.

neg.

5.33

0.0066

0.0090

0.0013

5

300 g fly ash per day

8.26

neg.

neg.

4.53

0.00097

0.0080

0.0014

6

300 g fly ash per day

8.34

neg.

neg.

5.11

0.0043

0.0302

0.0031

7

1500 - 1800 g fly ash per day

8.08

neg.

neg.

3.85

0.0084

0.0100

0.0013

8

1500 - 1800 g fly ash per day

8.40

neg.

neg.

6.33

0.0041

0.0357

0.0022

9

1500 - 1800 g fly ash per day

8.38

neg.

neg.

5.80

0.0233

0.0411

0.0025

aMgO was only analysed from one laboratorium

Applicant's conclusion:

Two years of oral administration of two different doses of fly ash did not influence the composition of the urine regarding the analysed parameters.

 

Analysis of faeces sampled on December 10th, 1952

(Values in % of fresh faeces)

Animal

Treatment up to the sampling date

Ash

SiO2

Al2O3

Fe2O3

MgO

CaO

SO3

P2O5

1

concurrent no treatment

2.77

1.51

0.119

0.066

0.118

0.270

0.057

0.183

2

concurrent notreatment

2.23

1.11

0.086

0.054

0.150

0.250

0.044

0.164

3

concurrent no treatment

2.28

1.13

0.091

0.062

0.111

0.259

0.052

0.167

4

300 g fly ash per day

2.68

1.32

0.296

0.142

0.131

0.255

0.054

0.190

5

300 g fly ash per day

2.36

1.17

0.240

0.148

0.111

0.240

0.054

0.170

6

300 g fly ash per day

2.98

1.55

0.431

0.201

0.131

0.350

0.077

0.270

7

1500 - 1800 g fly ash per day

4.81

2.49

0.716

0.615

0.286

0.372

0.107

0.182

8

1500 - 1800 g fly ash per day

6.21

2.84

0.827

0.643

0.352

0.477

0.135

0.246

9

1500 - 1800 g fly ash per day

4.76

2.31

0.644

0.506

0.288

0.492

0.105

0.208

aMgO was only analysed from one laboratorium

Applicant's conclusion:

Two years of oral administration of two different doses of fly ash influenced the ash and mineral contents of the faeces in a dose-dependent manner.

Analysis of trace elements in liver and bone samples:

At the end of the 3-year experiment duration, liver and bone samples of all animals were analysed for their contents of Arsenic, Manganese, Lead, Iron, Copper, Zinc and Cobalt. Bones were additionally analysed for their CaO and P2O5content.

In summary, there was no significant influence of the fly ash administration on the trace element contents in liver and bone samples.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
The chemical analyses of milk, blood, urine and faeces indicate, that no systemic absorption after oral administration of 1850 mg/kg/day of the test substance occured.
Executive summary:

Fly ash derived from coal combustion in Scholven, Germany was fed at 0, 300 and 1500 g/animal/day to cows over a period of 3 years. After two years the control and intermediate dose groups were exchanged and therefore as far as possible only the results from this time point were taken into the present considerations.

Body weight development in cows were not disturbed by the oral administration of fly ash. Because treated animals showed a slightly higher milk production rate than control animals, the general condition of treated animals was considered to be better. Chemical analyses of milk, blood, urine and faeces samples after two years indicate that the test substance was practically not bioavailable for resorption.