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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientifically acceptable

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report Date:
1974

Materials and methods

Objective of study:
distribution
Principles of method if other than guideline:
determination tissue distribution of lead after acute oral treatment of test rats with test substance
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): chromgelb 62 F and chromgelb 72 GS
- Physical state: crystal mixture
- Analytical purity: chromgelb 62 F: 85% PbCrO4; chromgelb 72 GS: 85% PbCrO4
- Composition of test material, percentage of components: 85% PbCrO4 and 3%, also containing PbSO4, SbF3, Sb2O3 and SiO2 at unspecified percentages; chromgelb 72 GS: 85% PbCrO4 and 5% PbSO4, 4.5% Sb2O3 and 5% SiO2

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: SPF breed from WIGA, Sulzfeld
- Age at study initiation: no data
- Weight at study initiation: 205 g for males, 155 for females
- Fasting period before study: no data
- Diet: Altromin-R, Altrogge, Lage/L; ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on exposure:
VEHICLE (aquous suspension with 0.5% CMC)
Dose (mg/kg bw) /10000
Concentrationof test substance in vehicle (%) /35
Applied volume (ml/kg) /28.57
Duration and frequency of treatment / exposure:
once
Doses / concentrations
Remarks:
Doses / Concentrations:
10000 mg/kg bw
No. of animals per sex per dose:
2 in negative control and test substance groups, 1 in positive control groups
Control animals:
yes
Positive control:
lead(II)acetate (109.89 and 1904.76 mg/kg bw, respectively administered as 1.5 and 15% aqueous solution
Details on study design:
- Dose selection rationale: appr. 1/4 of LD50
Details on dosing and sampling:
PHARMACOKINETIC STUDY (distribution)

METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: kidneys, bone (femur)
- Time and frequency of sampling: 14 days after treatment
- From how many animals: 2
- Method type(s) for identification: atomic absorption spectroscopy
- Limits of detection and quantification: 1 µg

All animals were fasted for 16 hours before they were sacrificed by CO2 asphyxiation on day 14 after administration of the test substance. The body weight and the fresh weight of the kidneys and both femurs were determined.
The kidneys and femurs were subsequently dried at 105 °C until they reached weight constancy. The dried samples were cracked with 3 ml sulfuric acid; 2 ml mixed acid (sulfuric acid, nitric acid, hypochloric acid) were added and the liquid parts subsequently evaporated. The residue was disolved in diluted hydrochloric acid and sodium hydroxide solution was added until a pH of 5 was reached. The solution was extracted with 10 ml methylisobutylketone and ammoniumprrolidone diisothiocarbamate. The lead content of the organic phase was determined by atomic absorption spectroscopy.
The solubility of the test substance in 0.25% HCl was determined by stirring 1 g of the test substance in 1000 ml 0.25% HCl at 20 °C for 1 hour, followed by a period of 1 hour during which the insoluble parts were allowed to sink to the bottom of the vessel. The amount of lead was determined in the liquid phase.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
14 days after single oral administration of the lead chromate pigments Chromgelb 62 F, Chromgelb 72 GS and the equivalent amount of lead in the form of lead(II)acetate, the metal was detectable in kidneys and femurs of exposed animals.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
see Table 1

Any other information on results incl. tables

Table 1: lead content of kidneys and femurs

Treatment group

Start mean body weight (g)

Final mean body weight (g)

Final mean body weight after exsan-guination (g)

Wet kidneys (2) weight (g)

Wet femur (2) weight (g)

Dry kidneys (2) weight (g)

Dry femur (2) weight (g)

Lead content (µg/total wet kidneys weight)

Lead content (ppm in total dry kidneys weight

Lead content (µg/total wet femur)

Lead content (ppm in total dry femur)

Neg control

115

152.5

148.2

1.52

1.32

0.34

0.65

1

1

1

1

Chromgelb 62 F

112

161.8

150.5

1,39

1.28

0.31

0.59

1

2*

6.1

10.38

Chromgelb 62 F

107.5

158

151.5

1.38

1.16

0.30

0.59

3.0*

11.4*

6.05

5.68

Lead(II)acetate 1904.76 mg/kg bw

116.5

170

161.9

1.55

1.23

0.34

0.61

4.2

12.88

42.5

70.1

Lead(II)acetate 109.8 mg/kg bw

109

164

156.6

1.45

1.16

0.31

0.59

1

1

1.4*

2.35

*: only 1-2 values over the measurement limit

Applicant's summary and conclusion