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Description of key information

BIOAVAILABILITY FOR ABSORPTION
Bioelution test with simulated gastric, interstitial, intracellular and perspiration fluid show highest bioavailability of both lead and chromium for oral absorption. The low dissolution of lead in interstitial fluid indicates that lead will not be very bioavailable via this route, whereas for chromium bioavailability is relevant via inhalation. Bioavailability via dermal absorption may be indicated by dissolution in perspiration fluid. This is very low for chromium and therefore dermal absorption will not be relevant for chromium. Lead concentrations in perspiration fluid are <2%, therefore bioavailability for dermal absorption will also be very low.
DISTRIBUTION OF TEST SUBSTANCE METABOLITES
Blood lead, chromium and/or molybdenum blood absorption and tissue distribution were observed in oral subchronic toxicity studies in rat (BASF AG, 1974; Report No: XXIV/61, BASF Farben & Fasern AG, 1976; Report No: 622-06329) and in dogs (BASF Farben & Fasern AG, 1976; Report No: 611-06328).

Key value for chemical safety assessment

Additional information

No toxicokinetics studies are available for C.I. Pigment Yellow 34 and C.I. Pigment Red 104, but information on distribution is available from repeated dose toxicity studies. Furthermore, bioelution studies with C.I. Pigment Yellow 34 and C.I. Pigment Red 104 were performed in simulated gastric, interstitial, intracellular and perspiration fluid to determine bioavailability for absorption via the oral, inhalation and dermal route.

Information from repeated dose toxicity studies

In the first rat study the animals received one treatment (10000 mg/kg bw; Chromgelb 62 F, Chromgelb 72 GS and the equivalent amount of lead in the form of lead(II)acetate as positive control) test substance by gavage (BASF AG, 1974). In the remaining studies the animals received 0, 2000, 5000 and 20000 ppm test substance (CI Pigment Yellow 34) in diet (corresponding to appr. 0, 152.9, 287.5 and 1602.1 mg/kg bw per day in rats and to appr. 0, 75.4, 179.6 and 287.1 mg/kg bw per day in dogs). In the first study, lead content levels were determined (atomic absorption spectroscopy; detection limit 1 µg) in kidneys and bone (femur) 14 days after treatment. In the second and third studies, tissues and body fluids sampled - blood (lead); liver, kidney, brain, and bone (lead and chromium) – were analyzed using atomic absorption spectrophotometry (limits of detection and quantification: Pb 0.001 µg/g; Cr 0.010 µg/g in brain tissue; Cr 0.050 µg/g in bone, liver, and kidney). Additional groups fed lead carbonate as positive control were also evaluated.

 

Blood Lead determination:

In both oral subchronic studies, noticeable and dose-related increases were observed in the blood lead concentrations of all test animals after 30, 60, and 84 days of testing with test and positive control substances.

 

Tissue distribution:

1) Lead:

14 days after single oral administration of the test substance and the equivalent amount of lead in the form of lead(II)acetate, the metal was detectable in kidneys and femurs of exposed animals.

 

The lead content of the bone and kidney samples was markedly increased at all levels in the subchronic studies. The brain lead content (males only) and liver lead content (males and females) were slightly increased when compared with control values in the rat subchronic study and in all sexes in the dog subchronic study. Increases were generally directly proportional to length of time on test and/or dietary concentration.

 

2) Chromium:

Increases in chromium content were noted in the kidney and liver tissues among most test animals.

 

In the rat subchronic study, the brain chromium content was slightly increased among a few females fed 2000 ppm or more and among the males fed 20000 ppm. Brain chromium content among male test animals fed 2000 or 5000 ppm was either less than or comparable to that of the controls. Increases in chromium content in bone samples from animals fed either 5000 or 20000 ppm were due to detectable amounts in 1 of 5 males fed 5000 ppm and in 1 of 5 females fed 20000 ppm. No detectable amount of chromium was found in the bone samples from any of the 2000 ppm animals.

 

Following observations were made in the dog subchronic study:

- At 2000 ppm test substance, chromium content was elevated in all 4 tissues examined, the liver showing the highest concentration, kidneys the next highest, then bone; brain tissue showed the lowest concentration.

- At 5000 ppm, a similar pattern of elevations was seen, with the concentrations in kidney, bone and brain tissues essentially comparable to those found in 2000 ppm animals. However, in liver tissue, the chromium content in 2000 ppm animals was considerably higher than that found in 5000 ppm animals, though both levels were tested for 90 days.

- At 20000 ppm, chromium content of liver and kidney tissues was much lower than that found in either 2000 or 5000 ppm dogs and in bone, chromium was below detectable limits. These findings correlate with the short time (3 weeks) the animals were on test. In brain tissue, however, chromium content was comparable to concentrations found at the 2 lower levels.

Bio-elution studies

The bio-elution potential of C.I. Pigment Yellow 34 and C.I. Pigment 104 was determined in four kinds of simulated body fluids: gastric, interstitial, intracellular and perspiration fluid, to determine bioavailability of chrome and lead for absorption. Incubation times were 2h for gastric fluid, and 24h and 7 days for interstitial, intracellular and perspiration fluid. Chrome and lead concentrations were measured by ICP-MS analysis.


Results show highest bio-elution in gastric fluid, in which 22-24% of chromium and 23-26% of lead dissolved. For chromium, the percentages dissolved were 8.34 and 1.33% in interstitial, 3.44 and 3.77% in intracellular and 0.07 and 0.08% in perspiration fluid, for C.I. Pigment Yellow 34 and C.I. Pigment Red 104 respectively. For lead, the percentages dissolved were 0 and 0.02% in interstitial, 4.17 and 9.37% in intracellular and 1.64 and 1.8% in perspiration fluid, for C.I. Pigment Yellow 34 and C.I. Pigment Red 104 respectively.

The values may be used to determine bioavailability of lead and chrome for absorption via the different exposure routes. The relatively high percentage of dissolved chrome and lead in simulated gastric fluid indicates that the highest bioavailability will result from oral exposure. Interstitial fluid may be a measure for dissolution in lung fluid and bioavailability after inhalation. The low dissolution of lead in this fluid indicates that lead will not be very bioavailable via this route, whereas for chromium bioavailability is relevant via inhalation. Bioavailability via dermal absorption may be indicated by dissolution in perspiration fluid. This is very low for chromium (<0.1%) and therefore dermal absorption will not be relevant for chromium. Lead dissolution from C.I. Pigment Yellow 34 and C.I. Pigment Red 104 in perspiration fluid is less than 1.8%. Therefore, bioavailability of lead for dermal absorption will also be very low.