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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
0.067 µg/m³
Most sensitive endpoint:
carcinogenicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: DMEL was derived based on the OEL for hexavalent Chromium compounds as proposed by Seidler et al. (2012) and in the ECHA report on establishing a reference dose response relationship for carcinogenicity of hexavalent chromium (RAC/27/2013/06 Rev. 1)
Modified dose descriptor starting point:
other: OEL
DNEL value:
0.067 µg/m³
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
5 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: DMEL was derived based on the BMDL01 as presented in the Scientific Opinion on lead in food by the European Food Safety Authority (EFSA, 2010)
Modified dose descriptor starting point:
other: BMDL01
DNEL value:
0.5 µg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The BMDL01 of 0.5 µg/kg bw/day was corrected for the poor dermal absorption of pigments (0.01%), arriving at a DMEL long-term systemic dermal of 5000 µg/kg bw/day or 5 mg/kg bw/day.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Carcinogenicity

In accordance with the current EU classification for C.I. Pigment Yellow 34 and C.I. Pigment Red 104, which was based on read across from other more soluble and more respirable hexavalent chromium compounds, C.I. Pigment Yellow 34 and C.I. Pigment Red 104 are classified for carcinogenicity, although the likelihood of carcinogenicity risk is considered very low due to very poor bioavailability of these two substances. Three epidemiological studies in lead chromate pigment manufacturing plants "did not produce evidence supporting any association between lead chromate [pigments] and lung cancer". However limitations in cohort size, due to the limited number of workers in this industry, limits the use of such studies. Nonetheless as the worst case, the carcinogenicity risk of these two pigments will be assessed, using the carcinogenic properties of hexavalent chromium compounds as described by Seidler et al. (2012) and the RAC (RAC/27/2013/06 Rev.1, 2013) documents for Cr(VI) compounds. Based on the very poor solubility and bioavailability of these two lead sulfochromate pigments, the currently derived DMEL will vastly overestimate the carcinogenic potential of the pigments.

 

Lung cancer associated with Cr(VI) exposure

Several health effects are associated with occupational exposure to hexavalent chromium compounds, with carcinogenicity (specifically lung cancer) being the most serious. Therefore, lung cancer is the critical effect upon which to base an occupational exposure limit. In 2012, Seidler et al. published a review and quantification of respiratory cancer risk for occupational exposure to Hexavalent Chromium.

Seidler et al. reviewed a large number of epidemiological studies and selected 5 studies from 2 cohorts for their Risk Assessment, based on the presence of multiple exposure levels, consideration of smoking as confounder and overall adequate methodology used. They calculated that the numbers of excess lung cancers per 1000 male workers exposed for a working lifetime to 1 µg/m3 of hexavalent chromium and followed to age 74 - 89 years are predicted to be in the range of 3.4 - 4.1.

This means that Seidler et al. (2012) derive an Occupational Exposure Level (OEL) associated with 4 excess lung cancer cases per 100,000 workers for life time (40 years, 5 days/week, 8 hours/day) exposure to hexavalent chromium of 0.01 µg/m3.

 

C.I. Pigment Yellow 34 and C.I. Pigment Red 104

Based on a maximum chromium level of 15% in C.I. Pigment Yellow 34 and C.I. Pigment Red 104, this value of Seidler corresponds to a Cr (VI) exposure for both pigments of 0.0667 µg/m3. Unfortunately, the available epidemiological data do not allow for a reliable ranking of the carcinogenic potency of the various hexavalent chromium compounds encountered in industry. The data indicate, however, that poorly soluble hexavalent chromium compounds have a lower carcinogenic potency than soluble compounds. The relatively lower bioavailability of chromium ions to the intracellular target in the respiratory epithelium might explain this effect. The Scientific Committee on Occuptional Exposure Levels (SCOEL/SUM/086, 2004) distinguishes three classes of hexavalent chromium compounds based on water solubility and defines them as: poorly soluble (<1g/L), sparingly soluble (1-10g/L); highly soluble (>100g/L) compounds.

In addition, SCOEL published a health-based Risk Assessment for lead chromate (SCOEL/SUM/117, 2004). In this document it is concluded that, based on the specific data available for lead chromate, the OEL could be based on the information on inorganic lead compounds in general, as, based on the low solubility (a value of 0.06 g/L is mentioned), the likelihood of risk of genotoxicity and carcinogenicity is considered low. SCOEL recommends an OEL of 100μg Pb/m3 ambient air (corresponding to a Blood Lead Value (BLV) of 30μg Pb/dL blood). This value would be equivalent to a concentration of 25μg Cr/m3.

Despite the SCOEL recommendations for lead chromate and hexavalent chromium, it is decided to use the hexavalent chromium OEL from Seidler et al. (2012) as a basis for the DMEL for C.I. Pigment Yellow 34 and C.I. Pigment Red 104. However, the overestimation of the carcinogenic potential at the current DMEL is illustrated by the extremely low solubility of Cr(VI) derived from C.I. Pigment Yellow 34 and C.I. Pigment Red 104 in aqueous media. This value ranges from 3*10-6 to 2.3*10-2 g/L, depending on the Transformation/Dissolution or bio-elution protocol in aqueous simulated biological fluids (ECTX studies X02d-022 and X02d-023). These solubility values are about 40 – 30,000 times lower than the limit for poorly soluble of 1 g/L in the SCOEL report. The most relevant aqueous medium (simulated interstitial lung fluid) showed Cr(VI) solubilities from C.I. Pigment Red 104 and C.I. Pigment Yellow 34 of 0.0035 g/L and 0.0225 g/L, respectively. This is at least 44.4 times less soluble than the level for low solubility given in the SCOEL report. So this approach will overestimate the risks in the case of exposure to insoluble chromates, like C.I. Pigment Yellow 34 and C.I. Pigment Red 104.

 

Derived Minimum Effect Level (DMEL)

A DMEL long-term systemic inhalation of 0.0667 µg/m3 for both C.I. Pigment Yellow 34 and C.I. Pigment Red 104 is derived.

The excess lung cancer risk from Cr(VI) exposure can only be attributed to the respirable fraction of the hexavalent chromium compound. The non-respirable fraction will be cleared from the respiratory tract and swallowed in the gastrointestinal tract. From the particle size distribution and dustiness tests for C.I. Pigment Yellow 34 and C.I. Pigment Red 104 (see section 4.5) it can be estimated that the respirable fraction is < 2% for both pigments. This implies that the inhalable, non-respirable fraction must be evaluated for excess cancer risk from exposure by the oral route. It should be noted that the distribution of respirable and non-respirable fractions may vary among different uses, based on the formulation of the pigments. This will be taken into account in the risk assessment. In the report on the carcinogenicity dose-response analysis of Cr(VI)-containing substances (RAC/27/2013/06 Rev.1), it was concluded that for oral exposures, the Occupational Exposure Limit associated with 4 excess intestinal cancer cases per 100,000 workers for life-time (40 years, 5 days/week, 8 hours/day) exposure to hexavalent chromium is 0.2 µg Cr(VI)/ kg body weight/day. The assessment is based on linear extrapolation from intestinal tumour data in mice.

Based on a maximum chromium level of 15% in C.I. Pigment Yellow 34 and C.I. Pigment Red 104, this DMEL for oral Cr(VI) exposure corresponds to 0.2/0.15 = 1.33 µg/kg body weight/day for both pigments. This value will be used as an oral DMEL in the risk assessment to determine the risk due to swallowed non-respirable dust.

 

Toxicity to reproduction/developmental toxicity

From the available data it is evident that the carcinogenicity risk related to Cr(VI) will occur via the inhalation and oral routes only. However, effects of the inorganic lead in C.I. Pigment Yellow 34 and C.I. Pigment Red 104 should also be assessed to exclude all possible effects. Therefore, the available information with regard to effects on development and reproduction of inorganic lead compounds were assessed. In the voluntary Risk Assessment Report for lead and inorganic lead compounds, all available studies in humans and experimental animals have been evaluated for the observed effect of lead upon sexual maturation and semen quality, pregnancy outcome, and neurobehavioural effects of prenatal and postnatal lead exposure.

Based on the available data it is concluded that effects on neurobehavioural performance after pre-natal and post-natal exposure to inorganic lead, are the most critical effects, although a dose-effect relationship was not observed. This conclusion was based on a meta-analysis of several cohort studies correlating blood-lead concentrations to IQ deficits (Lanphear et al. 2005 and other studies). The result showed that IQ points were lost at blood-lead concentrations of < 10μg/dL and < 7.5μg/dL and that there was no indication of a threshold below these levels. In the risk assessment on lead from food which was performed by the European Food Safety Authority (EFSA, 2010), the Bench Mark Dose approach (BMD) is used to estimate the BMDL01, which is the blood-lead concentration corresponding to the lower 5-percentile of the Confidence Interval of the chosen Bench Mark Response of an IQ deficit of 1 IQ point. The BMR is chosen and set at 1 IQ point by the CONTAM panel of EFSA.

Using this approach, the BMDL01 for lead was estimated to be 1.2 μg/dL (mentioned as 12 μg/L by EFSA) and must be regarded as a DMEL for “minimal” IQ loss due to neurodevelopmental toxicity. This DMEL can be converted from 1.2 μg/dL to 0.5μg/kg body weight/day, which corresponds to 35 μg/day for a 70 kg person. Oral 35μg/day corresponds to 3.5 μg/m3 (the inhalation volume of a worker is 10 m3 per workday). This value can be compared to the DMEL for carcinogenic effects, corrected for the percentage of lead (maximally 60%) in both pigments. The maximum lead exposure for workers exposed by inhalation to the DMEL of 0.0667 μg/m3 (total pigment) is 0.04 μg/m3, which is lower than the BMDL01 of 3.5 µg/m3. Therefore, it can be concluded that the DMEL for carcinogenicity will be valid for neurodevelopmental effects as well (an insignificant decrease in IQ of about 0.01 IQ point). In order to perform a combined risk assessment for the effects on neurobehavioural development, a DMEL of 5.8 µg/m3 can be taken into account, based on maximally 60% lead in pigment.

With regard to dermal exposure, the VRAR mentions that lead uptake rates via the dermal route are <0.01%, both for adults and for children. This is supported by an in vitro skin absorption study (HERAG Fact Sheet 01, Occupational dermal exposure and dermal absorption, 2007; Toner and Roper, 2006) and bio-elution studies showing <2% solubility of C.I. Pigment Yellow.34 and C.I. Pigment Red.104 in artificial sweat. Therefore it can be assumed that dermal exposure will not contribute to higher blood lead levels to a large extent. However, to exclude possible effects from dermal exposure, a DMEL was derived based on the BMDL01 for oral exposure as presented in the EFSA report. This value of 0.5 µg/kg bw/day should be corrected for dermal absorption, arriving at a DMEL long-term systemic dermal of 5000 µg/kg bw/day or 5 mg/kg bw/day.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Not relevant as no consumer uses are anticipated and no consumer exposure is expected