Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 215-149-9
CAS number: 1306-25-8
Repeated dose toxicity, inhalation:
In a 28-Day Dose Range Finding Inhalation Toxicity Study
(Nose-only) in the Rat, exposures to Cadmium telluride (CdTe) in
the form of a dry aerosol at concentration levels of 0.003, 0.01, 0.03
and 0.09 mg/L were associated with adverse effects. The associated
adverse effects at the lowest tested concentration were slight,
transient tachypnea during the last week of the exposure, increase in
lungs weights (by about 1.5-2 times), which correlated with minimal
alveolar/interstitial/bronchiolar inflammation and minimal hyperplasia
of the Type II pneumocytes. Since at the lowest possible concentration
(0.003mg/L achieved by 2 hours exposure session to 0.01 mg/L) adverse
effects on the respiratory tract were observed, a LOAEC of 3 mg/m3 could
be set but no NOAEL could be determined in this study (Grosz, M 2013).
28-day inhalation toxicity study (nose-only) in the rat was
finalised by CiTox LAB Hungary Limited (Grósz,
M 2015). The
study followed the guideline OECD 412 and was conducted according to the
principles of GLP. Doses were selected based on the previous results of
the 28 -Day Dose Range Finding inhalation Toxicity Study (Grosz, M 2013)
OECD 412 guideline requires that the substance to be tested has a Mass
Median Aerodynamic Diameter(MMAD)
< 3 µm to ensure that the substance is respirable under the conditions
of the test. The
substance that was tested had to be milled to achieve a suitable MMAD. Due
to the large particle size of CdTe, the sample was therefore extensively
abraded by milling and grinding with a Retsch Mixer Mill MM 400 before
testing, to achieve a MMAD of 1.08 – 1.8 µm. This
process significantly altered the substance to a size and form not
representative of CdTe at manufacturing sites, as placed on the EU
market and used downstream (information
from exposure questionnaires sent to cadmium telluride downstream users).
dose levels chosen were 1 mg/m3, 0.3 mg/m3and 0.1
mg/m3as a result of dose range finding studies of 7-day and
28-day duration. Typically,
in a nose only repeat dose study, the rats are exposed to the test
concentration for 6 hours per day, however in this study an atmosphere
generation at concentration <1 mg/m3could not be achieved.
At concentrations < 1.0 mg/m3the laboratory could not
achieve stability, reproducibility and accuracy of the gravimetric
analysis, due to the standard commercial equipment available at the
laboratory, which was designed to run at test concentrations in the > 1
the laboratory proposed to conduct the “full” study by reducing the
exposure time at the 1 mg/m3dose level to achieve the 0.1 and
0.3 mg/m3dose levels. This
was done by the application of Haber’s Rule/Law (concentration x time of
exposure = dose). The
final dosing strategy resulted in the situation where each
group was exposed to a target concentration of 1 mg/m3and the
exposure doses at 0.3 mg/m3and 0.1 mg/m3were
achieved by reduction of the exposure time to 2 hours and 40 minutes
animals were exposed for 6 hours/day to clean air.
this dosing strategy does introduce a high level of uncertainty into
this study and it is impossible to know if testing at the actual lower
dose levels over 6 hours would give rise to a different toxicity profile. It
would have been much more desirable to obtain the correct testing
equipment in order to achieve the low dose levels.
a further group of animals at the high dose were retained for 14-days
post exposure to determine any reversibility of effects observed during
the study. As
cadmium and cadmium compounds are known to have a long clearance time
from the lung, the choice of a 14-day reversibility period was on
reflection, too short. A
more useful reversibility period would have been 3 months.
conclusion, the study design does raise uncertainties which could have
had a significant effect on the outcome of the study and the
interpretation of the results. These
milling and grinding required to achieve a respirable sample of CdTe.
use of Haber’s Rule/Law to achieve the required dose levels at low
Findings of the 28-day Repeat Dose Toxicity inhalation Study
exposure to Cadmium telluride (CdTe) in the form of a dry aerosol to
Hannover Wistar rats for 28 consecutive days at concentration of 1 mg/m3
for 6 hours and 0.3 mg/m3 (achieved by exposure to the
1.0 mg/m3for two hours) was associated with the following
findings, taken from the study report:
grey mottled lungs and enlarged, grey coloured lung associated lymph,
increase in lungs weight (absolute and relative values) in both sexes by
approximately 94-106% (at 1 mg/m3) and 50-65% (0.3 mg/m3).
above effect was correlated with minimal to mild diffuse
alveolar/interstitial inflammation, accumulation of foamy alveolar
macrophages and black cytoplasmic pigment in interstitial macrophages of
hyperplasia and aggregates of macrophages, presence of black pigment in
macrophages and degeneration/necrosis of the macrophages were found in
the lung associated lymph nodes.
changes of lungs were detectable by bronchoalveolar lavage.
in neutrophil granulocyte count in peripheral blood detected at
changes were still present following 14-day treatment free period.
at 0.1 mg/m3(achieved by exposure to the 1.0 mg/m3 for 40
minutes) resulted in increase of lungs weight by approximately 35-45%
(males) and 20-24% (females), without any macroscopic observation,
except enlarged lung associated lymph nodes. Microscopically
minimal diffuse alveolar/interstitial inflammation was observed in lungs
in 4 of 5 males and 4 of 5 females, in addition to mild changes in
lung-associated lymph nodes (mild lymphoid hyperplasia and aggregates of
macrophages, presence of black pigment).
LOAEL of this study was therefore determined to be 0.1 mg/m3,
the lowest dose tested, and no NOAEL could be established.
were no reported incidences of nasal irritation or irritation/cell
damage in the lung. No
investigation into the presence or incidence of fibrosis was carried out
during the study or in the reversibility satellite group. Unlike
the blood analysis, a full white cell count in the BAL fluid was not
of the findings in this study are indicative of cadmium toxicity e.g.
cell proliferation, hyperplasia, particle accumulation (long clearance
the duration of exposure in this study is too short to be conclusive and
only partial histopathology was conducted as is typical for studies of
study was given a Klimisch score of 2 due to the dosing regime and the
toxicological uncertainty of reducing the exposure period to achieve the
low dose levels. The
severe attrition of the substance to achieve a respirable dose also
raises the question of the representativeness of the tested substance in
comparison to the form placed and subsequently used on the EU market.
Repeated dose toxicity, oral:
No animal studies were located regarding long
term effects after oral exposure to cadmium telluride.
Results from studies with cadmium and cadmium
compounds in animals and observations in humans indicate that the
sensitive targets of cadmium toxicity are kidney and bone following oral
exposure and kidney and lungs following inhalation exposure (ATSDR,
Cadmium being a cumulative toxicant, the
systemic manifestations associated with chronic exposure are related to
the body burden of the element (liver and kidney content), assessed with
biomarkers such as urinary concentration (Cd-U).
Therefore, as cadmium accumulates in tissues over time in a repeat
dose study, a critical cumulative dose has to be achieved before
toxicity is observed. The integrated testing strategy for cadmium
telluride proposes to conduct a toxicokinetic study over 90 days to show
that cadmium telluride does not cause an accumulation of cadmium in the
kidney and liver (two sensitive target organs) and is therefore not
bioavailable by the oral route.
Repeated dose toxicity, dermal:
No animal studies were located regarding long
term effects after dermal exposure to cadmium telluride. However,
repeated dose toxicity via the dermal route is not expected to be
significant as uptake of less-soluble cadmium compounds applied onto the
skin of animals appears to be low (<1%) (see Toxicokinetics-absorption).
No human studies were located regarding
chronic effects after specific exposure to CdTe. Reference is made to
human data after exposure to the more soluble cadmium compounds.
Considering the lower bioaccessibility of Cd in CdTe, these human
exposure data are considered very conservative for CdTe.
In workers exposed to cadmium, a body
burden corresponding to 200 ppm in kidney cortex, ie ca. 10μg
Cd/g creatinine is considered to represent a critical level based on the
occurrence of low molecular weight proteinuria. SCOEL (2010) recommends
an Occupational Exposure Level (OEL) equivalent to 4 µg Cd/m3 (respirable
fraction) as protective against long-term local effects (respiratory
effects, including lung cancer). This is based on human data that shows
changes in residual volume of the lung for a cumulative exposure to CdO
fumes of 500 µg Cd/m3 x years, corresponding to 40 years exposure to
12.5 µg Cd/m3 (LOAEL) (Cortona et al.,1992). Applying an
uncertainty factor of 3 (LOAEL to NOAEL) leads to a value of 4 µg/m3
On the basis of studies conducted in Europe
(Buchet et al.,1990; Hotz et al.,1999; Järup et
al.,2000), the United States (Noonan et al.,2002) and Asia
(Jin et al.,2002), it appears that renal effects can be detected
in the general population for Cd-U below 5μg
Cd/g creatinine and even from 2μg
Cd/g creatinine or below. These
studies show associations between Cd-U and markers of tubular effect.
There is, however, a scientific debate about the health significance of
these early changes. This lower value in the general population compared
to that identified in workers is thought to reflect, among other
parameters, an interaction of cadmium exposure with pre-existing,
concurrent or subsequent renal diseases (mainly renal complications of
diabetes) that are less prevalent in healthy young individuals in
occupational settings (SCOEL, 2010).
Recent evidence questions the causality of
these associations between U-Cd and biomarkers of kidney effects
(urinary proteins) in populations with low levels of exposure.
Literature is showing that the association between Cd and protein
excretion probably represents normal variability in renal physiology
resulting in a temporarily increased or decreased Cd excretion,
independent of kidney cadmium concentration (Kidney Cd) (Chaumont et
al., 2012, Akerstrom et al., 2013). The excretion of Cd and proteins is
assumed to change in the same direction due to temporary changes in the
renal activity, since Cd bound to metallothionein and LMW proteins share
the same tubular binding site (Christensen et al., 2009), thus resulting
in an association between U-Cd and urinary proteins excretion. Overall,
Akerstrom concludes that “these associations are unlikely to be caused
by Cd toxicity but rather reflect temporary changes in urinary flow or
other sources of normal physiological variability that affect the
excretion of U-Cd and urinary proteins in the same direction, resulting
in an overestimation of the risk of renal toxicity from low-level Cd
exposure” (Akerstrom et al. 2013). These recent findings suggest that at
low environmental exposures, U-Cd would be more a reflection of the
functional integrity of the nephron than of the Cd exposure or of the Cd
body burden (Chaumont 2012).
These reverse causality mechanisms might have
important implications in the risk assessment of Cd for the general
population, which currently largely relies on the use of U-Cd as
exposure indicator (Chaumont et al 2012). In
conclusion, the scientific debate on the causal effect of low Cd
exposures (measured as Cd-U) on kidney function is ongoing. Taking this
debate into account, it is strongly recommended to consider the
anticipated effects on kidney at low Cd exposure with caution. However,
it is emphasized that at higher exposures, the causal relationship is
not questioned (Chaumont et al. 2011). The use of biological indicators
in e. g. worker environment is thus justified.
Based on the following findings, as documented under IUCLID 7.5.2
Waiving RDT inhalation:
the non-inhalable nature of cadmium telluride, it is proposed that the
substance does not require classification as a STOT-RE via the
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again