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EC number: 700-323-3
CAS number: 908020-52-0
to the REACH Guidance on information requirements and chemical safety
assessment, a leading DN(M) EL needs to be derived for every relevant
human population and every relevant route, duration and frequency of
exposure, if feasible. In the present case, DNELs have been derived
according to the ECETOC guidance (ECETOC, Technical Report No. 110,
(absorption figures for oral, dermal and inhalation route of exposure)
toxicokinetic studies investigating oral, dermal and inhalation
absorption are available.
classified for acute toxicity as Harmful if swallowed (Xn, R22 or Acute
oral toxicity Cat. 4 - H302). Therefore a DNEL for acute toxicity needs
to be derived in case peak exposures occur. However, oral exposure is
expressed as amount (per kg bw) per day. Therefore acute oral exposure
peaks (in mg/kg bw/day) will not be higher than a calculated total
exposure per day (chronic; in mg/kg bw/day). Practically relevant peak
exposure via the oral route therefore does not occur for EEA-NH4. Thus
no DNEL has been derived for the oral route of exposure.
not classified for acute systemic dermal or acute inhalation toxicity.
Therefore no dermal or inhalation DNELacutefor systemic
effectshave been derived.
causes serious damage to the eyes (Xi, R41 or Eye Damage 1, H318);
however, it is not possible to derive a DNEL on the basis of the
available data. It is necessary to stipulate risk management measures
that prevent the occurrence of eye damage (see chapter 9 and 10 of the
CSR). The substance is not irritating and sensitising to skin.
repeated dose oral toxicity study and an oral reproduction/developmental
toxicity screening study were available for assessment. Effects noted in
the 28-day study were increased absolute and relative kidney weights
from 25 mg/kg bw/day group and higher. Therefore a NOAEL of 5 mg/kg
bw/day was derived.
reproduction/developmental screening study a neonatal NOAEL of 5 mg/kg
bw/day was determined based on lower live litter size and clinical
findings at 100 mg/kg bw/day and on reduced postnatal survival and lower
mean male and female pup body weights in the 25 and 100 mg/kg bw/day
groups. The highest tested dose level of 100 mg/kg bw/day was considered
to be the NOAEL for effects on fertility due to the lack of effects on
reproductive parameters in this study.The
NOAEL for systemic toxicity was 5 mg/kg bw/day based on lower mean body
weights, body weight gains and food consumption (significantly affected)
during lactation days 1-4 in the 100 mg/kg bw/day group females and
higher absolute and relative liver weights in the 25 and 100 mg/kg
bw/day group males.
been derived using both the NOAEL of 5 mg/kg bw/day from the 28-day
repeated dose oral toxicity study and the neonatal NOAEL of 5 mg/kg
bw/day from the reproduction/developmental screening study. The systemic
NOAEL of 5 mg/kg bw/day observed in the reproduction/developmental
screening study is not used for DNEL derivation as the neonatal NOAEL
results in a lower DNEL (due to a correction for reduced group size, see
Tables) and as the figure is similar to the NOAEL from the 28-day
repeated dose oral toxicity study resulting in a similar DNEL.
EEA-NH4 is assessed as
being non-mutagenic, therefore no DNEL has been derived for this
inhalation, systemic effects (based on 28-day oral (gavage) study in
Step 1) Relevant dose-descriptor
NOAEL: 5.0 mg/kg bw/day
Based on the increased absolute and relative kidney weights.
Step 2) Modification of starting point
0.38 m3/kg bw
6.7 m3/10 m3
In case of oral to inhalation route to route extrapolation, in the absence of route-specific information on both routes, a default factor of 2 is applied.
Standard respiratory volume of a rat, corrected for 8 h exposure, as proposed in the REACH Guidance on information requirements and chemical safety assessment (R.8.4.2)
Correction for activity driven differences of respiratory volumes in workers compared to workers in rest.
5.0 x 6.7 / 2 / 0.38 / 10 = 4.4 mg/m3
Step 3) Assessment factors
No assessment factor for allometric scaling needs to be applied in case of oral to inhalation route-to-route extrapolation
Default assessment factor for workers
Since the material is soluble in water (516 mg/L) and is unlikely to accumulate (Log Kow = 1.18) the sub-acute to sub-chronic assessment factor is considered 1.5 rather than the default factor 3 (Bitsch et al. (2006), Regul Toxicol Pharmacol 46, 202-210)). Combination with the default sub-chronic to chronic factor 2 leads to a correction factor of 3.
Note: this factor is based on data from scientific literature not specifically mentioned in the ECETOC documentation.
Quality of database
4.4 / (1 x 3 x 3 x 1 x 1) =0.49 mg/m3
Long-term – dermal,
systemic effects (based on 28-day oral (gavage) study in rats)
On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor should be introduced when performing oral-to-dermal extrapolation (see REACH Guidance on information requirements and chemical safety assessment (Chapter R.8.4.2)).
5.0 x 1 = 5.0 mg/kg bw/day
Assessment factor for allometric scaling for rat
5.0 / (4 x 3 x 3 x 1 x 1) =0.14 mg/kg bw/day
inhalation, systemic effects (based on reproduction/developmental
screening study in
Based on live litter size, clinical findings, reduced postnatal survival and lower mean male and female pup body weights.
5.0 x 6.7 / 1 / 0.38 / 10 = 8.8 mg/m3
No assessment factor for exposure duration is needed
Reduced group size
Assessment factor to correct for differences in group size compared to an OECD guideline 416 study.
8.8 / (1 x 3 x 1 x 1 x 1 x 1.4) =2.1 mg/m3
Long-term – dermal,
systemic effects (based on reproduction/developmental
screening study in
5.0 / (4 x 3 x 1 x 1 x 1 x 1.4) =0.30 mg/kg bw/day
EEA-NH4 will not be
placed on the market, therefore DN(M)ELs for the general population have
not been determined.
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.
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