Registration Dossier

Administrative data

Hazard for aquatic organisms

Freshwater

Hazard assessment conclusion:
PNEC aqua (freshwater)
PNEC value:
0.2 µg/L
Assessment factor:
100
Extrapolation method:
assessment factor
PNEC freshwater (intermittent releases):
2 µg/L

Marine water

Hazard assessment conclusion:
PNEC aqua (marine water)
PNEC value:
0.02 µg/L
Assessment factor:
1 000
Extrapolation method:
assessment factor

STP

Hazard assessment conclusion:
PNEC STP
PNEC value:
0.1 mg/L
Assessment factor:
100
Extrapolation method:
assessment factor

Sediment (freshwater)

Hazard assessment conclusion:
no exposure of sediment expected

Sediment (marine water)

Hazard assessment conclusion:
no exposure of sediment expected

Hazard for air

Air

Hazard assessment conclusion:
no hazard identified

Hazard for terrestrial organisms

Soil

Hazard assessment conclusion:
PNEC soil
PNEC value:
0.08 µg/kg soil dw
Extrapolation method:
equilibrium partitioning method

Hazard for predators

Secondary poisoning

Hazard assessment conclusion:
no potential for bioaccumulation

Additional information

PNEC aqua- freshwater

As indicated in REACH Guidance R10, "In establishing the size of these assessment factors, a number of uncertainties have been addressed to extrapolate from single-species laboratory data to a multi-species ecosystem. These areas comprise: intra- and inter-laboratory variation of toxicity data; intra- and inter-species variations (biological variance); short-term to long-term toxicity extrapolation; laboratory data to field impact extrapolation.

Application to MMH:

Summary of ecotoxicity results with MMH

Trophic level Species Size/Length in the test Test lab Klimisch rating RSS/study N° EC50 or LC50 result
Type Nominal (mg/L) Measured (mg/L)
Algae Pseudokirchneriella subcapitata  Single cell CIT 1 (specific analytical method) 36966 EAA 72h-ErC50 0.73 <0.019*
Invertebrate Daphnia magna ~5 mm 36967 EAD 48h-EC50 0.26 0.04*
Hyalella azteca (amphipod) ~5 mm Wright-Patterson Air Force Base 4 (unspecific analytical method) AMRL-TR-79-93 48h-LC50 1.2 NR
Asillidae (isopod) NR AMRL-TR-79-93 48h-LC50 0.82 NR
Fish Ictalurus punctatus (catfish) ~8 cm AMRL-TR-79-93 96h-LC50 2.27 1.1 to 2.1
Notemigonus crysoleucas (shiner) ~6 cm AMRL-TR-79-93 96h-LC50 3.54 NR
Lebistes reticulatus = Poecilia reticulata (guppy) ~3 cm 4 (no analytical follow-up) None (Slonim publication) 96h-LC50 2.58 NP

*: extrapolated by taking into account the same "measured/nominal" ratio as at the top-dose of the test (algae: below LOD at the top-dose, daphnia: taken as geometrical mean of LOD and LOQ at the top-dose).

NR: not reported; NP: not performed

Additionally (Klimisch 4, non-standard result): the nominal EC50 for teratogenoicity in amphibian embryos (Xenopus laevis) was between 5 and 7.5 mg/L, with an extremely steep dose-effect curve.

- intra-lab variability was low in the fish studies by Fisher (WP AFB test), in which two independent assays led to very coherent results (in both tested fish species);

- inter-lab variability can not be assessed because tests in different labs were on different species;

- inter-species variability at the trophic level "fish", is very low since very consistent 96h-LC50 results were obtained for three fish species (nominal of 2.58 mg/L in guppy, of 3.54 mg/L for channel catfish, and measured value between 1.1 and 2.1 mg/L for golden shiner corresponding to nominal of 2.27 mg/L);

- inter-trophic variability was low between algae and daphnids, both highly sensitive to MMH, and again low between larger animals like chitine-protected invertebrates, fish or amphibians; this suggests that the most primitive/smallest species, are the most sensitive to MMH;

- intra-species variability can not be assessed since each test is done on a homogeneous group of individuals from the same source; however it is necessarily lower than the inter-species variability (above);

- short-term to long-term extrapolation is not applicable: for the most sensitive trophic level, algae, the test lasting 72h has the status of a long-term assay;

- lab-to-field extrapolations stays the only significant source of uncertainty, and data on degradation suggest possibility of oxidation of MMH in aerated water in presence of catalysts like Cu2+.

Based on these considerations, the data showing high sensitivity of algae to MMH are considered to be already at the extreme end of the sensitivity band for long-term effects of MMH, and a safety factor of 100 is considered sufficient for derivation of PNEC freshwater.

PNECfreshwater = <0.019 mg/L / 100: < 0.2 µg/L

PNEC aqua- marine water

For the reasons indicated above, the standard AF of 10000 is reduced to 1000 for the derivation from acute EC50/LC50 values from three trophic levels.

PNECmarine water = <0.019 mg/L / 1000: < 0.02 µg/L

PNEC intermittent

For the reasons indicated above, the standard AF of 100 is reduced to 10 for the derivation from acute EC50/LC50 values from three trophic levels.

PNECmarine water = <0.019 mg/L / 10: < 2 µg/L

PNEC soil

According to ECHA Guidance R7c, as only aquatic toxicity data, degradation and adsorption data or estimates are available, the substance should be assigned to a “soil hazard category” for a screening assessment:

- adsorption is negligible due to high water solubility and negative log Kow

- the substance is not expected to have a soil half-life> 180 days (EPIsuite estimate: 30 days)

- but the substance is very toxic to aquatic organisms (see water toxicity data)

Therefore the substance falls in Hazard category 2 according to ECHA Guidance Table R.7.11-2.

In this case, equilibrium partitioning is applied as follows for PNECsoil derivation (Equations R.16-5, R.16-6, R.16-7, R.16-74 and R.10-5); a confirmatory short-term soil toxicity testing with the most sensitive organism group should be proposed, but only at 100 t/year according to REACH Annexes VII-VIII, i.e. this proposal is not required for the intended registration band:

Kair-water = "dimensionless Henry's law constant" = Henry's law constant / (R x Temp) = 3.071E-1 (highest estimate from EPIsuite) / (8.314 x 285) = 1.30E-4

Kpsoil (L/kg) = Focsoil x Koc = 0.02 kg o.c./kg solid x 13.31 L/kg (highest estimate from EPIsuite) = 0.2662

Ksoil-water = Fair(soil) x Kair-water + Fwater(soil) + (Fsolid(soil) x Kpsoil x RHOsolid / 1000)

= 0.2 m3 air/m3 soil x 1.30E-4 + 0.2 m3 water/m3 soil + (0.6 m3 solid/m3 soil x 0.2662 L/kg x 2500 kg/m3 / 1000) = 0.60

PNECsoil (w.w.)= 1000 x PNECwater x Ksoil-water /RHOsoil = < 0.2 mg/m3 x 0.60 / 1150 kg/m3 = <0.1 µg/kg soil w.w.

Unit conversion per soil dry weight:

PNECsoil (d.w.)= PNECsoil(w.w.) x CONVsoil = 1000 x PNECwater x Ksoil-water/RHOsoil x [RHOsoil / (Fsolid x RHOsolid)] = < 0.2 mg/m3 x 0.60 / (0.6 m3 solid/m3 soil x 2500 kg/m3) = <0.08 µg/kg soil d.w.

Conclusion on classification

Based on:

- high acute aquatic toxicity (lowest EC50 or LC50: algae: < 0.019 mg/L),

- absence of readily degradability (a degradation was shown, which depends on dissolved oxygen/Cu2+ and pH but it can not be taken into account for classification),

The substance should be classified as:

-Aquatic Acute Category 1 according to GHS/CLP.

- Aquatic Chronic Category 1 according to GHS/CLP.

And the Multiplying factor "M" according to GHS/CLP Table 4.1.3, is "at least 10" as the exact value of the critical EC50/LC50 (algae) is unknown. Due to this incertitude, it is not recommended to use this M factor to assess environmental risks related to MMH-containing formulations.