REVIEW OF NEW INFORMATION ON MERCURY FOR A POSSIBLE REVISION OF SECONDARY POISONING STANDARD
1.QSsecpois_biota as reported in the existing EQS dossier (2005)
The assessment for secondary poisoning of top predators is based on methylmercury which is more toxic and accumulated than inorganic mercury. The value used for standard derivation is based on the lowest NOEC reported for mammal and bird oral toxicity exposed to methylmercury. In the 2005 EQS Hg Data Sheet, it was noticed that data for birds and mammals very similar: the lowest NOEC for mammals and birds are 0.22 and 0.25 mg/kg, respectively and the QSsecpois.biota was derived with the lowest one and an assessment factor of 10. This reduced factor of 10 instead of the default AF of 30, had been chosen because of the large number of NOECs available for methyl mercury.
As identified by UK during the review process of exiting EQS, references quoted in the existing EQS Hg Data Sheet were all published between 1970 and 1988. UK suggested then that the dataset used to derive the current EQS could be completed with recent references and provided a list of about 87 studies for terrestrial vertebrate toxicity from recent literature search.
Mercury has been extensively studied and it was not expected that these studies would be drastically different from the existing values, although new sensitive endpoint, relevant for the environment, could be identified. The new information could also help to reduce the uncertainty associated with QS derivation, possibly with the use of the SSD approach and a reduced assessment factor.
2Review of the 87 studies for secondary poisoning
The 87 new studies referenced by UK, were evaluated and we tried to extract the toxicity values required for the SSD.
The data could be used in the derivation of QS secondary poisoning of top predators provided that the test endpoints relate to the effects at the population level of the species. The following OECD guidelines are most important in this respect:
-OECD guideline 401: Acute Oral Toxicity
-OECD guideline 407: Repeated Dose 28-day Oral Toxicity Study in Rodents
-OECD guideline 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents
-OECD guideline 409: Repeated Dose 90-Day Oral Toxicity Study in Non-Rodents
-OECD guideline 414: Prenatal Development Toxicity Study
-OECD guideline 415: One-Generation Reproduction Toxicity Study
-OECD guideline 416: Two-Generation Reproduction Toxicity
Relevant are those toxicity tests in which the animals are dosed orally. This might be achieved via a direct method (intubation, gavage) or by dosing via the food or water.
A short list of application routes is given below:
-intubation or gavage
-capsule
-diet
-water or feeding solution
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Secondary poisoning only aims at taking into account effects at the population level. Therefore, relevant endpoints are :
-body weight
-egg production
-eggshell thickness
-hatchability
-hatchling survival
-mortality
-reproduction (e.g. litter size, teratogenic effect, malformation, gestation duration…)
-viability (percentage of viable embryos per total number of eggs)
The majority of the studies are deemed not relevant mainly for the following reasons (see table 1):
-7 studies are not relevant because no concentration of exposure is reported. This is mainly the case for field study because internalized or accumulated Hg concentration in organisms is the subject of such a study.
-9 studies seem to be not relevant due to the lack of effect consideration, for example, as is the case in studies that seek to assess the distribution of mercury in different organs or tissues.
-In 8 studies the route of exposure is not relevant for secondary poisoning approach (for example direct or subcutaneous injection.
-Most of those studies, 39 of them, are not acceptable due to a weak number of concentrations tested and the NOEC is not available.
-9 studies are not relevant for other reasons and mainly for reason concerning the type of endpoint taken into account
These tests are listed in table 1.
Table 1: List of non acceptable studies for secondary poisoning assessment (the number of the study corresponds to that used in the excel sheet accompanying this document).
General comment / Study numberNo concentration of exposure or only internal concentration is reported / 1, 2, 6, 18, 22, 24, 27,
No effects are considered or evaluated / 5, 10, 17, 19, 20, 21, 23, 29, 60,
The route of exposure is different from ingestion (drinking water or diet), for example direct injection / 7, 26, 31, 32, 39, 58, 68, 87
An insufficient number of concentrations tested and/or no NOEC or NOAEL can be determined / 4, 8, 14, 15; 28, 33, 34, 35, 40, 42, 44, 45, 46, 47, 48, 49, 50, 54, 56, 57, 59, 62, 63, 65, 66, 69, 70, 73, 74,76, 77, 78, 79, 80, 81, 82, 83, 85, 86
Other / 3 (Model construction),
11, 16, 25, 37 (review), 38, 43,
61 (Mice, reproductive performance, MTD (14-day gavage) = 1 mg/kg/day adverse effect observed for 0.25 MTD)
84
The acceptable tests are listed in table 2. Among these tests, the list of species contains rat, mice, mink, monkey and two birds: American kestrel and loon chicks. The two species of birds are not previously included in the dataset.
Table 2: acceptable data for secondary poisoning assessment
Study number / Type / Endpoint values9 / American kestrels
T= 59 days
Meat Diet containing MeHg Chloride / NOEC = 3 ppm (dry weight) Methylmercury Chloride , and EC50 between 3 and 6 ppm
12 / Loon chicks
T= 105 d
Daily Hg doses were administered via a rainbow
trout containing a gelatin capsule with the prescribed daily dose of CH3HgCl / NOEC = 0.08µg/g
EC50 = 0.4 µg/g
13 / See 12 / Common loon chick immune systems may be compromised at an ecologically relevant dietary exposure concentration (0.4 µg Hg/g wet wt food intake)
30 / Mammals, neurological function, TRV / a TRVs range for mild neurological impairment of 0.012–0.029 mg/kg/day,
and a TRV for clinical symptoms of 0.046 mg/kg/day
36 / Monkey, neurotoxicity / TDI monkey = 0.025 mg Hg/kg/day
TDI human = 0.0046 mg Hg/kg/day
51 / Rat, drinking water contamination, long term auditory deficits / NOEC = 4.5 ppm MeHg in drinking water
53 / Rat, prenatally exposure, motor activity / NOEC MeHg= 0.1 mg/kg bw/day
55 / PTWI (JECFA, 2003) / 1.6 µg/kg bw/week
64 / Rat / NOEC = 0.5 mg MeHg/kg (body weight)/day
71 / Mink, 89-day exposure, dietary, cholinergic system / NOEC = 17 µg/kg b.w./day.
75 / Rat, cerebellar function, drinking water / NOEC = 0.5 ppm
Other comments:
- Study n°4: This study could be taken into account for BAF determination
- Study n°72: Supporting study for human exposure via fishery products consumption.
As a conclusion, comparison with the previous values are not always possible because threshold values are sometimes expressed as ADI, TRV…which are aggregated values including a safety factor. Nevertheless, the reviewed studies are in the same range as this used for reference EQS. The number of additional species tested (2 birds) compare to the previous QS is insufficient to use the SSD approach and lower the assessment factor. Therefore,we would recommend to keep the existing value of 20 µg/kg as reference EQS.
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