Commission Regulation (EU) No 546/2011Show full title

2.6. Impact on human or animal health U.K.

The impact on human or animal health must be evaluated. In particular, [F1 competent authorities] must take account of the following principles:

Textual Amendments

F1 Words in Annex Pt. 2.B point 2.6 substituted (31.12.2020) by The Plant Protection Products (Miscellaneous Amendments) (EU Exit) Regulations 2019 (S.I. 2019/556), regs. 1(1), 18(9)(b)(xv); 2020 c. 1, Sch. 5 para. 1(1)

(a)

due to the ability of micro-organisms to replicate, there is a clear difference between chemicals and micro-organisms used as plant protection products. Hazards arising are not necessarily of the same nature as those presented by chemicals, especially in relation to the capacity of micro-organisms to persist and multiply in different environments;

(b)

the pathogenicity of the micro-organism to humans and non-target animals, the infectiveness of the micro-organism, the ability of the micro-organism to colonise, the toxicity of metabolites/toxins as well as the toxicity of the residual growth medium, contaminants and co-formulants, are important endpoints in assessing adverse effects arising from the plant protection product;

(c)

colonisation, infectiveness and toxicity comprise a complex set of interactions between micro-organisms and hosts and these endpoints may not be resolved easily as independent endpoints;

(d)

in combining these endpoints, the most important aspects of the micro-organism that must be assessed are:

• ability to persist and multiply in a host (indicative of colonisation or infectivity),

• ability to produce non-adverse or adverse effects in a host, indicative of infectivity, pathogenicity, and/or toxicity;

(e)

moreover, the complexity of the biological issues shall be taken into account in evaluating the hazards and risks presented by use of these plant protection products for human and animals. An assessment of pathogenicity and infectiveness is necessary even if the potential of exposure is deemed low;

(f)

for risk assessment purposes the acute toxicity studies used shall, where available, include at least two doses (e.g. one very high dose and one corresponding to the expected exposure under practical conditions).

2.6.1. Effects on human or animal health arising from the plant protection product U.K.

2.6.1.1. [F2 Competent authorities] shall evaluate operator exposure to the micro-organism, and/or to toxicologically relevant compounds in the plant protection product (e.g. their metabolites/toxins, residual growth medium, contaminants and co-formulants), likely to occur under the proposed conditions of use (including in particular dose, application method and climatic conditions). Realistic data on exposure levels must be used and, if such data are not available, a suitable, validated calculation model. F3 ... U.K.

Textual Amendments

F2 Words in Annex Pt. 2.B point 2.6.1.1 substituted (31.12.2020) by The Plant Protection Products (Miscellaneous Amendments) (EU Exit) Regulations 2019 (S.I. 2019/556), regs. 1(1), 18(9)(b)(xvi)(aa); 2020 c. 1, Sch. 5 para. 1(1)

F3 Words in Annex Pt. 2.B point 2.6.1.1 omitted (31.12.2020) by virtue of The Plant Protection Products (Miscellaneous Amendments) (EU Exit) Regulations 2019 (S.I. 2019/556), regs. 1(1), 18(9)(b)(xvi)(bb); 2020 c. 1, Sch. 5 para. 1(1)

(a)

This evaluation shall take into consideration the following information:

(i)

the medical data and the toxicity, infectivity and pathogenicity studies as provided for in part B of the Annex to Regulation (EU) No 544/2011, and the results of the evaluation thereof. Tier 1 tests shall permit an evaluation to be made of a micro-organism with respect to its ability to persist or grow in the host and its ability to cause effects/reactions in the host. Parameters that indicate the absence of ability to persist and multiply in the host, and the absence of ability to produce non-adverse or adverse effects in a host, include fast and complete clearance from the body, no activation of the immune system, no histopathological changes, and for replication temperatures far below or far above mammalian body temperatures. These parameters can in some cases be assessed using acute studies and existing human data, and sometimes can only be assessed using repeated dose studies.

Evaluation based on relevant parameters of Tier 1 tests shall lead to an assessment of the possible effects of occupational exposure, taking into account the intensity and duration of exposure including exposure due to repeated use during practical use.

The toxicity of certain metabolites/toxins can only be assessed, if it has been demonstrated that the test animals are actually exposed to these metabolites/toxins;

(ii)

other relevant information on the micro-organism, the metabolites/toxins, residual growth medium, contaminants and co-formulants in the plant protection product, such as their biological, physical and chemical properties (e.g. survival of the micro-organism at the body temperature of humans and animals, ecological niche, behaviour of the micro-organism and/or metabolites/toxins during application);

(iii)

the toxicological studies provided for in part B of the Annex to Regulation (EU) No 545/2011;

(iv)

other relevant information provided for in part B of the Annex to Regulation (EU) No 545/2011 such as:

• composition of the preparation,

• nature of the preparation,

• size, design and type of packaging,

• field of use and nature of the crop or target,

• method of application including handling, loading and mixing of the plant protection product,

• exposure reduction measures recommended,

• protective clothing recommendations,

• maximum application rate,

• minimum spray application volume stated on the label,

• number and timing of applications.

(b)

On the basis of the information refereed to in (a) the following overall end-points should be established for single or repeated operator exposure following the intended use:

• persistence or growth of the micro-organism in the host,

• adverse effects observed,

• observed or expected effects of contaminants (including contaminating micro-organisms),

• observed or expected effects of relevant metabolites/toxins.

If there are indications of colonisation in the host and/or if any adverse effects, indicative of toxicity/infectivity are observed, taking into account the exposure scenario (i.e. acute or repeated exposure), further testing is indicated.

(c)

This evaluation shall be made for each type of application method and application equipment proposed for use of the plant protection product as well as for the different types and sizes of containers to be used, taking into account mixing, loading operations, application of the plant protection product and cleaning and routine maintenance of application equipment. Where relevant, other authorised uses of the plant protection product in the area of envisaged use containing the same active substance or which give rise to the same residues may also be taken into account. It shall be taken into account that if replication of the micro-organism is expected, exposure assessment could be highly speculative.

(d)

The absence or presence of the potential for colonisation or the possibility of effects in operators at the tested dose levels as provided for in part B of the Annex to Regulation (EU) No 544/2011 and in part B of the Annex to Regulation (EU) No 545/2011 shall be assessed with regard to measured or estimated levels of human exposure. This risk assessment, preferably quantitative, shall include consideration of e.g. mode of action, biological, physical and chemical properties of the micro-organism and other substances in the formulation.

2.6.1.2. [F4 Competent authorities] shall examine information relating to the nature and characteristics of the packaging proposed with particular reference to the following aspects: U.K.

Textual Amendments

F4 Words in Annex Pt. 2.B points 2.6.1.2, 2.6.1.3, 2.6.1.4 substituted (31.12.2020) by The Plant Protection Products (Miscellaneous Amendments) (EU Exit) Regulations 2019 (S.I. 2019/556), regs. 1(1), 18(9)(b)(xvii); 2020 c. 1, Sch. 5 para. 1(1)

(a)

the type of packaging;

(b)

its dimensions and capacity;

(c)

the size of the opening;

(d)

the type of closure;

(e)

its strength, leakproofness and resistance to normal transport and handling;

(f)

its resistance to and compatibility with the contents.

2.6.1.3. [F4 Competent authorities] shall examine the nature and characteristics of the protective clothing and equipment proposed with particular reference to the following aspects: U.K.

(a)

obtainability and suitability;

(b)

effectiveness;

(c)

ease of wearing taking into account physical stress and climatic conditions;

(d)

resistance to and compatibility with the plant protection product.

2.6.1.4. [F4 Competent authorities] shall evaluate the possibility of exposure of other humans (workers exposed after the application of the plant protection product, such as re-entering workers, or bystanders) or animals to the micro-organism and/or to other toxicologically relevant compounds in the plant protection product under the proposed conditions of use. This evaluation shall take into consideration the following information: U.K.

(a)

the medical data and the toxicity, infectivity and pathogenicity studies provided for in part B of the Annex to Regulation (EU) No 544/2011, and the results of the evaluation thereof. Tier 1 tests shall permit an evaluation to be made of a micro-organism with respect to its ability to persist or grow in the host and its ability to cause effects/reactions in the host. Parameters that indicate the absence of ability to persist and multiply in the host, and the absence of ability to produce non-adverse or adverse effects in a host, include rapid and complete clearance from the body, no activation of the immune system, no histopathological changes, and inability to replicate at mammalian body temperatures. These parameters can in some cases be assessed using acute studies and existing human data, and sometimes can only be assessed using repeated dose studies.

Evaluation based on relevant parameters of Tier 1 tests shall lead to an assessment of the possible effects of occupational exposure, taking into account the intensity and duration of exposure, including exposure due to repeated use during practical use.

The toxicity of certain metabolites/toxins can only be assessed, if it has been demonstrated that the test animals are actually exposed to these metabolites/toxins;

(b)

other relevant information on the micro-organism, the metabolites/toxins, residual growth medium, contaminants and co-formulants in the plant protection product, such as their biological, physical and chemical properties (e.g. survival of the micro-organism at the body temperature of humans and animals, ecological niche, behaviour of the micro-organism and/or metabolites/toxins during application);

(c)

the toxicological studies provided for in part B of the Annex to Regulation (EU) No 545/2011;

(d)

other relevant information on the plant protection product as provided for in part B of the Annex to Regulation (EU) No 545/2011, such as:

• re-entry periods, necessary waiting periods or other precautions to protect humans and animals,

• method of application, in particular spraying,

• maximum application rate,

• minimum spray application volume,

• composition of the preparation,

• excess remaining on plants and plant products after treatment, taking into account the influence of factors such as temperature, UV light, pH and the presence of certain substances,

• further activities whereby workers are exposed.

2.6.2. Effects on human or animal health arising from residues U.K.

In the evaluation, non-viable and viable residues must be addressed separately. Viruses and viroids should be considered as viable residues since they are capable of transferring genetic material, although strictly speaking they are not living.

2.6.2.1. Non-viable residues U.K.

(a) [F5 Competent authorities] shall evaluate the possibility of exposure of humans or animals to non-viable residues and their degradation products via the food chain due to the possible occurrence of such residues in or on edible parts of treated crops. In particular, the following information should be taken into account: U.K.

• the stage of development of the micro-organism at which non-viable residues are produced,

• the development stages/life cycle of the micro-organism under typical environmental conditions; in particular, attention shall be paid to the assessment of the likelihood of survival and multiplication of the micro-organism in or on crops, food or feed, and, as a consequence, the likelihood of the production of non-viable residues,

• the stability of relevant non-viable residues (including the effects of factors such as temperature, UV light, pH and the presence of certain substances),

• any experimental study showing whether or not relevant non-viable residues are translocated in plants,

• data concerning the proposed good agricultural practice (including number and timing of applications, maximum application rate and minimum spray application volume, proposed pre-harvest intervals for envisaged uses, or withholding periods or storage periods, in the case of post-harvest uses) and additional data on application as provided for in part B of the Annex to Regulation (EU) No 545/2011,

• where relevant, other authorised uses of plant protection products in the area of envisaged use, i.e. containing the same residues, and

• the natural occurrence of non-viable residues on edible plant parts as a consequence of naturally occurring micro-organisms.

Textual Amendments

F5 Words in Annex Pt. 2.B points 2.6.2.1, 2.6.2.2 substituted (31.12.2020) by The Plant Protection Products (Miscellaneous Amendments) (EU Exit) Regulations 2019 (S.I. 2019/556), regs. 1(1), 18(9)(b)(xviii); 2020 c. 1, Sch. 5 para. 1(1)

(b) [F5 Competent authorities] shall evaluate the toxicity of non-viable residues and their degradation products having regard in particular to the specific information provided in accordance with part B of the Annex to Regulation (EU) No 544/2011 and in part B of the Annex to Regulation (EU) No 545/2011. U.K.

(c) Where non-viable residues or their degradation products are considered toxicologically relevant for humans and/or animals and when exposure is not considered negligible, the actual levels in or on the edible parts of treated crops shall be determined, taking into consideration: U.K.

• analytical methods for the non-viable residues,

• the growth curves of the micro-organism under optimal conditions,

• the production/formation of non-viable residues at relevant moments (e.g. at the anticipated harvest time).

2.6.2.2. Viable residues U.K.

(a) [F5 Competent authorities] shall evaluate the possibility of exposure of humans or animals to viable residues via the food chain due to the possible occurrence of such residues in or on edible parts of treated crops. In particular, the following information should be taken into account: U.K.

• the likelihood of survival, the persistence and multiplication of the micro-organism in or on crops, food or feed. The various development stages/life cycle of the micro-organism shall be addressed,

• information concerning its ecological niche,

• information on fate and behaviour in the various parts of the environment,

• the natural occurrence of the micro-organism (and/or a related micro-organism),

• data concerning the proposed good agricultural practice (including number and timing of applications, maximum application rate and minimum spray application volume, proposed pre-harvest intervals for envisaged uses, or withholding periods or storage periods in the case of post-harvest uses) and additional data on application as provided for in part B of the Annex to Regulation (EU) No 545/2011,

• where relevant, other authorised uses of plant protection products in the area of envisaged use, i.e. containing the same micro-organism or which result in the same residues.

(b) [F5 Competent authorities] shall evaluate the specific information concerning the ability of viable residues to persist or grow in the host and the ability of such residues to cause effects/reactions in the host. In particular, the following information shall be taken into account: U.K.

• the medical data and toxicity, infectivity and pathogenicity studies provided for in part B of the Annex to Regulation (EU) No 544/2011 and the results of the evaluation thereof,

• the development stages/life cycle of the micro-organism under typical environmental conditions (e.g. in or on the treated crop),

• the mode of action of the micro-organism,

• the biological properties of the micro-organism (e.g. host specificity).

The various development stages/life cycle of the micro-organism shall be addressed.

(c) In the event that viable residues are considered to be toxicologically relevant for humans and/or animals and if exposure is not considered negligible, the actual levels in or on the edible parts of treated crops shall be determined, taking into consideration: U.K.

• analytical methods for the viable residues,

• the growth curves of the micro-organism under optimal conditions,

• the possibilities of extrapolating data from one crop to another.