The proposed extension for use involves an application on soybean for which the risk assessment for the bystander, resident and worker can be extrapolated from the current authorisation based on the method of application and dosage (downward application with a maximum dosage of 7.5 g
a.s./ha).Therefore, the proposed extension remains within the existing risk envelope for the bystander, resident and worker.
For the operator, mechanical downward spraying is within the risk envelope of the existing authorisation. However for this minor use in soybean manual downward spraying cannot be
excluded. A risk assessment is performed for manual downward spraying for the operator, since this application method is not covered by the existing risk envelope.
List of Endpoints
The final List of Endpoints presented below is taken from the final Review Report on thifensulfuron-methyl (SANCO/7577/VI/97 – final, d.d. 12 December 2001). Where relevant, some additional remarks/information are given in italics.
1 Toxicology and metabolism
Absorption, distribution, excretion and metabolism in mammals
Distribution: Widely
Potential for accumulation: No accumulation Rate and extent of excretion: > 90 % in 96 h, urine Toxicologically significant compounds: Parent compound
Metabolism in animals: Radioactivity mainly excreted as the parent compound in rat and goat
Eye irritation: Not irritating
Skin sensitization (test method used and result):
Not sensitising (Magnusson and Kligman test)
Short term toxicity
Target / critical effect: No target identified / decreased body weight gain and food consumption
Lowest relevant oral NOAEL / NOEL: 7 mg/kg bw/d, 90 d oral rat
The lowest NOEL was 1.3 mg/kg bw/d in the 1 y dog study but was not considered relevant for setting AOEL
Lowest relevant dermal NOAEL / NOEL: No data , No t requ ired Lowest relevant inhalation NOAEL / NOEL: No data, Not required
Genotoxicity Negative
Long term toxicity and carcinogenicity
Target / critical effect: Not identified / decreased body weight gain Lowest relevant NOAEL: 0.96 mg/kg bw/d, 2 y rat
Carcinogenicity: Negative
Reproductive toxicity
Target / critical effect - Reproduction: Not identified / decreased body weight gain Lowest relevant reproductive NOAEL /
NOEL:
43 mg/kg bw/d, maternal toxicity 175 mg/kg bw/d, reproductive toxicity Target / critical effect - Developmental
toxicity:
Retarded ossification (rat) Lowest relevant developmental NOAEL /
NOEL:
200 mg/kg bw/d, maternal and developmental toxicity (rat)
Delayed neurotoxicity No data , no co nce rn fro m o ther stu dies
Other toxicological studies No other studies submitted (not necessary)
Medical data No occupational or accidental poisoning reported
Summary
Value Study Safety factor
ADI: 0.01mg/kg bw/d 2 y rat 100
AOEL systemic: 0.07 mg/kg bw/d 90 d rat 100
AOEL inhalation: Not allocated ( not necessary)
AOEL dermal: Not allocated ( not necessary)
ARfD (acute reference dose): Not allocated ( not necessary)
Dermal absorption 10% default value ( no study required)
Local effects
Thifensulfuron-methyl does not produce local effects, neither after a single nor repeated exposure.
Data requirements active substance
No additional data requirements are identified.
4.1 Toxicity of the formulated product (IIIA 7.1)
The formulation DuPont HARMONY SX does not need to be classified on the basis of its acute oral (LD50 rat >5000 mg/kg bw), dermal (LD50 rat >5000 mg/kg bw), and inhalation toxicology (no study, not required).
The formulation DuPont HARMONY SX is considered not irritating to skin and eyes.
The formulation DuPont HARMONY SX does not have sensitising properties in a Maximisation test.
4.1.1 Data requirements formulated product No additional data requirements are identified.
4.2 Dermal absorption (IIIA 7.3)
The original authorisation was based on a mutual recognition.
Germany used a value of 100% for both the concentrate and spray dilution for dermal absorption in the risk assessment and these values were used for the mutual recognition. For the current minor use extension the same values are used.
4.3 Available toxicological data relating to non-active substances (IIIA 7.4)
The available toxicological data relating to non-active substances will be taken into account in the classification and labelling of the formulated product.
An application has been submitted for the minor use extension of the authorisation of the plant protection product DuPont HARMONY SX, a herbicide based on the active substancethifensulfuron-methyl.
DuPont HARMONY SX is a SG (water soluble granule) formulation and contains 500 g/kg thifensulfuron-methyl.
4.4.1 Operator exposure/risk
According to the Dutch Plant Protection Products and Biocides Regulations the risk assessment is performed according to a tiered approach. There are four possible tiers:
Tier 1: Risk assessment using the EU-AOEL without the use of PPE Tier 2: Risk assessment using the NL-AOEL without the use of PPE
Tier 3: Refinement of the risk assessment using new dermal absorption data Tier 4: Prescription of PPE
Tier 1
Calculation of the EU-AOEL / Tolerable Limit Value (TLV)
For thifensulfuron-methyl no TLV has been set. The AOEL will be used for the risk assessment.
Since thifensulfuron-methyl is included in Annex I of 91/414/EEC and approved under Regulation (EC) 1107/2009, the semi-chronic EU-AOEL of 0.07 mg/kg bw/day (= 4.9 mg/day for a 70-kg operator), based on the 90-day study with rats, is used for the risk assessment.
Exposure/risk
Exposure to thifensulfuron-methyl during mixing and loading and application of
DuPont HARMONY SX is estimated with models. The exposure is estimated for the unprotected operator. In general, mixing and loading and application is performed by the same person. Therefore, for the total exposure, the respiratory and dermal exposure during mixing/loading and application have to be combined. In the Table below the estimated internal exposure is compared with the systemic EU-AOEL.
Table T.1 Internal operator exposure to thifensulfuron-methyl and risk assessment for the use of DuPont HARMONY SX
Route Estimated internal exposure a (mg/day)
Systemic EU-AOEL (mg/day)
Risk-index b
Manual downward spraying on soybean (0.0075 kg a.s./ha, uncovered) Mixing/
Loadingc
Respiratory 0.004 4.9 <0.01
Dermal 0.50 4.9 0.10
Applicationd Respiratory 0.006 4.9 <0.01
Dermal 5.10 4.9 1.04
Total 5.61 4.9 1.14
a Internal exposure was calculated with:
• biological availability via the dermal route: 100% (concentrate) and 100% (spray dilution) (see 4.2)
• biological availability via the respiratory route: 100% (worst case)
b The risk-index is calculated by dividing the internal exposure by the systemic AOEL.
c External exposure is estimated with the NL-model for mixing and loading.
d External exposure is estimated with UK POEM.
Since the EU-AOEL is exceeded without the use of PPE, a higher tier assessment has to be performed using the NL-AOEL.
Tier 2
The risk index calculated with the EU-AOEL is >1. Therefore, the Plant Protection Products and Biocides Regulations (NL: Rgb) prescribes the calculation of the risk with an AOEL based on allometric extrapolation (known as the NL-AOEL). This method takes into account the caloric demand of the species studied and results in a more specific value than the EU-AOEL for which a standard factor of 100 is applied.
The calculation of the systemic AOEL for semi-chronic exposure is based on the NOAEL of 1.3 mg/kg bw/day in the 1-year study with the dog. Calculations from other studies result in higher AOELs.
Safety factors are used to compensate for the uncertainties, which arise, for example, from extrapolation from the tested species to humans and the differences between experimental circumstances, and to ensure that at the acceptable exposure level no adverse health effects will occur.
Used factors are:
• extrapolation dog→ human on basis of caloric demand 1.4
• other interspecies differences: 3
• intraspecies differences: (professional use) 3
• biological availability via oral route: 100%*
• weight of professional operator/worker: 70 kg
* If the absorbed dose is significantly lower (<80%) than the administered dose, this is adjusted by a correction factor equal to the percentage absorption.
AOELsystemic: 1.3 x 100 x 70 / (1.4 x 3 x 3) = 7.22 mg/day
Table T.2 Internal operator exposure to thifensulfuron-methyl and risk assessment for the use of DuPont HARMONY SX
Route Estimated internal exposure a (mg/day)
Systemic NL-AOEL (mg/day)
Risk-index b
Manual downward spraying on soybean (0.0075 kg a.s./ha, uncovered) Mixing/
Loadingc
Respiratory 0.004 7.22 <0.01
Dermal 0.50 7.22 0.07
Applicationd Respiratory 0.006 7.22 <0.01
Dermal 5.10 7.22 0.71
Total 5.61 7.22 0.78
a Internal exposure was calculated with:
* biological availability via the dermal route: 100% (concentrate) and 100% (spray dilution) (see 4.2)
* biological availability via the respiratory route: 100% (worst case)
b The risk-index is calculated by dividing the internal exposure by the systemic AOEL.
c External exposure is estimated with the NL-model for mixing and loading.
d External exposure is estimated with UK POEM.
Since the EU-AOEL is not exceeded without the use of PPE, a higher tier assessment is not required.
4.4.2 Bystander exposure/risk
of application and dosage (downward application with a maximum dosage of 7.5 g a.s./ha).
Therefore, the proposed extension remains within the existing risk envelope.
4.4.3 Worker exposure/risk
The proposed extension for use involves an application on soybean for which the risk assessment for the worker can be extrapolated from the current authorisation, based on the method of application and dosage (downward application with a maximum dosage of 7.5 g a.s./ha) in vegetable crops.
Therefore, the proposed extension remains within the existing risk envelope.
4.4.4 Re-entry
See 4.4.3 Worker exposure/risk.
Overall conclusion of the exposure/risk assessments of operator, bystander, and worker The product complies with the Uniform Principles.
Operator exposure
Based on the risk assessment, it can be concluded that no adverse health effects are expected for the unprotected operator after dermal and respiratory exposure to thifensulfuron-methyl as a result of the application of DuPont HARMONY SX in soybean.
Bystander exposure
The bystander and resident exposure is within the risk envelope of the existing authorisation. It is concluded that no adverse health effects are expected for the unprotected bystander or resident due to exposure to thifensulfuron-methyl during application of DuPont HARMONY SX in soybean.
Worker exposure
The worker exposure is within the risk envelope of the existing authorisation. It is concluded that no adverse health effects are expected for the unprotected worker after dermal and respiratory exposure during re-entry activities in soybean due to exposure to thifensulfuron-methyl after application of DuPont HARMONY SX.
The current classification and labelling of the formulation can be maintained.
4.5 Appropriate mammalian toxicology and operator exposure end-points relating to the product and approved uses
See List of Endpoints.
4.6 Data requirements No additional data required.
4.7 Combination toxicology
DuPont HARMONY SX contains only one active substance and it is not described that it should be used in combination with other formulations.