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Link to relevant study record(s)

Description of key information

NOEC (20 weeks) = 42.9 mg a.s./kg/d (M-570069-02-01, Anas platyrhynchos, OECD 206; OCSPP 850.2300, most sensitive study)

Key value for chemical safety assessment

Long-term EC10, LC10 or NOEC for birds:
42.9 mg/kg food

Additional information

Several experimental studies on the toxicity of the test item to birds according to GLP are available. The studies used 3 different bird species investigated the acute oral toxicity, toxicity due to 5 days dietary exposure and reproduction toxicity, respectively.The most sensitive species was adult mallard (M-570069-02-01, reproduction toxicity, 20 weeks) with a NOEC of 42.9 mg a.s./kg/d (dietary).

  

For the key study (M-570069-02-01) eighteen pairs of adult mallard (Anas platyrhynchos) per treatment (approx. 25 weeks old) were exposed to treated feed (or control feed without the test substance) during a period of 20 weeks according to OECD 206 and US EPA OPPTS 850.2300. Nominal concentrations in feed were 0 (control), 111, 333 and 1000 mg a.s./kg feed (=ppm), respectively, which corresponded to mean measured concentrations of 0, 109 (98% of nominal), 325 (98% of nominal) and 938 (94% of nominal) ppm, respectively. The achieved daily doses were 0, 14.1, 42.9 and 129.5 mg a.s./kg body weight per day. Birds were observed for mortality, abnormal behavior and signs of toxicity; adult body weight and feed consumption were measured; gross pathology was conducted; reproductive parameters, as well as hatchling health, growth and survival, were examined. The overall NOEC (20 weeks) for mallard exposed to the test item in the diet during the study was considered to be 42.9 mg a.s./kg/day (333 ppm).

For the second study (M-522801-01-1), twentysix-week old adult Northern Bobwhite quail were orally dosed via gelatine capsules at a limit dose level of 2000 mg a.s./kg body weight, adjusted for purity, in comparison to an untreated control group, and subsequently monitored for a period of 14 d, following OECD 223 and OPPTS 850.2100. Mortality, signs of intoxication, food consumption, body weight and gross necropsy results were evaluated to determine the endpoints. There were no mortalities in the control or the 2000 mg a.s./kg b.w. treatment group. There were no observed effects in the control or 2000 mg a.s./kg b.w. treatment group during the study. Thus, the acute oral LD50 (14d) was > 2000 mg a.s./kg body weight.

For the third study (M-521692-01-1) northern Bobwhite Quail (Colinus virginianus) hatchlings (10 d old) were exposed to treated feed for a period of 5 d and observed thereafter for another 3 d while fed with untreated feed, following the guidelines OECD 205 and OPPTS 850.2200. Nominal concentrations in feed were 0 (untreated control), 313, 625, 1250, 2500 and 5000 mg a.s./kg feed. The average measured amounts of the test item were determined to be 0 (<LOQ), 394, 691, 1308, 2579, and 5391 mg a.s./kg feed, respectively. The recovery ranged from 103% to 126% of nominal. The dietary LC50 (10 d) was >5391 mg a.s./kg feed (>772 mg a.s./kg body weight). Based on all parameters measured, the NOEC (10 d) was 2579 mg a.s./kg feed (473 mg a.s./kg body weight/day) and the LOEC (10 d) was 5391 mg a.s./kg feed (772 mg a.s./kg body weight/day).

For the fourth study (M-542825-02-1) approx. 23 weeks old northern bobwhite quail (Colinus virginianus) were exposed to treated feed for a period of 23 weeks, following the guideline OECD 206 and OPPTS 850.2300. Nominal concentrations in feed were 0 (control), 111, 333 and 1000 mg a.s./kg feed (=ppm), respectively corresponding to mean measured concentrations of 0, 120 (108% of nominal), 350 (105% of nominal) and 1078 (108% of nominal) ppm. Based on this results daily doses of 0, 9, 25 and 78 mg a.s./kg body weight per day were derived. The No Observed Effect Level (NOEL) for both parental toxicity and reproduction endpoints of northern bobwhite quail exposed to the test item over a 23 -week period was 1000 ppm mg a.s./kg feed (nominal), corresponding to a measured concentration of 1078 mg a.s./kg feed and a mean achieved dose of 78 mg a.s./kg bw/day. The Lowest Observed Effect Level (LOEL) was >1000 ppm (nominal test level) equivalent to the measured concentration of 1078 ppm and the achieved dose of 78 mg a.s./kg bw/day.

The fifth study (M-508260 -01 -1) was performed according to the OECD 205 and OPPTS 850.2200. Five days old mallard (Anas platyrhynchos) hatchlings were exposed to treated feed during a period of 5 d and observed thereafter for another 3 d while fed with untreated feed. Nominal concentrations in feed were 0 (control), 313, 625, 1250, 2500 and 5000 ppm (mean measured: 329, 648, 1294, 2573 and 5121 ppm) which corresponded to daily uptake doses of 94, 176, 374, 660 and 1450 mg a.s./kg body weight/day, respectively. Mortality, signs of intoxication, food consumption, body weight and gross necropsy results were evaluated to determine the endpoints. No clinical signs of toxicity or mortalities were noted at any treatment level. Post-mortem examinations revealed no gross lesions or unusual observations. The body weight and feed consumption for the 648 mg a.s./kg feed treatment level was not considered to be biologically significant as the birds lost weight prior to the addition of treated feed (Day -3 to -1). In addition, there were no abnormal clinical observations or necropsy findings noted for the 648 mg a.s./kg feed treatment level. Furthermore, no statistically significant effects for body weight or body weight change were observed for the 1294 mg a.s./kg feed treatment level. Feed consumption was reduced in the 648, 2573, and 5121 mg a.s./kg feed during the exposure and recovery periods. The dietary LC50 was >5121 mg a.s./kg feed (>1450 mg a.s./kg body weight).

For the sixth study (M-521691 -01 -1) two experimental trials were performed according to the OECD 223 and OPPTS 850.2100 with the same methods for all aspects of the study with the exception of the number of birds dosed to Canary (Serinus canaria). Trial 1: Adult Serinus canaria (ten males; ten females; 8 months to 2 ½ years old) were orally dosed via gelatine capsules at a limit dose level of 2000 mg a.s./kg body weight, adjusted for purity and a control group and subsequently monitored for a period of 14 d. Mortality, signs of intoxication, food consumption, body weight and gross necropsy results were evaluated to determine the endpoints. Trial 2: An additional five birds (two males, three females; 9 to 12 months old) were dosed at the limit dose level of 2000 mg a.s./kg body weight and a control group in parallel (in accordance with OECD 223 guideline). This strategy, assuming no additional mortality occurs in the second trial, allows the establishment of the oral LD50 relative to the limit dose of 2000 mg a.s./kg body weight, while also limiting the number of birds needed for testing. The oral LD50 was clearly established with the testing paradigm.Only one bird mortality occurred at this limit testing dose. The acute oral LD50 was > 2000 mg a.s./kg body weight.

For the seventh study (M-529716 -01 -1) 18 d-old chicken were used for the test according to OECD 223. The limit dose group of five chickens was dosed with 2000 mg a.i. per kg body weight. Additionally, five control chickens were dosed with empty capsules (the control group was used for two studies in parallel to reduce the number of test chickens). After dosing, all chickens were continuously observed for a time period of 14 d. Mortality and signs of intoxication were observed, Body weights were recorded Feed consumption was measured. At the end of the test gross necropsies were carried out on all the sacrificed chickens. No effects were observed for mortality and behavior, feeding consumption, body weight development, and gross pathology. The acute LD50 for chicken was >2000 mg a.i./kg bw.

 

Reference:

Bryden, M.; Temple, D.; Danos, L.; Martin, K.; 2016: [Test Item]: A reproduction study with the mallard unpublished data, Report no.: 149B-226; Study no.: M-570069 -01 -1; NOEC 42.9 mg a.s./kg/day.

Loveall, J. L.; Christ, M. T.; 2014: Toxicity of [test item] during an acute oral LD50 with the northern bobwhite quail (Colinus virginianus); unpublished data, Report no.: 7SRLS14C15; Study no.: M-522801 -01 -1; > 2000 mg a.s./kg b.w.

Christ, M. T.; Moore, S. M.; 2015; Toxicity of [test item] during a dietary LC50 with the northern bobwhite quail (Colinus virginianus); unpublished data, Report no.: 7SRLS14C3; Study no.: M-521692-01-1; LC50 > 5391 mg a.s./kg feed (= > 772 mg a.s./kg body weight/day); NOEC = 2579 mg a.i./kg feed (473 mg a.i./kg body weight/day).

Shepherd, J.; Christ, M. T.; Moore, S.; 2016: Toxicity of [test item] on the reproduction of the northern bobwhite quail (Colinus virginianus) - Amended final report; unpublished data; Report no: 07SRLS14C4; Study no: M-542825-02-1; NOEL (parental toxicity and reproduction) = 1000 ppm (nominal) and 1078 mg a.s./kg feed (measured concentration) or 78 mg a.s./kg bw/day (mean achieved dose). 

Shepherd, J.; Christ, M. T.; Moore, S. M.; 2014: Toxicity of [test item] during a dietary LC50 with the mallard duck (Anas platyrhynchos); unpublished data; Report no: 07SRLS13C68; Study no.: M-508260-01-1; LC 50 >1450 mg a.s./kg body weight.

Loveall, J. L.; Christ, M. T.; 2015: Toxicity of [test item] during an acute oral LD50 with the canary (Serinus canaria); unpublished data; Report no.: 7SRLS14C16; Study no: M-521691 -01 -1; LD 50 > 2000 mg a.s./kg body weight

Hahne,J.; Breuer-Rehm, M.; 2015: Acute Oral LIMIT-Test of [test item] to Chicken (Gallus gallus domesticus); unpublished data; Report no.: EnSa-15-0435; Study no: M-529716 -01 -1; LD50 >2000 mg a.i./kg bw.; NLD ≥2000 mg a.i./kg bw.