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Administrative data

Description of key information

Two acute oral and one acute dermal toxicity studies were conducted on MTDID 15670. The result of the studies were:

 

The rat oral LD50 is between 300-2,000 mg/kg body weight when tested according to OECD 423 (2001).

The rat oral LD50 is greater than 2,000 mg/kg body weight when tested according to OECD 401 (1987).

The rat dermal LD50 is greater than 2,000 mg/kg when tested according to OECD 402 (1987).

Key value for chemical safety assessment

Additional information

Acute Oral Lethality:

 

The acute oral lethality of the test article was determined in rats. Female Wistar rats received 300 mg/kg (6 females) or 2000 mg/kg (3 females) test article dissolved in DMSO via oral gavage. Observations for mortality (recorded twice daily), body weights (day 1, 8, 15 or at death), clinical signs (once daily), and macroscopic examination (at necropsy). At 2000 mg/kg all animals exhibited clinical signs of toxicity including lethargy (3/3), spasms (3/3), abnormal and/or hunched posture (3/3), abnormal gait (3/3), uncoordinated movements (2/3), ventro-lateral recumbency (1/3), loss of righting reflex (1/3), increased activity (1/3), hypotonia (1/3), deep breathing (1/3), piloerection (3/3), shaking head (1/3), paleness (1/3), salivation (1/3), dehydration (2/3), and ptosis (3/3). On Day 2 one animal in the 2000 mg/kg group was euthanized for humane reasons after exhibiting symptoms including lethargy, tremors, and pale and lean appearance. Another animal was found dead on Day 4 in this dose group. These two animals had reduced spleen sizes, and gastrointestinal distension upon post mortem examination. At the 300 mg/kg animals exhibited piloerection and hunched posture (6/6), lethargy (3/6), ptosis (3/6), rales (1/6), and slow breathing (1/6) between Days 1 and 8. No mortality was seen at this dose level, however, and only one animal had gastrointestinal distention due to gas noted on necropsy. Based on the results of the study, the rat oral LD50 of the test article is between 300 -2000 mg/kg bw.

 

Male and female Wistar rats (3/sex/dose) were exposed to 2000 mg/kg bw MTDID 15670 (Flunit) in 10 mL 4% CMC sodium salt purum in a single oral gavage dose. Animals were fasted for 12 -18 hours prior to gavage and for one hour post dosing. Over the 15 day observation period, body weights (day 1, 8 and 15), clinical signs (1, 2, 3 and 5 hours post dosing and once daily for remaining observation period), and macroscopic organ examination (at necropsy) findings were recorded. On day 15 all surviving animals were necropsied. No unscheduled mortality occurred. Body weight was not affected by exposure and no macroscopic findings were noted at necropsy. Males receiving 2000 mg/kg bw MTDID 15670 showed no clinical signs of toxicity. Females recieving 2000 mg/kg bw MTDID 15670 showed hunched posture (1), ventral recumbancy (1), ruffled fur (2), sedated behavior (2), and spasms (1). Based on these results, the rat oral LD50 for MTDID 15670 is > 2000 mg/kg bw.

 

Acute Dermal Lethality:

 

MTDID 15670 was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred. Chromodacryorrhoea and/or ptosis were noted for most animals on Day 1. The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity. No abnormalities were found at macroscopic post mortem examination of the animals. Based on the results of the study, the dermal LD50 in rats was > 2000 mg/kg bw for MTDID 15670.

Justification for classification or non-classification

Based on the results of the studies, the test article meets the criteria for acute oral lethality GHS Category 4 and does not meet the GHS classification criteria for acute dermal lethality.