Registration Dossier

Administrative data

Description of key information

One acute oral toxicity study (BASF Co, 1998, report no. 80203064; conducted according to the EPA guideline 870.1100) and one acute dermal toxicity study (BASF Co, 1998, report no. 80203065; conducted according to the EPA guideline 870.1200) are available. The acute LD50 is determined to be 334 mg/kg after oral exposure of young adult rats (224 mg/kg bw in female and 583 mg/kg bw in male animals) and between >1000 and =1510 mg/kg bw  after dermal exposure of young adult rabbits (> 1000 mg/kg in female and =1510 in male animals).

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
334 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
1 510 mg/kg bw

Additional information

ACUTE TOXICITY STUDY

In the oral acute toxicity study, 5 Crl:CD®(SD)BR rats (204-299 g, 8-12 weeks) per sex and per dose (exception: only male animals in the highest dose group) received 100, 500, 1000, and 1500 mg/kg of body weight per gavage. The animals were then observed for clinical signs, mortality, and body weight gain. All animals, whether found dead during the study, sacrificed in a moribund condition, or euthanized at study termination, were subjected to an abbreviated gross necropsy examination and any abnormalities were recorded. After necropsy, the animals were discarded and only those tissues with lesions were collected for possible histopathological evaluation.

For statistical purposes in this study, the animals sacrificed in a moribund condition were considered to have died due to the test material. Using this information, the estimated LD50 values for males, females, and the sexes combined were determined by a Computer program using a modified Behrens-Reed-Muench cumulant method. No other statistical evaluations were required by the protocol.

 

Based on the mortality observed in the study (considering the animals which were sacrificed in a moribund condition as having died on study), the estimated oral LD50 values in rats were determined to be 583, 224, and 334 mg/kg for males, females, and the sexes combined, respectively.Clinical signs of toxicity included thin appearance, cold to touch, hunched posture, flaccidity, sensitivity to touch, hypoactivity, staggered gait, absence of righting reflex, prostration, red-stained face, mydriasis, lacrimation, dyspnea, gasping, red discharge around the nose and mouth, wet area around the mouth, brown-stained mouth, tremors, red discharge in the urogenital area, wetlred-/yellow-/or brown-stained urogenital area, and clonic convulsions. The onset of clinical signs was more immediate at the 1000 and 1500 mg/kg dose levels and occurred primarily within 24 hours of treatment. All mortality (and/or moribund sacrifice) occurred within 10 days of test material administration. Animals surviving to the end of the observation period exhibited body weight gain during the study with the exception of one male treated at 500 mg/kg and one male treated at 1000 mg/kg which exhibited weight losses of 61 and 24 g, respectively, during the first week. The one male treated at 500 mg/kg also exhibited an additional weight loss of 17 g during the second week, while the one male at 1000 mg/kg showed recovery from the Week 1 weight loss. At necropsy, most of the findings observed were in the animals that died or that were sacrificed in a moribund condition. These changes pertained to the content (containing dark-red fluid) and coloration changes (dark-red areas) in the gastrointestinal tract. In some of the animals treated at 500 mg/kg there were adhesions between the stomach and adjacent organs or tissues. These are considered to be test material-related. All other findings are considered to be incidental and unrelated to the test material.

 

ACUTE DERMAL TOXICITY STUDY

In the acute dermal study 5 young adult Hra:(NZW)SPF rabbits (2013-2562 g; 14-15 weeks) per sex per dosed were used (except the 3000 mg/kg dose group, where the treatment was interrupted for humane reasons, after 3 males were treated). Unchanged test substance was applied to approximate 180 cm2 of a shaved area at the back of test animals under occlusive conditions and washed out with after 24 hours. The animals were then observed for 14 days for clinical signs, mortality and body weight gains. All animals, whether found dead during the study, sacrificed in a moribund condition, or euthanized at study termination, were subjected to an abbreviated gross necropsy examination and any abnormalities were recorded. After necropsy, the animals ere discarded and only those tissues with lesions were collected for possible histopathological evaluation. Because signs of irritation were observed initial dermal irritation reading was made 30 minutes after removal of the test material according to the Draize technique (recorded as the Day 1 score). Subsequent readings of dermal irritation were made on Days 3, 7, 10, and 14.

 

One male animal treated at 1000 mg/kg was sacrificed in a moribund condition on Day 1 and is counted as having died on study. All three males treated at 3000 mg/kg were found dead within 1 day of test material administration. No other mortality was observed during the study.

 

Based on the mortality observed in the study (considering the animal treated at 1000 mg/kg which was sacrificed in a moribund condition as having died on study), the estimated dermal LD50 value in male rabbits was determined to be 1510 mg/kg. The female LD50 value was estimated to be greater than 1000 mg/kg.

Clinical signs of toxicity included vocalization after dose administration, decreased food consumption, hypoactivity, staggered gait, prostration, dyspnea, few feces, and convulsions. All mortality (including the moribund sacrifice) occurred within 1 day of test material administration. Two males and all five females treated at 500 mg/kg and one male and three females treated at 1000 mg/kg exhibited weight losses during the first week of the study (probably associated with the observed dermal irritation). Recovery from these weight losses were noted during the second week. The test material produced severe dermal irritation/injury which was still present at the end of the respective observation period. The dermal lesions observed at necropsy were indicative of the severe irritation caused by the test material.

Justification for classification or non-classification

Based on the oral acute LD50 (224 mg/kg bw in female, 583 mg/kg bw in male animals and 334 for both male and female animals) the test substance should be classified as harmful (R22) according to the EU and in category 3 (toxic; based on females as more sensible group) according to GHS.

The dermal acute effects follow the severe irritating effects of the substance and will not be classified.