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Administrative data

Description of key information

Oral: The acute oral LD50 was determined to be > 2000 mg/kg bw in rats.

Inhalation: The acute inhalation LC50 was > 2.4 mg/L in rats.

Dermal: The acute dermal LD50 was determined to be > 5000 mg/kg bw in rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Key study performed under GLP and according to OECD Guideline (Klimisch 1).

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
2.4 mg/m³
Quality of whole database:
Key study performed under GLP and according to OECD Guideline (Klimisch 1).

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw
Quality of whole database:
Key study performed under GLP and according to OECD Guideline (Klimisch 1).

Additional information

ACUTE ORAL TOXICITY

 

Key Study (BASF SE, 2012/1247223, rat, 2013)

In an acute oral toxicity study performed according to OECD guideline 423, 2000 mg/kg bw of the test item (preparation in 0.5% CMC solution) was administered to two test groups of three fasted young adult Wistar rats by gavage. During the 14 -days observation period, the mean body weight increased within the normal range throughout the study period. Two animals showed only a small weight gain during the second post-exposure week. In the first 2000 mg/kg bw test group impaired general state and piloerection were observed in two animals from hour 2 until hour 5 after administration (one animal of this group did not show any symptoms). No mortality appeared. There were no macroscopic pathological findings at the end of the observation period. Under the conditions of this study the median lethal dose of the test item after oral administration was found to be greater than 2000 mg/kg bw in rats.

Supporting Study (American Cyanamid Company, IZ-411-002, rat, 1997)

In an acute oral toxicity study according to EPA OPP 81 -1, young adult male and female albino rats (Crl: CD(SD)Br strain) were dosed with the test item at a limit dose of 2500 mg/kg bw. The test item was administered, as 25% w/v dispersion in corn oil, by oral gavage.  No overt signs of toxicity were observed during the course of 14-day study period. Weight gains in surviving rats were generally unaffected by administration of the test material. No mortality appeared. There were no gross pathological changes which could be attributed to ingestion of the test material. Under the conditions of this study, it was concluded that the oral LD50 of the test item was greater than 2500 mg/kg bw for both male and female rats.

Supporting Study (American Cyanamid Company, IZ-411-006, rat, 1998)

In an acute oral toxicity study according to EPA-OPP 81 -1, young adult Sprague-Dawley rats (5 males and 5 females) were dosed with the test item at a limit dose of 5000 mg/kg bw. The test dispersion was prepared at a nominal concentration of 25%. Mortality occurred immediately after dosing in one male animal. All surviving animals gained weight during the 14-day study period.  Clinical signs appeared immediately after dosing in males only. Surviving males returned to normal by 2 hours post-dosing. There were no gross pathological findings observed in the one male that died or in the animals which were sacrificed at the termination of the study. Based on the mortality data, it was determined that the oral LD50 of the test item was greater than 5000 mg/kg bw for both male and female rats.

Supporting Study (American Cyanamid Company, IZ-411-003, dog, 1986)

In an acute oral toxicity study equivalent to OECD guideline 401, two year-old Beagle dogs (3 males and 3 females) were dosed with the test item at a limit dose of 5000 mg/kg bw. The test dispersion was prepared at a nominal concentration of 37.5%. Toxic signs were limited to emesis which occurred 1 to 1.5 hours after dosing in 5/6 of the dogs. All animals had recovered at 24 hours post-dosing. No other signs of toxicity were observed during the 14-day observation period. Weight gains in surviving dogs were generally unaffected by administration of the test material. One of 3 female dogs died on day 1 of the 14-day observation period. The death appeared to be unintentionally, because the dose had been administered in the lung. All male dogs survived the 14-day observation period. There were no gross pathological findings. Based on the mortality data, it was determined that the oral LD50 of the test item was greater than 5000 mg/kg bw for dogs.

Supporting Study (Cyanamid International Corporation, IZ-411-004, rabbit, 1983)

In an acute oral toxicity study according to OECD guideline 401, male and female albino rabbits (New Zealand White strain) were dosed with the test item at doses of 4000, 5000 and 6400 mg/kg bw. Mortalities occurred amongst rabbits treated at 5000 and 6400 mg/kg within two to 13 days of dosing. From the animals treated with 5000 mg/kg bw 2/5 female and 3/5 male animals died, and from the animals treated with 6400 mg/kg bw 2/2 male and female animals died during the observation period. One moribund animal was killed in extremis on Day 10 following treatment at 4000 mg/kg. Recovery of surviving rabbits as judged by external appearance and behaviour was complete by Day 10. Bodyweight gains of all surviving rabbits were apparently normal on Day 15. Terminal autopsy findings were normal. The acute median lethal oral dose (LD50) of the test item to male and female rabbits were estimated to be 4800 mg/kg bw (95% confidence limit).

 

ACUTE INHALATION TOXICITY

Key Study (BASF SE, 2012/1294646, rat, 2013)

In an acute inhalation toxicity study according to OECD guideline 403 , five male and five female Wistar rats were exposed to an aerosol containing 2.4 mg/L of the test item for four hours. Animals were observed for 14 days. There was no indication of relevant sex-related differences in toxicity of the test item and no treatment-related macroscopic findings. The LC50 for 4-hour exposure to the test item in this study was greater than 2.4 mg/L air (chemically determined mean aerosol concentration). The target concentration was considered to be the highest technically achievable concentration with a respirable particle size as determined in the technical trials. Therefore, 2.4 mg/L is an accepted concentration for a limit test according to OECD 403.

Supporting Study (American Cyanamid Company, IZ-413-001, rat, 1983)

In an acute inhalation toxicity study according to OECD guideline 403, ten male and ten female Sprague-Dawley rats were exposed to an aerosol containing 5.1 mg/L (nominal concentration) of the test item for four hours. Animals were observed for 14 days. Gross necropsy failed to demonstrate the presence of any lesions or abnormalities related to the test item. Under the conditions of this study, the test item failed to cause mortality or irreversible signs of toxicity. The LC50 for 4-hour exposure to the test item in this study was greater than 5.1 mg/L air (nominal concentration).

 

ACUTE DERMAL TOXICITY

Key Study (BASF SE, 2012/1247224, rat, 2013)

In an acute dermal toxicity study according to OECD guideline 402 (Limit test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 5000 mg/kg bw of the test item (suspension in 0.5 % CMC-solution). The skin was clipped (dorsal and dorsolateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. No signs of systemic toxicity or skin effects were observed in all animals. The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weight of the female animals only slightly increased during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range.

No mortality occured. No macroscopic pathologic abnormalities were noted in the animals examined on the last day of observation. Accordingly, the acute dermal median lethal dose (LD50) was determined to be greater than 5000 mg/kg bw.

 

Supporting Study (American Cyanamid Company, IZ-412-001, rabbit, 1990)

In an acute dermal toxicity study according to OECD guideline 402 (Limit test), male and female albino rabbits (New Zealand White strain) were dermally exposed to a single dose of 2000 mg/kg bw of the test item. The animals were observed for 14 days. No overt signs of toxicity were observed during the study period other than slight erythema at the application site in 2/5 males on days 1 and 2 of the study. All test animals survived the 14-day observation period. No treatment related gross lesions were observed at the terminal necropsy. Accordingly, the acute dermal median lethal dose (LD50) was determined to be greater than 5000 mg/kg bw.

 

Supporting Study (Cyanamid International Corporation, IZ-412-002, rat, 1983)

In a acute dermal toxicity study according to OECD guideline 402 (Limit test), young adult HC/CFY (remote Sprague-Dawley) rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the test item. The animals were observed for 14 days after dosing. No signs of toxicity were observed following treatment or throughout the 14 day post-dose observation period. Bodyweight gains of all the remaining female and all male rats were normal throughout the study period. No mortality occurred amongst rats treated at 2000 mg/kg bw. Terminal autopsy findings were normal. Accordingly, the acute dermal lethal dose (LD 50) was determined to be greater than 2000 mg/kg bw.

CONCLUSION

The key studies revealed an acute oral LD50 of >2000 mg/kg bw, an acute inhalation LC50 of >2.4 mg/L and an acute dermal LD50 of >5000 mg/kg bw for rats. These findings were corroborated by all supporting studies (including the following additional animals tested: dog, mouse and rabbit).

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result, the substance is not considered to be classified for acute oral, inhalation and dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the ninth time in Regulation (EU) No. 2016/1179.