D-Glucitol, 1-deoxy-1-(methylamino)-, N-C8-10 acyl derivs.

Endpoint summary

Description of key information

With regard to the acute toxicity of the registered substance, key studies for the oral and dermal exposure route are available. Using the acute toxic class method according OECD test TG 423, the LD50 cut-off value of Glucamide 810 (93.9% pure) is 500 mg/kg body weight. Intoxicated animals showed a consistent clinical picture pointing to an unspecific mode of action. The acute dermal toxicity of the registered substance was evaluated in an OECD 402 study according to GLP. After topical treatment with the limit dose of 2000 mg/kg body weight neither mortality nor significant clinical symptoms of intoxication were observed. The LD50 after dermal treatment was established to be greater 2000 mg/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

500 mg/kg bw

Quality of whole database:

Data reliable and meet criteria for classification & labelling requirements.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating conc.

Value:

5 000 mg/m³ air

Quality of whole database:

Data reliable and meet criteria for classification & labelling requirements.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Acute studies with Glucamide 810 (Test material GA AC93/13) have revealed a moderate to low toxicity for all routes of exposure. Using the acute toxic class method according OECD test guideline 423, Glucamide 810 exhibits a low to moderate acute oral toxicity (CLP category 4). The LD50 cut-off value following single oral application of Glucamide 810 to rats via gavage is 500 mg/kg body weight. Intoxicated animals showed a consistent clinical picture (e.g. reduced spontaneous activity, piloerection, prone or hunched position) pointing to an unspecific mode of action. All symptoms recovered within 24 hours (5 out of 6 animals) or up to 3 days post-dose (1 out of 6 animals). There was no evidence of an effect on body weight gain.

Data regarding acute oral toxicity are also available on the read-across compound Glucamide 24 (Test material E-4086.01, 45% active). In an OECD TG 401 (1987 study, Wistar rats were exposed via oral gavage to 900 mg a.i./kg bw (2000 mg test article/kg bw) or 2000 mg a.i./kg bw (4444 mg test article/kg bw). No deaths occurred in the study. Weight loss was observed in one female at the high dose on Days 8 – 15 and body weight gain was reduced in 2 high-dose and 1 low-dose females. At the lower dose, signs were observed in a few male rats which included slight sedation and slight ruffled fur; in the high dose group, slightly ruffled fur was observed in two animals of each sex. The acute oral LD50 was concluded to be greater than 2000 mg Glucamide/kg body weight.

Collectively, these data suggest vary comparable acute oral toxicities. Moreover, when the two compounds are compared based on studies conducted on the test formulations (50 or 45% solutions of Glucamide 810 and Glucamide 24) the acute oral LD₅₀values are very comparable in that both compounds exhibit low oral toxicity.There are no data on unformulated Glucamide 24 to compare to the Glucamide 810 study performed using the 93.9% concentrated material. To be conservative, the concentrated material tested value obtained for the > 90% pure material is used for categorization of Glucamide 810 for acute oral toxicity.

With regard to acute systemic dermal toxicity, single administration of 2000 mg/kg body weight to rats according OECD test guideline 402 was not associated with mortality or with any clinical signs of toxicity. However, reversible signs of dermal irritation were observed at the treated skin sites. The LD50 of Glucamide 810 (Test material GA AC93/13) in rats is thus greater 2000 mg/kg body weight. The read-across compound, Glucamide 24 (Test material, E-4194.01, 98.8%), also has low acute toxicity via the dermal route; testing in male/female New Zealand White rabbits using EEC Methods Directive 84/449/EEC, Part B, Method B3 (1984) indicated a comparable LD50 of greater 2000 mg/kg body weight.

The moderate to low toxicity of Glucamide 810 was also revealed for the inhalation route of exposure using the acute toxic class method according to OECD TG 436. For technical reasons a 50% formulation of Glucamide 810 in water was used for the experiment. The test material was administered as aerosol by inhalation for 4 hours to two groups of 3 male and 3 female Wistar rats at analytical verified exposure concentration of 1.1 mg/L and 5.1 mg/L per group. The subsequent observation period was 14 days. At 5 mg/L, unspecific clinical signs of toxicity consisting of e.g. lethargy, hunched posture, abnormal gait, laboured respiration, and/or ptosis were observed between days 1 and 9. Two male and one female animal were found dead within 3 days post-treatment. No further mortality occurred. At 1 mg/L neither clinical signs nor mortality was noted. Based on the results and in accordance with OECD TG 436, the LD50 cut-off value was 5 mg/L.

Justification for selection of acute toxicity – oral endpoint
Guideline study according to GLP. No derivations and/or confounders. Klimisch rating 1 representing reliability without restrictions. Information is valid and meet data requirements.

Justification for selection of acute toxicity – inhalation endpoint
Guideline study according to GLP. No derivations and/or confounders. Klimisch rating 1 representing reliability without restrictions. Information is valid and meet data requirements

Justification for selection of acute toxicity – dermal endpoint
Guideline study according to GLP. No derivations and/or confounders. Klimisch rating 1 representing reliability without restrictions. Information is valid and meet data requirements.

Justification for classification or non-classification

Based on the results from an OECD TG 423 guideline study which revealed a LD50 cut-off value of 500 mg/kg body weight, category 4 classification according to CLP of Glucamide 810 is warranted with regard to acute oral toxicity.

Based on the results from an OECD TG 436 guideline study which revealed a LC50 cut-off value of 5 mg/L, category 4 classification according to CLP is warranted with regard to acute inhalation toxicity.

Based on the results from an OECD 402 guideline study which revealed a LD50 greater 2000 mg/kg body weight, no classification according to CLP is warranted with regard to acute dermal toxicity.