Registration Dossier

Administrative data

Description of key information

Acute toxicity: oral
The key study (Kynoch, 1984) was conducted according to the OECD 401 guideline and was given a reliability score of 2 according to the criteria of Klimisch et al, 1997, based upon the level of reporting. The study reported an LD50 value of 24mg/kg bw for the registered substance.
Acute toxicity: dermal
The key study (Kynoch, 1984) was conducted according to the OECD 402 guideline and was given a reliability score of 2 according to the criteria of Klimisch et al, 1997, based upon the level of reporting. The study reported an LD50 value of 217.5mg/kg bw for the registered substance.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
24 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
217.5 mg/kg bw

Additional information

Acute toxicity: oral

The key study for the oral route (Kynoch, 1984) was conducted according to the OECD 401 guideline and was performed on male and female rats at dose levels of 64, 100 and 160 mg/kg bodyweight. The rats were observed for 14 days in the main study for mortality, clinical signs and bodyweight changes. At the end of the observation period all animals were subject to a gross necropsy. Mortalities occurred in all 3 dose groups within 3 hours of the study initiation, and clinical signs of systemic toxicity were observed shortly after dosing. Bodyweights were slightly reduced in rats with unscheduled deaths, however surviving rats exhibited body weight gains on days 8 and 15. Gross necropsy revealed congestion of the lungs and pallor of the liver, kidneys and spleen amongst animals that died during the study, while surviving animals exhibited normal organ appearance.

Based upon the evidence of the study the LD50 value for acute oral toxicity was set at 24 mg/kg bw. The supporting studies provide similar LD50 values of 27 mg/kg bw (Harper & Ginn, 1964), between 25 and 40 mg/kg bw (Bough et al, 1963) and 5 and 60 mg/kg bw (Spencer et al, 1948) for acute oral toxicity to the registered substance, however these studies are considered of lesser reliability due to age of the study reports and deviations from recognised testing methods.

Acute toxicity: dermal

The key study for the dermal route (Kynoch, 1984) was selected as the most recent and reliable study available. The key study was conducted according to the OECD 402 guideline and performed on male and female rats at doses of 500, 640, 800, 1260 and 2000 mg/kg with exposure duration of 24 hours. The animals were observed for 14 days in the main study for mortality, clinical signs of toxicity and bodyweight. At the end of the observation period all animals were subject to gross necropsy.

Mortalities were observed within 4 hours of exposure at dose levels of 640mg/kg bw and above. Clinical signs were noted during the first 24 hours of the exposure but by day 3 all surviving animals have recovered completely. Bodyweights of animals which died during the exposure and observation periods were reduced, however bodyweights of surviving animals were normal the end of the observation period. The study reported an LD50 value of 217.5mg/kg for male and female animals. Similar results are reported by Bough et al, 1963, where 2 of 10 animals died at a dose of 100mg/kg bw and nine of ten at a dose of 500 mg/kg bw, and Spencer et al, 1948, where the LD0 was set at 100mg/kg bw and the LD100 set at 500 mg/kg bw.

Much lower LD50 values were reported by Kynoch & Lloyd, 1976, and Kynoch and Lloyd, 1977, where the LD50 values were set at 30mg/kg bw and 47.7mg/kg bw respectively. These studies were considered to be of reduced reliability based upon the criteria of Klimisch et al, 1977, and so were not considered for the chemical safety assessment.

Justification for classification or non-classification

Based upon the above information the substance meets the criteria for classification as set out by both 67/548/EEC and EC Regulation 1272/2008 and should therefore be classified as follows:

R28 toxic if swallowed and R24 toxic in contact with skin;

Acute oral category 2, H300 Fatal if swallowed, Acute dermal category 3, H311 Toxic in contact with skin

It should also be noted that the official Annex I classification for the substance is given as R25 as opposed to R28. In light of the official classification and the proximity of the oral LD50 to the threshold value, the registrant proposes to retain the more severe classification.