Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
1 500 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Oral Studies

The acute oral toxicity of 2,2,4,4-tetramethyl-1,3-cyclobutanediol (TMCD) is well understood. The key study followed OECD guideline 425 and GLP assurances. The results of that study indicated the material to have an estimated LD50 in rats of approximately 1,500 mg/kg with a 95% confidence interval of 1,043 – 4,350 mg/kg per day. Surviving animals showed no gross pathology and primary clinical signs in animals that died consisted on hypoactivity, haunched posture, and piloerection. Several other acute oral studies were conducted in rats between 1958 and 1963. In these studies mortality was induced at dose levels of 800 mg/kg and above. This value is in approximately in the range of the recent guideline study. Interestingly though is that the clinical signs in these studies indicate evidence of neurotoxicity (ataxia, tremors, and convulsions) in the animals that died.   Such clinical signs of neurotoxicity are consistent with what was observed in the 28 day study at dose levels of 750 -1,000 mg/kg per day. All animals in these studies died within minutes to hours after administration of test material and may also be agonal in nature. The absence of such signs in the key study may simply be that the material is excitatory at lower doses but ultimately induces inhibitory neural responses at higher doses as noted by hypoactivity prior to death at the 1,500 mg/kg doses in the key study. These older studies only utilized one animal per dose and were not well documented. The acute toxicity of TMCD was also evaluated in mice in two older studies (1958 and 1960). These studies also only used one animal per dose. Like rats neurological stimulation was noted (ataxia and convulsions). However, mice seemed to be even more sensitive to the test material with death occurring at dose levels of 200 mg/kg in one study and 400 mg/kg in the other study.

Dermal Studies

Two acute dermal toxicity studies were identified. The key study being conducted in 2006 followed OECD guideline 402 and GLP assurances, while the later was conducted in 1960 and was primarily designed to assess dermal irritation potential. Neither study showed evidence of toxicity or death with the key study using the highest dose (2,000 mg/kg) as well as the most animals (10; 5/sex). 

Justification for classification or non-classification

The oral acute toxicity value (1500 mg/kg bw) fell within the criteria for Acute Category 4.