Registration Dossier

Administrative data

Description of key information

For both oral and dermal acute toxicity, one key and one supporting study have been identified: in each case, the key study was conducted according to a recognised guideline and performed to GLP standards.  For acute inhalation toxicity, four whole-body exposure studies have been identified and a weight-of -evidence approach is taken. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
560 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
1 843 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
440 mg/kg bw

Additional information

Acute oral toxicity

The key study shows that TBHP is moderately toxic to rats following oral administration, with an acute LD50 value of 560 mg/kg. The supporting study confirmed this result (showing LD50 567 mg/kg).

The key parameter LD50 has been adjusted for water content of the tested TBHP.

Acute inhalation toxicity

One of the four available studies is considered sufficiently reliable to be considered definitive (Klimisch 1 or 2). A rat study using methods comparable to those of OECD guideline 403 (non-GLP; uncertain test material characterisation) gave a 4h inhalation

(aerosol) LC50 value of 1.85 mg/l (aerosol). In other studies, results in rats and mice performed under non-guideline methods gave 4h inhalation LC50 values of 500 ppm (rat) and 350 ppm (mouse). There is a lack of clarity regarding aerosol or vapour status of test atmospheres, but it is considered that these LC50 value probably represent TBHP vapour exposure: in this case, 4h vapour inhalation LC50 values are 1.84 mg/l (rat) and 1.29 mg/l (mouse).

The fourth study exposed rats for 1h only (non-guideline method, no GLP): a 1h (aerosol) inhalation LC50 value of 85.4 mg/l was reported.

Applying a conservative approach to resolve the uncertainties over the physical state of test atmospheres, it is concluded that the lowest reported rat 4h LC50 value of 1.84 mg/l (1843 mg/m3), taken to represent vapour exposure, can be taken to represent the acute inhalation toxicity of TBHP.

The key parameter LD50 has been adjusted for water content of the tested TBHP.

Acute dermal toxicity

The key study shows that TBHP is harmful to rabbits via dermal exposure. Although dermal penetration was probably aided in this study by abrasion of the test sites, the resultant LD50 value of 440 mg/kg is comparable to that obtained in the (less completely documented, but with no skin abrasion) supporting study: 553 mg/kg. The key parameter has been adjusted for water content of the tested TBHP.


Justification for classification or non-classification

Acute oral toxicity

Based on the results of the key study (oral LD50 560 mg/kg), TBHP should be classified as:

-Acute Toxicity Category 4 (Harmful if swallowed) under Regulation 1272/2008 (EU CLP)

Acute inhalation toxicity

From the results of three of the four available studies, it is evident that TBHP should be classified for this endpoint. Based on the rat 4h LC50 value concluded to be representative of the acute toxicity of TBHP (1843 mg/m3), TBHP should be classified as:

- Acute Toxicity Category 2 (Fatal if inhaled) under Regulation 1272/2008 (EU CLP)

Acute dermal toxicity

Based on the results of the key study (rabbit dermal LD50 440 mg/kg), TBHP should be classified as:

- Acute Toxicity Category 3 (Toxic in contact with skin) under Regulation 1272/2008 (EU CLP)