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Description of key information

The acute toxicity of TBEP has been studied by all routes relevant to occupational exposure from which it can be concluded that the acute toxicity of TBEP is low. For oral toxicity, a GLP-compliant guideline study in rats (Rel. 1) by Roth (2000) has been chosen as key study. Supporting studies of Rel. 2 are Wolfe (1979), Picirillo (1981), Bullock (1972), Freeman (1991) and Gabriel (1980). The key study for dermal toxicity (Rel. 2) is Picirillo (1981)

For inhalation toxicity, a GLP-compliant guideline study in rats (assigned Rel. 2 because data on test substance purity are not available) by Hofmann (1990) has been chosen as key study. Supporting studies of Rel. 2 are Mount, 1991 and Pinkerton, 1981.

Key value for chemical safety assessment

Additional information

Oral Toxicity

Reported oral LD50 values range from >2000 to >13,000 mg/kg for rat, guinea pig and hen. Some, though not all, studies show females as more sensitive to the effects of TBEP than males. Inthe Reliability 1 key study by Roth (2000) the LD50 in rat was >2000 mg/kg (limit dose). Supporting studies of reliability 2 by Wolfe (1979), Piccirillo (1981), Bullock (1972), Gabriel (1980) and Freeman (1991) suggest that the LD50 is >5000 mg/kg for males and approximately 5000 mg/kg for females. Other reports of lower reliability and LD50 values from secondary literature are also consistent with the conclusion that TBEP is of low acute toxicity. All available data are summarised in Table 1

Table 1: Acute Oral Toxicity Studies on TBEP 

Species

LD50

Reference

Rel.

Rat

>2000

Roth, 2000

1

Rat

13,278 (m), 5,383 (f)

Wolfe, 1979

2

Rat

>5000 (m), <5000 (f)

Piccirillo, 1981

2

Rat

>5000 (m),500-5000(f)

Freeman, 1991

2

Rat (m)

>4640

Bullock, 1972

2

Rat

>5000

Gabriel, 1980

2

Hen

>5000

Carrington, 1989

2

Rat

>5000

Moreno, 1978

3

Rat

ca 10000

Heinemann, 1970

3

Rat (m)

>5000 (m)

Holsing, 1969 (EPA 1982)

3

Rat

10000

Holsing, 1969

3

Rat

9490

FMC, 1976a

4

Rat

4700

Monsanto, 1984a

4

Rat

3000

Sax, 1988

4

Rat

3000

Eldefrawi, 1977

4

Guinea pig

3000

Sax

4

Inhalation Toxicity

The Rel. 2 key study by Hofman (1990) gives inhalation LC50 >6.4 mg/l for a 4-hour exposure in rats. The values given in the Rel. 2 supporting studies by Mount (1991) and Pinkerton (1981) are consistent with this value. Studies of lower reliability give values which are consistent with those of the key and supporting studies, as shown in Table 2.

Table 2: Acute Inhalation Toxicity Studies on TBEP

Species

LC50 (aerosol)

Reference

Rel.

Rat

>6.4 mg/l 4h

Hofmann, 1990

2

Rat

>4.43mg/l / 4h

Mount, 1991

2

Rat

>0.52 < 5.03 mg/L 4h

Pinkerton, 1981

2

Rat

21.08 / 1h nominal

Wolfe, 1979

3

Rat

21.1 / 1h nominal

Gabriel, 1980

3

Rat

30 / 1h nominal

FMC, 1976

4

Mouse

180 mg/kg

Sax , 1988

4

Dermal Toxicity

Two Rel. 2 key studies conducted at limit doses give dermal LD50 as > 2000 mg/kg (Picirillo, 1981) or > 5000 mg/kg (Wolfe, 1979). Two supporting Rel. 2 studies (Bullock, 1973; Gabriel, 1980) confirm dermal LD50 values >5000 mg/kg, as do data from sources of lower reliability. All available data are summarised in Table 3.

Table 3: Acute Dermal Toxicity Studies on TBEP

Species

LD50

Reference

Rel.

Rabbit

> 2000

Picirillo, 1981

2

Rabbit

> 5000

Wolfe, 1979

2

Rabbit

> 5000

Doyle, 1979

2

Rabbit

> 4640

Bullock, 1973

2

Rabbit

>5000

Gabriel, 1980

2

Rabbit

> 2000

Moreno, 1978

3

Rabbit

>10000

FMC, 1976

4

Justification for classification or non-classification

Oral:

The limit value for classification of a substance as harmful on acute exposure by the oral route according to the criteria ofAnnex VI Directive 67/748/EEC (R22) and EU/GHS criteria (Acute toxicity Cat. 4) is oral LD50 2000 mg/kg. All the available studies on TBEP give LD50 > 2000 mg/kg.

TBEP is therefore not classified for acute oral toxicity according to the criteria of Annex VI Directive 67/748/EEC or EU GHS.

Dermal:

The limit value for classification of a substance as harmful on acute exposure by the dermal route according to the criteria ofAnnex VI Directive 67/748/EEC (R21) and EU/GHS criteria (Acute toxicity Cat. 4) is dermal LD50 2000 mg/kg. All the available studies on TBEP give LD50 > 2000 mg/kg.

TBEP is therefore not classified for acute dermal toxicity according to the criteria of Annex VI Directive 67/748/EEC or EU GHS.

Inhalation:

The limit value for classification of a substance as harmful on acute exposure by inhalation of an aerosol according to the criteria of Annex VI Directive 67/748/EEC (R21) and EU/GHS criteria (Acute toxicity Cat. 4) is inhalation LC50 5 mg/l (4-hour exposure). The key study and the majority of supporting studies on TBEP give LC50 > 5 mg/l.

TBEP is therefore not classified for acute inhalation toxicity according to the criteria of Annex VI Directive 67/748/EEC or EU GHS.