Registration Dossier

Diss Factsheets

Administrative data

specific investigations: other studies
Type of information:
other: review of secondary literature
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The assessment is based on a review conducted under the EU Existing Chemicals Regulation (Risk Assessment)

Data source

Reference Type:
other: EU Risk Assessment Report
European Union Risk Assessment Report: P-TERT-BUTYLPHENOL
European Communities
Bibliographic source:
Luxembourg: Office for Official Publications of the European Communities

Materials and methods

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Test material form:
solid: flakes
Details on test material:
- Name of test material (as cited in study report): p-tertiary butylphenol
- Molecular formula (if other than submission substance): C10H14O
- Molecular weight (if other than submission substance): 150.21 g/mol
- Physical state: solid white flakes
- Analytical purity: 99.9%

Results and discussion

Details on results:
A full EU risk assessment report is available and presents an up to date overview of available information. Several parts of this dossier refer to the EU Risk Assessment report. The current evaluation for the "skin depigmentation effects" caused by p-tert-butylphenol are taken from the EU report, which is based on an up to date review of the data.

Any other information on results incl. tables

There are several human and animal studies on depigmentation by ptBP, however, most of these studies in humans are concluded on sensitisation reactions and not depigmentation. There are conflicting results in these studies and there is a discussion within the scientific community regarding possible false positives and false negatives in the human studies due to the use of different solvents and lack of proper controls. A systemic LOAELanimal for oral administration of ptBP in C57 black mice was calculated to be 103 mg/kg bw/day [6 mg x 3 days divided with 7 days and divided by 0.025 kg (mouse body weight)]. This systemic LOAELanimal of 103 mg/kg/d will be forwarded to the risk characterization concerning risk of depigmetation. The lowest subcutaneous injected dose inducing depigmentation in C57 black mice is the 0.075 mg ptBP which gives a systemic LOAELanimal at 3 mg/kg bw/day [0.075 mg/day divided with 0.025 kg (mouse body weight). Since the subcutaneous injection is considered as not relevant for humans this LOAEL value will not be forwarded to risk characterisation. Overall there seems to be sufficient evidence that ptBP can cause depigmentation in humans and this is supported by animal studies. Animal studies have shown depigmentation after patch tests with 10 mg of ptBP both in DMSO and propylene glycol as solvents. Human studies have shown depigmentation at concentrations of ptBP ¿¿50 %. However, there are some studies in humans showing depigmentation at 2 % ptBP and one study showing reduced production of melanin and lowering of melanocytes in the exposed area. The depigmentation is reversible after some months when the inducing material is removed from the skin. Due to these data an estimated local LOAEL for humans due to the dose in a patch test drop. The volum of a drop is estimated to be in the range of 30-50¿l of 2 % solution of ptBP. This gives a local LOAEL for humans in the range of 0.0086 to 0.014 mg/kg [(20g/l ptBP x 0.000030 l x 1000 mg/g /70 kg (weight of a man); (20g/l ptBP x 0.000050 l) x 1000 mg/g /70 kg (weight of a man)]. This is an estimanted local LOAEL based on a patch test drop this will not be discussed in the risk characterisation. A human exposure study by Ikeda et al, 1978 (see human exposure page 27) have shown that industrial exposure for ptBP detected in urine may cause depigmentation at high doses but since there are no information about the exposure dose or route this will not be discussed any further. Another study by Bajaj et al., (1996) showed that some footwear may induce depigmentation related to adhesives used in shoemaking in tropical countries outside EU, however, this is not considered relevant within EU countries. Concerning depigmentation, the available human studies is of low quality and the lack of information in the studies renders these studies less suitable to be used in the risk characterisation. However, there is a single dose depigmentation study performed on C57 black mice exposed orally for ptBP which is the basis for a systemic LOAEL of 103 mg/kg/day. This LOAEL will be forwarded to the risk characterisation to scenarios where there is risk for depimentation. The reason for using two different values for repeated dose toxicity and depigmentation is based on the fact that the systemic NOAEL is from a study with albino Sprague-Dawley rats in the 2-generation study. This strain of rats is not suitable to be used for detection of depigmentation. The only study with reliable data and information showing depigmentation is a single dose oral exposure study on C57 black mice resulting in a the systemic LOAEL of 103 mg/kg/day.

Applicant's summary and conclusion