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Administrative data

Description of key information

The toxicity of the substance has been assessed by the repeated exposure over a period of 28-days by the three routes of exposure, oral, dermal and inhalation.  Effects observed by oral exposure demonstrate a reduction in serum cholesterol at the highest tested dose.  Furthermore, the results obtained by inhalation exposure are considered unsafe for determination of the intrinsic hazard of the substance by inhalation due to the a high proportion (65%) of mineral oil in the test sample.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
500 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
881.58 mg/m³
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
881.58 mg/m³
Study duration:
subacute
Species:
rat

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/cm²
Study duration:
subacute
Species:
rat

Additional information

The repeat dose toxicity has been determined by subacute 28-day oral toxicity studies by oral, dermal and inhalation exposure. Based on the data available, the substance may have the potential for haemotological effects with a reduction in cholesterol observed in one of the studies by oral exposure.

Effects observed in the repeat dose inhalation toxicity study available demonstrated enlarged lungs in high and intermediate dose animals which are likely to be physical effects due to the inhalation of mineral oil [Test material: Product as manufactured in mineral oil solvent further diluted in mineral oil (65/35)] and not necessarily a direct toxicological effect of the registered substance. The data are therefore considered unsuitable for determination of the intrinsic hazard of the substance as effects due to the registered substance may well be masked by the effects due to inhalation of mineral oil mist. For example, Occupation Exposure Limits (OELs) expressed for human exposure in the work place are typically 5 mg/m³. Considering a typical intraspecies assessment factor of 10 the results demonstrate good correlation to the anticipated effect level for mineral oil mist.

In view of this it is considered justifiable, for the purposes of assessing DNELs, to extrapolate inhalation hazard from the oral exposure data available.

Oral-to-inhalation extrapolation was based on the following conditions:

(1)         the available repeated dose toxicity study on EC 274-263-7 was reliable;

(2)         the critical effect for the oral exposure were systemic, i.e., decreased serum cholesterol levels;

(3)         the considered systemic toxic effects was independent of the route of exposure;

(4)         the chemical is relatively soluble in body fluid.

RtR extrapolation may require corrections for difference in absorptions between oral (starting route) and the inhalation (extrapolation route) (Dethloff, L. Z. 1993; Gerrity T. R., 1990; Sharrat M. 1988). Rennen et al. ran a critical assessment on oral-to-inhalation route extrapolation for 215 substances with various physicochemical properties. In this study, they compared the experimentally established NOAEL for inhalation study to the values predicted from oral toxicity study by RtR extrapolation using various absorption assumptions, such as 100% oral and 100% inhalation; 100% oral and 75% inhalation; 50% oral and 100% inhalation. And they demonstrated that when using systemic effect as criterion and under assuming equal absorption, 55% of the predication were regarded as “safe extrapolation”, whereas 45% as underestimation of the level of toxicity via inhalation route. Based on this study, it is feasible to assume that equal absorption for this substance. Correcting from oral to inhalation route of exposure was based on REACH guidance R8, and the mathematic formula was described in DNEL derivations.

Furthermore, one dermal repeat dose study exists noting effects which resulted in the Study Director being unable to assign a NOAEL. Due consideration of these data has been taken, but the results are considered not representative of the toxicological effects of the substance since the observations have not been repeated in the remaining study with dermal exposure, nor following exposure by oral and inhalation routes which are generally considered to represent greater systemic exposure routes. Furthermore, effects to the testes of male rats were not been observed in the reproductive toxicity study. In consequence, although data are not available to adequately determine the cause of these effects, the fact that no similar observations have been found in any other study undertaken is considered adequate justification to regard these data as not representative of the toxicological profile of the registered substance.

Notwithstanding these effects, no further effects were observed in the studies and each study achieved a NOAEL. The data are therefore considered adequate to assess the toxicological profile of the substance and for the purposes of classification.

The following information is taken into account for any hazard / risk assessment:

The toxicity of the substance has been assessed by the repeated exposure over a period of 28-days by the three routes of exposure, oral, dermal and inhalation. Effects observed by oral exposure demonstrate a reduction in serum cholesterol at the highest tested dose. Furthermore, the results obtained by inhalation exposure are considered unsuitable for determination of the intrinsic hazard of the substance by inhalation due to the high proportion of mineral oil in the test sample [Test material: Product as manufactured in mineral oil solvent further diluted in mineral oil (65/35)].

Value used for CSA (route: oral):

NOAEL: 500 mg/kg bw/day (subacute; rat)

Target organs: cardiovascular / hematological: other: serum cholesterol

Value used for CSA (route: dermal):

NOAEL: 1000 mg/kg bw/day (subacute; rat)

Value used for CSA (route: inhalation):

NOAEC: 881.58 mg/m³ (subacute; rat)

Target organs: respiratory: cardiovascular / hematological: other: serum cholesterol


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Data from two studies are available with exposure by oral gavage to linear and branched alkaryl benzene sulphonates upto a maximum dose of 1000 mg/ml/day. Relatively slight effects were observed in either study, limited to a reduction in cholesterol in serum at high dose animals only in one study. The lowest dose at which no adverse effects were observed effects were observed is, therefore, taken as the appropriate effect level.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
The data from only one repeat dose toxicity test by the inhalation route is available. The test substance is, however, extremely difficult to test by this route and, due to the nature of the substance in mineral oil, any effects due to the test sample are masked by the effects of the mineral oil. The NOAEC is, therefore, determined by extrapolation to oral exposure.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
The data from only one repeat dose toxicity test by the inhalation route is available. The test substance is, however, extremely difficult to test by this route and, due to the nature of the substance in mineral oil, any effects due to the test sample are masked by the effects of the mineral oil. The NOAEC is, therefore, determined by extrapolation to oral exposure.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
The data from two studies are available to assess dermal toxicity by repeated dose. No systemic toxicity was observed in either study.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
Effects of skin irritation were observed by repeated exposure. The effects were relatively slight.

Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: other

Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: lung

Justification for classification or non-classification

Based on the NOAEL values available from these data, the substance is considered to be not classified under CLP