Registration Dossier

Administrative data

Description of key information

Studies available for dermal and inhalation routes of repeated exposure on structural analogues, Distillates (petroleum), straight-run middle (EC: 265-044-7), Distillates (petroleum), hydrotreated middle (EC: 265 -148 -2) and Distillates (Petroleum) hydrodesulfurised middle (EC: 265 -183 -3)

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
23 mg/m³
Study duration:
subacute
Species:
rat

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
200 mg/kg bw/day
Study duration:
subacute
Species:
rabbit

Additional information

Subacute and subchronic studies conducted have been conducted to assess dermal exposure to the analogous substances

Distillates (petroleum), straight-run middle (EC: 265-044-7) and Distillates (petroleum), hydrotreated middle (EC: 265 -148 -2).

In the 28 -day subacute study using rabbit, local irritation effects were observed at each dose level, however, these effects were minimal in the lowest dose group. A NOAEL = 200 mg/kg/day seems appropriate for local effects during dermal route adminstration.

However, there were no systemic findings that were considered treatment related. Accordingly, the systemic NOAEL is greater than or equal to 1000 mg/kg/day. Body weight changes seen at 2000 mg/kg are not necessarily considered as adverse.

The 13 -week subchronic study (preliminary study to 2 -year dermal carcinogenicity study) supports the conclusions of the 28 -day study that repeat dermal exposure can lead to local effects (e.g. dermal irritation at site of application).

Inhalation repeated dose toxicity has been assessed in a subacute study using the analogous substance, Distillates (Petroleum) hydrodesulfurised middle (EC: 265 -183 -3). No exposure-related clinical signs or bodyweights were observed. Statistically significant organ weights variations were observed in males (Group 2: lung, brain and body, Group 3: kidney, liver, testis) and in females (Group 2: lung, liver, pituitary). In the absence of microscopic or other macroscopic changes, these were considered not toxicologically significant. NOAEL was determined as 23 mg/cu.m.

Repeated dose testing via oral route is not necessary because the primary routes of exposure for humans are the dermal and inhalation routes.

Justification for classification or non-classification

Repeated dose study conducted on rabbit (dermal) and rat (inhalation) shows limited toxicological effects at the highest tested dose in both studies. Based on available data on analogous substances: specific target organ toxicity classification is not warranted for Renewable Diesel.