[No public or meaningful name is available]

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich) was formerly a member of the LOA Category L (Resin Oils and Cyclic Dienes), and the following Category L streams, with which these studies were conducted, resemble Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich) from a compositional standpoint, only containing much lower levels of benzene.

Additional data are available for constituents of Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich), including benzene, toluene and DCPD.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Adequate information is available on the constituents to characterise the reproductive hazards of Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich) after ingestion.

Effect on fertility: via inhalation route

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Adequate information is available on the constituents to characterise the reproductive hazards of Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich) after inhalation.

Effect on fertility: via dermal route

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Adequate information is available on the constituents to characterise the reproductive hazards of Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich) after skin contact.

Additional information

Data is available on similar UVCBs (CAS 68477-54-3 (Low Dicyclopentadiene Resin Oil), CAS 68478-10-4 (Dicyclopentadiene/Codimer Concentrate)) and on benzene, toluene and ethylbenzene do not reveal effects on fertility and none are classified for this endpoint.

CAS 68477-54-3 (Low Dicyclopentadiene Resin Oil): In a combined repeated dose toxicity/reproduction/developmental toxicity study in rats there was no evidence of adverse effects on any measures of reproductive function. At 375 mg/Kg/day clinical signs of toxicity, lower body weight and food consumption and histopathological changes were observed in adults. In addition, effects on body weight, clinical signs and food consumption were observed in males at 125 mg/Kg/day. The NOAEL for reproductive toxicity was 375 mg/Kg/day (the highest dose tested) (ACC, 2004k).

CAS 68478 -10 -4 (Dicyclopentadiene/Codimer Concentrate): Following oral dosing at 0, 5, 25 or 100 mg/Kg/day during premating (approximately 2 weeks), gestation (approximately 3 weeks), and lactation through day 4 no evidence of adverse effects on any measures of reproductive function were seen. There were no test substance-related effects on mean pup weight, number of pups born, number of pups born alive, sex ratio, gestation index, clinical observations, or litter survival for postnatal days 0-4 in the offspring from any dosage group. The NOAEL for reproductive toxicity was 100 mg/Kg/day (the highest dose tested) (ACC, 2004j).

Further higher-tier studies on Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich) are waived on the basis that benzene is present in the composition at 15% and consequently maximum risk management measures are employed in the handling of Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich).

Effects on developmental toxicity

Description of key information

The developmental toxicity data are limited to general toxicity and reproduction/developmental toxicity screening studies (OECD 422) by oral (gavage) exposure to rats to CAS 68477-54-3 (Low dicyclopentadiene resin oil) and CAS 68478-10-4 (Dicyclopentadiene/Codimer Concentrate). These studies showed no evidence of teratogenicity. For CAS 68477-54-3 (Low Dicyclopentadine Resin Oil) lower pup body weight was seen at maternally toxic doses. Developmental toxicity of inhaled benzene has been investigated in 3 species (rat, mouse and rabbit). No evidence of teratogenicity was seen in any species. Minor fetotoxic effects (reduced foetal weight, length and associated delays in skeletal ossification) were seen at concentration > 50 ppm and generally accompanied by maternal toxicity. The NOAEC for maternal and pre-natal developmental toxicity was 10 ppm (32 mg/m3). Data on the developmental toxicity of other constituents of Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich) indicate that only toluene is labelled with respect to developmental toxicity. Therefore, classification and labelling with respect to developmental toxicity will be driven by the concentration of toluene in Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich).

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Adequate information is available on the constituents to characterise the reproductive hazards of Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich) after ingestion.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Adequate information is available on the constituents to characterise the reproductive hazards of Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich) after inhalation.

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Adequate information is available on the constituents to characterise the reproductive hazards of Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich) after skin contact.

Additional information

Data is available for similar UVCBs, including CAS 68477-54-3 (Low Dicyclopentadiene Resin Oil) and CAS 68478-10-4 (Dicyclopentadiene/Codimer Concentrate), as well benzene and C8 aromatics (xylenes, ethylbenzene) indicate no hazard with respect to developmental toxicity and no labelling is warranted. Toluene is labelled for possible developmental toxicity:

CAS 68477-54-3 (Low Dicyclopentadiene Resin Oil): A combined repeated dose toxicity/reproduction/developmental toxicity study in rats showed no evidence of teratogenicity at any dose tested. Gestation length, implantation site numbers, implantation efficiency, mean number of pups per litter, percent of pups born alive, day 0-4 viability of pups, viability index, number of corpora lutea, sex ratio, pre-implantation loss, and post-implantation loss were comparable to controls. Maternal toxicity characterised by lower body weight and/or weight gain was observed throughout the dosing period at 375 mg/Kg/day. There was no evidence of teratogenicity at any dose tested. Pups from the 375 mg/Kg/day group had slightly lower body weight on day 4. The NOAEL for maternal and developmental toxicity was 125 mg/Kg/day (ACC, 2004k).

CAS 68478-10-4 (Dicyclopentadien/Codimer Concentrate): Female rats were dosed at 0, 5, 25 or 100 mg/Kg/day during premating (approx 2 weeks), cohabitation (approx 2 weeks), gestation, and lactation (4 days). Gestation length, implantation site numbers, implantation efficiency, mean number of pups per litter, percent of pups born alive, day 0-4 viability of pups, viability index, number of corpora lutea, sex ratio, pre-implantation loss, and post-implantation loss were determined. Maternal toxicity at 25 and 100 mg/Kg/day comprised histopathogical changes to the thyroid. There was no evidence of teratogenicity at any dose tested. The NOAEL for maternal toxicity was 5 mg/Kg/day and for developmental toxicity was 100 mg/Kg/day (ACC, 2004j).

Toluene (Classification: GHS/CLP – Category 2, H361d):

LOA is currently reviewing the human and animal data supporting Human Health for Toluene. It is expected to be completed by Q4 2021.

There is no evidence that toluene produces malformation in animals or humans. There is some evidence of developmental toxicity (lower body weight at birth and delayed vaginal opening) at toluene exposure concentrations ≥ 1000 ppm, concentrations which are associated with slight maternal toxicity. The NOAEC for developmental and maternal effects is 600 ppm (2261 mg/m3) (Thiel and Chahoud, 1997).

Benzene (classified as reproductive or developmental toxicant is not warranted under (EC) No 1272/2008 (CLP)):

The pre-natal developmental toxicity (or teratogenic) potential of benzene inhaled at doses ranging from 1 to 500 ppm by pregnant Sprague-Dawley rats on gestation days 6-15 has been investigated in two studies (Coate et al, 1984; Kuna and Kapp, 1981). No maternal toxicity was observed at 100ppm (Coate et al, 1984) but maternal body weight and bodyweight gain were decreased at 50 and 500 ppm (Kuna and Kapp, 1981). Reduced foetal weight was seen at 100 ppm (Coate et al, 1984) and at 50 and 500 ppm (Kuna and Kapp). Reduced crown rump lengths and associated delay in ossification of extremities and sternebrae were seen in the same foetuses.

Overall, the NOAEC for teratogenicity in the rat was 500 ppm (1600 mg/m3), the NOAEC for maternal and developmental toxicity was 10 ppm(32 mg/m3).

The effect of inhaled benzene on pre-natal developmental toxicity/teratogenicity was also assessed in CF-1 mice and New Zealand white rabbits.There were no significant effects on maternal clinical condition, body weight or body weight gain. Benzene exposure did not significantly affect the incidence of pregnancies or the average number of live foetuses or resorptions per litter in either species. Mean foetal body weight, but not crown-rump length, was decreased significantly in benzene exposed mice but there were no effects in rabbits. No teratogenic malformations were observed in either species. However, increases in the occurrence of several minor skeletal variants (including delayed ossification of sternebrae, skull bones and of unfused occipital bones of the skull) were reported in offspring of benzene-exposed mice.

The NOAEC for maternal toxicity was 500 ppm (1600 mg/m3) in rabbits and mice. 500 ppm (1600 mg/m3) was the NOAEC for pre-natal developmental toxicity in rabbits and the LOAEC for pre-natal developmental toxicity in mice.

Further higher-tier studies on Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich) are waived on the basis that benzene is present in the composition at 15% and consequently maximum risk management measures are employed in the handling of Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich).

Justification for classification or non-classification

Data available the streams CAS 68477-54-3 (Low Dicyclopentadiene Resin Oil), CAS 68478-10-4 (Dicyclopentadiene/Codimer Concentrate) and on constituents indicate that UVCBs that contain more than 3% toluene are reproductive toxicants and do not require a label for this endpoint. There is no evidence that toluene has any effect on fertility. Lower birth weight in the absence of significant maternal toxicity and weak evidence of behavioural effects (water maze and open field performance) was seen in offspring of dams exposed to toluene from day 7 of pregnancy until day 18 post-natally.

Based on the results of a rat single generation toxicity/fertility study and developmental toxicity studies in 3 species, classification of benzene as a reproductive or developmental toxicant is not warranted under (EC) No 1272/2008 (CLP).

Distillates (Petroleum), steam-cracked, dimerised (C5-12, C10-rich) contains 5% toluene and, therefore, should be classified "Suspected of damaging the unborn child" Category 2, H361d according to Reg (EC) 1272/2008.