Shale oils

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Screening for reproductive / developmental toxicity

In accordance with column 2 of REACH Annex VIII, information requirement 8.7.1 (a screening study for reproductive/ developmental toxicity) does not need to be conducted as a pre-natal developmental toxicity study is available on the substance (as required under REACH Annex IX, 8.7.2).

In addition, the substance is considered to be carcinogenic, mutagenic and toxic to reproduction (category 1B) and the appropriate risk management measures are implemented.

Extended one-generation reproductive toxicity

According to column 2 of REACH Annex IX, section 8.7, a reproductive toxicity study does not need to be conducted if the substance is known to have an adverse effect on fertility, meeting the criteria for classification as toxic for reproduction category 1A or 1B: May damage fertility (H360F), and the available data are adequate to support a robust risk assessment. Since the substance is reasonably known to be toxic for reproduction category 1B, and specifically may damage fertility (H360F), and bearing in mind the exposure assessment indicates no risk (due to the operational controls and risk management measures that are implemented), further testing for reproductive toxicity is neither considered necessary nor considered to be an expedient or responsible use of animals.

Additionally, column 2 of REACH Annex IX further stipulates that additional reproductive toxicity studies do not need to be conducted if the substance is known to be a genotoxic carcinogen and/or a known germ cell mutagen and appropriate risk management measures are implemented. Since the substance is reasonably known to be carcinogenic and mutagenic (category 1B), and since appropriate risk management measures are implemented, this further substantiates the lack of need for additional testing.

Please refer to the document ‘Consideration of the long term toxicity of Distillates (shale oil)’, as included in section 13, for further information.

Link to relevant study records

Reference

Reference 1

Endpoint:

screening for reproductive / developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because a pre-natal developmental toxicity study is available

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with column 2 of REACH Annex VIII, information requirement 8.7.1 (a screening study for reproductive/ developmental toxicity) does not need to be conducted as a pre-natal developmental toxicity study is available on the substance (as required under REACH Annex IX, 8.7.2).
In addition, the substance is considered to be carcinogenic, mutagenic and toxic to reproduction (category 1B) and the appropriate risk management measures are implemented.

Reference 2

Endpoint:

extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)

Study period:

to be confirmed

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is known to be a genotoxic carcinogen and appropriate risk management measures are implemented

the study does not need to be conducted because the substance is known to be a germ cell mutagen and appropriate risk management measures are implemented

no further testing on fertility is necessary because the substance is known to have an adverse effect on fertility, meeting the criteria for classification as toxic for reproduction category 1A or 1B: May damage fertility (H360F), and the available data are adequate to support a robust risk assessment and classification and labelling

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
According to column 2 of REACH Annex IX, section 8.7, a reproductive toxicity study does not need to be conducted if the substance is known to have an adverse effect on fertility, meeting the criteria for classification as toxic for reproduction category 1A or 1B: May damage fertility (H360F), and the available data are adequate to support a robust risk assessment. Since the substance is reasonably known to be toxic for reproduction category 1B, and specifically may damage fertility (H360F), and bearing in mind the exposure assessment indicates no risk (due to the operational controls and risk management measures that are implemented), further testing for reproductive toxicity is neither considered necessary nor considered to be an expedient or responsible use of animals.
Additionally, column 2 of REACH Annex IX further stipulates that additional reproductive toxicity studies do not need to be conducted if the substance is known to be a genotoxic carcinogen and/or a known germ cell mutagen and appropriate risk management measures are implemented. Since the substance is reasonably known to be carcinogenic and mutagenic (category 1B), and since appropriate risk management measures are implemented, this further substantiates the lack of need for additional testing.
Please refer to the attached document '1904651.UK0 - 7899 Consideration of the long term toxicity of Distillates (shale oil)' for further information.

Principles of method if other than guideline:

Shale oil, a UVCB (Unknown or Variable composition, Complex reaction products or Biological materials) substance mainly consisting of hydrocarbons, is produced by VKG Oil and marketed in three shale oil fractions: a Light, Middle and Heavy fraction.
Given the supply levels of these fractions, the performance of a repeated-dose sub-chronic oral (90-day) and an extended one-generation reproductive toxicity study (EOGRTS) for each shale oil fraction, is triggered. Nevertheless, VKG Oil proposed to test only the Heavy shale oil fraction and apply the endpoints to all three shale oil fractions.
ECHA studied this proposal and issued a Draft decision on the testing proposal for each fraction, not accepting that the Heavy fraction results would represent a worst-case result for the Light and Middle fractions.
From the responses, it is evident that although ECHA’s concerns are at first glance reasonable, scientific evidence gives confidence in the proposed read-across.
More specifically, the Heavy fraction can be considered to offer worst-case results to the Light and Middle fraction when tested for repeated-dose toxicity (90-day oral study). Furthermore, the Heavy fraction can be considered as worst case when tested for reproductive toxicity (EOGRTS).

In order to allay the concerns regarding human health safety, VKG Oil makes a new proposal, according to which no further animal testing is performed, and VKG Oil adopts a conservative classification and labelling regarding human health effects:

Risk assessment is performed based on the most toxicologically relevant component, benzo(a)pyrene. Classification and DNELs can be derived based on calculation from the OEL recognised at European level. Even at 12% , the presence of PAHs are still the only component that need to be taken into consideration in the derivation of DNELs, because comparison of existing reference doses and exposure limits show that for PAHs are 10,000 lower than next lowest reference dose i.e. extrapolating the OEL for each oil fraction from the PAH content still results in the lowers OEL, than if were done based on the content of the remaining materials. See the attached document: "Shale oil: comments on ECHA’s Draft decision".

Reproductive effects observed:

not specified

Additional information

Risk assessment is performed based on the most toxicologically relevant component, benzo(a)pyrene. Classification and DNELs can be derived based on calculation from the OEL recognised at European level. Even at 5% , the presence of PAHs are still the only component that need to be taken into consideration in the derivation of DNELs, because comparison of existing reference doses and exposure limits show that for PAHs are 10000 lower than next lowest reference dose i.e. extrapolating the OEL for each oil fraction from the PAH content still results in the lowers OEL, than if were done based on the content of the remaining materials.

Effects on developmental toxicity

Description of key information

Developmental toxicity (rat)

Under the conditions of the study the No Observed Adverse Effect Level (NOAEL) for maternal toxicity was 100 mg/kg bw/day. The NOAEL for embryofoetal development was 100 mg/kg bw/day and the NOAEL for teratogenic effects was 500 mg/kg bw/day, the highest dose level tested.

Developmental toxicity (rabbit)

According to column 2 of REACH Annex X, information requirement 8.7.2, a study does not need to be conducted if the substance is known to cause developmental toxicity meeting the criteria for classification as toxic for reproduction category 1A or 1B: May damage the unborn child (H360D), and the available data are adequate to support a robust risk assessment. Since the registered substance is reasonably known to be toxic for reproduction category 1B, and specifically may damage the unborn child (H360D), and bearing in mind the exposure assessment indicates no risk (due to the operational controls and risk management measures that are implemented), further testing for developmental toxicity is neither considered necessary nor considered to be an expedient or responsible use of animals.

Additionally, column 2 of REACH Annex X further stipulates that additional reproductive toxicity studies do not need to be conducted if the substance is known to be a genotoxic carcinogen and/or a known germ cell mutagen and appropriate risk management measures are implemented. Since the registered substance is reasonably known to be carcinogenic and mutagenic (category 1B), and since appropriate risk management measures are implemented, this further substantiates the lack of need for additional testing.

Please refer to the document ‘Consideration of the long term toxicity of Distillates (shale oil)’, as included in section 13, for further information.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Developmental toxicity (rat)

The developmental toxicity of the test material was investigated in a study which was conducted under GLP conditions and in accordance with the standardised guidelines OECD 414 and EU Method B.31.

During the study, the test material was administered by oral gavage to groups of mated female Wistar rats at dose levels of 0 (corn oil vehicle control), 50, 100 and 500 mg/kg bw/day. The females received treatment from day 6 to day 19 post coitum. During the treatment period the females were observed for mortality and morbidity as well as for any adverse clinical signs. Body weights and food consumption were recorded. On day 20 post coitum the females were sacrificed, subjected to necropsy and the foetuses removed by caesarean section. Post mortem examination included a gross macroscopic examination of all internal organs with emphasis on the uterus, uterine contents, position of foetuses in the uterus and the number of corpora lutea were counted and recorded.

Foetuses were removed from the uterus, sexed, weighed individually, examined for gross external abnormalities and then sacrificed. Half of the litter was subjected to skeletal examination while the other half was subjected to visceral examination.

Salivation after administration was recorded at 100 and 500 mg/kg bw/day in a dose-dependent manner. Lower food consumption and slightly lower body-weight gain were observed at 100 and 500 mg/kg bw/day; however, these values did not deviate from the control group by more than 11 and 29 % for food consumption and 5 and 11 % for body weight, respectively.

In the observations deriving from the hysterectomies, test material-related embryofetal toxicity was observed at 500 mg/kg bw/day (higher number of post-implantation losses and, consequently, lower mean number of foetuses per litter).

Treatment showed no effects on mean foetal weight evaluated on a per litter basis but lower body weight (6 %) with respect to the control group was recorded at the dose of 500 mg/kg bw/day when analysis was done on an individual basis.

There were no findings at the external examination.

The skeletal examination of the foetuses did not reveal any toxicologically relevant alterations. The slight delay in ossification (skull bones and sternebrae) recorded in some litters from 500 mg/kg bw/day compared to the control group should be considered a variation without pathological significance and secondary to the maternal toxicity recorded.

The visceral examination at 100 and 500 mg/kg bw/day/day showed an increase in foetus and litters with left-sided umbilical artery. Two litters at 500 mg/kg each showed one foetus with abnormalities; one foetus had total situs inversus and the other had no recognisable eye structures.

Furthermore, common variations mainly involving urogenital morphology (dilated renal pelvis, and dilated and/or convoluted ureter, malpositioned kidney, malpositioned cranial testis) and other findings (dilated stomach, long cranial thymus, additional small lobe in the liver and bilateral azygos vein) were recorded in all the groups including the control group. These alterations should be regarded as spontaneous variations with limited pathological relevance.

Therefore, based on the results of this study, the dose of 100 mg/kg bw/day (the middle dose tested) was considered the No Observed Adverse Effect Level (NOAEL) for pregnant females, based on the significant decrease in food consumption and body-weight gain recorded at 500 mg/kg bw/day; there was a 10 % difference compared to the control group.

With respect to the effects on embryofoetal development, 100 mg/kg bw/day is considered the NOAEL, based on the statistically significant higher post-implantation losses recorded at 500 mg/kg bw/day.

Regarding the potential for teratogenic effects, 500 mg/kg bw/day is considered to be the NOAEL.

Developmental toxicity (rabbit)

According to column 2 of REACH Annex X, information requirement 8.7.2, a study does not need to be conducted if the substance is known to cause developmental toxicity meeting the criteria for classification as toxic for reproduction category 1A or 1B: May damage the unborn child (H360D), and the available data are adequate to support a robust risk assessment. Since the registered substance is reasonably known to be toxic for reproduction category 1B, and specifically may damage the unborn child (H360D), and bearing in mind the exposure assessment indicates no risk (due to the operational controls and risk management measures that are implemented), further testing for developmental toxicity is neither considered necessary nor considered to be an expedient or responsible use of animals.

Additionally, column 2 of REACH Annex X further stipulates that additional reproductive toxicity studies do not need to be conducted if the substance is known to be a genotoxic carcinogen and/or a known germ cell mutagen and appropriate risk management measures are implemented. Since the registered substance is reasonably known to be carcinogenic and mutagenic (category 1B), and since appropriate risk management measures are implemented, this further substantiates the lack of need for additional testing.

Please refer to the document ‘Consideration of the long term toxicity of Distillates (shale oil)’, as included in section 13, for further information.

Justification for classification or non-classification

The substance is classified as toxic for reproduction (category 1B FD) in consideration of the presence of polyaromatic hydrocarbons (PAHs) analysed in the substance at a level greater than the generic cut-off limits for classification for reproductive toxicity. PAHs are widely acknowledged to possess CMR properties. The harmonised classification of the PAH substance benzo[a]pyrene is applied to this substance as it has been established that this substance is considered to be representative of the PAHs contained within the registered substance. Furthermore, the hazard of benzo[a]pyrene is well established in light of the wealth of toxicological data that are available on the substance.

Please refer to the document ‘Consideration of the long term toxicity of Distillates (shale oil)’, as included in section 13, for further information.