Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

No studies were conducted for this substance since the production process is still in pilot phase and thus no representative sample is currently available. Also for animal welfare reasons animal testing is not justified since the composition of the product has not stabilized.

The current assessment of the effect on fertility is based on the composition information of the UVCB substance.

This substance contains n-hexane (max. 2 %) which is classified toxic to fertility with harmonized C&L entry of Repr. 2 H361f. However, the generic limit value in CLP reg. which triggers the classification of mixtures to reproduction (Repr. 2) based on the concentrations of individual ingredients is ≥ 3%. Thus, no classification is warranted to the substance based on CLP mixture rules.


Short description of key information:
No studies were identified to assess the potential impact of diesel fuels on reproduction/fertility. For animal welfare reasons, no testing proposal for reproduction toxicity is prepared.

Justification for selection of Effect on fertility via oral route:
No oral studies conducted for the substance itself and no studies available from the read-across substances.Evaluation was based on the composition and the maximum concentrations of the critical constituents in the substance.

Justification for selection of Effect on fertility via inhalation route:
No inhalation studies conducted for the substance itself and no studies available from the read-across substances. Evaluation was based on the composition and the maximum concentrations of the critical constituents in the substance.

Justification for selection of Effect on fertility via dermal route:
No dermal studies conducted for the substance itself and no studies available from the read-across substances. Evaluation was based on the composition and the maximum concentrations of the critical constituents in the substance.

Effects on developmental toxicity

Description of key information
In the absence of any experimental studies on the substance itself, the read-across data is used to evaluate the reproduction toxicity of renewable hydrocarbons of wood origin. Result of one inhalation developmental toxicity study conducted for read-across substance indicates a NOAEC > 2 110 mg/m3.
Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study is considered as reliable with restrictions since it is conducted for read-across substance, but is well documented and performed similar to OECD 414. Read-across justification: Based on the chemical composition, the renewable hydrocarbons produced from raw materials such as fatty acid rich oil like Crude Tall Oil (CTO) or triglyserides, using a hydrotreatment process have similar hydrocarbon fractions and they contain the same critical constituents than fossil diesel fuels. According to the identified hydrocarbon blocks, the typical carbon number ranges and the physicochemical properties, the renewable hydrocarbons with diesel type fractions can be considered as having structural similarities and similar behaviour in contact with water and in the physiological processes than the analogue source substances (fossil diesel fuels). Their irritation properties, skin sensitisation property as well as acute and long-term adverse effects to human health is similar. Therefore, and in order to avoid the unnecessary animal testing, the read-across data from the analogue fossil diesel fuels is used to evaluate skin and eye irritation, the genetic toxicity, carcinogenicity, developmental toxicity and short term and/or long-term toxicological effects of the target substance.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
other: CRL:COBS CD (SD)BR
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage, Michigan
- Age at study initiation: not reported
- Weight at study initiation: Not reported
- Housing: Individually except during mating
- Diet (e.g. ad libitum): Purina Laboratory Chow ad libitum
- Water (e.g. ad libitum):acidified water (pH 2.5) ad libitum
- Acclimation period: 7-19 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light
Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Vehicle:
unchanged (no vehicle)
Details on exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Exposures to jet fuel A, naphtha and fuel oil were carried out in 0.25 cubic meter stainless steel and plexiglass dynamíc inhalatíon chambers. These chambers were of rectangular crosssection with pyramidal tops and bases. Chamber room air was used as dilution air. All chamber exhausts were treated to remove the test material before discharge to the atmosphere.

- Temperature, humidity, pressure in air chamber: 26.7 deg. C - 28.2 deg. C

TEST ATMOSPHERE
- Brief description of analytical method used: The exposure chambers were periodícal1y monitored throughout the exposure by use of a Scott Model 216 Hydrocarbon Ana]yzer.
- Samples taken from breathing zone: no
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The exposure chambers were periodícally monitored throughout the exposure by use of a Scott Model 216 Hydrocarbon Ana]yzer.
Details on mating procedure:
After acclimation each female was paired with a sexually-mature maIe of the same strain obtained from the same supplier at the same time as the females. Each day the females were examined for the presence of a copulatory plug. The presence of such a plug was taken as evidence of mating. The day the plug was discovered was designated Day O of gestation.
Duration of treatment / exposure:
From Day 6 through 15 of gestatíon.
Frequency of treatment:
Daily for six hours.
Duration of test:
14 days
No. of animals per sex per dose:
20 pregnant females per dose
Control animals:
yes, sham-exposed
Details on study design:
Mated female rats were assigned sequentially to exposure groups until there were 20 in each group.
Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations included changes in general appearance, behavior and condition.

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 6, 15, 20 of gestation

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: Visceral and thoracic organs

Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: No
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: one third per litter
- Skeletal examinations: Yes: one third per litter
- Head examinations: Yes: one third per litter
Statistics:
Dunnett's t-test was used to determine statistical significance (p<0.05) with regard to difference between means with near-normal distribution (body weights and food consumption of dams, mean pup weight based on litter averages). Ratios, Le., sex and pregnancy ratios, were analyzed with a 2 x 2 contingency table with Yates' correction. With regard to discontinuous parameters, such as the number of abnormal fetuses within a litter, Wilcoxon Rank Sum was used.
Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
Exposure to fuel oil was without effect with regard to eye irritation or irritation of mucous membranes. Neither body weight nor food consumption reflected a compound related change.




Dose descriptor:
NOAEC
Effect level:
400 ppm (analytical)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEC
Effect level:
400 ppm (analytical)
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Data did not suggest any significant changes. The sex ratio derived from the examinatíon of the Bouin's fixed specimen, likewise, did not differ between the exposed and control groups. Examination of the Bouin's fixed specimen revealed one fetus from a 100 ppm with an internal hydrocephalus. This was not judged to be compound related.
The results of skeletal examinations did not indicate an adverse effects on fetal growth and development or teratogenic potential.
Dose descriptor:
NOAEL
Effect level:
400 ppm
Based on:
test mat.
Basis for effect level:
other: no observed effects at the highest dose tested
Remarks on result:
not determinable due to absence of adverse toxic effects
Abnormalities:
not specified
Developmental effects observed:
not specified
Conclusions:
Exposure of pregnant rats to fuel oil was investigated by exposure to vapour concentrations of 0, 100 and 400 ppm on days 6 through to 15 of gestation. Exposure to fuel oil (vapour) did not result in compound-induced maternal toxicity or development of foetuses. Therefore the NOAEC was concluded to be 400 ppm (2 110 mg/m3), the highest concentration tested.
Executive summary:

The study was conducted for the read-across substance, fuel oil, no.2, which is similar to diesel fuel. The result of this study is used as weight of evidence to evaluate the reproduction toxicity of renewable hydrocarbons of wood origin (diesel type fraction). The study is regarded as reliable with restrictions since it is conducted for read-across substance, but is well documented and performed similar to OECD 414.

Pregnant female rats were exposed on day 6 -15 of gestation fuel oil vapour at concentrations of 400 or 100 ppm. The substance did not produce any signs of eye irritation or mucous membrane irritation at both 100 and 400 ppm in the exposed animals. There was no evidence of fuel oil induced effects on litter size, fetal sex ratio, embryotoxicity or inhibition of fetal growth.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
2 110 mg/m³
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

No studies were conducted for this substance since the production process is still in pilot phase and thus no representative sample is currently available. Also for animal welfare reasons animal testing is not justified since the composition of the product has not stabilized.

In the absence of any experimental studies on the substance itself, the read-across data is used to evaluate the reproduction toxicity of renewable hydrocarbons of wood origin (diesel type fraction). There is available only one prenatal developmental toxicity study from fuel oils conducted in rats showing no effect on foetal development (Beliles and Mecler, 1982). In this study pregnant female rats were exposed on day 6 -15 of gestation fuel oil vapour at concentrations of 0 ppm (0 mg/m3), 100 ppm (530 mg/m3) or 400 ppm (2110 mg/m3). The substance did not produce any signs of eye irritation or mucous membrane irritation at any concentration in the exposed animals. There was no evidence of fuel oil induced effects on litter size, foetal sex ratio, embryotoxicity or inhibition of foetal growth. Based on these observations, NOAEC > 2110 mg/m3was established. The study is regarded as reliable with restrictions since it is conducted for read-across substance, but is well documented and performed similar to OECD 414.


Justification for selection of Effect on developmental toxicity: via oral route:
No oral studies conducted for the substance itself and no studies available from the read-across substances. Evaluation was based on the composition and the maximum concentrations of the critical constituents in the substance.

Justification for selection of Effect on developmental toxicity: via inhalation route:
No study was conducted for the substance. The selected reliable study is conducted using read-across substance similar to renewable hydrocarbons of wood origin (diesel type fraction).

Justification for selection of Effect on developmental toxicity: via dermal route:
No dermal studies conducted for the substance itself and no studies available from the read-across substances. Evaluation was based on the composition and the maximum concentrations of the critical constituents in the substance.

Justification for classification or non-classification

The current information on the harmonized classification entries of the critical ingredients of renewable hydrocarbons (diesel type fraction) and on the study result from analogue read-across substance does not warrant classifying the substance for toxic to reproduction.

Additional information