Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via inhalation route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via dermal route
Endpoint conclusion:
no adverse effect observed
Additional information

Data available on the specific components benzene, toluene, xylene, 1,3–butadiene, naphthalene, isoprene and anthracene do not reveal effects on fertility of a severity that would warrant classification. Hexane is suspected to have effects on fertility:

n-hexane (Classification: Category 2, H361f): Testicular atrophy in male rats is seen after repeated dose oral or inhalation exposure to generally high doses of n-hexane which also produce peripheral neuropathy and other systemic effects.

Short description of key information:

It is recognised that there is a data gap for a multi-generation study (REACH reference 8.7.3). The applicant submits that this study does not need to be conducted as High Benzene Naphtha streams contain at least 0.1% benzene which is known to be mutagenic and carcinogenic and appropriate risk management measures are implemented (handled in controlled conditions). Data on the reproductive toxicity of specific components present in some streams indicate that only n-hexane possesses specific effects which warrant classification with respect to fertility. Therefore for streams that contain n-hexane at concentrations greater than or equal to 3% (Reg (EC) 1272/2008), classification is required for effects on fertility.

Justification for selection of Effect on fertility via oral route:

Information on the component substances present indicates they are unlikely to affect fertility, although streams that contain n-hexane may require classification for effects on fertility. Controls to protect against carcinogenicity will mitigate any risk to reproduction.

Justification for selection of Effect on fertility via inhalation route:

Information on the component substances present indicates they are unlikely to affect fertility, although streams that contain n-hexane may require classification for effects on fertility. Controls to protect against carcinogenicity will mitigate any risk to reproduction.

Justification for selection of Effect on fertility via dermal route:

Information on the component substances present indicates they are unlikely to affect fertility, although streams that contain n-hexane may require classification for effects on fertility. Controls to protect against carcinogenicity will mitigate any risk to reproduction.

Effects on developmental toxicity

Description of key information

It is recognised that there is a data gap for a developmental toxicity study (REACH reference 8.7.2). The applicant submits that this study does not need to be conducted as High Benzene Naphtha streams contain at least 0.1% benzene which is known to be mutagenic and carcinogenic and appropriate risk management measures are implemented (handled in controlled conditions).  Data on the developmental toxicity of specific components present in some streams indicate that toluene possesses specific effects which warrant classification. Therefore there are sufficient data on component substances to indicate that no further testing is warranted. Streams that contain ≥3% (Reg (EC) 1272/2008) toluene will be required to be classified.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no adverse effect observed
Additional information

Data available on the specific components benzene, hexane, xylene, 1,3–butadiene, naphthalene, isoprene and anthracene indicate no hazard with respect to developmental toxicity and no classification is warranted. Toluene is classified for possible developmental toxicity:

Toluene (Classification: Category 2, H361d): 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).

Justification for selection of Effect on developmental toxicity: via oral route:

Information on the component substances present indicates they are unlikely to affect foetal development, although streams that contain toluene may require classification. Controls to protect against carcinogenicity will mitigate any risk to the foetus.

Justification for selection of Effect on developmental toxicity: via inhalation route:

Information on the component substances present indicates they are unlikely to affect foetal development, although streams that contain toluene may require classification. Controls to protect against carcinogenicity will mitigate any risk to the foetus.

Justification for selection of Effect on developmental toxicity: via dermal route:

Information on the component substances present indicates they are unlikely to affect foetal development, although streams that contain toluene may require classification. Controls to protect against carcinogenicity will mitigate any risk to the foetus.

Justification for classification or non-classification

The need for 2-generation reproduction toxicity and full developmental toxicity studies for High Benzene Naphtha streams is waived as they contain > 0.1% benzene and are classified as mutagenic and carcinogenic.

There are sufficient data available on component substances to conclude that streams within this class that contain less than 3% toluene and n-hexane are not reproductive toxicants and do not require a label for this endpoint under Reg (EC) 1272/2008).

High Benzene Naphtha streams which contain >3% toluene should be classified “Suspected of damaging the unborn child” Category 2, H361d according to Reg (EC) 1272/2008.

Hexane causes testicular atrophy. Consequently High Benzene Naphtha streams which contain >3% n-hexane should be classified “Suspected of damaging fertility” Category 2, H361f according to Reg (EC) 1272/2008.