Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

It is recognised that there is a data gap for an Extended One-Generation Reproductive Toxicity 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 Category 1B and carcinogenic Category 1A.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Adequate information is available on the component substances to characterise the reproductive hazards of these streams after ingestion.
Effect on fertility: via inhalation route
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Adequate information is available on the component substances to characterise the reproductive hazards of these streams after inhalation.
Effect on fertility: via dermal route
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Adequate information is available on the component substances to characterise the reproductive hazards of these streams after skin contact.
Additional information

The available data on stream marker constituents: benzene, cyclohexane, ethylbenzene, and xylene do not indicate reproductive toxicity of a severity that would warrant classification. Rep Cat 2 (H361) self-classification is applied to DCPD based on the WoE on a number of studies that suggest that it produced foetotoxic effects at doses at or below those that produced clear signs of maternal toxicity. 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.

 

The following information is taken into account for any hazard / risk assessment:

It is recognised that there is a data gap for an Extended One-Generation Reproductive Toxicity 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 Category 1B and carcinogenic Category 1A.

 

Justification for selection of Effect on fertility via oral route:

n-Hexane and DCPD present in some streams, have been shown to adversely affect fertility. However, controls to protect against the carcinogenicity of benzene (present in all streams at 0.1% and above) will mitigate

such risks to reproduction.

 

Justification for selection of Effect on fertility via inhalation route:

n-Hexane present in some streams, has been shown to adversely affect fertility. However, controls to protect against the carcinogenicity of benzene (present in all streams at 0.1% and above) will mitigate such risks to reproduction.

 

Justification for selection of Effect on fertility via dermal route:

n-Hexane present in some streams, has been shown to adversely affect fertility. However, controls to protect against the carcinogenicity of benzene (present in all streams at 0.1% and above) will mitigate such risks to reproduction.

Effects on developmental toxicity

Description of key information

It is recognised that there is a data gap for developmental toxicity studies in two species (REACH reference 8.7.2). The applicant submits that these studies do not need to be conducted as High Benzene Naphtha streams contain at least 0.1% benzene which is known to be mutagenic Category 1B and carcinogenic Category 1A and appropriate risk management measures are implemented (handled in controlled conditions).

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Adequate information is available on the component substances to characterise the reproductive hazards of these streams 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 component substances to characterise the reproductive hazards of these streams 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 component substances to characterise the reproductive hazards of these streams after skin contact.
Additional information

The available data on the specific marker constituents: benzene, isoprene, cyclohexane, ethylbenzene, and xylenes do not reveal developmental toxicity of a severity that would warrant classification. Rep Cat 2 (H361) self-classification is applied to DCPD based on the WoE on a number of studies that suggest that it produced developmental effects at doses at or below those that produced clear signs of maternal toxicity. 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 concentrations1000 ppm, concentrations which are associated with slight maternal toxicity. The NOAEC for developmental and maternal effects is 600 ppm (2261mg/m3) (Thiel and Chahoud, 1997).

 

Styrene (Classification: Category 2, H361d):Styrene is classified in Annex VI of the CLP regulation as suspected of being damaging the unborn child.

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

Toluene and DCPD present in some streams, have been shown to adversely affect the foetus. However, controls to protect against the carcinogenicity of benzene (present in all streams at 0.1% and above) will mitigate such risks to foetal development.

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

Toluene, present in some streams, has been shown to adversely affect the foetus. However, controls to protect against the carcinogenicity of benzene (present in all streams at 0.1% and above) will mitigate such risks to foetal development.

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

Toluene, present in some streams, has been shown to adversely affect the foetus. However, controls to protect against the carcinogenicity of benzene (present in all streams at 0.1% and above) will mitigate such risks to foetal development.

Justification for classification or non-classification

There are sufficient data available on component substances to conclude that streams within the High Benzene Naphtha category that contain less than 3% toluene, n-hexane, DCPD, or styrene are not reproductive toxicants and do not require a label for this endpoint. High Benzene Naphtha streams which contain3% DCPD should be classified as Category 2, H361 according to Reg (EC) 1272/2008. Streams that contain 3% n-hexane should be classified as Category 2, H361f according to Reg (EC) 1272/2008. Streams that contain 3% toluene or styrene should be classified as Category 2, H361d according to Reg (EC) 1272/2008.