Registration Dossier

Administrative data

Description of key information

Available data for one stream within this category (CAS 68516-20-1), two related streams (API 83-04 [light catalytic reformed naphtha], API 83-05 [catalytic reformed naphtha]), summary information available for pyrolysis gasoline (68606-10-0, 68921-67-5, 64742-91-2, 68955-29-3) and data on specific components (benzene, toluene, hexane, xylenes, 1,3-butadiene, naphthalene, isoprene and anthracene) that are present in some streams indicate that acute toxicity is expected to be low. High Benzene Naphtha streams do not pose an acute hazard following skin contact (dermal LD50 > 5000 mg/kg) or acute inhalation (4 hour LC50 > 20 mg/L) exposures although streams containing a high proportion of naphthalene (≥25%) are expected to be hazardous following oral exposures. Naphthalene has been shown to be acutely toxic (producing haemolytic anaemia) in humans.  Xylenes are considered to be hazardous following inhalation and dermal exposure.  Following acute inhalation exposures toluene and n-hexane can cause neurobehavioural effects.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw
Quality of whole database:
Adequate information is available to characterise the short-term hazards of these streams.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
20 000 mg/m³
Quality of whole database:
Adequate information is available to characterise the short-term hazards of these streams.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Adequate information is available to characterise the short-term hazards of these streams.

Additional information

Non-human information

Acute oral, dermal and inhalation toxicity data are available on the stream 68516-20-1 and two related streams API 83-04 [light catalytic reformed naphtha] and API 83-05 [catalytic reformed naphtha]. API 83-04 (CAS 64741-63-5) and API 83-05 (CAS 68955-35-1) are two petroleum based naphthas comprising up to 100% aromatics, including substituted mono and di-aromatics with approximately 2-5% benzene and are considered appropriate for read-across to high benzene naphthas. These data indicate low toxicity with LD50 values in rats > 2000 mg/kg and no acute inhalation toxicity at the highest achievable concentrations. Information included in the Category Summary for High Benzene Naphthas (ACC, 2004) also confirms that acute oral and dermal LD50 values for pyrolysis gasoline (68606-10-0, 68921-67-5, 64742-91-2, 68955-29-3) exceed 2000 mg/kg. Data on the components benzene, toluene, n-hexane, 1,3-butadiene, naphthalene, isoprene and anthracene, indicate that no classification is warranted on the basis of acute lethality following exposure via oral, dermal or inhalation routes. However, toluene produces unsteady gait and other indications of neurobehavioural activity at concentrations < 20 mg/L justifying R67. n-Hexane is also classified R67. Mixed xylenes are considered to be harmful following acute dermal and inhalation exposures and are classified R20 and R21.

Human information

There are no specific studies on the oral, inhalation or dermal toxicity in humans for streams in this category.

Data from human exposures that provide information on acute exposures that are of value to the risk assessment process are available for benzene, toluene and naphthalene:

Benzene (Classification: Category 1, H304): Human data on oral toxicity indicate that ingestion of 15 mL (176 mg/kg bw) benzene can cause death after collapse, bronchitis and pneumonia (EU, 2008b). Exposure for 5-10 minutes to benzene vapours of 65-61 mg/L is fatal and exposure to 25 mg/L for 30 minutes is dangerous to life, while a one-hour exposure to 1.6 mg/L causes only some symptoms of illness.

Toluene (Classification: Category 1, H304, Cat 3 H336): The acute effects of toluene inhalation exposure include headache, dizziness, feeling of intoxication, irritation and sleepiness and decreases in acute neurobehavioural performance at concentrations ≥ 75 ppm (EU RAR, 2003). A NOAEC of 50 ppm (188 mg/m3) can be determined for acute neurobehavioural effects in humans (Muttray et al, 2005).

Naphthalene (Classification: Cat 4 H302) The EU RAR (2003b) concluded “Naphthalene is of low toxicity in rats, with mice being more sensitive. It appears that rodents are not suitable animal models for the acutely toxic human health effects of naphthalene in relation to haemolytic anaemia. Thus, while the LD50 results from the rat suggest relatively low acute toxicity in this species, the available information in humans indicates significant toxicity. Very severe haemolytic anaemia occurred in one case report (of a 16 year old female) at an estimated single oral dose of approximately 6 g. It is possible that this represents a lethal dose given that a number of blood transfusions were required. ”

Xylenes (Classification: Category 4 H332; Category 4 H312): Although xylenes are classified as Xn, R20 Harmful by inhalation under Annex I of Dir 67/548/, the rationale for this is not clear since the LC50 is clearly above 20,000 mg/m3and classification would appear not to be justified. Similarly, although xylenes are currently classified under DSD Xn, R21 Harmful in contact with skin under Annex I of Dir 67/548/, the rationale for this is not clear since the LC50 is clearly above 2,000 mg/kg bw and classification would appear not to be justified.

References

ACC (2004). US High Production Volume Chemical Program: category summary for High benzene Naphthas Category. http://www.epa.gov/HPV/pubs/summaries/hibenznp/c13436tc.htm

EU (2003a). European Union Risk Assessment Report for Toluene.EC Joint Research Centre http://ecb.jrc.ec.europa.eu/DOCUMENTS/Existing- Chemicals/RISK_ASSESSMENT/REPORT/toluenereport032.pdf

EU (2003b). European Union Risk Assessment Report for Naphthalene. EC Joint Research Centre. http://ecb.jrc.ec.europa.eu/DOCUMENTS/Existing-Chemicals/RISK_ASSESSMENT/REPORT/naphthalenereport020.pdf

EU (2008b). European Union Risk Assessment Report for Benzene. EC Joint Research Centre. http: //ecb. jrc. ec. europa. eu/documents/Existing-chemicals/RISK_ASSESSMENT/REPORT/benzenereport063. pdf.

Justification for selection of acute toxicity – oral endpoint

Acute oral toxicity data available for representative streams and their component substances indicate LD50 values greater than 2000 mg/kg, although streams containing a high proportion of naphthalene are expected to be hazardous and therefore subject to classification.

Justification for selection of acute toxicity – inhalation endpoint

Acute inhalation toxicity data available for representative streams indicate LC50 values greater than 20 mg/l, although those containing a high proportion of toluene and/or n-hexane are expected to be hazardous and therefore subject to classification.

Justification for selection of acute toxicity – dermal endpoint

Acute dermal toxicity data available for representative streams indicate LD50 values greater than 2000 mg/kg.

Justification for classification or non-classification

There are sufficient data on tested streams and component substances to indicate that High Benzene Naphtha streams are of low acute toxicity by the dermal and inhalation routes and do not warrant classification for these end-points under the CLP Regulation.

Naphthalene is acutely toxic in humans producing haemolytic anaemia. Consequently High Benzene Naphtha streams that contain ≥25% naphthalene will justify the following classification: Category 4 H302 under Reg (EC) 1272/2008.

Xylenes are classified under DSD as harmful (inhalation and dermal routes). Consequently High Benzene Naphtha streams which contain ≥12.5% or ≥55% xylenes require the following classification: Category 4 H332 and H312 under Reg (EC) 1272/2008.

The viscosity and surface tension of three possible components of High Benzene Naphtha streams (benzene, toluene and xylenes) are such that classification is required, and it is proposed that all streams are classified as follows: "Aspiration toxicity Category 1, H304".

Data from experimental exposure of human volunteers with toluene show that dizziness and sleepiness are experienced at air levels < 20 mg/L. Similar effects are considered to occur with n-hexane. Therefore, High Benzene Naphtha streams that contain a total concentration of toluene and n-hexane of ≥20 % will justify classification Category 3 H336 under Reg (EC) 1272/2008.