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Administrative data

Description of key information

Acute toxicity – Oral LD50 > 5000 mg/kg (OECD TG 401)
Acute toxicity – Inhalation LD50 >5250 mg/m3 (OECD TG 403)
Acute toxicity – Dermal LD50 > 2000 mg/kg (OECD TG 402)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report similar or equivalent to OECD 401 performed under GLP conditions on an analogue substance.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Method: other: API procedure (see Reference).
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
5000 mg/kg
No. of animals per sex per dose:
5 male and 5 female/dose
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
No deaths resulted.
Clinical signs:
Clinical signs noted in the study were hypoactivity, ataxia and diarrhea.
Body weight:
Animals experienced normal weight gain during the study period.
Gross pathology:
No visible lesions were observed at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the parameters of this study, the acute oral LD50 of API 81-03 is greater than 5000 mg/kg. These findings do not warrant classification of the test article as an acute oral toxicant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

Five male and five female SD rats were given a dosage of 5000 mg/kg test article API 81-03 by oral gavage. The test animals were observed hourly for the first six hours after dosing and twice daily for fourteen days. No animals died during the study period. Clinical signs observed were diarrhea, ataxia, and hypoactivity. At necropsy, no visible lesions were observed. Based on the parameters of this study, the acute oral LD50 of the test material is greater than 5000 mg/kg. These findings do not warrant classification of the test article as an acute oral toxicant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Value:
5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report similar or equivalent to OECD TG 403 performed under GLP conditions on an analogue substance.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: no vehicle
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Scott Model 216 Hydrocarbon Analyzer
Duration of exposure:
ca. 4 h
Concentrations:
nominal: 5000 mg/m³
analytical: 5250 mg/m³
No. of animals per sex per dose:
5 male and 5 female rats
Control animals:
yes
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 250 mg/m³ air (analytical)
Exp. duration:
4 h
Mortality:
No animals died during the course of the exposure or the subsequent 14-day observation period.
Clinical signs:
other: No treatment-related effects.
Body weight:
No treatment-related effects.
Gross pathology:
No treatment-related effects.

The study report reported in units of mg/L. Conversions assumption was 1 mg/L = 1000 mg/m³.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the conditions of this study, the LC50 for acute inhalation exposure to API 81-04 is > 5250 mg/m³. This finding does not warrant classification of API 81-04 vapor as an acute inhalation toxicant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

API 81-04 was administered via individual inhalation chambers for four hours to ten Sprague-Dawley rats at the analytical vapor concentration of 5250mg/m³ to assess acute inhalation toxicity. Animals were observed for fourteen days following exposure. There were no mortalities and no other treatment-related effects. No gross abnormalities were observed at necropsy. Based on the conditions of this study, the LC50 for acute inhalation exposure to API 81-04 is > 5250mg/m³. This finding does not warrant classification of API 81-04 vapor as an acute inhalation toxicant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Value:
5 250 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report similar or equivalent to OECD TG 402 performed under GLP conditions on an analogue substance.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 hours
Doses:
2000 mg/kg and 3000 mg/kg
No. of animals per sex per dose:
4 males and 4 females per dose
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 000 mg/kg bw
Mortality:
No deaths resulted.
Clinical signs:
Dermal irritation ranged from slight to severe, and from slight to marked for atonia, desquamation and fissuring. Blanching and eschar formation were noted at the test sites for both doses. Subcutaneous haemorrhage was only found at the 3000 mg/kg dose.
Body weight:
All animals gained weight as normal at the 3000 mg/kg dosage level. At the 2000 mg/kg dosage level, one female lost weight.
Gross pathology:
At necropsy, thickened and crusted skin at the test site was noted.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 for light catalytic cracked naphtha (API 83-20) is >3000 mg/kg. This finding does not warrant classification of the test material as an acute dermal toxicant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.
Executive summary:

The acute toxicity of light catalytic cracked naphtha (API 83-20) was evaluated in rabbits via occlusive dermal application at 2000 mg/kg and 3000 mg/kg body weight. Observations were made hourly for the first 4 hours immediately after dosing and twice daily (a.m. and p.m.) for the following14 days. All animals at the higher dose level survived to termination of the study period; two animals died at the 2000 mg/kg dosage level. Dermal irritation ranged from slight to severe, and from slight to marked for atonia, desquamation and fissuring. Blanching and eschar formation were noted at the test sites for both doses. Subcutaneous haemorrhage was only found at the 3000 mg/kg dose. At necropsy, thickened and crusted skin at the test site was noted.The LD50 for light catalytic cracked naphtha (API 83-20) is >3000 mg/kg. This finding does not warrant classification of the test material as an acute dermal toxicant under the new Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Value:
3 000 mg/kg bw

Additional information

The hydroformylation process, involves the preparation of oxygenated organic compounds by the reaction of carbon monoxide and hydrogen (synthesis gas) with olefinic carbon compounds. Olefins which do not react, and paraffins produced by side reactions are the primary components of Mixed LOF.

The oxo reaction is performed under hydroformylation conditions in the presence of a carbonylation catalyst or catalyst precursor such as dicobaltoctacarbonyl, and results in the formation of a compound (e.g. an aldehyde) which has one more carbon atom in its molecular structure than the feedstock. Subsequent hydrogenation of the hydroformylation product leads to formation of the desired product alcohols. By virtue of the nature of the feedstock commonly available to industry, and indeed of the catalyst and reaction parameters employed, the hydroformylation reaction inevitably yields a range of products due to the numerous secondary reactions which take place.

Mixed LOF (Alkenes, C6-10, hydroformylation products, low-boiling; no CAS RN; EC number 931-285-8) is a byproduct from C7-C11 alcohol production. In the hydroformylation process olefins (alkenes) are catalytically reacted with carbon monoxide and hydrogen, resulting in a range of products including primary alcohols. Alcohols are separated from the reaction mixture by distillation, with the remaining LOF containing unreacted olefins (alkenes) and paraffins (alkanes), frequently of the branched [iso-] form. Compositional analysis indicates Mixed LOF is approximately a 50/50% mixture of olefins and paraffins with a boiling point range of 102 – 182 ºC.

While toxicity data are not available for LOF, based on composition and physical chemical characteristics it is appropriate to use data from naphtha petroleum streams with low levels of aromatic groups and carbon number ranges similar to C6-10. Naphtha streams are derived from the same original feedstock (crude petroleum) with a key process difference – feedstocks to the hydroformylation process (e.g., propylene, butene, and pentenes and combinations thereof) have very low to neglible aromatic material (e.g., benzene or toluene). Thus, use of naphtha streams can generally be considered a conservative read-across approach.

Light Catalytic Cracked Naphtha (LCCN; CAS No. 64741-55-5, consisting of hydrocarbons derived from a catalytic cracking process in the range of 4 to 11 carbons with a boiling range of approximately 65 to 230 degrees centigrade;) or Light Straight Run Naphtha (LSRN; CAS No. 64741-46-4, 64741-46-4, consisting predominantly of aliphatic [paraffinic and isoparaffinic] hydrocarbons in the range of 4 to 10 carbons and boiling between -20 to 180 degree centigrade) as read-across.

 

Human evidence indicates that gasoline has very low acute oral, dermal or inhalation toxicity. However, it can produce severe injury if taken into the lung as a liquid, and there may be profound central nervous system depression following prolonged exposure to high levels of vapor. Laboratory animals respond similarly to humans. Neither gasoline itself, nor any of the naphtha blending stocks, such as LCCN, produces acute oral, dermal or inhalation toxicity under conditions defined by regulatory testing protocols.


Justification for selection of acute toxicity – oral endpoint
No animals died during the study period. Clinical signs observed were diarrhea, ataxia, and hypoactivity. At necropsy, no visible lesions were observed.

Justification for selection of acute toxicity – inhalation endpoint
There were no mortalities and no other treatment-related effects. No gross abnormalities were observed at necropsy.

Justification for selection of acute toxicity – dermal endpoint
Death occured for two rabbits at 2000 mg/kg, but no deaths occured at the higher dose of 3000 mg/kg, indicating the deaths were unlikely to be treatment related.

Justification for classification or non-classification

No classification for acute toxicity is indicated according to the general classification and labeling requirements for dangerous substances and preparations (Directive 67-548-EEC) or the classification, labeling and packaging (CLP) regulation (EC) No 1272/2008.

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