Naphtha (petroleum), light straight-run, co-processed with hydrocarbons derived from thermally cracked waste plastics

Endpoint summary

Description of key information

The acute toxicity has been evaluated using read-across data from studies with gasoline. Based on these data the acute toxicity is summarised as follows:

Acute toxicity – Oral LD50 > 14063 mg/kg (OECD TG 401)

Acute toxicity – Dermal LD50 > 3750 mg/kg (OECD TG 402 under occlusive conditions)

Acute toxicity – Inhalation LC50 > 5610  mg/m3 (OECD TG 403)

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report similar or equivalent to OECD 403. GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

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:

7500, 11250, 13125, 15000 and 18750 mg/kg of test substance.

No. of animals per sex per dose:

Four groups, each consisting of 5 male and 5 female Sprague-Dawley rats, and a fifth group containing 7 male and 6 female rats.

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

14 063 mg/kg bw

Mortality:

Mortality rates, in ascending dose order, were 0%, 30%, 60%,40% and 90%.

Clinical signs:

other: Clinical signs included diarrhea and blood around the nose and mouth.

Gross pathology:

At necropsy, lungs showed effects ranging from mild irritation and congestion to fluid-filled abscesses. Intestines, and often the stomach, were found to be haemorrhaging. In some animals the heart was enlarged or irregular.

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 the test material is 14063 mg/kg. These findings do not warrant classification of the test article as an acute oral toxicant under Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).

Executive summary:

Four groups, each consisting of 5 male and 5 female Sprague-Dawley rats, and a fifth group containing 7 male and 6 female rats were dosed with 7500, 11250, 13125, 15000 and 18750 mg/kg of test substance by oral gavage. The test animals were observed hourly for the first six hours after dosing and twice daily for fourteen days. Mortality rats of the five dose groups (7500, 11250, 13125, 15000 and 18750 mg/kg) were 0%, 31%, 60%, 40% and 90%, respectively. Clinical signs included diarrhea and blood around the nose and mouth. At necropsy, lungs showed effects ranging from mild irritation and congestion to fluid-filled abscesses. Intestines, and often the stomach, were found to be hemorrhaging. In some animals the heart was enlarged or irregular.

Based on the parameters of this study, the acute oral LD50 of the test material is 14063 mg/kg. These findings do not warrant classification of the test article as an acute oral toxicant under Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

14 063 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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report in agreement with OECD guideline 403-GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Sasco, Inc., Omaha, Nebraska
- Age at study initiation: young adults
- Weight at study initiation: approximately 200-300 grams
- Housing: individually
- Diet (e.g. ad libitum): Fresh Certified Rodent feed, ad llibitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week (7 days)

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-76 °F
- Humidity (%): 40 to 60 percent relative humidity
- Photoperiod (hrs dark / hrs light): 12hrs dark /12 hrs light

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Rats were exposed in to the test atmosphere in a Hazleton 1000 whole body inhalation chamber. The test atmosphere was generated by delivering the test article to a Sonimist nozzle (nebulizer) under pressure by compressed breathing air
- Volume: 1m3 (1000L)
- Temperature, pressure in air chamber: 23
- Air flow rate: 200 L/min (avg)

TEST ATMOSPHERE
- The test atmosphere shall be generated using an appropriate system selected according to the physical state and characteristics of the test article.
- Groups of individually caged rats will be exposed collectively to the test atmosphere under dynamic air flow conditions for four hours in an appropriate sized whole body chamber (50 in. x 48 in. x 25 in.).
- Air flow rate shall be monitored continuously and documented every thirty minutes
- An exposure environment of at least 19% oxygen shall be insured
-Temperature and humidity shall be monitored continuously and documented every thirty minutes
- Nominal concentrations of test article for each exposure shall be determined gravimetrically
- actual concentrations of airborn test article shall be measured near the breathing zone at one hour intervals during the test period
- particle size distribution measurements shall be made near the breathing zone during the exposed period

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Concentrations:

- nominal (gravimetric) concentration: 7630 +/- 900 mg/m³
- actual (miran) vapor concentration: 5610 +/- 300 mg/m³

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

One group of ten rats (5 of each sex) will be collectively exposed to either 5.0 mg/l or the maximum attainable concentration (whichever is the lesser) of the test article. The sponsor representative shall be notified immediately if any deaths occur during the acute screening study. After obtaining the sponsor's representative's approval, groups of twenty rats (10 male, 10 female) will be collectively exposed. Exposure levels for this LC50 study shall be approved by the Sponsor Representative after reviewing the results of the screening study. On post dosing day 13, all surviving animals shall be sacrificed. All animals will undergo a complete gross necropsy.

Statistics:

-Mean and standard deviations shall be calculated for animal body weights at the following intervals: day 0, day 7 and termination.
-The ratio of vapor to aerosol phases generated shall be calculated for liquids
-Mean and standard deviations shall be calculated for air flow, temperature, test article concentration and humidity during the testing procedure
-If an LC50 study is performed, median lethal dose values shall be calculated for each sex by an accepted method such as Finney, D.J. (1971) Probit Analysis, 3rd Ed., Cambridge Univ. Press, London. A 95% confidence interval for the median lethal dose should be calculated.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 7 630 mg/m³ air (nominal)

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 610 mg/m³ air (analytical)

Mortality:

none

Clinical signs:

other: All animals survived to the scheduled sacrifice. There were no remarkable clinical signs noted during the course of treatment.

Body weight:

- male rats gained an average of 60 g (s.d. 9 g) with a range of 50-73 g over the two week period
- female rats gained an average of 18 g (s.d. 6 g) with a range of 11-27 g over the two week period

Gross pathology:

Three of the five male rats exhibited lungs with small round lesions. There were no other visible gross pathological lesions observed on any of the animals at necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The inhalation LC50 of test article F-101 is greater than an average nominal (gravimetric) concentration of 7630 +/- 900 mg/m³ and an average actual (calculated by Miran) concentration of 5610 +/- 300 mg/m³. These findings do not warrant classification of the test article as an acute inhalation toxicant under Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).

Executive summary:

Five male and five female rats were exposed to an average nominal (gravimetric) concentration of 7630 +/- 900 mg/m³ and an average actual (measured by Miran) vapor concentration of 5610 +/- 300 mg/m³ of test article F-101 for four consecutive hours. No in-life observation effects were observed during the 14 day observation period. At necropsy, three of the five male rats had lung lesions that may be test article related. None of the animals died during the 14 day observation period. Based on the parameters of this study, the inhalation LC50 of test article F-101 is greater than an average nominal (gravimetric) concentration of 7630 +/- 900 mg/m³ and an average actual (calculated by Miran) concentration of 5610 +/- 300 mg/m³.

These findings do not warrant classification of the test article as an acute inhalation toxicant under Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 610 mg/m³ air

Quality of whole database:

supported by two human volunteer studies

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report similar or equivalent to OECD 402. GLP.

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:

3750 mg/kg

No. of animals per sex per dose:

4 males and 4 females/dose

Control animals:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 750 mg/kg bw

Mortality:

One animal died on day 6 of the 14-day post-exposure observation period.

Clinical signs:

other: Erythema and edema were observed at the test site.

Gross pathology:

Necropsy revealed congested lungs and white areas on the liver. In addition, four animals were found to have congested lungs, but it was not clear that this effect was treatment-related.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 for unleaded gasoline (API PS-6) in the rabbit is >3750 mg/kg. This finding does not warrant classification of the test material as an acute dermal toxicant under Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).

Executive summary:

The acute toxicity of unleaded gasoline (API PS-6) was evaluated in rabbits via occlusive dermal application at 3750 mg/kg. Observations were made hourly for the first 4 hours immediately after dosing and twice daily (a.m. and p.m.) for the following 14 days. One animal died on day 6 post-exposure. Erythema and edema were observed at the test site during the observation period. Necropsy revealed congested lungs and white areas on the liver. In addition, four animals were found to have congested lungs, but it was not clear that this effect was treatment-related. The LD50 for unleaded gasoline (API PS-6) is >3750 mg/kg.

This finding does not warrant classification of the test material as an acute dermal toxicant under Regulation (EC) 1272/2008 on classification, labeling, and packaging of substances and mixtures (CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 750 mg/kg bw

Additional information

The acute toxicity has been evaluated using read-across data from studies with gasoline. Based on these data the acute toxicity is summarised as follows:

Acute toxicity – Oral LD50 > 14063 mg/kg (OECD TG 401)

Acute toxicity – Dermal LD50 > 3750 mg/kg (OECD TG 402 under occlusive conditions)

Acute toxicity – Inhalation LC50 > 5610 mg/m3 (OECD TG 403

Human evidence also 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. Gasoline does not produce acute oral, dermal or inhalation toxicity under conditions defined by regulatory testing protocols.

Justification for selection of acute toxicity – oral endpoint

We3ll conducted acute oral study in rats

Justification for selection of acute toxicity – inhalation endpoint

Well conducted acute inhalation study in rats

Justification for selection of acute toxicity – dermal endpoint

A well conducted acute dermal toxicity study

Justification for classification or non-classification

These studies were conducted many years ago, they were generally, conducted in accordance with regulatory guidelines good laboratory practice recommendations. The data are this considered adequate for regulatory purposes and no additional testing is warranted.

The data do not meet the criteria for hazard classification for acute, dermal or inhalation toxicity according to EU CLP Regulation (EC No. 1272/2008); however, warnings for aspiration hazard and potential narcotic effects at high concentrations are considered appropriate.